Sample records for heat shock-triggered released

  1. Fish in hot water: hypoxaemia does not trigger catecholamine mobilization during heat shock in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Currie, S; Ahmady, E; Watters, M A; Perry, S F; Gilmour, K M

    2013-06-01

    Rainbow trout (Oncorhynchus mykiss) exposed to an acute heat shock (1 h at 25 °C after raising water temperature from 13 °C to 25 °C over 4 h) mount a significant catecholamine response. The present study investigated the proximate mechanisms underlying catecholamine mobilization. Trout exposed to heat shock in vivo exhibited a significant reduction in arterial O(2) tension, but arterial O(2) concentration was not affected by heat shock, nor was catecholamine release during heat shock prevented by prior and concomitant exposure to hyperoxia (to prevent the fall in arterial O(2) tension). Thus, catecholamine mobilization probably was not triggered by impaired blood O(2) transport. Heat-shocked trout also exhibited an elevation of arterial CO(2) tension coupled with a fall in arterial pH, but these factors are not expected to trigger catecholamine release. The changes in blood O(2) and CO(2) tension occurred despite a significant hyperventilatory response to heat shock. Future studies should investigate whether catecholamine mobilization during heat shock in rainbow trout is triggered by a specific effect of high temperature activating the sympathetic nervous system via a thermosensitive transient receptor potential channel. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Heat shock protein 72: release and biological significance during exercise.

    PubMed

    Whitham, Martin; Fortes, Matthew Benjamin

    2008-01-01

    The cumulative stressors of exercise manifest themselves at a cellular level by threatening the protein homeostasis of the cell. In these conditions, Heat Shock Proteins (HSP) are synthesised to chaperone mis-folded and denatured proteins. As such, the intracellular HSP response is thought to aid cell survival in the face of otherwise lethal cellular stress. Recently, the inducible isoform of the 70 Kda heat shock protein family, Hsp72 has been detected in the extracellular environment. Furthermore, the release of this protein into the circulation has been shown to occur in response to a range of exercise bouts. The present review summarises the current research on the exercise Hsp72 response, the possible mediators and mechanisms of extracellular (e)Hsp72 release, and the possible biological significance of this systemic response. In particular, the possible role of eHsp72 in the modulation of immunity during exercise is discussed.

  3. Heat shock, but not temperature, is a biological trigger for the exsheathment of third-stage larvae of Haemonchus contortus.

    PubMed

    Bekelaar, Kiliana; Waghorn, Tania; Tavendale, Michael; McKenzie, Catherine; Leathwick, Dave

    2018-05-21

    Gastrointestinal parasites are an important health issue in grazing ruminants. Understanding the processes involved in the transition from the free living to the parasitic life stage of these nematodes is one avenue to identifying new targets amenable to future intervention. The transition to parasitism is initiated by exsheathment and is triggered by the sudden change in environment after ingestion of the infective larva by the host. Two major changes in environment are the increases in temperature and carbon dioxide (CO 2 ) levels. For CO 2 a role in exsheathment has been described previously, but the exact role of temperature was unclear. The current study is the first to investigate the importance of temperature in triggering exsheathment of Haemonchus contortus. Carbon dioxide induced exsheathment in H. contortus proved to be temperature dependent, as no exsheathment was observed at room temperatures. However, the temperature requirement to trigger exsheathment was quite specific. A rapid change in temperature (heat shock) very efficiently induced high levels of exsheathment. In contrast, when the larvae were exposed to a slow increase in temperature, the exsheathment response was smaller and delayed. Further investigation revealed that timing of the heat shock in relation to the CO 2 administration was crucial, as well as the final temperature and magnitude of the heat shock. In conclusion, these data indicate that heat shock rather than temperature itself is a crucial aspect in triggering the biological exsheathment cascade, and thus infection process, of H. contortus.

  4. Not changes in membrane fluidity but proteotoxic stress triggers heat shock protein expression in Chlamydomonas reinhardtii.

    PubMed

    Rütgers, Mark; Muranaka, Ligia Segatto; Schulz-Raffelt, Miriam; Thoms, Sylvia; Schurig, Juliane; Willmund, Felix; Schroda, Michael

    2017-12-01

    A conserved reaction of all organisms exposed to heat stress is an increased expression of heat shock proteins (HSPs). Several studies have proposed that HSP expression in heat-stressed plant cells is triggered by an increased fluidity of the plasma membrane. Among the main lines of evidence in support of this model are as follows: (a) the degree of membrane lipid saturation was higher in cells grown at elevated temperatures and correlated with a lower amplitude of HSP expression upon a temperature upshift, (b) membrane fluidizers induce HSP expression at physiological temperatures, and (c) membrane rigidifier dimethylsulfoxide dampens heat-induced HSP expression. Here, we tested whether this holds also for Chlamydomonas reinhardtii. We show that heat-induced HSP expression in cells grown at elevated temperatures was reduced because they already contained elevated levels of cytosolic HSP70A/90A that apparently act as negative regulators of heat shock factor 1. We find that membrane rigidifier dimethylsulfoxide impaired translation under heat stress conditions and that membrane fluidizer benzyl alcohol not only induced HSP expression but also caused protein aggregation. These findings support the classical model for the cytosolic unfolded protein response, according to which HSP expression is induced by the accumulation of unfolded proteins. Hence, the membrane fluidity model should be reconsidered. © 2017 John Wiley & Sons Ltd.

  5. Roles of heat shock factors in gametogenesis and development.

    PubMed

    Abane, Ryma; Mezger, Valérie

    2010-10-01

    Heat shock factors form a family of transcription factors (four in mammals), which were named according to the first discovery of their activation by heat shock. As a result of the universality and robustness of their response to heat shock, the stress-dependent activation of heat shock factor became a ‘paradigm’: by binding to conserved DNA sequences (heat shock elements), heat shock factors trigger the expression of genes encoding heat shock proteins that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stress and in several pathological conditions. Besides their roles in the stress response, heat shock factors perform crucial roles during gametogenesis and development in physiological conditions. First, during these process, in stress conditions, they are either proactive for survival or, conversely, for apoptotic process, allowing elimination or, inversely, protection of certain cell populations in a way that prevents the formation of damaged gametes and secure future reproductive success. Second, heat shock factors display subtle interplay in a tissue- and stage-specific manner, in regulating very specific sets of heat shock genes, but also many other genes encoding growth factors or involved in cytoskeletal dynamics. Third, they act not only by their classical transcription factor activities, but are necessary for the establishment of chromatin structure and, likely, genome stability. Finally, in contrast to the heat shock gene paradigm, heat shock elements bound by heat shock factors in developmental process turn out to be extremely dispersed in the genome, which is susceptible to lead to the future definition of ‘developmental heat shock element’.

  6. Small Heat Shock Proteins Can Release Light Dependence of Tobacco Seed during Germination1[OPEN

    PubMed Central

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

    2015-01-01

    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

  7. Systemic Analysis of Heat Shock Response Induced by Heat Shock and a Proteasome Inhibitor MG132

    PubMed Central

    Kim, Hee-Jung; Joo, Hye Joon; Kim, Yung Hee; Ahn, Soyeon; Chang, Jun; Hwang, Kyu-Baek; Lee, Dong-Hee; Lee, Kong-Joo

    2011-01-01

    The molecular basis of heat shock response (HSR), a cellular defense mechanism against various stresses, is not well understood. In this, the first comprehensive analysis of gene expression changes in response to heat shock and MG132 (a proteasome inhibitor), both of which are known to induce heat shock proteins (Hsps), we compared the responses of normal mouse fibrosarcoma cell line, RIF- 1, and its thermotolerant variant cell line, TR-RIF-1 (TR), to the two stresses. The cellular responses we examined included Hsp expressions, cell viability, total protein synthesis patterns, and accumulation of poly-ubiquitinated proteins. We also compared the mRNA expression profiles and kinetics, in the two cell lines exposed to the two stresses, using microarray analysis. In contrast to RIF-1 cells, TR cells resist heat shock caused changes in cell viability and whole-cell protein synthesis. The patterns of total cellular protein synthesis and accumulation of poly-ubiquitinated proteins in the two cell lines were distinct, depending on the stress and the cell line. Microarray analysis revealed that the gene expression pattern of TR cells was faster and more transient than that of RIF-1 cells, in response to heat shock, while both RIF-1 and TR cells showed similar kinetics of mRNA expression in response to MG132. We also found that 2,208 genes were up-regulated more than 2 fold and could sort them into three groups: 1) genes regulated by both heat shock and MG132, (e.g. chaperones); 2) those regulated only by heat shock (e.g. DNA binding proteins including histones); and 3) those regulated only by MG132 (e.g. innate immunity and defense related molecules). This study shows that heat shock and MG132 share some aspects of HSR signaling pathway, at the same time, inducing distinct stress response signaling pathways, triggered by distinct abnormal proteins. PMID:21738571

  8. Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update

    PubMed Central

    2013-01-01

    Heat shock proteins (HSP) are a subset of the molecular chaperones, best known for their rapid and abundant induction by stress. HSP genes are activated at the transcriptional level by heat shock transcription factor 1 (HSF1). During the progression of many types of cancer, this heat shock transcriptional regulon becomes co-opted by mechanisms that are currently unclear, although evidently triggered in the emerging tumor cell. Concerted activation of HSF1 and the accumulation of HSPs then participates in many of the traits that permit the malignant phenotype. Thus cancers of many histologies exhibit activated HSF1 and increased HSP levels that may help to deter tumor suppression and evade therapy in the clinic. We review here the extensive work that has been carried out and is still in progress aimed at: (1) understanding the oncogenic mechanisms by which HSP genes are switched on, (2) determining the roles of HSF1 / HSP in malignant transformation and, (3) discovering approaches to therapy based on disrupting the influence of the HSF1 controlled transcriptome in cancer. PMID:22885793

  9. Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides

    PubMed Central

    Jia, Haibo; Halilou, Amadou I.; Hu, Liang; Cai, Wenqian; Liu, Jing; Huang, Bo

    2011-01-01

    Heat shock protein 10 (Hsp10) in eukaryotes, originally identified as a mitochondrial chaperone, now is also known to be present in cytosol, cell surface, extracellular space and peripheral blood. Functionally besides participating in mitochondrial protein folding in association with Hsp60, Hsp10 appears to be related to pregnancy, cancer and autoimmune inhibition. Hsp10 can be released to peripheral blood at very early time point of pregnancy and given another name called early pregnancy factor (EPF), which seems to play a critical role in developing a pregnant niche. In malignant disorders, Hsp10 is usually abnormally expressed in the cytosol of malignant cells and further released to extracellular space, resulting in tumor-promoting effect from various aspects. Furthermore, distinct from other heat shock protein members, whose soluble form is recognized as danger signal by immune cells and triggers immune responses, Hsp10 after release, however, is designed to be an inhibitory signal by limiting immune response. This review discusses how Hsp10 participates in various physiological and pathological processes from basic protein molecule folding to pregnancy, cancer and autoimmune diseases, and emphasizes how important the location is for the function exertion of a molecule. PMID:21969171

  10. Extracellular Release and Signaling by Heat Shock Protein 27: Role in Modifying Vascular Inflammation

    PubMed Central

    Batulan, Zarah; Pulakazhi Venu, Vivek Krishna; Li, Yumei; Koumbadinga, Geremy; Alvarez-Olmedo, Daiana Gisela; Shi, Chunhua; O’Brien, Edward R.

    2016-01-01

    Heat shock protein 27 (HSP27) is traditionally viewed as an intracellular chaperone protein with anti-apoptotic properties. However, recent data indicate that a number of heat shock proteins, including HSP27, are also found in the extracellular space where they may signal via membrane receptors to alter gene transcription and cellular function. Therefore, there is increasing interest in better understanding how HSP27 is released from cells, its levels and composition in the extracellular space, and the cognate cell membrane receptors involved in effecting cell signaling. In this paper, the knowledge to date, as well as some emerging paradigms about the extracellular function of HSP27 is presented. Of particular interest is the role of HSP27 in attenuating atherogenesis by modifying lipid uptake and inflammation in the plaque. Moreover, the abundance of HSP27 in serum is an emerging new biomarker for ischemic events. Finally, HSP27 replacement therapy may represent a novel therapeutic opportunity for chronic inflammatory disorders, such as atherosclerosis. PMID:27507972

  11. Effect of diadenosine tetraphosphate microinjection on heat shock protein synthesis in Xenopus laevis oocytes.

    PubMed Central

    Guedon, G; Sovia, D; Ebel, J P; Befort, N; Remy, P

    1985-01-01

    Bisnucleosides polyphosphates are thought to be chemical messengers signalling to the cell the onset of various stresses. Diadenosine tri- and tetraphosphates (respectively, Ap3A and Ap4A) accumulate in prokaryotic and eukaryotic cells under heat shock conditions, suggesting they could trigger the synthesis of heat shock proteins (hsps). In this study, Ap4A, Ap3A and, as a control, Ap4 (adenosine tetraphosphate) were injected into Xenopus oocytes. Whereas none of these compounds is able to trigger the synthesis of hsps in the absence of hyperthermic treatment, nuclear microinjection of Ap4A after a mild heat shock specifically enhances the synthesis of the 70-kd hsp, which is involved in the regulation and possibly the termination of the heat shock response. The microinjection of Ap4A prior to the hyperthermic treatment results in a strong inhibition of hsps synthesis (with the exception of the 70-kd hsp) suggesting that Ap4A is involved in the regulation and/or termination of the heat shock response. Ap3A and Ap4 do not induce any detectable modification of hsps expression. Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. PMID:4092696

  12. Thermo-sensitive nanoparticles for triggered release of siRNA.

    PubMed

    Yang, Zheng; Cheng, Qiang; Jiang, Qian; Deng, Liandong; Liang, Zicai; Dong, Anjie

    2015-01-01

    Efficient delivery of small interfering RNA (siRNA) is crucially required for cancer gene therapy. Herein, a thermo-sensitive copolymer with a simple structure, poly (ethylene glycol) methyl ether acrylate-b-poly (N-isopropylacrylamide) (mPEG-b-PNIPAM) was developed. A novel kind of thermo-sensitive nanoparticles (DENPs) was constructed for the cold-shock triggered release of siRNA by double emulsion-solvent evaporation method using mPEG-b-PNIPAM and a cationic lipid, 3β [N-(N', N'-dimethylaminoethane)-carbamoyl] cholesterol [DC-Chol]. DENPs were observed by transmission electron microscopy and dynamical light scattering before and after 'cold shock' treatment. The encapsulation efficiency (EE) of siRNA in DENPs, which was measured by fluorescence spectrophotometer was 96.8% while it was significantly reduced to be 23.2% when DC-Chol was absent. DENPs/siRNA NPs exhibited a thermo-sensitive siRNA release character that the cumulatively released amount of siRNA from cold shock was approximately 2.2 folds higher after 7 days. In vitro luciferase silencing experiments indicated that DENPs showed potent gene silencing efficacy in HeLa-Luc cells (HeLa cells steadily expressed luciferase), which was further enhanced by a cold shock. Furthermore, MTT assay showed that cell viability with DENPs/siRNA up to 200 nM remained above 80%. We also observed that most of siRNA was accumulated in kidney mediated by DENPs instead of liver and spleen in vivo experiments. Thus, DENPs as a cold shock responsive quick release model for siRNA or hydrophilic macromolecules delivery provide a new way to nanocarrier design and clinic therapy.

  13. Heat Shock Protein 70: Roles in Multiple Sclerosis

    PubMed Central

    Mansilla, María José; Montalban, Xavier; Espejo, Carmen

    2012-01-01

    Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE. PMID:22669475

  14. Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage

    PubMed Central

    Baker, Todd A.; Romero, Jacqueline; Bach, Harold H.; Strom, Joel A.; Gamelli, Richard L.; Majetschak, Matthias

    2011-01-01

    Objective To define systemic release kinetics of a panel of cytokines and heat shock proteins (HSP) in porcine polytrauma/hemorrhage models and to evaluate whether they could be useful as early trauma biomarkers. Design and Setting Prospective study in a research laboratory. Subjects Twenty-one Yorkshire pigs. Measurements and Main Results Pigs underwent polytrauma (femur fractures/lung contusion, P), hemorrhage (mean arterial pressure 25-30mmHg, H), polytrauma plus hemorrhage (P/H) or sham procedure (S). Plasma was obtained at baseline, in 5-15min intervals during a 60min shock period without intervention and in 60-120min intervals during fluid resuscitation for up to 300min. Plasma was assayed for IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-17, IL-18, IFNγ, TGFβ, TNFα, HSP40, HSP70 and HSP90 by ELISA. All animals after S, P and H survived (n=5/group). Three of six animals after P/H died. IL-10 increased during shock after P and this increase was attenuated after H. TNFα increased during the shock period after P, H and also after S. P/H abolished the systemic IL-10 and TNFα release and resulted in 20-30% increased levels of IL-6 during shock. As fluid resuscitation was initiated TNFα and IL-10 levels decreased after P, H and P/H, HSP 70 increased after P, IL-6 levels remained elevated after P/H and also increased after P and S. Conclusions Differential regulation of the systemic cytokine release after polytrauma and/or hemorrhage, in combination with the effects of resuscitation, can explain the variability and inconsistent association of systemic cytokine/HSP levels with clinical variables in trauma patients. Insults of major severity (P/H) partially suppress the systemic inflammatory response. The plasma concentrations of the measured cytokines/HSPs do not reflect injury severity or physiological changes in porcine trauma models and are unlikely to be able to serve as useful trauma biomarkers in patients. PMID:21983369

  15. RNAi screen in Drosophila larvae identifies histone deacetylase 3 as a positive regulator of the hsp70 heat shock gene expression during heat shock.

    PubMed

    Achary, Bhavana G; Campbell, Katie M; Co, Ivy S; Gilmour, David S

    2014-05-01

    The transcription regulation of the Drosophila hsp70 gene is a complex process that involves the regulation of multiple steps, including the establishment of paused Pol II and release of Pol II into elongation upon heat shock activation. While the major players involved in the regulation of gene expression have been studied in detail, additional factors involved in this process continue to be discovered. To identify factors involved in hsp70 expression, we developed a screen that capitalizes on a visual assessment of heat shock activation using a hsp70-beta galactosidase reporter and publicly available RNAi fly lines to deplete candidate proteins. We validated the screen by showing that the depletion of HSF, CycT, Cdk9, Nurf 301, or ELL prevented the full induction of hsp70 by heat shock. Our screen also identified the histone deacetylase HDAC3 and its associated protein SMRTER as positive regulators of hsp70 activation. Additionally, we show that HDAC3 and SMRTER contribute to hsp70 gene expression at a step subsequent to HSF-mediated activation and release of the paused Pol II that resides at the promoter prior to heat shock induction. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Magnetically triggered dual functional nanoparticles for resistance-free apoptotic hyperthermia.

    PubMed

    Yoo, Dongwon; Jeong, Heeyeong; Noh, Seung-Hyun; Lee, Jae-Hyun; Cheon, Jinwoo

    2013-12-02

    Overcoming resistance: Heat-treated cancer cells possess a protective mechanism for resistance and survival. Resistance-free apoptosis-inducing magnetic nanoparticles (RAINs) successfully promote hyperthermic apoptosis, obstructing cell survival by triggering two functional units of heat generation and the release of geldanamycin (GM) for heat shock protein (Hsp) inhibition under an alternating magnetic field (AMF). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Stabilizing Alginate Confinement and Polymer Coating of CO-Releasing Molecules Supported on Iron Oxide Nanoparticles To Trigger the CO Release by Magnetic Heating.

    PubMed

    Meyer, Hajo; Winkler, Felix; Kunz, Peter; Schmidt, Annette M; Hamacher, Alexandra; Kassack, Matthias U; Janiak, Christoph

    2015-12-07

    Maghemite (Fe2O3) iron oxide nanoparticles (IONPs) were synthesized, modified with covalent surface-bound CO-releasing molecules of a tri(carbonyl)-chlorido-phenylalaninato-ruthenium(II) complex (CORM), and coated with a dextran polymer. The time- and temperature-dependent CO release from this CORM-3 analogue was followed by a myoglobin assay. A new measurement method for the myoglobin assay was developed, based on confining "water-soluble" polymer-coated Dextran500k@CORM@IONP particles in hollow spheres of nontoxic and easily prepared calcium alginate. Dropping a mixture of Dextran500k@CORM@IONP and sodium alginate into a CaCl2 solution leads to stable hollow spheres of Ca(2+) cross-linked alginate which contain the Dextran500k@CORM@IONP particles. This "alginate-method" (i) protects CORM-3 analogues from rapid CO-displacement reactions with a protein, (ii) enables a spatial separation of the CORM from its surrounding myoglobin assay with the alginate acting as a CO-permeable membrane, and (iii) allows the use of substances with high absorptivity (such as iron oxide nanoparticles) in the myoglobin assay without interference in the optical path of the UV cell. Embedding the CORM@IONP nanoparticles in the alginate vessel represents a compartmentation of the reactive component and allows for close contact with, yet facile separation from, the surrounding myoglobin assay. The half-life of the CO release from Dextran500k@CORM@IONP particles surrounded by alginate was determined to be 890 ± 70 min at 20 °C. An acceleration of the CO release occurs at higher temperature with a half-life of 172 ± 27 min at 37 °C and 45 ± 7 min at 50 °C. The CO release can be triggered in an alternating current magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mT) through local magnetic heating of the susceptible iron oxide nanoparticles. With magnetic heating at 20 °C in the bulk solution, the half-life of CO release from Dextran500k@CORM@IONP particles decreased to 155 ± 18 min

  18. Remotely Triggered Cisplatin Release from Carbon Nanocapsules by Radiofrequency Fields

    PubMed Central

    Raoof, Mustafa; Cisneros, Brandon T.; Guven, Adem; Corr, Stuart J.; Wilson, Lon J.; Curley, Steven A.

    2013-01-01

    The efficacy of nanoparticle-mediated drug delivery is limited by its peri-vascular sequestration, thus necessitating a strategy to trigger drug release from such intra-tumoral nanocarrier-drug depots. In our efforts to explore remotely-activated nanocarriers, we have developed carbon nanocapsules comprised of an ultrashort carbon nanotube shell (US-tubes) loaded with cisplatin (CDDP@US-tubes) and covered with a Pluronic surfactant wrapping to minimize passive release. We demonstrate here that non-invasive radiofrequency (RF) field activation of the CDDP@US-tubes produces heat that causes Pluronic disruption which triggers cisplatin release in an RF-dependent manner. Furthermore, release-dependent cytotoxicity is demonstrated in human hepatocellular carcinoma cell lines. PMID:23228421

  19. Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.

    PubMed

    Lajunen, Tatu; Kontturi, Leena-Stiina; Viitala, Lauri; Manna, Moutusi; Cramariuc, Oana; Róg, Tomasz; Bunker, Alex; Laaksonen, Timo; Viitala, Tapani; Murtomäki, Lasse; Urtti, Arto

    2016-06-06

    Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.

  20. Magnetically triggered release of molecular cargo from iron oxide nanoparticle loaded microcapsules

    NASA Astrophysics Data System (ADS)

    Carregal-Romero, Susana; Guardia, Pablo; Yu, Xiang; Hartmann, Raimo; Pellegrino, Teresa; Parak, Wolfgang J.

    2014-12-01

    Photothermal release of cargo molecules has been extensively studied for bioapplications. For instance, microcapsules decorated with plasmonic nanoparticles have been widely used in in vitro assays. However, some concerns about their suitability for some in vivo applications cannot be easily overcome, in particular the limited penetration depth of light (even infrared). Magnetic nanoparticles are alternative heat-mediators for local heating, which can be triggered by applying an alternating magnetic field (AMF). AMFs are much less absorbed by tissue than light and thus can penetrate deeper overcoming the above mentioned limitations. Here we present iron oxide nanocube-modified microcapsules as a platform for magnetically triggered molecular release. Layer-by-layer assembled polyelectrolyte microcapsules with 4.6 μm diameter, which had 18 nm diameter iron oxide nanocubes integrated in their walls, were synthesized. The microcapsules were further loaded with an organic fluorescent polymer (Cascade Blue-labelled dextran), which was used as a model of molecular cargo. Through an AMF the magnetic nanoparticles were able to heat their surroundings and destroy the microcapsule walls, leading to a final release of the embedded cargo to the surrounding solution. The cargo release was monitored in solution by measuring the increase in both absorbance and fluorescence signal after the exposure to an AMF. Our results demonstrate that magnetothermal release of the encapsulated material is possible using magnetic nanoparticles with a high heating performance.Photothermal release of cargo molecules has been extensively studied for bioapplications. For instance, microcapsules decorated with plasmonic nanoparticles have been widely used in in vitro assays. However, some concerns about their suitability for some in vivo applications cannot be easily overcome, in particular the limited penetration depth of light (even infrared). Magnetic nanoparticles are alternative heat

  1. Heat shock proteins and toll-like receptors.

    PubMed

    Asea, Alexzander

    2008-01-01

    Researchers have only just begun to elucidate the relationship between heat shock proteins (HSP) and Toll-like receptors (TLR). HSP were originally described as an intracellular molecular chaperone of naïve, aberrantly folded, or mutated proteins and primarily implicated as a cytoprotective protein when cells are exposed to stressful stimuli. However, recent studies have ascribed novel functions to the Hsp70 protein depending on its localization: Surface-bound Hsp70 specifically activate natural killer (NK) cells, while Hsp70 released into the extracellular milieu specifically bind to Toll-like receptors (TLR) 2 and 4 on antigen-presenting cells (APC) and exerts immunoregulatory effects, including upregulation of adhesion molecules, co-stimulatory molecule expression, and cytokine and chemokine release-a process known as the chaperokine activity of Hsp70. This chapter discusses the most recent advances in the understanding of heat shock protein (HSP) and TLR interactions in general and highlights recent findings that demonstrate Hsp70 is a ligand for TLR and its biological significance.

  2. Chromosome behavior of heat shock induced triploid in Fenneropenaeus chinensis

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaojun; Li, Fuhua; Xiang, Jianhai

    2003-09-01

    Triploidy was induced in Chinese shrimp Fenneropenaeus chinensis by 30±0.5°C heat shock treatment (initiated at 20 min after fertilization) for 10 min to inhibit the release of PB2 at 18.0°C. The highest triploid rate obtained was 84.5% in nauplius stage. The effect of heat shock treatment on meiosis and cleavage of eggs was investigated in this work aimed to establish efficient procedures for triploid induction and to gain understanding of the mechanism of triploid production. Three pronuclei that could be observed in the treated eggs under fluorescence microscope developed into triploid embryos. Some abnormal chromosome behavior was observed in heat shocked eggs.

  3. Thermosensitive liposomes for localized delivery and triggered release of chemotherapy

    PubMed Central

    Ta, Terence; Porter, Tyrone M.

    2016-01-01

    Liposomes are a promising class of nanomedicine with the potential to provide site-specific chemotherapy, thus improving the quality of cancer patient care. First-generation liposomes have emerged as one of the first nanomedicines used clinically for localized delivery of chemotherapy. Second-generation liposomes, i.e. stimuli-responsive liposomes, have the potential to not only provide site-specific chemotherapy, but also triggered drug release and thus greater spatial and temporal control of therapy. Temperature-sensitive liposomes are an especially attractive option, as tumors can be heated in a controlled and predictable manner with external energy sources. Traditional thermosensitive liposomes are composed of lipids that undergo a gel-to-liquid phase transition at several degrees above physiological temperature. More recently, temperature-sensitization of liposomes has been demonstrated with the use of lysolipids and synthetic temperature-sensitive polymers. The design, drug release behavior, and clinical potential of various temperature-sensitive liposomes, as well as the various heating modalities used to trigger release, are discussed in this review. PMID:23583706

  4. Endogenous extra-cellular heat shock protein 72: releasing signal(s) and function.

    PubMed

    Fleshner, M; Johnson, J D

    2005-08-01

    Exposure to acute physical and/or psychological stressors induces a cascade of physiological changes collectively termed the stress response. The stress response is demonstrable at the behavioural, neural, endocrine and cellular levels. Stimulation of the stress response functions to improve an organism's chance of survival during acute stressor challenge. The current review focuses on one ubiquitous cellular stress response, up-regulation of heat shock protein 72 (Hsp72). Although a great deal is known about the function of intra-cellular Hsp72 during exposure to acute stressors, little is understood about the potential function of endogenous extra-cellular Hsp72 (eHsp72). The current review will develop the hypothesis that eHsp72 release may be a previously unrecognized feature of the acute stress response and may function as an endogenous 'danger signal' for the immune system. Specifically, it is proposed that exposure to physical or psychological acute stressors stimulate the release of endogenous eHsp72 into the blood via an alpha1-adrenergic receptor-mediated mechanism and that elevated eHsp72 functions to facilitate innate immunity in the presence of bacterial challenge.

  5. Heat shock protein-containing exosomes in mid-trimester amniotic fluids.

    PubMed

    Asea, Alexzander; Jean-Pierre, Claudel; Kaur, Punit; Rao, Preethi; Linhares, Iara M; Skupski, Daniel; Witkin, Steven S

    2008-10-01

    Exosomes are multivesicular bodies formed by inverse membrane budding into the lumen of an endocytic compartment. Fusion with the plasma membrane leads to their release into the external milieu. The incorporation of heat shock proteins into exosomes has been associated with immune regulatory activity. We have examined whether heat shock protein-containing exosomes are present in mid-trimester amniotic fluid. Exosomes were isolated from mid-trimester amniotic fluids by sequential low-speed and high-speed centrifugation followed by sucrose density gradient centrifugation. Biochemical characterization included floatation pattern in sucrose gradients, acetylcholinesterase (AChE) activity and Western blot analysis for exosome-containing proteins. Exosomes were present in each of 23 amniotic fluids tested. They banded at a density of 1.17g/ml in sucrose gradients, were positive for AChE activity and contained tubulin, the inducible 72kDa heat shock protein, Hsp72 and the constitutively expressed heat shock protein, Hsc73; they were negative for calnexin. Exosome concentrations correlated positively with the number of pregnancies. Heat shock protein-containing exosomes are constituents of mid-trimester amniotic fluids and may contribute to immune regulation within the amniotic cavity.

  6. Simulating Shock Triggered Star Formation with AstroBEAR2.0

    NASA Astrophysics Data System (ADS)

    Li, Shule; Frank, Adam; Blackman, Eric

    2013-07-01

    Star formation can be triggered by the compression from shocks running over stable clouds. Triggered star formation is a favored explanation for the traces of SLRI's in our solar system. Previous research has shown that when parameters such as shock speed are within a certain range, the gravitational collapse of otherwise stable, dense cloud cores is possible. However, these studies usually focus on the precursors of star formation, and the conditions for the triggering. We use AstroBEAR2.0 code to simulate the collapse and subsequent evolution of a stable Bonnor-Ebert cloud by an incoming shock. Through our simulations, we show that interesting physics happens when the newly formed star interacts with the cloud residue and the post-shock flow. We identify these interactions as controlled by the initial conditions of the triggering and study the flow pattern as well as the evolution of important physics quantities such as accretion rate and angular momentum.

  7. Shock loading and release behavior of silicon nitride

    NASA Astrophysics Data System (ADS)

    Kawai, N.; Tsuru, T.; Hidaka, N.; Liu, X.; Mashimo, T.

    2017-01-01

    Shock-reshock and shock-release experiments were performed on silicon nitride ceramics above and below its phase transition pressure. Experimental results clearly show the occurrence of elastic-plastic transition and phase transition during initial shock loading. The HEL and phase transition stress are determined as 11.6 and 34.5 GPa, respectively. Below the phase transition stress, the reshock profile consists of the single shock with short rise time, while the release profile shows the gradual release followed by rapid one. Above phase transition stress, reshock and release behavior varies with the initial shock stress. In the case of reshock and release from about 40 GPa, the reshock structure is considerably dispersed, while the release structure shows rapid release. In the reshock profile from about 50 GPa, the formation of the shock wave with the small ramped precursor is observed. And, the release response from same shocked condition shows initial gradual release and subsequent quite rapid one. These results would provide the information about how phase transformation kinetics effects on the reshock and release behavior.

  8. How specialized volatiles respond to chronic and short-term physiological and shock heat stress in Brassica nigra.

    PubMed

    Kask, Kaia; Kännaste, Astrid; Talts, Eero; Copolovici, Lucian; Niinemets, Ülo

    2016-09-01

    Brassicales release volatile glucosinolate breakdown products upon tissue mechanical damage, but it is unclear how the release of glucosinolate volatiles responds to abiotic stresses such as heat stress. We used three different heat treatments, simulating different dynamic temperature conditions in the field to gain insight into stress-dependent changes in volatile blends and photosynthetic characteristics in the annual herb Brassica nigra (L.) Koch. Heat stress was applied by either heating leaves through temperature response curve measurements from 20 to 40 °C (mild stress), exposing plants for 4 h to temperatures 25-44 °C (long-term stress) or shock-heating leaves to 45-50 °C. Photosynthetic reduction through temperature response curves was associated with decreased stomatal conductance, while the reduction due to long-term stress and collapse of photosynthetic activity after heat shock stress were associated with non-stomatal processes. Mild stress decreased constitutive monoterpene emissions, while long-term stress and shock stress resulted in emissions of the lipoxygenase pathway and glucosinolate volatiles. Glucosinolate volatile release was more strongly elicited by long-term stress and lipoxygenase product released by heat shock. These results demonstrate that glucosinolate volatiles constitute a major part of emission blend in heat-stressed B. nigra plants, especially upon chronic stress that leads to induction responses. © 2016 John Wiley & Sons Ltd.

  9. Alcohol induces synaptotagmin 1 expression in neurons via activation of heat shock factor 1.

    PubMed

    Varodayan, F P; Pignataro, L; Harrison, N L

    2011-10-13

    Many synapses within the central nervous system are sensitive to ethanol. Although alcohol is known to affect the probability of neurotransmitter release in specific brain regions, the effects of alcohol on the underlying synaptic vesicle fusion machinery have been little studied. To identify a potential pathway by which ethanol can regulate neurotransmitter release, we investigated the effects of acute alcohol exposure (1-24 h) on the expression of the gene encoding synaptotagmin 1 (Syt1), a synaptic protein that binds calcium to directly trigger vesicle fusion. Syt1 was identified in a microarray screen as a gene that may be sensitive to alcohol and heat shock. We found that Syt1 mRNA and protein expression are rapidly and robustly up-regulated by ethanol in mouse cortical neurons, and that the distribution of Syt1 protein along neuronal processes is also altered. Syt1 mRNA up-regulation is dependent on the activation of the transcription factor heat shock factor 1 (HSF1). The transfection of a constitutively active Hsf1 construct into neurons stimulates Syt1 transcription, while transfection of Hsf1 small interfering RNA (siRNA) or a constitutively inactive Hsf1 construct into neurons attenuates the induction of Syt1 by ethanol. This suggests that the activation of HSF1 can induce Syt1 expression and that this may be a mechanism by which alcohol regulates neurotransmitter release during brief exposures. Further analysis revealed that a subset of the genes encoding the core synaptic vesicle fusion (soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor; SNARE) proteins share this property of induction by ethanol, suggesting that alcohol may trigger a specific coordinated adaptation in synaptic function. This molecular mechanism could explain some of the changes in synaptic function that occur following alcohol administration and may be an important step in the process of neuronal adaptation to alcohol. Copyright © 2011 IBRO. Published by

  10. Shock loading and release behavior of silicon nitride

    NASA Astrophysics Data System (ADS)

    Kawai, Nobuaki; Tsuru, Taiki; Hidaka, Naoto; Liu, Xun; Mashimo, Tsutomu

    2015-06-01

    Shock-reshock and shock-release experiments were performed on silicon nitride ceramics above and below its phase transition pressure. Experimental results clearly show the occurrence of elastic-plastic transition and phase transition during initial shock loading. The HEL and phase transition stress are determined as 11.6 GPa and 34.5 GPa, respectively. Below the phase transition point, the reshock profile consists of the single shock with short rise time, while the release profile shows the gradual release followed by more rapid one. Above the phase transition point, reshock and release behavior varies with the initial shock stress. In the case of reshock and release from about 40 GPa, the reshock structure is considerably dispersed, while the release structure shows rapid release. In the reshock profile from about 50 GPa, the formation of the shock wave with the small ramped precursor is observed. And, the release response from same condition shows initial gradual release and subsequent quite rapid one. These results would provide the information about how phase transformation kinetics effects on the reshock and release behavior.

  11. Remotely triggered earthquakes following moderate main shocks

    USGS Publications Warehouse

    Hough, S.E.

    2007-01-01

    Since 1992, remotely triggered earthquakes have been identified following large (M > 7) earthquakes in California as well as in other regions. These events, which occur at much greater distances than classic aftershocks, occur predominantly in active geothermal or volcanic regions, leading to theories that the earthquakes are triggered when passing seismic waves cause disruptions in magmatic or other fluid systems. In this paper, I focus on observations of remotely triggered earthquakes following moderate main shocks in diverse tectonic settings. I summarize evidence that remotely triggered earthquakes occur commonly in mid-continent and collisional zones. This evidence is derived from analysis of both historic earthquake sequences and from instrumentally recorded M5-6 earthquakes in eastern Canada. The latter analysis suggests that, while remotely triggered earthquakes do not occur pervasively following moderate earthquakes in eastern North America, a low level of triggering often does occur at distances beyond conventional aftershock zones. The inferred triggered events occur at the distances at which SmS waves are known to significantly increase ground motions. A similar result was found for 28 recent M5.3-7.1 earthquakes in California. In California, seismicity is found to increase on average to a distance of at least 200 km following moderate main shocks. This supports the conclusion that, even at distances of ???100 km, dynamic stress changes control the occurrence of triggered events. There are two explanations that can account for the occurrence of remotely triggered earthquakes in intraplate settings: (1) they occur at local zones of weakness, or (2) they occur in zones of local stress concentration. ?? 2007 The Geological Society of America.

  12. Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1.

    PubMed

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

    2017-08-04

    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 Cys 132 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 Cys 132 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 Cys 132 in hnRNP K is critical for this inhibition. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation

    PubMed Central

    Beck, Ilse M.; Drebert, Zuzanna J.; Hoya-Arias, Ruben; Bahar, Ali A.; Devos, Michael; Clarisse, Dorien; Desmet, Sofie; Bougarne, Nadia; Ruttens, Bart; Gossye, Valerie; Denecker, Geertrui; Lievens, Sam; Bracke, Marc; Tavernier, Jan; Declercq, Wim; Gevaert, Kris; Berghe, Wim Vanden; Haegeman, Guy; De Bosscher, Karolien

    2013-01-01

    Compound A possesses glucocorticoid receptor (GR)-dependent anti-inflammatory properties. Just like classical GR ligands, Compound A can repress NF-κB-mediated gene expression. However, the monomeric Compound A-activated GR is unable to trigger glucocorticoid response element-regulated gene expression. The heat shock response potently activates heat shock factor 1 (HSF1), upregulates Hsp70, a known GR chaperone, and also modulates various aspects of inflammation. We found that the selective GR modulator Compound A and heat shock trigger similar cellular effects in A549 lung epithelial cells. With regard to their anti-inflammatory mechanism, heat shock and Compound A are both able to reduce TNF-stimulated IκBα degradation and NF-κB p65 nuclear translocation. We established an interaction between Compound A-activated GR and Hsp70, but remarkably, although the presence of the Hsp70 chaperone as such appears pivotal for the Compound A-mediated inflammatory gene repression, subsequent novel Hsp70 protein synthesis is uncoupled from an observed CpdA-induced Hsp70 mRNA upregulation and hence obsolete in mediating CpdA’s anti-inflammatory effect. The lack of a Compound A-induced increase in Hsp70 protein levels in A549 cells is not mediated by a rapid proteasomal degradation of Hsp70 or by a Compound A-induced general block on translation. Similar to heat shock, Compound A can upregulate transcription of Hsp70 genes in various cell lines and BALB/c mice. Interestingly, whereas Compound A-dependent Hsp70 promoter activation is GR-dependent but HSF1-independent, heat shock-induced Hsp70 expression alternatively occurs in a GR-independent and HSF1-dependent manner in A549 lung epithelial cells. PMID:23935933

  14. The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response.

    PubMed

    Bernardini, Alejandra; Corona, Fernando; Dias, Ricardo; Sánchez, Maria B; Martínez, Jose L

    2015-01-01

    Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However, different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained Stenotrophomonas maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps' overexpression. Our objective is to get information on novel mechanisms of S. maltophilia quinolone resistance. For this purpose, a transposon-insertion mutant library was obtained in S. maltophilia D457. One mutant presenting reduced susceptibility to nalidixic acid was selected. Inverse PCR showed that the inactivated gene encodes RNase G. Complementation of the mutant with wild-type RNase G allele restored the susceptibility to quinolones. Transcriptomic and real-time RT-PCR analyses showed that several genes encoding heat-shock response proteins were expressed at higher levels in the RNase defective mutant than in the wild-type strain. In agreement with this situation, heat-shock reduces the S. maltophilia susceptibility to quinolone. We can then conclude that the inactivation of the RNase G reduces the susceptibility of S. maltophilia to quinolones, most likely by regulating the expression of heat-shock response genes. Heat-shock induces a transient phenotype of quinolone resistance in S. maltophilia.

  15. Inflammatory stress of pancreatic beta cells drives release of extracellular heat-shock protein 90α.

    PubMed

    Ocaña, Gail J; Pérez, Liliana; Guindon, Lynette; Deffit, Sarah N; Evans-Molina, Carmella; Thurmond, Debbie C; Blum, Janice S

    2017-06-01

    A major obstacle in predicting and preventing the development of autoimmune type 1 diabetes (T1D) in at-risk individuals is the lack of well-established early biomarkers indicative of ongoing beta cell stress during the pre-clinical phase of disease. Recently, serum levels of the α cytoplasmic isoform of heat-shock protein 90 (hsp90) were shown to be elevated in individuals with new-onset T1D. We therefore hypothesized that hsp90α could be released from beta cells in response to cellular stress and inflammation associated with the earliest stages of T1D. Here, human beta cell lines and cadaveric islets released hsp90α in response to stress induced by treatment with a combination of pro-inflammatory cytokines including interleukin-1β, tumour necrosis factor-α and interferon-γ. Mechanistically, hsp90α release was found to be driven by cytokine-induced endoplasmic reticulum stress mediated by c-Jun N-terminal kinase (JNK), a pathway that can eventually lead to beta cell apoptosis. Cytokine-induced beta cell hsp90α release and JNK activation were significantly reduced by pre-treating cells with the endoplasmic reticulum stress-mitigating chemical chaperone tauroursodeoxycholic acid. The hsp90α release by cells may therefore be a sensitive indicator of stress during inflammation and a useful tool in assessing therapeutic mitigation of cytokine-induced cell damage linked to autoimmunity. © 2017 John Wiley & Sons Ltd.

  16. Evaluation of thermo-triggered drug release in intramuscular-transplanted tumors using thermosensitive polymer-modified liposomes and MRI.

    PubMed

    Kokuryo, Daisuke; Nakashima, Seiji; Ozaki, Fuminori; Yuba, Eiji; Chuang, Kai-Hsiang; Aoshima, Sadahito; Ishizaka, Yukihito; Saga, Tsuneo; Kono, Kenji; Aoki, Ichio

    2015-01-01

    Multi-modal thermo-sensitive polymer-modified liposomes (MTPLs) containing an anticancer drug, MR contrast agent, and fluorescent dye have been investigated as "theranostic" nanodevices that can be used to monitor drug delivery in cancer therapy. Here, we measured the physical characteristics of MTPLs, observed the dynamics of MTPLs in vivo, visualized heat-triggered drug release using MRI, and evaluated the treatment effects of the MTPLs with and without heating. In vitro experiments demonstrated that the MTPLs released drugs at temperatures above 41°C. In vivo MTPLs accumulated in tumor tissue, with the accumulation maximized for 4-12hours. MR signal in the tumor was significantly elevated after mild heating for 15 minutes, indicating release of the contrast agent from the MTPLs was facilitated by heat-triggering. Tumor size after treatment with MTPLs and heating was significantly smaller than those of the control groups. In conclusion, MTPLs with MRI are useful for low-invasive cancer theranostics. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  17. Heat shock factor 1 induces crystallin-αB to protect against cisplatin nephrotoxicity

    PubMed Central

    Lou, Qiang; Hu, Yanzhong; Ma, Yuanfang

    2016-01-01

    Cisplatin, a wildly used chemotherapy drug, induces nephrotoxicity that is characterized by renal tubular cell apoptosis. In response to toxicity, tubular cells can activate cytoprotective mechanisms, such as the heat shock response. However, the role and regulation of the heat shock response in cisplatin-induced nephrotoxicity remain largely unclear. In the present study, we demonstrated the induction of heat shock factor (Hsf)1 and the small heat shock protein crystallin-αB (CryAB) during cisplatin nephrotoxicity in mice. Consistently, cisplatin induced Hsf1 and CryAB in a cultured renal proximal tubular cells (RPTCs). RPTCs underwent apoptosis during cisplatin treatment, which was increased when Hsf1 was knocked down. Transfection or restoration of Hsf1 into Hsf1 knockdown cells suppressed cisplatin-induced apoptosis, further supporting a cytoprotective role of Hsf1 and its associated heat shock response. Moreover, Hsf1 knockdown increased Bax translocation to mitochondria and cytochrome c release into the cytosol. In RPTCs, Hsf1 knockdown led to a specific downregulation of CryAB. Transfection of CryAB into Hsf1 knockdown cells diminished their sensitivity to cisplatin-induced apoptosis, suggesting that CryAB may be a key mediator of the cytoprotective effect of Hsf1. Taken together, these results demonstrate a heat shock response in cisplatin nephrotoxicity that is mediated by Hsf1 and CryAB to protect tubular cells against apoptosis. PMID:27194715

  18. Shock Wave Treatment Enhances Cell Proliferation and Improves Wound Healing by ATP Release-coupled Extracellular Signal-regulated Kinase (ERK) Activation*

    PubMed Central

    Weihs, Anna M.; Fuchs, Christiane; Teuschl, Andreas H.; Hartinger, Joachim; Slezak, Paul; Mittermayr, Rainer; Redl, Heinz; Junger, Wolfgang G.; Sitte, Harald H.; Rünzler, Dominik

    2014-01-01

    Shock wave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shock waves have not yet been fully revealed. Because cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shock wave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation. We identified extracellular ATP, released in an energy- and pulse number-dependent manner, as a trigger of the biological effects of shock wave treatment. Shock wave treatment induced ATP release, increased Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose tissue-derived stem cells, and a human Jurkat T cell line) in vitro. Purinergic signaling-induced Erk1/2 activation was found to be essential for this proliferative effect, which was further confirmed by in vivo studies in a rat wound healing model where shock wave treatment induced proliferation and increased wound healing in an Erk1/2-dependent fashion. In summary, this report demonstrates that shock wave treatment triggers release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings shed further light on the molecular mechanisms by which shock wave treatment exerts its beneficial effects. These findings could help to improve the clinical use of shock wave treatment for wound healing. PMID:25118288

  19. Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation.

    PubMed

    Weihs, Anna M; Fuchs, Christiane; Teuschl, Andreas H; Hartinger, Joachim; Slezak, Paul; Mittermayr, Rainer; Redl, Heinz; Junger, Wolfgang G; Sitte, Harald H; Rünzler, Dominik

    2014-09-26

    Shock wave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shock waves have not yet been fully revealed. Because cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shock wave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation. We identified extracellular ATP, released in an energy- and pulse number-dependent manner, as a trigger of the biological effects of shock wave treatment. Shock wave treatment induced ATP release, increased Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose tissue-derived stem cells, and a human Jurkat T cell line) in vitro. Purinergic signaling-induced Erk1/2 activation was found to be essential for this proliferative effect, which was further confirmed by in vivo studies in a rat wound healing model where shock wave treatment induced proliferation and increased wound healing in an Erk1/2-dependent fashion. In summary, this report demonstrates that shock wave treatment triggers release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings shed further light on the molecular mechanisms by which shock wave treatment exerts its beneficial effects. These findings could help to improve the clinical use of shock wave treatment for wound healing. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Effect of prior heat shock on heat resistance of Listeria monocytogenes in meat.

    PubMed Central

    Farber, J M; Brown, B E

    1990-01-01

    The effect of prior heat shock on the thermal resistance of Listeria monocytogenes in meat was investigated. A sausage mix inoculated with approximately 10(7) L. monocytogenes per g was initially subjected to a heat shock temperature of 48 degrees C before being heated at a final test temperature of 62 or 64 degrees C. Although cells heat shocked at 48 degrees C for 30 or 60 min did not show a significant increase in thermotolerance as compared with control cells (non-heat shocked), bacteria heat shocked for 120 min did, showing an average 2.4-fold increase in the D64 degrees C value. Heat-shocked cells shifted to 4 degrees C appeared to maintain their thermotolerance for at least 24 h after heat shock. PMID:2116757

  1. Electron heating at interplanetary shocks

    NASA Technical Reports Server (NTRS)

    Feldman, W. C.; Asbridge, J. R.; Bame, S. J.; Gosling, J. T.; Zwickl, R. D.

    1982-01-01

    Data for 41 forward interplanetary shocks show that the ratio of downstream to upstream electron temperatures, T/sub e/(d/u) is variable in the range between 1.0 (isothermal) and 3.0. On average, (T/sub e/(d/u) = 1.5 with a standard deviation, sigma e = 0.5. This ratio is less than the average ratio of proton temperatures across the same shocks, (T/sub p/(d/u)) = 3.3 with sigma p = 2.5 as well as the average ratio of electron temperatures across the Earth's bow shock. Individual samples of T/sub e/(d/u) and T/sub p/(d/u) appear to be weakly correlated with the number density ratio. However the amounts of electron and proton heating are well correlated with each other as well as with the bulk velocity difference across each shock. The stronger shocks appear to heat the protons relatively more efficiently than they heat the electrons.

  2. Insect heat shock proteins during stress and diapause.

    PubMed

    King, Allison M; MacRae, Thomas H

    2015-01-07

    Insect heat shock proteins include ATP-independent small heat shock proteins and the larger ATP-dependent proteins, Hsp70, Hsp90, and Hsp60. In concert with cochaperones and accessory proteins, heat shock proteins mediate essential activities such as protein folding, localization, and degradation. Heat shock proteins are synthesized constitutively in insects and induced by stressors such as heat, cold, crowding, and anoxia. Synthesis depends on the physiological state of the insect, but the common function of heat shock proteins, often working in networks, is to maintain cell homeostasis through interaction with substrate proteins. Stress-induced expression of heat shock protein genes occurs in a background of protein synthesis inhibition, but in the course of diapause, a state of dormancy and increased stress tolerance, these genes undergo differential regulation without the general disruption of protein production. During diapause, when ATP concentrations are low, heat shock proteins may sequester rather than fold proteins.

  3. A two-domain protein triggers heat shock pathway and necrosis pathway both in model plant and nematode.

    PubMed

    Ruan, Lifang; Wang, Huihui; Cai, Ge; Peng, Donghai; Zhou, Hua; Zheng, Jinshui; Zhu, Lei; Wang, Xixi; Yu, Haoquan; Li, Seng; Geng, Ce; Sun, Ming

    2015-11-01

    The entomopathogen Bacillus thuringiensis is equipped with multiple virulent factors. The genome sequence of B. thuringiensis YBT1520 revealed the presence of a two-domain protein named Nel which is composed of a necrosis-inducing phytophthora protein 1-like domain found in phytopathogens and a ricin B-like lectin domain. The merging of two distantly related domains is relatively rare. Nel induced necrosis and pathogen-triggered immunity (PTI) on model plants. The Nel also exhibited inhibition activity to nematode. Microscopic observation showed that the toxicity of Nel to nematodes targets the intestine. Quantitative proteomics revealed that Nel stimulated the host defence. The Nel thus possesses dual roles, as both toxin and elicitor. Remarkably, the Nel protein triggered a similar response, induction of the heat shock pathway and the necrosis pathway, in both model plants and nematodes. The unusual ability of Nel to function across kingdom suggests a highly conserved mechanism in eukaryotes that predates the divergence of plants and animal. It is also speculated that the two-domain protein is the result of horizontal gene transfer (HGT) between phytopathogens and entomopathogens. Our results provide an example that HGT occurs between members of different species or even genera with lower frequency are particularly important for evolution of new bacterial pathogen lineages with new virulence. Bacillus thuringiensis occupies the same ecological niches, plant and soil, as phytopathogens, providing the opportunity for gene exchange. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. Measurements of the Shock Release Of Quartz and Paralyene-N

    NASA Astrophysics Data System (ADS)

    Hawreliak, James; Karasik, Max; Oh, Jaechul; Aglitskiy, Yefim

    2017-06-01

    The shock and release properties of Quartz and hydrocarbons are important to high energy density (HED) research and inertial confinement fusion (ICF) science. The bulk of HED material research studies single shock or multiple shock conditions. The challenge with measuring release properties is unlike shocks which have a single interface from which to measure the properties, the release establishes gradients in the sample. The streaked x-ray imaging capability of the NIKE laser allow the interface between quartz and CH to be measured during the release, giving measurements of the interface velocity and CH density. Here, we present experimental results from the NIKE laser where quartz and parylene-N are shock compressed to high pressure and temperature and the release state is measured through x-ray imaging. The shock state is characterized by shock front velocity measurements using VISAR and the release state is characterized by using side-on streaked x-ray radiography Work supported by DOE/NNSA.

  5. Shock heating of the solar wind plasma

    NASA Technical Reports Server (NTRS)

    Whang, Y. C.; Liu, Shaoliang; Burlaga, L. F.

    1990-01-01

    The role played by shocks in heating solar-wind plasma is investigated using data on 413 shocks which were identified from the plasma and magnetic-field data collected between 1973 and 1982 by Pioneer and Voyager spacecraft. It is found that the average shock strength increased with the heliocentric distance outside 1 AU, reaching a maximum near 5 AU, after which the shock strength decreased with the distance; the entropy of the solar wind protons also reached a maximum at 5 AU. An MHD simulation model in which shock heating is the only heating mechanism available was used to calculate the entropy changes for the November 1977 event. The calculated entropy agreed well with the value calculated from observational data, suggesting that shocks are chiefly responsible for heating solar wind plasma between 1 and 15 AU.

  6. ATF1 Modulates the Heat Shock Response by Regulating the Stress-Inducible Heat Shock Factor 1 Transcription Complex

    PubMed Central

    Takii, Ryosuke; Fujimoto, Mitsuaki; Tan, Ke; Takaki, Eiichi; Hayashida, Naoki; Nakato, Ryuichiro; Shirahige, Katsuhiko

    2014-01-01

    The heat shock response is an evolutionally conserved adaptive response to high temperatures that controls proteostasis capacity and is regulated mainly by an ancient heat shock factor (HSF). However, the regulation of target genes by the stress-inducible HSF1 transcription complex has not yet been examined in detail in mammalian cells. In the present study, we demonstrated that HSF1 interacted with members of the ATF1/CREB family involved in metabolic homeostasis and recruited them on the HSP70 promoter in response to heat shock. The HSF1 transcription complex, including the chromatin-remodeling factor BRG1 and lysine acetyltransferases p300 and CREB-binding protein (CBP), was formed in a manner that was dependent on the phosphorylation of ATF1. ATF1-BRG1 promoted the establishment of an active chromatin state and HSP70 expression during heat shock, whereas ATF1-p300/CBP accelerated the shutdown of HSF1 DNA-binding activity during recovery from acute stress, possibly through the acetylation of HSF1. Furthermore, ATF1 markedly affected the resistance to heat shock. These results revealed the unanticipated complexity of the primitive heat shock response mechanism, which is connected to metabolic adaptation. PMID:25312646

  7. Conditions for shock revival by neutrino heating in core-collapse supernovae

    NASA Astrophysics Data System (ADS)

    Janka, H.-Th.

    2001-03-01

    Energy deposition by neutrinos can rejuvenate the stalled bounce shock and can provide the energy for the supernova explosion of a massive star. This neutrino-heating mechanism, though investigated by numerical simulations and analytic studies, is not finally accepted or proven as the trigger of the explosion. Part of the problem is that different groups have obtained seemingly discrepant results, and the complexity of the hydrodynamic models often hampers a clear and simple interpretation of the results. This demands a deeper theoretical understanding of the requirements of a successful shock revival. A toy model is developed here for discussing the neutrino heating phase analytically. The neutron star atmosphere between the neutrinosphere and the supernova shock can well be considered to be in hydrostatic equilibrium, with a layer of net neutrino cooling below the gain radius and a layer of net neutrino heating above. Since the mass infall rate to the shock is in general different from the rate at which gas is advected into the neutron star, the mass in the gain layer varies with time. Moreover, the gain layer receives additional energy input by neutrinos emitted from the neutrinosphere and the cooling layer. Therefore the determination of the shock evolution requires a time-dependent treatment. To this end the hydrodynamical equations of continuity and energy are integrated over the volume of the gain layer to obtain conservation laws for the total mass and energy in this layer. The radius and velocity of the supernova shock can then be calculated from global properties of the gain layer as solutions of an initial value problem, which expresses the fact that the behavior of the shock is controlled by the cumulative effects of neutrino heating and mass accumulation in the gain layer. The described toy model produces steady-state accretion and mass outflow from the nascent neutron star as special cases. The approach is useful to illuminate the conditions that can

  8. Heat shock treatment improves Trametes versicolor laccase production.

    PubMed

    Wang, Feng; Guo, Chen; Wei, Tao; Zhang, Tian; Liu, Chun-Zhao

    2012-09-01

    An efficient heat shock strategy has been developed to improve laccase production in submerged Trametes versicolor cultures. The optimized heat shock strategy consists of subjecting T. versicolor mycelial pellets to three heat shock treatments at 45 °C for 45 min, starting at culture day 0, with a 24-h interval between treatments. Laccase production increased by more than 1.6-fold relative to the control in both flasks and a 5-L bioreactor because the expression of the laccase gene was enhanced by heat shock induction. The present work demonstrates that heat shock induction is a promising method because it both improves fungal laccase production and has a good potential in industrial application.

  9. Heat stress and cardiovascular, hormonal, and heat shock proteins in humans.

    PubMed

    Iguchi, Masaki; Littmann, Andrew E; Chang, Shuo-Hsiu; Wester, Lydia A; Knipper, Jane S; Shields, Richard K

    2012-01-01

    Conditions such as osteoarthritis, obesity, and spinal cord injury limit the ability of patients to exercise, preventing them from experiencing many well-documented physiologic stressors. Recent evidence indicates that some of these stressors might derive from exercise-induced body temperature increases. To determine whether whole-body heat stress without exercise triggers cardiovascular, hormonal, and extracellular protein responses of exercise. Randomized controlled trial. University research laboratory. Twenty-five young, healthy adults (13 men, 12 women; age = 22.1 ± 2.4 years, height = 175.2 ± 11.6 cm, mass = 69.4 ± 14.8 kg, body mass index = 22.6 ± 4.0) volunteered. Participants sat in a heat stress chamber with heat (73°C) and without heat (26°C) stress for 30 minutes on separate days. We obtained blood samples from a subset of 13 participants (7 men, 6 women) before and after exposure to heat stress. Extracellular heat shock protein (HSP72) and catecholamine plasma concentration, heart rate, blood pressure, and heat perception. After 30 minutes of heat stress, body temperature measured via rectal sensor increased by 0.8°C. Heart rate increased linearly to 131.4 ± 22.4 beats per minute (F₆,₂₄ = 186, P < .001) and systolic and diastolic blood pressure decreased by 16 mm Hg (F₆,₂₄ = 10.1, P < .001) and 5 mm Hg (F₆,₂₄ = 5.4, P < .001), respectively. Norepinephrine (F₁,₁₂ = 12.1, P = .004) and prolactin (F₁,₁₂ = 30.2, P < .001) increased in the plasma (58% and 285%, respectively) (P < .05). The HSP72 (F₁,₁₂ = 44.7, P < .001) level increased with heat stress by 48.7% ± 53.9%. No cardiovascular or blood variables showed changes during the control trials (quiet sitting in the heat chamber with no heat stress), resulting in differences between heat and control trials. We found that whole-body heat stress triggers some of the physiologic responses observed with exercise. Future studies are necessary to investigate whether

  10. Ultrafast collisional ion heating by electrostatic shocks.

    PubMed

    Turrell, A E; Sherlock, M; Rose, S J

    2015-11-13

    High-intensity lasers can be used to generate shockwaves, which have found applications in nuclear fusion, proton imaging, cancer therapies and materials science. Collisionless electrostatic shocks are one type of shockwave widely studied for applications involving ion acceleration. Here we show a novel mechanism for collisionless electrostatic shocks to heat small amounts of solid density matter to temperatures of ∼keV in tens of femtoseconds. Unusually, electrons play no direct role in the heating and it is the ions that determine the heating rate. Ions are heated due to an interplay between the electric field of the shock, the local density increase during the passage of the shock and collisions between different species of ion. In simulations, these factors combine to produce rapid, localized heating of the lighter ion species. Although the heated volume is modest, this would be one of the fastest heating mechanisms discovered if demonstrated in the laboratory.

  11. Heat shock proteins: the missing link between hormonal and reproductive factors and rheumatoid arthritis?

    PubMed

    da Silva, J A

    1991-10-01

    Epidemiologic data suggest a strong link between hormonal and reproductive factors and the incidence of rheumatoid arthritis. Of interest is a possible protective effect of oral contraceptives or estrogen replacement therapy against the development of rheumatoid arthritis. At least 1 pregnancy also appears to reduce the risk of this disease. It has been hypothesized that hormonal contraceptive use and pregnancy elicit the production of higher amounts of endogenous heat shock proteins, which, in turn, induce immunotolerance to subsequent exposure to the actual triggering agent of rheumatoid arthritis. A related possibility is that pregnant women are exposed to specific types of heat shock proteins produced by the fetus in high concentrations. Heat shock proteins are known to be the predominant antigens related to the induction of reactive arthritis. The production of some such proteins is dependent on sex hormones in a tissue-specific way and their concentrations are raised dramatically by stimulation with estrogen and progesterone. A possible mechanism for heat protein-induced immunotolerance would be the predominant stimulation of a suppressor T cell clone. More research on the pathogenesis of rheumatic diseases and the activity of sex hormones could result in the development of a vaccine against rheumatoid arthritis.

  12. The interactive association between heat shock factor 1 and heat shock proteins in primary myocardial cells subjected to heat stress.

    PubMed

    Tang, Shu; Chen, Hongbo; Cheng, Yanfen; Nasir, Mohammad Abdel; Kemper, Nicole; Bao, Endong

    2016-01-01

    Heat shock factor 1 (HSF1) is a heat shock transcription factor that rapidly induces heat shock gene transcription following thermal stress. In this study, we subjected primary neonatal rat myocardial cells to heat stress in vitro to create a model system for investigating the trends in expression and association between various heat shock proteins (HSPs) and HSF1 under adverse environmental conditions. After the cells were subjected to heat stress at 42˚C for different periods of time, HSP and HSF1 mRNA and protein levels were detected by qPCR and western blot analysis in the heat-stressed cells. The HSF1 expression levels significantly increased in the cells following 120 min of exposure to heat stess compared to the levels observed at the beginning of heat stress exposure. HSP90 followed a similar trend in expression to HSF1, whereas HSP70 followed an opposite trend. However, no significant changes were observed in the crystallin, alpha B (CRYAB, also known as HSP beta-5) expression levels during the 480‑min period of exposure to heat stress. The interaction between the HSPs and HSF1 was analyzed by STRING 9.1, and it was found that HSF1 interacted with HSP90 and HSP70, and that it did not play a role in regulating CRYAB expression. Based on our findings, HSP70 may suppress HSF1 in rat myocardial cells under conditions of heat stress. Furthermore, our data demonstrate that HSF1 is not the key factor for all HSPs, and this was particularly the case for CRYAB.

  13. The interactive association between heat shock factor 1 and heat shock proteins in primary myocardial cells subjected to heat stress

    PubMed Central

    TANG, SHU; CHEN, HONGBO; CHENG, YANFEN; NASIR, MOHAMMAD ABDEL; KEMPER, NICOLE; BAO, ENDONG

    2016-01-01

    Heat shock factor 1 (HSF1) is a heat shock transcription factor that rapidly induces heat shock gene transcription following thermal stress. In this study, we subjected primary neonatal rat myocardial cells to heat stress in vitro to create a model system for investigating the trends in expression and association between various heat shock proteins (HSPs) and HSF1 under adverse environmental conditions. After the cells were subjected to heat stress at 42°C for different periods of time, HSP and HSF1 mRNA and protein levels were detected by qPCR and western blot analysis in the heat-stressed cells. The HSF1 expression levels significantly increased in the cells following 120 min of exposure to heat stess compared to the levels observed at the beginning of heat stress exposure. HSP90 followed a similar trend in expression to HSF1, whereas HSP70 followed an opposite trend. However, no significant changes were observed in the crystallin, alpha B (CRYAB, also known as HSP beta-5) expression levels during the 480-min period of exposure to heat stress. The interaction between the HSPs and HSF1 was analyzed by STRING 9.1, and it was found that HSF1 interacted with HSP90 and HSP70, and that it did not play a role in regulating CRYAB expression. Based on our findings, HSP70 may suppress HSF1 in rat myocardial cells under conditions of heat stress. Furthermore, our data demonstrate that HSF1 is not the key factor for all HSPs, and this was particularly the case for CRYAB. PMID:26719858

  14. Shock heating in numerical simulations of kink-unstable coronal loops

    PubMed Central

    Bareford, M. R.; Hood, A. W.

    2015-01-01

    An analysis of the importance of shock heating within coronal magnetic fields has hitherto been a neglected area of study. We present new results obtained from nonlinear magnetohydrodynamic simulations of straight coronal loops. This work shows how the energy released from the magnetic field, following an ideal instability, can be converted into thermal energy, thereby heating the solar corona. Fast dissipation of magnetic energy is necessary for coronal heating and this requirement is compatible with the time scales associated with ideal instabilities. Therefore, we choose an initial loop configuration that is susceptible to the fast-growing kink, an instability that is likely to be created by convectively driven vortices, occurring where the loop field intersects the photosphere (i.e. the loop footpoints). The large-scale deformation of the field caused by the kinking creates the conditions for the formation of strong current sheets and magnetic reconnection, which have previously been considered as sites of heating, under the assumption of an enhanced resistivity. However, our simulations indicate that slow mode shocks are the primary heating mechanism, since, as well as creating current sheets, magnetic reconnection also generates plasma flows that are faster than the slow magnetoacoustic wave speed. PMID:25897092

  15. Exciting cell membranes with a blustering heat shock.

    PubMed

    Liu, Qiang; Frerck, Micah J; Holman, Holly A; Jorgensen, Erik M; Rabbitt, Richard D

    2014-04-15

    Brief heat shocks delivered to cells by pulsed laser light can evoke action potentials in neurons and contraction in cardiomyocytes, but the primary biophysical mechanism has been elusive. In this report we show in the neuromuscular junction of Caenorhabditis elegans that application of a 500°C/s heat shock for 500 μs evoked ~35 pA of excitatory current and injected ~23 fC(femtocoulomb) of charge into the cell while raising the temperature only 0.25°C. The key variable driving the current was the rate of change of temperature (dT/dt heat shock), not temperature itself. The photothermal heat shock current was voltage-dependent and was from thermally driven displacement of ions near the plasma membrane. The charge movement was rapid during the heat shock and slow during thermal relaxation, thus leading to an asymmetrical capacitive current that briefly depolarized the cell. A simple quantitative model is introduced to describe modulation of the membrane potential and facilitate practical application of optical heat shock stimuli. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. [The evolution of heat shock genes and expression patterns of heat shock proteins in the species from temperature contrasting habitats].

    PubMed

    Garbuz, D G; Evgen’ev, M B

    2017-01-01

    Heat shock genes are the most evolutionarily ancient among the systems responsible for adaptation of organisms to a harsh environment. The encoded proteins (heat shock proteins, Hsps) represent the most important factors of adaptation to adverse environmental conditions. They serve as molecular chaperones, providing protein folding and preventing aggregation of damaged cellular proteins. Structural analysis of the heat shock genes in individuals from both phylogenetically close and very distant taxa made it possible to reveal the basic trends of the heat shock gene organization in the context of adaptation to extreme conditions. Using different model objects and nonmodel species from natural populations, it was demonstrated that modulation of the Hsps expression during adaptation to different environmental conditions could be achieved by changing the number and structural organization of heat shock genes in the genome, as well as the structure of their promoters. It was demonstrated that thermotolerant species were usually characterized by elevated levels of Hsps under normal temperature or by the increase in the synthesis of these proteins in response to heat shock. Analysis of the heat shock genes in phylogenetically distant organisms is of great interest because, on one hand, it contributes to the understanding of the molecular mechanisms of evolution of adaptogenes and, on the other hand, sheds the light on the role of different Hsps families in the development of thermotolerance and the resistance to other stress factors.

  17. Radio frequency induced hyperthermia mediated by dextran stabilized LSMO nanoparticles: in vitro evaluation of heat shock protein response

    NASA Astrophysics Data System (ADS)

    Bhayani, K. R.; Rajwade, J. M.; Paknikar, K. M.

    2013-01-01

    Dextran stabilized La0.7Sr0.3MnO3 (Dex-LSMO) is an alternative cancer hyperthermia agent holding considerable promise. Here, we have carried out a comparative study on radio frequency (˜264 kHz) induced Dex-LSMO mediated heating and extraneous heating (mimicking generalized hyperthermia) in terms of changes in the morphology, proliferation pattern and induction of heat shock proteins in a human melanoma cell line (A375). Our results clearly show that the cellular effects seen with extraneous heating (60 min at 43 °C) could be reproduced by just six minutes of radio frequency induced Dex-LSMO mediated heating. More importantly, the observed enhanced levels of HSP 70 and 90 (molecular markers of heat shock that trigger favorable immunological reactions) seen with Dex-LSMO mediated heating were comparable to extraneous heating. These results suggest the possible utility of Dex-LSMO as a cancer hyperthermia agent.

  18. Forkhead Box M1 Is Regulated by Heat Shock Factor 1 and Promotes Glioma Cells Survival under Heat Shock Stress*

    PubMed Central

    Dai, Bingbing; Gong, Aihua; Jing, Zhitao; Aldape, Kenneth D.; Kang, Shin-Hyuk; Sawaya, Raymond; Huang, Suyun

    2013-01-01

    The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G2-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance. PMID:23192351

  19. Vaginal Toxic Shock Reaction Triggering Desquamative Inflammatory Vaginitis

    PubMed Central

    Pereira, Nigel; Edlind, Thomas D.; Schlievert, Patrick M.; Nyirjesy, Paul

    2012-01-01

    Objective To report two cases of desquamative inflammatory vaginitis (DIV) associated with toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus strains. Materials and Methods Case report of two patients, one with an acute and one with a chronic presentation, diagnosed with DIV on the basis of clinical findings and wet mount microscopy. Pre- and posttreatment vaginal bacterial and yeast cultures were obtained. Results Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial cultures following oral antibiotic therapy were negative. Conclusions DIV may be triggered through TSST-1-mediated vaginal toxic shock reaction. PMID:23222054

  20. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

    PubMed

    Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

    2013-01-01

    The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

  1. Near-infrared remotely triggered drug-release strategies for cancer treatment

    NASA Astrophysics Data System (ADS)

    Goodman, Amanda M.; Neumann, Oara; Nørregaard, Kamilla; Henderson, Luke; Choi, Mi-Ran; Clare, Susan E.; Halas, Naomi J.

    2017-11-01

    Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.

  2. Effects of Friction and Plastic Deformation in Shock-Comminuted Damaged Rocks on Impact Heating

    NASA Astrophysics Data System (ADS)

    Kurosawa, Kosuke; Genda, Hidenori

    2018-01-01

    Hypervelocity impacts cause significant heating of planetary bodies. Such events are recorded by a reset of 40Ar-36Ar ages and/or impact melts. Here we investigate the influence of friction and plastic deformation in shock-generated comminuted rocks on the degree of impact heating using the iSALE shock-physics code. We demonstrate that conversion from kinetic to internal energy in the targets with strength occurs during pressure release, and additional heating becomes significant for low-velocity impacts (<10 km s-1). This additional heat reduces the impact-velocity thresholds required to heat the targets with the 0.1 projectile mass to temperatures for the onset of Ar loss and melting from 8 and 10 km s-1, respectively, for strengthless rocks to 2 and 6 km s-1 for typical rocks. Our results suggest that the impact conditions required to produce the unique features caused by impact heating span a much wider range than previously thought.

  3. Shock, release and reshock of PBX 9502: experiments and modeling

    NASA Astrophysics Data System (ADS)

    Aslam, Tariq; Gustavsen, Richard; Whitworh, Nicholas; Menikoff, Ralph; Tarver, Craig; Handley, Caroline; Bartram, Brian

    2017-06-01

    We examine shock, release and reshock into the tri-amino-tri-nitro-benzene (TATB) based explosive PBX 9502 (95% TATB, 5% Kel-F 800) from both an experimental and modeling point of view. The experiments are performed on the 2-stage light gas gun at Los Alamos National Laboratory and are composed of a multi-layered impactor impinging on PBX 9502 backed by a polymethylmethacrylate window. The objective is to initially shock the PBX 9502 in the 7 GPa range (too weak to start significant reaction), then allow a rarefaction fan to release the material to a lower pressure/temperature state. Following this release, a strong second shock will recompress the PBX. If the rarefaction fan releases the PBX to a very low pressure, the ensuing second shock can increase the entropy and temperature substantially more than in previous double-shock experiments without an intermediate release. Predictions from a variety of reactive burn models (AWSD, CREST, Ignition and Growth, SURF) demonstrate significantly different behaviors and thus the experiments are an excellent validation test of the models, and may suggest improvements for subsequent modeling efforts.

  4. Expression of hsrω-RNAi transgene prior to heat shock specifically compromises accumulation of heat shock-induced Hsp70 in Drosophila melanogaster.

    PubMed

    Singh, Anand K; Lakhotia, Subhash C

    2016-01-01

    A delayed organismic lethality was reported in Drosophila following heat shock when developmentally active and stress-inducible noncoding hsrω-n transcripts were down-regulated during heat shock through hs-GAL4-driven expression of the hsrω-RNAi transgene, despite the characteristic elevation of all heat shock proteins (Hsp), including Hsp70. Here, we show that hsrω-RNAi transgene expression prior to heat shock singularly prevents accumulation of Hsp70 in all larval tissues without affecting transcriptional induction of hsp70 genes and stability of their transcripts. Absence of the stress-induced Hsp70 accumulation was not due to higher levels of Hsc70 in hsrω-RNAi transgene-expressing tissues. Inhibition of proteasomal activity during heat shock restored high levels of the induced Hsp70, suggesting very rapid degradation of the Hsp70 even during the stress when hsrω-RNAi transgene was expressed ahead of heat shock. Unexpectedly, while complete absence of hsrω transcripts in hsrω (66) homozygotes (hsrω-null) did not prevent high accumulation of heat shock-induced Hsp70, hsrω-RNAi transgene expression in hsrω-null background blocked Hsp70 accumulation. Nonspecific RNAi transgene expression did not affect Hsp70 induction. These observations reveal that, under certain conditions, the stress-induced Hsp70 can be selectively and rapidly targeted for proteasomal degradation even during heat shock. In the present case, the selective degradation of Hsp70 does not appear to be due to down-regulation of the hsrω-n transcripts per se; rather, this may be an indirect effect of the expression of hsrω-RNAi transgene whose RNA products may titrate away some RNA-binding proteins which may also be essential for stability of the induced Hsp70.

  5. Light-Triggered Release of DNA from Plasmon-Resonant Nanoparticles

    NASA Astrophysics Data System (ADS)

    Huschka, Ryan

    Plasmon-resonant nanoparticle complexes show promising potential for lighttriggered, controllable delivery of deoxyribonucleic acids (DNA) for research and therapeutic purposes. For example, the approach of RNA interference (RNAi) . using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein . is very useful in dissecting genetic function and holds promise as a molecular therapeutic. Herein, we investigate the mechanism and probe the in vitro therapeutic potential of DNA light-triggered release from plasmonic nanoparticles. First, we investigate the mechanism of light-triggered release by dehybridizing double-stranded (dsDNA) via laser illumination from two types of nanoparticle substrates: gold (Au) nanoshells and Au nanorods. Both light-triggered and thermally induced releases are distinctly observable from nanoshell-based complexes. Surprisingly, no analogous measurable light-triggered release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in light-triggered DNA release. Second, we demonstrate the in vitro light-triggered release of molecules noncovalently attached within dsDNA bound to the Au nanoshell surface. DAPI (4',6- diamidino-2-phenylindole), a bright blue fluorescent molecule that binds reversibly to double-stranded DNA, was chosen to visualize this intracellular light-induced release process. Illumination through the cell membrane of the nanoshell-dsDNA-DAPI complexes dehybridizes the DNA and releases the DAPI molecules within living cells. The DAPI molecules diffuse to the nucleus and associate with the cell's endogenous DNA. This work could have future applications towards drug delivery of molecules that associate with dsDNA. Finally, we demonstrate an engineered Au nanoshell (AuNS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on

  6. TG2 regulates the heat-shock response by the post-translational modification of HSF1.

    PubMed

    Rossin, Federica; Villella, Valeria Rachela; D'Eletto, Manuela; Farrace, Maria Grazia; Esposito, Speranza; Ferrari, Eleonora; Monzani, Romina; Occhigrossi, Luca; Pagliarini, Vittoria; Sette, Claudio; Cozza, Giorgio; Barlev, Nikolai A; Falasca, Laura; Fimia, Gian Maria; Kroemer, Guido; Raia, Valeria; Maiuri, Luigi; Piacentini, Mauro

    2018-05-11

    Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter. We show that the inhibition of TG2 restores the unbalance in HSF1-HSP70 pathway in cystic fibrosis (CF), a human disorder characterized by deregulation of proteostasis. The absence of TG2 leads to an increase of about 40% in CFTR function in a new experimental CF mouse model lacking TG2. Altogether, these results indicate that TG2 plays a key role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat-shock response. © 2018 The Authors.

  7. Polymersomes from dual responsive block copolymers: drug encapsulation by heating and acid-triggered release.

    PubMed

    Qiao, Zeng-Ying; Ji, Ran; Huang, Xiao-Nan; Du, Fu-Sheng; Zhang, Rui; Liang, De-Hai; Li, Zi-Chen

    2013-05-13

    A series of well-defined thermoresponsive diblock copolymers (PEO45-b-PtNEAn, n=22, 44, 63, 91, 172) were prepared by the atom transfer radical polymerization of trans-N-(2-ethoxy-1,3-dioxan-5-yl) acrylamide (tNEA) using a poly(ethylene oxide) (PEO45) macroinitiator. All copolymers are water-soluble at low temperature, but upon quickly heating to 37 °C, laser light scattering (LLS) and transmission electron microscopy (TEM) characterizations indicate that these copolymers self-assemble into aggregates with different morphologies depending on the chain length of PtNEA and the polymer concentration; the morphologies gradually evolved from spherical solid nanoparticles to a polymersome as the degree of polymerization ("n") of PtNEA block increased from 22 to 172, with the formation of clusters with rod-like structure at the intermediate PtNEA length. Both the spherical nanoparticle and the polymersome are stable at physiological pH but susceptible to the mildly acidic medium. Acid-triggered hydrolysis behaviors of the aggregates were investigated by LLS, Nile red fluorescence, TEM, and (1)H NMR spectroscopy. The results revealed that the spherical nanoparticles formed from PEO45-b-PtNEA44 dissociated faster than the polymersomes of PEO45-b-PtNEA172, and both aggregates showed an enhanced hydrolysis under acidic conditions. Both the spherical nanoparticle and polymersome are able to efficiently load the hydrophobic doxorubicin (DOX), and water-soluble fluorescein isothiocyanate-lysozyme (FITC-Lys) can be conveniently encapsulated into the polymersome without using any organic solvent. Moreover, FITC-Lys and DOX could be coloaded in the polymersome. The drugs loaded either in the polymersome or in the spherical nanoparticle could be released by acid triggering. Finally, the DOX-loaded assemblies display concentration-dependent cytotoxicity to HepG2 cells, while the copolymers themselves are nontoxic.

  8. Measuring the properties of shock released Quartz and Parylene-N

    NASA Astrophysics Data System (ADS)

    Hawreliak, James; Karasik, Max; Oh, Jaechul; Aglitskiy, Yefim

    2016-10-01

    The high pressure and temperature properties of Quartz and hydrocarbons are important to high energy density (HED) research and inertial confinement fusion (ICF) science. The bulk of HED material research studies the single shock Hugoniot. Here, we present experimental results from the NIKE laser where quartz and parylene-N are shock compressed to high pressure and temperature and the release state is measured through x-ray imaging. The shock state is characterized by shock front velocity measurements using VISAR and the release state is characterized by using side-on streaked x-ray radiography.

  9. Mathematical Modeling of the Heat-Shock Response in HeLa Cells

    DTIC Science & Technology

    2015-07-01

    Petre et al. (16), but with some critical changes, which are detailed below. 2HSF4HSF2; (1) HSFþ HSF24HSF3; (2) HSF3 þ HSE4HSF3 : HSE ; (3) HSF3 : HSE ... HSE /HSP : HSFþ HSEþ 2HSF; (10) HSP/; (11) Prot/MFP; (12) HSPþMFP4HSP : MFP; (13) HSP : MFP/HSPþ Prot: (14) The heat-shock response is initiated by a... HSE , heat-shock element; HSF, heat-shock factor; HSP, heat-shock protein; MFP, misfolded protein; mRNA, heat-shock protein messenger RNA; and Prot

  10. Ventilation during cardiopulmonary bypass: impact on heat shock protein release.

    PubMed

    Beer, L; Szerafin, T; Mitterbauer, A; Kasiri, M M; Debreceni T Palotás, L; Dworschak, M; Roth, G A; Ankersmit, H J

    2014-12-01

    Cardiopulmonary bypass (CPB), utilized in on-pump coronary artery bypass graft procedures (CABG) induces generalized immune suppression, release of heat shock proteins (HSP), inflammatory markers and apoptosis-specific proteins. We hypothesized that continued mechanical ventilation during cardiopulmonary bypass attenuates immune response and HSP liberation. Thirty patients undergoing conventional coronary artery bypass graft (CABG) operation were randomized into a ventilated on CPB (VG; N.=15) and a non-ventilated CPB group (NVG; N.=15). Blood samples were drawn at the beginning and end of surgery, as well as on the five consecutive postoperative days (POD). Molecular markers were measured by ELISA. Data are given as mean ± (SD). Mann-Whitney-U-test was used for statistical analysis. Serum concentrations of HSP70 were significantly lower in VG compared to NVG on POD-1 (VG: 1629±608 vs. NVG: 5203±2128.6 pg/mL, P<0.001). HSP27 and HSP60 depicted a minor increase in both study groups at the end of surgery without any intergroup differences (HSP27: VG 6207.9±1252.5 vs. NVG 7424.1±2632.5; HSP60: VG 1046.2±478.8 vs. NVG 1223.5±510.1). IL-8 and CK-18 M30 evidenced the highest serum concentrations at the end of surgery (IL-8: VG 119.5±77.9 vs. NVG 148.0±184.55; CK-18 M30: VG 62.1±39.2 vs. NVG 67.5±33.9) with no differences between groups. Decreased ICAM-1 serum concentrations were detected postoperatively, however ICAM-1 concentrations on POD-1 to POD-5 showed slightly elevated concentrations in both study groups with no intergroup differences. Significantly less HSP70 was detectable in patients receiving uninterrupted mechanical lung ventilation on CPB, indicating either different inflammatory response, cellular stress or cell damage between the ventilated and non-ventilated group. These data suggest that continued mechanical ventilation has a modulatory effect on the immune response in patients after CABG surgery.

  11. BH3-Only Protein BIM Mediates Heat Shock-Induced Apoptosis

    PubMed Central

    Mahajan, Indra M.; Chen, Miao-Der; Muro, Israel; Robertson, John D.; Wright, Casey W.; Bratton, Shawn B.

    2014-01-01

    Acute heat shock can induce apoptosis through a canonical pathway involving the upstream activation of caspase-2, followed by BID cleavage and stimulation of the intrinsic pathway. Herein, we report that the BH3-only protein BIM, rather than BID, is essential to heat shock-induced cell death. We observed that BIM-deficient cells were highly resistant to heat shock, exhibiting short and long-term survival equivalent to Bax−/−Bak−/− cells and better than either Bid−/− or dominant-negative caspase-9-expressing cells. Only Bim−/− and Bax−/−Bak−/− cells exhibited resistance to mitochondrial outer membrane permeabilization and loss of mitochondrial inner membrane potential. Moreover, while dimerized caspase-2 failed to induce apoptosis in Bid−/− cells, it readily did so in Bim−/− cells, implying that caspase-2 kills exclusively through BID, not BIM. Finally, BIM reportedly associates with MCL-1 following heat shock, and Mcl-1−/− cells were indeed sensitized to heat shock-induced apoptosis. However, pharmacological inhibition of BCL-2 and BCL-XL with ABT-737 also sensitized cells to heat shock, most likely through liberation of BIM. Thus, BIM mediates heat shock-induced apoptosis through a BAX/BAK-dependent pathway that is antagonized by antiapoptotic BCL-2 family members. PMID:24427286

  12. Development of a flyer design to perform plate impact shock-release-shock experiments on explosives

    NASA Astrophysics Data System (ADS)

    Finnegan, Simon; Ferguson, James; Millett, Jeremy; Goff, Michael

    2017-06-01

    A flyer design to generate a shock-release-shock loading history within a gas gun target was developed before being used to study the response of an HMX based explosive. The flyer consisted of two flyer plates separated by a vacuum gap. This created a rear free surface that, with correct material choice, allowed the target to release to close to ambient pressure between the initial shock and subsequent re-shock. The design was validated by impacting piezoelectric pin arrays to record the front flyer deformation. Shots were performed on PCTFE targets to record the shock states generated in an inert material prior to subjecting an HMX based explosive to the same loading. The response of the explosive to this loading history was recorded using magnetic particle velocity (PV) gauges embedded within the targets. The behavior during the run to detonation is compared with the response to sustained shocks at similar input pressures.

  13. Simple, economical heat-shock devices for zebrafish housing racks.

    PubMed

    Duszynski, Robert J; Topczewski, Jacek; LeClair, Elizabeth E

    2011-12-01

    One reason for the popularity of the zebrafish (Danio rerio) as a model vertebrate is the ability to manipulate gene expression in this organism. A common method is to induce gene expression transiently under control of a heat-shock promoter (e.g., hsp70l). By making simple mechanical adjustments to small aquarium heaters (25-50W), we were able to produce consistent and reliable heat-shock conditions within a conventional zebrafish housing system. Up to two heat-shock intervals per day (>37°C) could be maintained under conditions of continuous flow (5-25 mL/min). Temperature logging every 30 s indicated rapid warm up times, consistent heat-shock lengths, and accurate and precise peak water temperatures (mean±SD=38°C±0.2°C). The biological effects of these heat-shock treatments were confirmed by observing inducible expression of enhanced green fluorescent protein (EGFP) and inhibition of caudal fin regeneration in a transgenic fish line expressing a dominant negative fibroblast growth factor receptor (Tg(hsp70l:dnfgfr1-EGFP)(pd1)). These devices are inexpensive, easily modified, and can be calibrated to accommodate a variety of experimental designs. After setup on a programmable timer, the heaters require no intervention to produce consistent daily heat shocks, and all other standard care protocols can be followed in the fish facility. The simplicity and stability of these devices make them suitable for long-term heat shocks at any stage of the zebrafish lifecycle (>7 days postfertilization), and useful for both laboratory and classroom experiments on transgenic zebrafish.

  14. Remotely Triggered Scaffolds for Controlled Release of Pharmaceuticals

    PubMed Central

    Roach, Paul; McGarvey, David J.; Lees, Martin R.; Hoskins, Clare

    2013-01-01

    Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold. PMID:23603890

  15. Chromospheric heating by acoustic shock waves

    NASA Technical Reports Server (NTRS)

    Jordan, Stuart D.

    1993-01-01

    Work by Anderson & Athay (1989) suggests that the mechanical energy required to heat the quiet solar chromosphere might be due to the dissipation of weak acoustic shocks. The calculations reported here demonstrate that a simple picture of chromospheric shock heating by acoustic waves propagating upward through a model solar atmosphere, free of both magnetic fields and local inhomogeneities, cannot reproduce their chromospheric model. The primary reason is the tendency for vertically propagating acoustic waves in the range of allowed periods to dissipate too low in the atmosphere, providing insufficient residual energy for the middle chromosphere. The effect of diverging magnetic fields and the corresponding expanding acoustic wavefronts on the mechanical dissipation length is then discussed as a means of preserving a quasi-acoustic heating hypothesis. It is argued that this effect, in a canopy that overlies the low chromosphere, might preserve the acoustic shock hypothesis consistent with the chromospheric radiation losses computed by Anderson & Athay.

  16. Heat-shock-specific phosphorylation and transcriptional activity of RNA polymerase II.

    PubMed

    Egyházi, E; Ossoinak, A; Lee, J M; Greenleaf, A L; Mäkelä, T P; Pigon, A

    1998-07-10

    The carboxyl-terminal domain (CTD) of the largest RNA polymerase II (pol II) subunit is a target for extensive phosphorylation in vivo. Using in vitro kinase assays it was found that several different protein kinases can phosphorylate the CTD including the transcription factor IIH-associated CDK-activating CDK7 kinase (R. Roy, J. P. Adamczewski, T. Seroz, W. Vermeulen, J. P. Tassan, L. Schaeffer, E. A. Nigg, J. H. Hoeijmakers, and J. M. Egly, 1994, Cell 79, 1093-1101). Here we report the colocalization of CDK7 and the phosphorylated form of CTD (phosphoCTD) to actively transcribing genes in intact salivary gland cells of Chironomus tentans. Following a heat-shock treatment, both CDK7 and pol II staining disappear from non-heat-shock genes concomitantly with the abolishment of transcriptional activity of these genes. In contrast, the actively transcribing heat-shock genes, manifested as chromosomal puff 5C on chromosome IV (IV-5C), stain intensely for phosphoCTD, but are devoid of CDK7. Furthermore, the staining of puff IV-5C with anti-PCTD antibodies was not detectably influenced by the TFIIH kinase and transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). Following heat-shock treatment, the transcription of non-heat-shock genes was completely eliminated, while newly formed heat-shock gene transcripts emerged in a DRB-resistant manner. Thus, heat shock in these cells induces a rapid clearance of CDK7 from the non-heat-shock genes, indicating a lack of involvement of CDK7 in the induction and function of the heat-induced genes. The results taken together suggest the existence of heat-shock-specific CTD phosphorylation in living cells. This phosphorylation is resistant to DRB treatment, suggesting that not only phosphorylation but also transcription of heat-shock genes is DRB resistant and that CDK7 in heat shock cells is not associated with TFIIH.

  17. Mechanical analysis of a heat-shock induced developmental defect

    NASA Astrophysics Data System (ADS)

    Crews, Sarah M.; McCleery, W. Tyler; Hutson, M. Shane

    2014-03-01

    Embryonic development in Drosophila is a complex process involving coordinated movements of mechanically interacting tissues. Perturbing this system with a transient heat shock can result in a number of developmental defects. In particular, a heat shock applied during the earliest morphogenetic movements of gastrulation can lead to apparent recovery, but then subsequent morphogenetic failure 5-6 hours later during germ band retraction. The process of germ band retraction requires an intact amnioserosa - a single layered extra-embryonic epithelial tissue - and heat shock at gastrulation can induce the later opening of holes in the amnioserosa. These holes are highly correlated with failures of germ band retraction. These holes could be caused by a combination of mechanical weakness in the amnioserosa or local increases in mechanical stress. Here, we assess the role of mechanical stress using confocal imaging to compare cell and tissue morphology in the amnioserosa of normal and heat-shocked embryos and laser hole drilling to map the stress field around the times and locations at which heat-shock induced holes open.

  18. Heat Shock Response of Archaeoglobus fulgidus†

    PubMed Central

    Rohlin, Lars; Trent, Jonathan D.; Salmon, Kirsty; Kim, Unmi; Gunsalus, Robert P.; Liao, James C.

    2005-01-01

    The heat shock response of the hyperthermophilic archaeon Archaeoglobus fulgidus strain VC-16 was studied using whole-genome microarrays. On the basis of the resulting expression profiles, approximately 350 of the 2,410 open reading frames (ORFs) (ca. 14%) exhibited increased or decreased transcript abundance. These span a range of cell functions, including energy production, amino acid metabolism, and signal transduction, where the majority are uncharacterized. One ORF called AF1298 was identified that contains a putative helix-turn-helix DNA binding motif. The gene product, HSR1, was expressed and purified from Escherichia coli and was used to characterize specific DNA recognition regions upstream of two A. fulgidus genes, AF1298 and AF1971. The results indicate that AF1298 is autoregulated and is part of an operon with two downstream genes that encode a small heat shock protein, Hsp20, and cdc48, an AAA+ ATPase. The DNase I footprints using HSR1 suggest the presence of a cis-binding motif upstream of AF1298 consisting of CTAAC-N5-GTTAG. Since AF1298 is negatively regulated in response to heat shock and encodes a protein only distantly related to the N-terminal DNA binding domain of Phr of Pyrococcus furiosus, these results suggest that HSR1 and Phr may belong to an evolutionarily diverse protein family involved in heat shock regulation in hyperthermophilic and mesophilic Archaea organisms. PMID:16109946

  19. Selective activation of human heat shock gene transcription by nitrosourea antitumor drugs mediated by isocyanate-induced damage and activation of heat shock transcription factor.

    PubMed Central

    Kroes, R A; Abravaya, K; Seidenfeld, J; Morimoto, R I

    1991-01-01

    Treatment of cultured human tumor cells with the chloroethylnitrosourea antitumor drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) selectively induces transcription and protein synthesis of a subset of the human heat shock or stress-induced genes (HSP90 and HSP70) with little effect on other stress genes or on expression of the c-fos, c-myc, or beta-actin genes. The active component of BCNU and related compounds appears to be the isocyanate moiety that causes carbamoylation of proteins and nucleic acids. Transcriptional activation of the human HSP70 gene by BCNU is dependent on the heat shock element and correlates with the level of heat shock transcription factor and its binding to the heat shock element in vivo. Unlike activation by heat or heavy metals, BCNU-mediated activation is strongly dependent upon new protein synthesis. This suggests that BCNU-induced, isocyanate-mediated damage to newly synthesized protein(s) may be responsible for activation of the heat shock transcription factor and increased transcription of the HSP90 and HSP70 genes. Images PMID:2052560

  20. Model Scramjet Inlet Unstart Induced by Mass Addition and Heat Release

    NASA Astrophysics Data System (ADS)

    Im, Seong-Kyun; Baccarella, Damiano; McGann, Brendan; Liu, Qili; Wermer, Lydiy; Do, Hyungrok

    2015-11-01

    The inlet unstart phenomena in a model scramjet are investigated at an arc-heated hypersonic wind tunnel. The unstart induced by nitrogen or ethylene jets at low or high enthalpy Mach 4.5 freestream flow conditions are compared. The jet injection pressurizes the downstream flow by mass addition and flow blockage. In case of the ethylene jet injection, heat release from combustion increases the backpressure further. Time-resolved schlieren imaging is performed at the jet and the lip of the model inlet to visualize the flow features during unstart. High frequency pressure measurements are used to provide information on pressure fluctuation at the scramjet wall. In both of the mass and heat release driven unstart cases, it is observed that there are similar flow transient and quasi-steady behaviors of unstart shockwave system during the unstart processes. Combustion driven unstart induces severe oscillatory flow motions of the jet and the unstart shock at the lip of the scramjet inlet after the completion of the unstart process, while the unstarted flow induced by solely mass addition remains relatively steady. The discrepancies between the processes of mass and heat release driven unstart are explained by flow choking mechanism.

  1. Uncoupling thermotolerance from the induction of heat shock proteins.

    PubMed Central

    Smith, B J; Yaffe, M P

    1991-01-01

    Exposure of cells to elevated temperatures causes a rapid increase in the synthesis of heat shock proteins (hsps) and induces thermotolerance, the increased ability of cells to survive exposure to lethal temperatures; however, the connection between hsp induction and the acquisition of thermotolerance is unclear. hsp induction in the yeast Saccharomyces cerevisiae is mediated by the activation of heat-shock transcription factor, and recently we have described a mutation, hsf1-m3, in heat-shock transcription factor that prevents the factor's activation. We now demonstrate that this mutation results in a general block in heat-shock induction but does not affect the acquisition of thermotolerance. Our results indicate that high-level induction of the major hsps is not required for cells to acquire thermotolerance. Images PMID:1763024

  2. Automated Scalable Heat Shock Modification for Standard Aquatic Housing Systems.

    PubMed

    Saera-Vila, Alfonso; Kish, Phillip E; Kahana, Alon

    2015-08-01

    Heat shock is a common technique for inducible gene expression system in a variety of organisms. Heat shock treatment of adult zebrafish is more involved and generally consists of manually transferring fish between housing rack tanks and preheated water tanks or the use of timed heaters in stand-alone aquaria. To avoid excessive fish handling and to take advantage of the continuous flow of a standard housing rack, proposed modifications consisted of installing an aquarium heater inside each tank, manually setting the heater to reach heat shocking temperatures (> 37°C) and, after that, testing that every tank responded equally. To address the limitations in the existing systems, we developed a novel modification of standard zebrafish housing racks to perform heat shock treatment in conditions of continuous water flow. By adding an extra manifold to the housing rack and connecting it to a recirculating bath to create a parallel water flow system, we can increase the temperature from standard conditions (28.5°C) to heat shock conditions with high precision (38.0-38.3°C, mean ± SD = 38.1°C ± 0.14°C) and minimal variation among experimental tanks (coefficient of variation [CV] = 0.04%). This means that there is virtually no need for laborious pretreatment calibrations or continuous adjustments to minimize intertank variation. To test the effectiveness of our design, we utilized this system to induce enhanced green fluorescent protein (EGFP) expression in hsp70-EGFP fish and performed a fin regeneration experiment with hsp70l:dnfgfr1-EGFP fish to confirm that heat-induced gene expression reached physiological levels. In summary, our newly described aquatic heat shock system minimizes effort during heat shock experiments, while ensuring the best water quality and fish welfare and facilitating large heat shock settings or the use of multiple transgenic lines for both research and teaching experiments.

  3. Synthesis of the low molecular weight heat shock proteins in plants

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

    Mansfield, M.A.; Key, J.L.

    1987-08-01

    Heat shock of living tissue induces the synthesis of a unique group of proteins, the heat shock proteins. In plants, the major group of heat shock proteins has a molecular mass of 15 to 25 kilodaltons. Accumulation to these proteins to stainable levels has been reported in only a few species. To examine accumulation of the low molecular weight heat shock proteins in a broader range of species, two-dimensional electrophoresis was used to resolve total protein from the following species: soybean (Glycine max L. Merr., var Wayne), pea (Pisum sativum L., var Early Alaska), sunflower (Helianthus annuus L.), wheat (Triticummore » asetivum L.), rice (Oryza sativa L., cv IR-36), maize (Zea mays L.), pearl millet (Pennisetum americanum L. Leeke, line 23DB), and Panicum miliaceum L. When identified by both silver staining and incorporation of radiolabel, a diverse array of low molecular weight heat shock proteins was synthesized in each of these species. These proteins accumulated to significant levels after three hours of heat shock but exhibited considerable heterogeneity in isoelectric point, molecular weight, stainability, and radiolabel incorporation. Although most appeared to be synthesized only during heat shock, some were detectable at low levels in control tissue. Compared to the monocots, a higher proportion of low molecular weight heat shock proteins was detectable in control tissues from dicots.« less

  4. Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice

    PubMed Central

    Cheung, Ricky; Shen, Fran; Phillips, Joseph H.; McGeachy, Mandy J.; Cua, Daniel J.; Heyworth, Paul G.; Pierce, Robert H.

    2011-01-01

    Systemic inflammatory response syndrome (SIRS) is a potentially lethal condition, as it can progress to shock, multi-organ failure, and death. It can be triggered by infection, tissue damage, or hemorrhage. The role of tissue injury in the progression from SIRS to shock is incompletely understood. Here, we show that treatment of mice with concanavalin A (ConA) to induce liver injury triggered a G-CSF–dependent hepatic infiltration of CD11b+Gr-1+Ly6G+Ly6C+ immature myeloid cells that expressed the orphan receptor myeloid DAP12–associated lectin–1 (MDL-1; also known as CLEC5A). Activation of MDL-1 using dengue virus or an agonist MDL-1–specific antibody in the ConA-treated mice resulted in shock. The MDL-1+ cells were pathogenic, and in vivo depletion of MDL-1+ cells provided protection. Triggering MDL-1 on these cells induced production of NO and TNF-α, which were found to be elevated in the serum of treated mice and required for MDL-1–induced shock. Surprisingly, MDL-1–induced NO and TNF-α production required eNOS but not iNOS. Activation of DAP12, DAP10, Syk, PI3K, and Akt was critical for MDL-1–induced shock. In addition, Akt physically interacted with and activated eNOS. Therefore, triggering of MDL-1 on immature myeloid cells and production of NO and TNF-α may play a critical role in the pathogenesis of shock. Targeting the MDL-1/Syk/PI3K/Akt/eNOS pathway represents a potential new therapeutic strategy to prevent the progression of SIRS to shock. PMID:22005300

  5. Design evolution of a low shock release nut

    NASA Technical Reports Server (NTRS)

    Otth, D. H.; Gordon, W.

    1976-01-01

    Design improvements and detailed functional analyses are reviewed to trace the development of a pyroactuated release device with segmented thread design from its intermediate design into one that reduces the levels of shock spectra generated during its operation by 50%. Comparisons of shock output and internal load distribution are presented, along with descriptions of mechanical operation for both designs. Results also show the potential areas where design development activity can gain further progress in lowering actuation shock levels.

  6. Glutathionylation of the Bacterial Hsp70 Chaperone DnaK Provides a Link between Oxidative Stress and the Heat Shock Response.

    PubMed

    Zhang, Hong; Yang, Jie; Wu, Si; Gong, Weibin; Chen, Chang; Perrett, Sarah

    2016-03-25

    DnaK is the major bacterial Hsp70, participating in DNA replication, protein folding, and the stress response. DnaK cooperates with the Hsp40 co-chaperone DnaJ and the nucleotide exchange factor GrpE. Under non-stress conditions, DnaK binds to the heat shock transcription factor σ(32)and facilitates its degradation. Oxidative stress results in temporary inactivation of DnaK due to depletion of cellular ATP and thiol modifications such as glutathionylation until normal cellular ATP levels and a reducing environment are restored. However, the biological significance of DnaK glutathionylation remains unknown, and the mechanisms by which glutathionylation may regulate the activity of DnaK are also unclear. We investigated the conditions under which Escherichia coli DnaK undergoesS-glutathionylation. We observed glutathionylation of DnaK in lysates of E. coli cells that had been subjected to oxidative stress. We also obtained homogeneously glutathionylated DnaK using purified DnaK in the apo state. We found that glutathionylation of DnaK reversibly changes the secondary structure and tertiary conformation, leading to reduced nucleotide and peptide binding ability. The chaperone activity of DnaK was reversibly down-regulated by glutathionylation, accompanying the structural changes. We found that interaction of DnaK with DnaJ, GrpE, or σ(32)becomes weaker when DnaK is glutathionylated, and the interaction is restored upon deglutathionylation. This study confirms that glutathionylation down-regulates the functions of DnaK under oxidizing conditions, and this down-regulation may facilitate release of σ(32)from its interaction with DnaK, thus triggering the heat shock response. Such a mechanism provides a link between oxidative stress and the heat shock response in bacteria. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Microbial and human heat shock proteins as 'danger signals' in sarcoidosis.

    PubMed

    Dubaniewicz, Anna

    2013-12-01

    In the light of the Matzinger's model of immune response, human heat shock proteins (HSPs) as main 'danger signals' (tissue damage-associated molecular patterns-DAMPs) or/and microbial HSPs as pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid granuloma by both infectious and non-infectious factors in genetically different predisposed host. Regarding infectious causes of sarcoid models, low-virulence strains of, e.g. mycobacteria and propionibacteria recognized through changed PRR and persisting in altered host phagocytes, generate increased release of both human and microbial HSPs with their molecular and functional homology. High chronic spread of human and microbial HSPs altering cytokines, co-stimulatory molecules, and Tregs expression, apoptosis, oxidative stress, induces the autoimmunity, considered in sarcoidosis. Regarding non-infectious causes of sarcoidosis, human HSPs may be released at high levels during chronic low-grade exposure to misfolding amyloid precursor protein in stressed cells, phagocyted metal fumes, pigments with/without aluminum in tattoos, and due to heat shock in firefighters. Therefore, human HSPs as DAMPs and/or microbial HSPs as PAMPs produced as a result of non-infectious and infectious factors may induce different models of sarcoidosis, depending on the genetic background of the host. The number/expression of PRRs/ligands may influence the occurrence of sarcoidosis in particular organs. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  8. Destabilization and recovery of a yeast prion after mild heat shock

    PubMed Central

    Newnam, Gary P.; Birchmore, Jennifer L.; Chernoff, Yury O.

    2011-01-01

    Yeast prion [PSI+] is a self-perpetuating amyloid of the translational termination factor Sup35. Although [PSI+] propagation is modulated by heat shock proteins (Hsps), high temperature was previously reported to have little or no effect on [PSI+]. Our results show that short-term exposure of exponentially growing yeast culture to mild heat shock, followed by immediate resumption of growth, leads to [PSI+] destabilization, sometimes persisting for several cell divisions after heat shock. Prion loss occurring in the first division after heat shock is preferentially detected in a daughter cell, indicating the impairment of prion segregation that results in asymmetric prion distribution between a mother cell and a bud. Longer heat shock or prolonged incubation in the absence of nutrients after heat shock lead to [PSI+] recovery. Both prion destabilization and recovery during heat shock depend on protein synthesis. Maximal prion destabilization coincides with maximal imbalance between Hsp104 and other Hsps such as Hsp70-Ssa. Deletions of individual SSA genes increase prion destabilization and/or counteract recovery. Dynamics of prion aggregation during destabilization and recovery is consistent with the notion that efficient prion fragmentation and segregation require a proper balance between Hsp104 and other (e. g. Hsp70-Ssa) chaperones. In contrast to heat shock, [PSI+] destabilization by osmotic stressors does not always depend on cell proliferation and/or protein synthesis, indicating that different stresses may impact the prion via different mechanisms. Our data demonstrate that heat stress causes asymmetric prion distribution in a cell division, and confirm that effects of Hsps on prions are physiologically relevant. PMID:21392508

  9. A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis

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

    Lin, Chen-Si; School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; He, Pei-Juin

    2010-02-05

    Helicobacter pylori has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results alsomore » indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis.« less

  10. Biophoton Emission Induced by Heat Shock

    PubMed Central

    Kobayashi, Katsuhiro; Okabe, Hirotaka; Kawano, Shinya; Hidaka, Yoshiki; Hara, Kazuhiro

    2014-01-01

    Ultraweak biophoton emission originates from the generation of reactive oxygen species (ROS) that are produced in mitochondria as by-products of cellular respiration. In healthy cells, the concentration of ROS is minimized by a system of biological antioxidants. However, heat shock changes the equilibrium between oxidative stress and antioxidant activity, that is, a rapid rise in temperature induces biophoton emission from ROS. Although the rate and intensity of biophoton emission was observed to increase in response to elevated temperatures, pretreatment at lower high temperatures inhibited photon emission at higher temperatures. Biophoton measurements are useful for observing and evaluating heat shock. PMID:25153902

  11. Automated Scalable Heat Shock Modification for Standard Aquatic Housing Systems

    PubMed Central

    Saera-Vila, Alfonso; Kish, Phillip E.

    2015-01-01

    Abstract Heat shock is a common technique for inducible gene expression system in a variety of organisms. Heat shock treatment of adult zebrafish is more involved and generally consists of manually transferring fish between housing rack tanks and preheated water tanks or the use of timed heaters in stand-alone aquaria. To avoid excessive fish handling and to take advantage of the continuous flow of a standard housing rack, proposed modifications consisted of installing an aquarium heater inside each tank, manually setting the heater to reach heat shocking temperatures (>37°C) and, after that, testing that every tank responded equally. To address the limitations in the existing systems, we developed a novel modification of standard zebrafish housing racks to perform heat shock treatment in conditions of continuous water flow. By adding an extra manifold to the housing rack and connecting it to a recirculating bath to create a parallel water flow system, we can increase the temperature from standard conditions (28.5°C) to heat shock conditions with high precision (38.0–38.3°C, mean±SD=38.1°C±0.14°C) and minimal variation among experimental tanks (coefficient of variation [CV]=0.04%). This means that there is virtually no need for laborious pretreatment calibrations or continuous adjustments to minimize intertank variation. To test the effectiveness of our design, we utilized this system to induce enhanced green fluorescent protein (EGFP) expression in hsp70-EGFP fish and performed a fin regeneration experiment with hsp70l:dnfgfr1-EGFP fish to confirm that heat-induced gene expression reached physiological levels. In summary, our newly described aquatic heat shock system minimizes effort during heat shock experiments, while ensuring the best water quality and fish welfare and facilitating large heat shock settings or the use of multiple transgenic lines for both research and teaching experiments. PMID:25942613

  12. Heat Shock Factor 1 Deficiency Affects Systemic Body Temperature Regulation.

    PubMed

    Ingenwerth, Marc; Noichl, Erik; Stahr, Anna; Korf, Horst-Werner; Reinke, Hans; von Gall, Charlotte

    2016-01-01

    Heat shock factor 1 (HSF1) is a ubiquitous heat-sensitive transcription factor that mediates heat shock protein transcription in response to cellular stress, such as increased temperature, in order to protect the organism against misfolded proteins. In this study, we analysed the effect of HSF1 deficiency on core body temperature regulation. Body temperature, locomotor activity, and food consumption of wild-type mice and HSF1-deficient mice were recorded. Prolactin and thyroid-stimulating hormone levels were measured by ELISA. Gene expression in brown adipose tissue was analysed by quantitative real-time PCR. Hypothalamic HSF1 and its co-localisation with tyrosine hydroxylase was analysed using confocal laser scanning microscopy. HSF1-deficient mice showed an increase in core body temperature (hyperthermia), decreased overall locomotor activity, and decreased levels of prolactin in pituitary and blood plasma reminiscent of cold adaptation. HSF1 could be detected in various hypothalamic regions involved in temperature regulation, suggesting a potential role of HSF1 in hypothalamic thermoregulation. Moreover, HSF1 co-localises with tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, suggesting a potential role of HSF1 in the hypothalamic control of prolactin release. In brown adipose tissue, levels of prolactin receptor and uncoupled protein 1 were increased in HSF1-deficient mice, consistent with an up-regulation of heat production. Our data suggest a role of HSF1 in systemic thermoregulation. © 2015 S. Karger AG, Basel.

  13. Destabilization and recovery of a yeast prion after mild heat shock.

    PubMed

    Newnam, Gary P; Birchmore, Jennifer L; Chernoff, Yury O

    2011-05-06

    Yeast prion [PSI(+)] is a self-perpetuating amyloid of the translational termination factor Sup35. Although [PSI(+)] propagation is modulated by heat shock proteins (Hsps), high temperature was previously reported to have little or no effect on [PSI(+)]. Our results show that short-term exposure of exponentially growing yeast culture to mild heat shock, followed by immediate resumption of growth, leads to [PSI(+)] destabilization, sometimes persisting for several cell divisions after heat shock. Prion loss occurring in the first division after heat shock is preferentially detected in a daughter cell, indicating the impairment of prion segregation that results in asymmetric prion distribution between a mother cell and a bud. Longer heat shock or prolonged incubation in the absence of nutrients after heat shock led to [PSI(+)] recovery. Both prion destabilization and recovery during heat shock depend on protein synthesis. Maximal prion destabilization coincides with maximal imbalance between Hsp104 and other Hsps such as Hsp70-Ssa. Deletions of individual SSA genes increase prion destabilization and/or counteract recovery. The dynamics of prion aggregation during destabilization and recovery are consistent with the notion that efficient prion fragmentation and segregation require a proper balance between Hsp104 and other (e.g., Hsp70-Ssa) chaperones. In contrast to heat shock, [PSI(+)] destabilization by osmotic stressors does not always depend on cell proliferation and/or protein synthesis, indicating that different stresses may impact the prion via different mechanisms. Our data demonstrate that heat stress causes asymmetric prion distribution in a cell division and confirm that the effects of Hsps on prions are physiologically relevant. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Effects of several factors on the heat-shock-induced thermotolerance of Listeria monocytogenes.

    PubMed Central

    Pagán, R; Condón, S; Sala, F J

    1997-01-01

    The influence of the temperature at which Listeria monocytogenes had been grown (4 or 37 degrees C) on the response to heat shocks of different durations at different temperatures was investigated. For cells grown at 4 degrees C, the effect of storage, prior to and after heat shock, on the induced thermotolerance was also studied. Death kinetics of heat-shocked cells is also discussed. For L. monocytogenes grown at 37 degrees C, the greatest response to heat shock was a fourfold increase in thermotolerance. For L. monocytogenes grown at 4 degrees C, the greatest response to heat shock was a sevenfold increase in thermotolerance. The only survival curves of cells to have shoulders were those for cells that had been heat shocked. A 3% concentration of sodium chloride added to the recovery medium made these shoulders disappear and decreased decimal reduction times. The percentage of cells for which thermotolerance increased after a heat shock was smaller the milder the heat shock and the longer the prior storage. PMID:9251209

  15. Hypotonic shock stimulates ascorbate release from coronary artery endothelial cells by a Ca2+ -independent pathway.

    PubMed

    Davis, Kim A; Samson, Sue E; Wilson, John X; Grover, Ashok K

    2006-10-24

    In endothelial cells, anion channels open upon osmotic swelling during shear stress and hypotonic shock. Therefore, we examined the effects of hypotonic shock on release of the antioxidant anion ascorbate from pig coronary artery endothelial cells. Hypotonic shock potentiated ascorbate release from freshly isolated or cultured pig coronary artery endothelial cells; subsequently cultured endothelial cells were used. The hypotonic shock-induced increase in Asc release was rapid, depended on the degree of hypotonic shock, and not due to membrane leakiness. Stimulating P2Y2 like receptors in endothelial cells with ATP causes ascorbate release via a Ca2+ -mediated pathway. Hypotonic shock-induced release differed from the Ca2+-mediated Asc release because: (a) the increase in release with hypotonic shock was additive to that with ATP or A23187 (Ca2+ -ionophore), (b) apyrase, suramin or removing extracellular Ca2+ did not affect the hypotonic shock-stimulated release, (c) anion channel blockers inhibited the release by the two pathways differently, and (d) hypotonic shock increased the ascorbate release from endothelial cells and cultured smooth muscle cells whereas the Ca2+ -mediated ascorbate release occurred only in endothelial cells. Accumulation of ascorbate by endothelial cells was examined at extracellular ascorbate concentrations of 10 (Na+ -ascorbate symporter not saturated) and 5000 microM (Na+ -ascorbate symporter saturated). Hypotonic shock and A23187 decreased ascorbate accumulation at 10 microM ascorbate but increased it at 5000 microM. The effects of the two treatments were additive and also differed from each other with substitution of gluconate for extracellular chloride. Thus, ascorbate release from endothelial cells can be potentiated by two distinct pathways - hypotonic shock mediated and ATP/Ca2+ stimulated.

  16. Infrared Emissivity of Tin upon Release of a 25 GPa Shock into a LiF Window

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

    Turley, W. D., Holtkamp, D. B., Marshall, B. R., Stevens, G. D., Veeser, L. R.

    We measured the emissivity of a tin sample at its interface with a lithium-fluoride window upon release of a 25 GPa shock wave from the tin into the window. Measurements were made over four wavelength bands between 1.2 and 5.4 μm. Thermal emission backgrounds from the tin, glue, and lithium fluoride were successfully removed from the reflectance signals. Emissivity changes for the sample, which was initially nearly specular, were small except for the longest wavelength band, where uncertainties were high because of poor signal-to-noise ratio at that wavelength. A thin glue layer, which bonds the sample to the window, wasmore » found to heat from reverberations of the shock wave between the tin and the lithium fluoride. At approximately 3.4 μm the thermal emission from the glue was large compared to the tin, allowing a good estimate of the glue temperature from the thermal radiance. The glue appears to remain slightly colder than the tin, thereby minimizing heat conduction into or out of the tin immediately after the shock passage.« less

  17. Self-regulation of 70-kilodalton heat shock proteins in Saccharomyces cerevisiae.

    PubMed Central

    Stone, D E; Craig, E A

    1990-01-01

    To determine whether the 70-kilodalton heat shock proteins of Saccharomyces cerevisiae play a role in regulating their own synthesis, we studied the effect of overexpressing the SSA1 protein on the activity of the SSA1 5'-regulatory region. The constitutive level of Ssa1p was increased by fusing the SSA1 structural gene to the GAL1 promoter. A reporter vector consisting of an SSA1-lacZ translational fusion was used to assess SSA1 promoter activity. In a strain producing approximately 10-fold the normal heat shock level of Ssa1p, induction of beta-galactosidase activity by heat shock was almost entirely blocked. Expression of a transcriptional fusion vector in which the CYC1 upstream activating sequence of a CYC1-lacZ chimera was replaced by a sequence containing a heat shock upstream activating sequence (heat shock element 2) from the 5'-regulatory region of SSA1 was inhibited by excess Ssa1p. The repression of an SSA1 upstream activating sequence by the SSA1 protein indicates that SSA1 self-regulation is at least partially mediated at the transcriptional level. The expression of another transcriptional fusion vector, containing heat shock element 2 and a lesser amount of flanking sequence, is not inhibited when Ssa1p is overexpressed. This suggests the existence of an element, proximal to or overlapping heat shock element 2, that confers sensitivity to the SSA1 protein. Images PMID:2181281

  18. The effects of salinity and temperature shock on Kappaphycus alvarezii seaweed spores release

    NASA Astrophysics Data System (ADS)

    Harwinda, F. K.; Satyantini, W. H.; Masithah, E. W.

    2018-04-01

    One of the reproductive aspects of development step that is considered as the solution of this issue is seaweed sporulation technique through which is induced through salinity and temperature shock. This study aims to determine the effect of combination and interaction of salinity and temperature shock on the release of K. alvarezii spores in order to produce superior seeds. This research was conducted using Complete Randomized Design Factorial which consists of nine combinations of treatments and three replications. The used treatment in this study is the combination of different environmental factors such as salinity shock and temperature shock. The data were analyzed using ANOVA (Analysis of Variance) followed by Duncan Multiple Range Test. The results showed that salinity (31 ppt, 33 ppt, and 35 ppt) and temperature (30°C, 32°C, and 34°C). shock affected the osmoregulation system and the release of K. alvarezii spores. The salinity shock and temperature shock had interaction with K. alvarezii spore release on the sixth and seventh day with the best treatment at 32°C temperature and 31 ppt salinity and released 5413 cells/ml spores on the seventh day.

  19. Heat Shock-Enhanced Conjugation Efficiency in Standard Campylobacter jejuni Strains

    PubMed Central

    Zeng, Ximin; Ardeshna, Devarshi

    2015-01-01

    Campylobacter jejuni, the leading bacterial cause of human gastroenteritis in the United States, displays significant strain diversity due to horizontal gene transfer. Conjugation is an important horizontal gene transfer mechanism contributing to the evolution of bacterial pathogenesis and antimicrobial resistance. It has been observed that heat shock could increase transformation efficiency in some bacteria. In this study, the effect of heat shock on C. jejuni conjugation efficiency and the underlying mechanisms were examined. With a modified Escherichia coli donor strain, different C. jejuni recipient strains displayed significant variation in conjugation efficiency ranging from 6.2 × 10−8 to 6.0 × 10−3 CFU per recipient cell. Despite reduced viability, heat shock of standard C. jejuni NCTC 11168 and 81-176 strains (e.g., 48 to 54°C for 30 to 60 min) could dramatically enhance C. jejuni conjugation efficiency up to 1,000-fold. The phenotype of the heat shock-enhanced conjugation in C. jejuni recipient cells could be sustained for at least 9 h. Filtered supernatant from the heat shock-treated C. jejuni cells could not enhance conjugation efficiency, which suggests that the enhanced conjugation efficiency is independent of secreted substances. Mutagenesis analysis indicated that the clustered regularly interspaced short palindromic repeats system and the selected restriction-modification systems (Cj0030/Cj0031, Cj0139/Cj0140, Cj0690c, and HsdR) were dispensable for heat shock-enhanced conjugation in C. jejuni. Taking all results together, this study demonstrated a heat shock-enhanced conjugation efficiency in standard C. jejuni strains, leading to an optimized conjugation protocol for molecular manipulation of this organism. The findings from this study also represent a significant step toward elucidation of the molecular mechanism of conjugative gene transfer in C. jejuni. PMID:25911489

  20. Heat Shock-Enhanced Conjugation Efficiency in Standard Campylobacter jejuni Strains.

    PubMed

    Zeng, Ximin; Ardeshna, Devarshi; Lin, Jun

    2015-07-01

    Campylobacter jejuni, the leading bacterial cause of human gastroenteritis in the United States, displays significant strain diversity due to horizontal gene transfer. Conjugation is an important horizontal gene transfer mechanism contributing to the evolution of bacterial pathogenesis and antimicrobial resistance. It has been observed that heat shock could increase transformation efficiency in some bacteria. In this study, the effect of heat shock on C. jejuni conjugation efficiency and the underlying mechanisms were examined. With a modified Escherichia coli donor strain, different C. jejuni recipient strains displayed significant variation in conjugation efficiency ranging from 6.2 × 10(-8) to 6.0 × 10(-3) CFU per recipient cell. Despite reduced viability, heat shock of standard C. jejuni NCTC 11168 and 81-176 strains (e.g., 48 to 54°C for 30 to 60 min) could dramatically enhance C. jejuni conjugation efficiency up to 1,000-fold. The phenotype of the heat shock-enhanced conjugation in C. jejuni recipient cells could be sustained for at least 9 h. Filtered supernatant from the heat shock-treated C. jejuni cells could not enhance conjugation efficiency, which suggests that the enhanced conjugation efficiency is independent of secreted substances. Mutagenesis analysis indicated that the clustered regularly interspaced short palindromic repeats system and the selected restriction-modification systems (Cj0030/Cj0031, Cj0139/Cj0140, Cj0690c, and HsdR) were dispensable for heat shock-enhanced conjugation in C. jejuni. Taking all results together, this study demonstrated a heat shock-enhanced conjugation efficiency in standard C. jejuni strains, leading to an optimized conjugation protocol for molecular manipulation of this organism. The findings from this study also represent a significant step toward elucidation of the molecular mechanism of conjugative gene transfer in C. jejuni. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. The Heat Shock Response and Acute Lung Injury

    PubMed Central

    Wheeler, Derek S.; Wong, Hector R.

    2006-01-01

    All cells respond to stress through the activation of primitive, evolutionarily conserved genetic programs that maintain homeostasis and assure cell survival. Stress adaptation, which is known in the literature by a myriad of terms, including tolerance, desensitization, conditioning, and reprogramming, is a common paradigm found throughout nature, in which a primary exposure of a cell or organism to a stressful stimulus (e.g., heat) results in an adaptive response by which a second exposure to the same stimulus produces a minimal response. More interesting is the phenomenon of cross-tolerance, by which a primary exposure to a stressful stimulus results in an adaptive response whereby the cell or organism is resistant to a subsequent stress that is different from the initial stress (i.e. exposure to heat stress leading to resistance to oxidant stress). The heat shock response is one of the more commonly described examples of stress adaptation and is characterized by the rapid expression of a unique group of proteins collectively known as heat shock proteins (also commonly referred to as stress proteins). The expression of heat shock proteins is well described in both whole lungs and in specific lung cells from a variety of species and in response to a variety of stressors. More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that heat shock proteins, especially Hsp27, Hsp32, Hsp60, and Hsp70 have an important cytoprotective role during lung inflammation and injury. PMID:17157189

  2. Barcoding heat shock proteins to human diseases: looking beyond the heat shock response.

    PubMed

    Kakkar, Vaishali; Meister-Broekema, Melanie; Minoia, Melania; Carra, Serena; Kampinga, Harm H

    2014-04-01

    There are numerous human diseases that are associated with protein misfolding and the formation of toxic protein aggregates. Activating the heat shock response (HSR)--and thus generally restoring the disturbed protein homeostasis associated with such diseases--has often been suggested as a therapeutic strategy. However, most data on activating the HSR or its downstream targets in mouse models of diseases associated with aggregate formation have been rather disappointing. The human chaperonome consists of many more heat shock proteins (HSPs) that are not regulated by the HSR, however, and researchers are now focusing on these as potential therapeutic targets. In this Review, we summarize the existing literature on a set of aggregation diseases and propose that each of them can be characterized or 'barcoded' by a different set of HSPs that can rescue specific types of aggregation. Some of these 'non-canonical' HSPs have demonstrated effectiveness in vivo, in mouse models of protein-aggregation disease. Interestingly, several of these HSPs also cause diseases when mutated--so-called chaperonopathies--which are also discussed in this Review.

  3. Barcoding heat shock proteins to human diseases: looking beyond the heat shock response

    PubMed Central

    Kakkar, Vaishali; Meister-Broekema, Melanie; Minoia, Melania; Carra, Serena; Kampinga, Harm H.

    2014-01-01

    There are numerous human diseases that are associated with protein misfolding and the formation of toxic protein aggregates. Activating the heat shock response (HSR) – and thus generally restoring the disturbed protein homeostasis associated with such diseases – has often been suggested as a therapeutic strategy. However, most data on activating the HSR or its downstream targets in mouse models of diseases associated with aggregate formation have been rather disappointing. The human chaperonome consists of many more heat shock proteins (HSPs) that are not regulated by the HSR, however, and researchers are now focusing on these as potential therapeutic targets. In this Review, we summarize the existing literature on a set of aggregation diseases and propose that each of them can be characterized or ‘barcoded’ by a different set of HSPs that can rescue specific types of aggregation. Some of these ‘non-canonical’ HSPs have demonstrated effectiveness in vivo, in mouse models of protein-aggregation disease. Interestingly, several of these HSPs also cause diseases when mutated – so-called chaperonopathies – which are also discussed in this Review. PMID:24719117

  4. Thermotolerant desert lizards characteristically differ in terms of heat-shock system regulation.

    PubMed

    Zatsepina, O G; Ulmasov, K A; Beresten, S F; Molodtsov, V B; Rybtsov, S A; Evgen'ev, M B

    2000-03-01

    We compare the properties and activation of heat-shock transcription factor (HSF1) and the synthesis of a major family of heat-shock proteins (HSP70) in lizard species inhabiting ecological niches with strikingly different thermal parameters. Under normal non-heat-shock conditions, all desert-dwelling lizard species studied so far differ from a northern, non-desert species (Lacerta vivipara) in the electrophoretic mobility and content of proteins constitutively bound to the regulatory heat-shock elements in the heat-shock gene promoter. Under these conditions, levels of activated HSF1 and of both HSP70 mRNA and protein are higher in the desert species than in the non-desert species. Upon heat shock, HSF1 aggregates in all species studied, although in desert species HSF1 subsequently disaggregates more rapidly. Cells of the northern species have a lower thermal threshold for HSP expression than those of the desert species, which correlates with the relatively low constitutive level of HSPs and high basal content of HSF1 in their cells.

  5. Electron Heating in Low-Mach-number Perpendicular Shocks. I. Heating Mechanism

    NASA Astrophysics Data System (ADS)

    Guo, Xinyi; Sironi, Lorenzo; Narayan, Ramesh

    2017-12-01

    Recent X-ray observations of merger shocks in galaxy clusters have shown that the postshock plasma has two temperatures, with the protons hotter than the electrons. By means of two-dimensional particle-in-cell simulations, we study the physics of electron irreversible heating in low-Mach-number perpendicular shocks, for a representative case with sonic Mach number of 3 and plasma beta of 16. We find that two basic ingredients are needed for electron entropy production: (1) an electron temperature anisotropy, induced by field amplification coupled to adiabatic invariance; and (2) a mechanism to break the electron adiabatic invariance itself. In shocks, field amplification occurs at two major sites: at the shock ramp, where density compression leads to an increase of the frozen-in field; and farther downstream, where the shock-driven proton temperature anisotropy generates strong proton cyclotron and mirror modes. The electron temperature anisotropy induced by field amplification exceeds the threshold of the electron whistler instability. The growth of whistler waves breaks the electron adiabatic invariance and allows for efficient entropy production. For our reference run, the postshock electron temperature exceeds the adiabatic expectation by ≃ 15 % , resulting in an electron-to-proton temperature ratio of ≃ 0.45. We find that the electron heating efficiency displays only a weak dependence on mass ratio (less than ≃ 30 % drop, as we increase the mass ratio from {m}i/{m}e=49 up to {m}i/{m}e=1600). We develop an analytical model of electron irreversible heating and show that it is in excellent agreement with our simulation results.

  6. DNA Microcapsule for Photo-Triggered Drug Release Systems.

    PubMed

    Kamiya, Yukiko; Yamada, Yoshinobu; Muro, Takahiro; Matsuura, Kazunori; Asanuma, Hiroyuki

    2017-12-19

    In this study we constructed spherical photo-responsive microcapsules composed of three photo-switchable DNA strands. These strands first formed a three-way junction (TWJ) motif that further self-assembled to form microspheres through hybridization of the sticky-end regions of each branch. To serve as the photo-switch, multiple unmodified azobenzene (Azo) or 2,6-dimethyl-4-(methylthio)azobenzene (SDM-Azo) were introduced into the sticky-end regions via a d-threoninol linker. The DNA capsule structure deformed upon trans-to-cis isomerization of Azo or SDM-Azo induced by specific light irradiation. In addition, photo-triggered release of encapsulated small molecules from the DNA microcapsule was successfully achieved. Moreover, we demonstrated that photo-triggered release of doxorubicin caused cytotoxicity to cultured cells. This biocompatible photo-responsive microcapsule has potential application as a photo-controlled drug-release system. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Atypical Particle Heating at a Supercritical Interplanetary Shock

    NASA Technical Reports Server (NTRS)

    Wilson, Lynn B., III

    2010-01-01

    We present the first observations at an interplanetary shock of large amplitude (> 100 mV/m pk-pk) solitary waves and large amplitude (approx.30 mV/m pk-pk) waves exhibiting characteristics consistent with electron Bernstein waves. The Bernstein-like waves show enhanced power at integer and half-integer harmonics of the cyclotron frequency with a broadened power spectrum at higher frequencies, consistent with the electron cyclotron drift instability. The Bernstein-like waves are obliquely polarized with respect to the magnetic field but parallel to the shock normal direction. Strong particle heating is observed in both the electrons and ions. The observed heating and waveforms are likely due to instabilities driven by the free energy provided by reflected ions at this supercritical interplanetary shock. These results offer new insights into collisionless shock dissipation and wave-particle interactions in the solar wind.

  8. Hugoniot and release measurements in diamond shocked up to 26 Mbar [Hugoniot and release measurements in diamond shocked up to 25 Mbar

    DOE PAGES

    Gregor, M. C.; Fratanduono, D. E.; McCoy, C. A.; ...

    2017-04-26

    The equation of state of carbon at extreme pressures is of interest to studies of planetary ice giants and white dwarfs and to inertial con nement fusion (ICF) because diamond is used as an ablator material at the National Ignition Facility (NIF). Knowledge of both the high-pressure shock and release responses of diamond are needed to accurately model an ICF implosion and design ignition targets. This article presents Hugoniot and release data for both single-crystal diamond and the high-density carbon (HDC), comprised of nanometer-scale grains, used as a NIF ablator. Experiments were performed at the Omega Laser Facility where diamondmore » was shock-compressed to multimegabar pressures and then released into reference materials with known Hugoniots (quartz, polystyrene, silica aerogel, and liquid deuterium). Impedance matching between diamond and the standards provided the data to constrain diamond release models. Hugoniot data were obtained by impedance matching with a quartz standard and results indicate that the HDC, which is ultrananocrystalline and ~4% less dense, has a sti er Hugoniot as compared to single-crystal diamond. Accuracy of the HDC data were improved using a non-steady waves correction [D. E. Fratanduono et al., J. Appl. Phys. 116, 033517 (2014)] to determine shock velocity pro les in the opaque HDC samples.« less

  9. Shuttle ascent and shock impingement aerodynamic heating studies

    NASA Technical Reports Server (NTRS)

    Lanning, W. D.; Hung, F. T.

    1971-01-01

    The collection and analysis of aerodynamic heating data obtained from shock impingement experimental investigation were completed. The data were categorized into four interference areas; fin leading edge, wing/fuselage fin/plate corners, and space shuttle configurations. The effects of shock impingement were found to increase the heating rates 10 to 40 times the undisturbed values. A test program was completed at NASA/Langley Research Center to investigate the magnitudes and surface patterns of the mated shock interference flowfield. A 0.0065 scale thin-skin model of the MDAC 256-20 space shuttle booster mated with a Stycast model of the MDAC Internal tank orbiter was tested in the 20-inch M=6 tunnel, the 31-inch M=10 tunnel, and the 48-inch Unitary Plan Tunnel. The gap region of the ascent configuration was the principal area of interest where both thermocouple and phase-change paint data were obtained. Pressure and heat transfer distributions data on the leeward surface of a 75-degree sweep slab delta wing are presented. The effects of surface roughness on boundary layer transition and aerodynamic heating were investigated.

  10. Regulation of the mammalian heat shock factor 1.

    PubMed

    Dayalan Naidu, Sharadha; Dinkova-Kostova, Albena T

    2017-06-01

    Living organisms are endowed with the capability to tackle various forms of cellular stress due to the presence of molecular chaperone machinery complexes that are ubiquitous throughout the cell. During conditions of proteotoxic stress, the transcription factor heat shock factor 1 (HSF1) mediates the elevation of heat shock proteins, which are crucial components of the chaperone complex machinery and function to ameliorate protein misfolding and aggregation and restore protein homeostasis. In addition, HSF1 orchestrates a versatile transcriptional programme that includes genes involved in repair and clearance of damaged macromolecules and maintenance of cell structure and metabolism, and provides protection against a broad range of cellular stress mediators, beyond heat shock. Here, we discuss the structure and function of the mammalian HSF1 and its regulation by post-translational modifications (phosphorylation, sumoylation and acetylation), proteasomal degradation, and small-molecule activators and inhibitors. © 2017 Federation of European Biochemical Societies.

  11. Cognitive Function and Heat Shock Protein 70 in Children With Temporal Lobe Epilepsy.

    PubMed

    Oraby, Azza M; Raouf, Ehab R Abdol; El-Saied, Mostafa M; Abou-Khadra, Maha K; Helal, Suzette I; Hashish, Adel F

    2017-01-01

    We conducted the present study to examine cognitive function and serum heat shock protein 70 levels among children with temporal lobe epilepsy. The Stanford-Binet Intelligence Test was carried out to examine cognitive function in 30 children with temporal lobe epilepsy and 30 controls. Serum heat shock protein 70 levels were determined with an enzyme-linked immunosorbent assay. The epilepsy group had significantly lower cognitive function testing scores and significantly higher serum heat shock protein 70 levels than the control group; there were significant negative correlations between serum heat shock protein 70 levels and short-term memory and composite scores. Children with uncontrolled seizures had significantly lower verbal reasoning scores and significantly higher serum heat shock protein 70 levels than children with controlled seizures. Children with temporal lobe epilepsy have cognitive dysfunction and elevated levels of serum heat shock protein 70, which may be considered a stress biomarker.

  12. Baculovirus IE2 Stimulates the Expression of Heat Shock Proteins in Insect and Mammalian Cells to Facilitate Its Proper Functioning.

    PubMed

    Tung, Hsuan; Wei, Sung-Chan; Lo, Huei-Ru; Chao, Yu-Chan

    2016-01-01

    Baculoviruses have gained popularity as pest control agents and for protein production in insect systems. These viruses are also becoming popular for gene expression, tissue engineering and gene therapy in mammalian systems. Baculovirus infection triggers a heat shock response, and this response is crucial for its successful infection of host insect cells. However, the viral protein(s) or factor(s) that trigger this response are not yet clear. Previously, we revealed that IE2-an early gene product of the baculovirus-could form unique nuclear bodies for the strong trans-activation of various promoters in mammalian cells. Here, we purified IE2 nuclear bodies from Vero E6 cells and investigated the associated proteins by using mass spectrometry. Heat shock proteins (HSPs) were found to be one of the major IE2-associated proteins. Our experiments show that HSPs are greatly induced by IE2 and are crucial for the trans-activation function of IE2. Interestingly, blocking both heat shock protein expression and the proteasome pathway preserved the IE2 protein and its nuclear body structure, and revived its function. These observations reveal that HSPs do not function directly to assist the formation of the nuclear body structure, but may rather protect IE2 from proteasome degradation. Aside from functional studies in mammalian cells, we also show that HSPs were stimulated and required to determine IE2 protein levels, in insect cells infected with baculovirus. Upon inhibiting the expression of heat shock proteins, baculovirus IE2 was substantially suppressed, resulting in a significantly suppressed viral titer. Thus, we demonstrate a unique feature in that IE2 can function in both insect and non-host mammalian cells to stimulate HSPs, which may be associated with IE2 stabilization and lead to the protection of the its strong gene activation function in mammalian cells. On the other hand, during viral infection in insect cells, IE2 could also strongly stimulate HSPs and

  13. Heat-flow equation motivated by the ideal-gas shock wave.

    PubMed

    Holian, Brad Lee; Mareschal, Michel

    2010-08-01

    We present an equation for the heat-flux vector that goes beyond Fourier's Law of heat conduction, in order to model shockwave propagation in gases. Our approach is motivated by the observation of a disequilibrium among the three components of temperature, namely, the difference between the temperature component in the direction of a planar shock wave, versus those in the transverse directions. This difference is most prominent near the shock front. We test our heat-flow equation for the case of strong shock waves in the ideal gas, which has been studied in the past and compared to Navier-Stokes solutions. The new heat-flow treatment improves the agreement with nonequilibrium molecular-dynamics simulations of hard spheres under strong shockwave conditions.

  14. The relationship between protein synthesis and heat shock proteins levels in rabbit reticulocyte lysates.

    PubMed

    Matts, R L; Hurst, R

    1992-09-05

    Besides heme deficiency, protein synthesis in rabbit reticulocyte lysates becomes inhibited upon exposure to a variety of agents that mimic conditions which induce the heat shock response in cells. This inhibition has been demonstrated to be due primarily to the activation of the heme-regulated eIF-2 alpha kinase (HRI) which causes an arrest in the initiation of translation. In this report, the sensitivity of protein synthesis in hemin-supplemented lysates to inhibition by Hg2+, GSSG, methylene blue, and heat shock was examined in six different reticulocyte lysate preparations. The extent to which translation was inhibited in response to Hg2+, GSSG, methylene blue, and heat shock correlated inversely with the relative levels of the 70-kDa heat shock proteins (hsp 70) and a 56-kDa protein (p56) present in the lysates determined by Western blotting. The ability of hemin to restore protein synthesis upon addition to heme-deficient lysates was also examined. While the restoration of protein synthesis correlated roughly with the levels of hsp 90 present, the results also suggest that the heme regulation of HRI probably involves the interaction of HRI with several factors present in the lysate besides hsp 90. A comparison of two lysate preparations, which had a 2-fold difference in their protein synthesis rates, indicated that the slower translational rate of the one lysate could be accounted for by its low level of constitutive eIF-2 alpha phosphorylation, with its accompanying decrease in the eIF-2B activity and lower level of polyribosome loading. The present study supports the notion that the previously demonstrated interaction of HRI with hsp 90, hsp 70, and p56 in reticulocyte lysates may play a direct role in regulating HRI activation or activity. We hypothesize that the competition of denatured protein and HRI for the binding of hsp 70 may be a molecular signal that triggers the activation of HRI in reticulocyte lysates in response to stress. Possible functions

  15. Microbial communities involved in biogas production exhibit high resilience to heat shocks.

    PubMed

    Abendroth, Christian; Hahnke, Sarah; Simeonov, Claudia; Klocke, Michael; Casani-Miravalls, Sonia; Ramm, Patrice; Bürger, Christoph; Luschnig, Olaf; Porcar, Manuel

    2018-02-01

    We report here the impact of heat-shock treatments (55 and 70 °C) on the biogas production within the acidification stage of a two-stage reactor system for anaerobic digestion and biomethanation of grass. The microbiome proved both taxonomically and functionally very robust, since heat shocks caused minor community shifts compared to the controls, and biogas yield was not decreased. The strongest impact on the microbial profile was observed with a combination of heat shock and low pH. Since no transient reduction of microbial diversity occured after the shock, biogas keyplayers, but also potential pathogens, survived the treatment. All along the experiment, the heat-resistant bacterial profile consisted mainly of Firmicutes, Bacteroidetes and Proteobacteria. Bacteroides and Acholeplasma were reduced after heat shocks. An increase was observed for Aminobacterium. Our results prove the stability to thermal stresses of the microbial communities involved in acidification, and the resilience in biogas production irrespectively of the thermal treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Small Heat Shock Proteins in Redox Metabolism: Implications for Cardiovascular Diseases

    PubMed Central

    Christians, Elisabeth S.; Ishiwata, Takahiro; Benjamin, Ivor J.

    2012-01-01

    A timely review series on small heat shock proteins has to appropriately examine their fundamental properties and implications in the cardiovascular system since several members of this chaperone family exhibit robust expression in the myocardium and blood vessels. Due to energetic and metabolic demands, the cardiovascular system maintains a high mitochondrial activity but irreversible oxidative damage might ensue from increased production of reactive oxygen species. How equilibrium between their production and scavenging is achieved becomes paramount for physiological maintenance. For example, heat shock protein B1 (HSPB1) is implicated in maintaining this equilibrium or redox homeostasis by upholding the level of glutathione, a major redox mediator. Studies of gain or loss of function achieved by genetic manipulations have been highly informative for understanding the roles of those proteins. For example, genetic deficiency of several small heat shock proteins such as HSPB5 and HSPB2 is well-tolerated in heart cells whereas a single missense mutation causes human pathology. Such evidence highlights both the profound genetic redundancy observed among the multigene family of small heat shock proteins while underscoring the role proteotoxicity plays in driving disease pathogenesis. We will discuss the available data on small heat shock proteins in the cardiovascular system, redox metabolism and human diseases. From the medical perspective, we envision that such emerging knowledge of the multiple roles small heat shock proteins exert in the cardiovascular system will undoubtedly open new avenues for their identification and possible therapeutic targeting in humans. PMID:22710345

  17. Stress-induced release of HSC70 from human tumors.

    PubMed

    Barreto, Alfonso; Gonzalez, John Mario; Kabingu, Edith; Asea, Alexzander; Fiorentino, Susana

    2003-04-01

    In this study, we demonstrate that the pro-inflammatory cytokine interferon-gamma (IFN-gamma) induces the active release of the constitutive form of the 70-kDa heat shock protein (HSC70) from K562 erythroleukemic cells. Treatment of K562 cells with IFN-gamma induced the upregulation of the inducible form of the 70-kDa heat shock protein (HSP70), but not the constitutive form of HSC70 within the cytosol, in a proteasome-dependent manner. In addition, IFN-gamma induced the downregulation of surface-bound HSC70, but did not significantly alter surface-bound HSP70 expression. These findings indicate that HSC70 can be actively released from tumor cells and is indicative of a previously unknown mechanism by which immune modulators stimulate the release of intracellular HSC70. This mechanism may account for the potent chaperokine activity of heat shock proteins recently observed during heat shock protein-based immunotherapy against a variety of cancers.

  18. Expression of cholesteryl glucoside by heat shock in human fibroblasts

    PubMed Central

    Kunimoto, Shohko; Kobayashi, Tetsuyuki; Kobayashi, Susumu; Murakami-Murofushi, Kimiko

    2000-01-01

    ABSTRACT We investigated the heat-induced alteration of glycolipids in human cultured cells, TIG-3 fibroblasts, to show the expression of steryl glucoside by heat shock. A glycolipid band was detected on a thin-layer chromatography plate in lipid extracts from TIG-3 cells exposed to high temperature (42°C) for 15 and 30 minutes, while it was hardly detectable without heat shock. Both cholesterol and glucose were almost exclusively detected by gas liquid chromatography as degradation products of the lipid. The structure of the lipid molecule was elucidated by electrospray mass spectrometry to be a cholesteryl glucoside. This is the first report to show the occurrence of a steryl glucoside in mammalian cells, and this substance is considered to have a significant role in heat shock responses in mammalian cells. PMID:10701833

  19. Near-Infrared-Induced Heating of Confined Water in Polymeric Particles for Efficient Payload Release

    PubMed Central

    2015-01-01

    Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution. PMID:24717072

  20. Near-infrared-induced heating of confined water in polymeric particles for efficient payload release.

    PubMed

    Viger, Mathieu L; Sheng, Wangzhong; Doré, Kim; Alhasan, Ali H; Carling, Carl-Johan; Lux, Jacques; de Gracia Lux, Caroline; Grossman, Madeleine; Malinow, Roberto; Almutairi, Adah

    2014-05-27

    Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution.

  1. Heat Shock Proteins in Association with Heat Tolerance in Grasses

    PubMed Central

    Xu, Yan; Zhan, Chenyang; Huang, Bingru

    2011-01-01

    The grass family Poaceae includes annual species cultivated as major grain crops and perennial species cultivated as forage or turf grasses. Heat stress is a primary factor limiting growth and productivity of cool-season grass species and is becoming a more significant problem in the context of global warming. Plants have developed various mechanisms in heat-stress adaptation, including changes in protein metabolism such as the induction of heat shock proteins (HSPs). This paper summarizes the structure and function of major HSPs, recent research progress on the association of HSPs with grass tolerance to heat stress, and incorporation of HSPs in heat-tolerant grass breeding. PMID:22084689

  2. Shock driven melting and resolidification upon release in cerium

    NASA Astrophysics Data System (ADS)

    Bolme, Cindy; Bronkhorst, Curt; Brown, Don; Cherne, Frank; Cooley, Jason; Furlanetto, Michael; Gleason, Arianna; Jensen, Brian; Owens, Charles; Ali, Suzanne; Fratanduono, Dayne; Galtier, Eric; Granados, Eduardo; Lee, Hae Ja; Nagler, Bob

    2017-06-01

    The temperature rise due to increasing entropy during shock compression and the corresponding temperature decrease due to isentropic expansion upon release cause the physics of melting and solidification under dynamic pressure changes to differ fundamentally from the more common liquid-solid transitions governed by thermal diffusion. We investigated laser shock driven melting and resolidification during release in cerium to examine the dynamics of these processes. Cerium was selected as the material of study due to the low pressure at which γ-cerium melts along the principle Hugoniot and due to cerium's anomalous melt boundary at low pressure, which facilitates its transition from liquid to solid during isentropic release. The structural phase of cerium was probed with X-ray diffraction using the LCLS X-ray free electron laser, which provided in situ measurements of the transition dynamics. The experimental results will be presented showing the resolidification occurring over 10s of ns.

  3. Hexavalent chromium, a lung carcinogen, confers resistance to thermal stress and interferes with heat shock protein expression in human bronchial epithelial cells.

    PubMed

    Abreu, Patrícia L; Cunha-Oliveira, Teresa; Ferreira, Leonardo M R; Urbano, Ana M

    2018-03-16

    Exposure to hexavalent chromium [Cr(VI)], a lung carcinogen, triggers several types of cellular stresses, namely oxidative, genotoxic and proteotoxic stresses. Given the evolutionary character of carcinogenesis, it is tempting to speculate that cells that survive the stresses produced by this carcinogen become more resistant to subsequent stresses, namely those encountered during neoplastic transformation. To test this hypothesis, we determined whether pre-incubation with Cr(VI) increased the resistance of human bronchial epithelial cells (BEAS-2B cells) to the antiproliferative action of acute thermal shock, used here as a model for stress. In line with the proposed hypothesis, it was observed that, at mildly cytotoxic concentrations, Cr(VI) attenuated the antiproliferative effects of both cold and heat shock. Mechanistically, Cr(VI) interfered with the expression of two components of the stress response pathway: heat shock proteins Hsp72 and Hsp90α. Specifically, Cr(VI) significantly depleted the mRNA levels of the former and the protein levels of the latter. Significantly, these two proteins are members of heat shock protein (Hsp) families (Hsp70 and Hsp90, respectively) that have been implicated in carcinogenesis. Thus, our results confirm and extend previous studies showing the capacity of Cr(VI) to interfere with the expression of stress response components.

  4. Synergistic Effects of Toxic Elements on Heat Shock Proteins

    PubMed Central

    Mahmood, Khalid; Mahmood, Qaisar; Irshad, Muhammad; Hussain, Jamshaid

    2014-01-01

    Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as “suit of biomarkers in a set of organisms” requires further investigation. PMID:25136596

  5. An in vitro model to consider the effect of 2 mM glutamine and KNK437 on endotoxin-stimulated release of heat shock protein 70 and inflammatory mediators.

    PubMed

    Marino, Luise V; Pathan, Nazima; Meyer, Rosan W; Wright, Victoria J; Habibi, Parviz

    2016-03-01

    Glutamine has been shown to promote the release of heat shock protein 70 (HSP70) both within experimental in vitro models of sepsis and in adults with septic shock. This study aimed to investigate the effects of 2 mM glutamine and an inhibitor of HSP70 (KNK437) on the release of HSP70 and inflammatory mediators in healthy adult volunteers. An in vitro whole blood endotoxin stimulation assay was used. The addition of 2 mM glutamine significantly increased HSP70 levels over time (P < 0.05). HSP70 release had a positive correlation at 4 h with IL-1 β (r = 0.51, P = 0.03) and an inverse correlation with TNF-α (r = -0.56, P = 0.02) and IL-8 levels (r = -0.52, P = 0.03), and there were no significant correlations between HSP70 and IL6 or IL-10 or glutamine. Glutamine supplementation significantly (P < 0.05) attenuated the release of IL-10 at 4 h and IL-8 at 24 h, compared with conditions without glutamine. In endotoxin-stimulated blood there were no significant differences in the release of IL-6, TNF-α, and IL-1 β with glutamine supplementation at 4 and 24 h. However, glutamine supplementation (2 mM) appeared to attenuate the release of inflammatory mediators (IL-1 β, IL-6, TNF-α), although this effect was not statistically significant. The addition of KNK437, a HSP70 inhibitor, significantly diminished HSP70 release, which resulted in lower levels of inflammatory mediators (P < 0.05). Glutamine supplementation promotes HSP70 release in an experimental model of sepsis. After the addition of KNK437, the effects of glutamine on HSP70 and inflammatory mediator release appear to be lost, suggesting that HSP70 in part orchestrates the inflammatory mediator response to sepsis. The clinical implications require further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Differential expression of heat shock transcription factors and heat shock proteins after acute and chronic heat stress in laying chickens (Gallus gallus).

    PubMed

    Xie, Jingjing; Tang, Li; Lu, Lin; Zhang, Liyang; Xi, Lin; Liu, Hsiao-Ching; Odle, Jack; Luo, Xugang

    2014-01-01

    Heat stress due to high environmental temperature negatively influences animal performances. To better understand the biological impact of heat stress, laying broiler breeder chickens were subjected either to acute (step-wisely increasing temperature from 21 to 35°C within 24 hours) or chronic (32°C for 8 weeks) high temperature exposure. High temperature challenges significantly elevated body temperature of experimental birds (P<0.05). However, oxidation status of lipid and protein and expression of heat shock transcription factors (HSFs) and heat shock proteins (HSPs) 70 and 90 were differently affected by acute and chronic treatment. Tissue-specific responses to thermal challenge were also found among heart, liver and muscle. In the heart, acute heat challenge affected lipid oxidation (P = 0.05) and gene expression of all 4 HSF gene expression was upregulated (P<0.05). During chronic heat treatment, the HSP 70 mRNA level was increased (P<0.05) and HSP 90 mRNA (P<0.05) was decreased. In the liver, oxidation of protein was alleviated during acute heat challenge (P<0.05), however, gene expression HSF2, 3 and 4 and HSP 70 were highly induced (P<0.05). HSP90 expression was increased by chronic thermal treatment (P<0.05). In the muscle, both types of heat stress increased protein oxidation, but HSFs and HSPs gene expression remained unaltered. Only tendencies to increase were observed in HSP 70 (P = 0.052) and 90 (P = 0.054) gene expression after acute heat stress. The differential expressions of HSF and HSP genes in different tissues of laying broiler breeder chickens suggested that anti-heat stress mechanisms might be provoked more profoundly in the heart, by which the muscle was least protected during heat stress. In addition to HSP, HSFs gene expression could be used as a marker during acute heat stress.

  7. Post-Transcriptional Regulation of the Trypanosome Heat Shock Response by a Zinc Finger Protein

    PubMed Central

    Droll, Dorothea; Minia, Igor; Fadda, Abeer; Singh, Aditi; Stewart, Mhairi; Queiroz, Rafael; Clayton, Christine

    2013-01-01

    In most organisms, the heat-shock response involves increased heat-shock gene transcription. In Kinetoplastid protists, however, virtually all control of gene expression is post-transcriptional. Correspondingly, Trypanosoma brucei heat-shock protein 70 (HSP70) synthesis after heat shock depends on regulation of HSP70 mRNA turnover. We here show that the T. brucei CCCH zinc finger protein ZC3H11 is a post-transcriptional regulator of trypanosome chaperone mRNAs. ZC3H11 is essential in bloodstream-form trypanosomes and for recovery of insect-form trypanosomes from heat shock. ZC3H11 binds to mRNAs encoding heat-shock protein homologues, with clear specificity for the subset of trypanosome chaperones that is required for protein refolding. In procyclic forms, ZC3H11 was required for stabilisation of target chaperone-encoding mRNAs after heat shock, and the HSP70 mRNA was also decreased upon ZC3H11 depletion in bloodstream forms. Many mRNAs bound to ZC3H11 have a consensus AUU repeat motif in the 3′-untranslated region. ZC3H11 bound preferentially to AUU repeats in vitro, and ZC3H11 regulation of HSP70 mRNA in bloodstream forms depended on its AUU repeat region. Tethering of ZC3H11 to a reporter mRNA increased reporter expression, showing that it is capable of actively stabilizing an mRNA. These results show that expression of trypanosome heat-shock genes is controlled by a specific RNA-protein interaction. They also show that heat-shock-induced chaperone expression in procyclic trypanosome enhances parasite survival at elevated temperatures. PMID:23592996

  8. Post-Shock Sampling of Shock-Heated Hydrocarbon Fuels

    DTIC Science & Technology

    2016-07-07

    on the ability to measure key hydrocarbon fragments (e.g. ethylene , methane, and acetylene) over a wide range of temperatures and pressures. The...series of experiments was conducted to validate the sampling system results and explore the thermal decomposition of ethylene and methane. Initially, a...1% ethylene /0.1% methane/balance argon fuel mixture was shock-heated to ~960 K – a temperature low enough that no reaction would occur. GC analysis

  9. HSF1 and HSF3 cooperatively regulate the heat shock response in lizards.

    PubMed

    Takii, Ryosuke; Fujimoto, Mitsuaki; Matsuura, Yuki; Wu, Fangxu; Oshibe, Namiko; Takaki, Eiichi; Katiyar, Arpit; Akashi, Hiroshi; Makino, Takashi; Kawata, Masakado; Nakai, Akira

    2017-01-01

    Cells cope with temperature elevations, which cause protein misfolding, by expressing heat shock proteins (HSPs). This adaptive response is called the heat shock response (HSR), and it is regulated mainly by heat shock transcription factor (HSF). Among the four HSF family members in vertebrates, HSF1 is a master regulator of HSP expression during proteotoxic stress including heat shock in mammals, whereas HSF3 is required for the HSR in birds. To examine whether only one of the HSF family members possesses the potential to induce the HSR in vertebrate animals, we isolated cDNA clones encoding lizard and frog HSF genes. The reconstructed phylogenetic tree of vertebrate HSFs demonstrated that HSF3 in one species is unrelated with that in other species. We found that the DNA-binding activity of both HSF1 and HSF3 in lizard and frog cells was induced in response to heat shock. Unexpectedly, overexpression of lizard and frog HSF3 as well as HSF1 induced HSP70 expression in mouse cells during heat shock, indicating that the two factors have the potential to induce the HSR. Furthermore, knockdown of either HSF3 or HSF1 markedly reduced HSP70 induction in lizard cells and resistance to heat shock. These results demonstrated that HSF1 and HSF3 cooperatively regulate the HSR at least in lizards, and suggest complex mechanisms of the HSR in lizards as well as frogs.

  10. HSF1 and HSF3 cooperatively regulate the heat shock response in lizards

    PubMed Central

    Takii, Ryosuke; Fujimoto, Mitsuaki; Matsuura, Yuki; Wu, Fangxu; Oshibe, Namiko; Takaki, Eiichi; Katiyar, Arpit; Akashi, Hiroshi; Makino, Takashi; Kawata, Masakado

    2017-01-01

    Cells cope with temperature elevations, which cause protein misfolding, by expressing heat shock proteins (HSPs). This adaptive response is called the heat shock response (HSR), and it is regulated mainly by heat shock transcription factor (HSF). Among the four HSF family members in vertebrates, HSF1 is a master regulator of HSP expression during proteotoxic stress including heat shock in mammals, whereas HSF3 is required for the HSR in birds. To examine whether only one of the HSF family members possesses the potential to induce the HSR in vertebrate animals, we isolated cDNA clones encoding lizard and frog HSF genes. The reconstructed phylogenetic tree of vertebrate HSFs demonstrated that HSF3 in one species is unrelated with that in other species. We found that the DNA-binding activity of both HSF1 and HSF3 in lizard and frog cells was induced in response to heat shock. Unexpectedly, overexpression of lizard and frog HSF3 as well as HSF1 induced HSP70 expression in mouse cells during heat shock, indicating that the two factors have the potential to induce the HSR. Furthermore, knockdown of either HSF3 or HSF1 markedly reduced HSP70 induction in lizard cells and resistance to heat shock. These results demonstrated that HSF1 and HSF3 cooperatively regulate the HSR at least in lizards, and suggest complex mechanisms of the HSR in lizards as well as frogs. PMID:28686674

  11. Silkworm Thermal Biology: A Review of Heat Shock Response, Heat Shock Proteins and Heat Acclimation in the Domesticated Silkworm, Bombyx mori

    PubMed Central

    Manjunatha, H. B.; Rajesh, R. K.; Aparna, H. S.

    2010-01-01

    Heat shock proteins (HSPs) are known to play ecological and evolutionary roles in this postgenomic era. Recent research suggests that HSPs are implicated in cardiovascular biology and disease development, proliferation and regulation of cancer cells, cell death via apoptosis, and several other key cellular functions. These activities have generated great interest amongst cell and molecular biologists, and these biologists are keen to unravel other hitherto unknown potential functions of this group of proteins. Consequently, the biological significance of HSPs has led to cloning and characterization of genes encoding HSPs in many organisms including the silkworm, Bombyx mori L. (Lepidoptera: Bombycidae). However, most of the past investigations in B. mori were confined to expression of HSPs in tissues and cell lines, whereas information on their specific functional roles in biological, physiological, and molecular processes is scarce. Naturally occurring or domesticated polyvoltines (known to be the tropical race) are more resistant to high temperatures and diseases than bi- or univoltines (temperate races). The mechanism of ecological or evolutionary modification of HSPs during the course of domestication of B. mori - particularly in relation to thermotolerance in geographically distinct races/strains - is still unclear. In addition, the heat shock response, thermal acclimation, and hardening have not been studied extensively in B. mori compared to other organisms. Towards this, recent investigations on differential expression of HSPs at various stages of development, considering the concept of the whole organism, open ample scope to evaluate their biological and commercial importance in B. mori which has not been addressed in any of the representative organisms studied so far. Comparatively, heat shock response among different silkworm races/strains of poly-, bi-, and univoltines varies significantly and thermotolerance increases as the larval development proceeds

  12. Effects of heat shock on neuroblastoma (N1E 115) cell proliferation and differentiation.

    PubMed

    Stoklosinski, A; Kruse, H; Richter-Landsberg, C; Rensing, L

    1992-05-01

    Heat shock (44 degrees C) applied for only 15 min induced the development of neurites in neuroblastoma cells 3-6 days later. During the first day after heat shock a transient increase in the rate of cytokinesis together with a synchronizing effect was observed, which led to waves of cytokinesis 14.5 h apart. Individual cell cycles were determined and showed a lengthening in the minimal cell cycle duration and a decrease in the cell cycle variance after shock. Two to 3 days after heat shock the proliferation rate decreased and then recovered. During the 6 days after heat shock, total protein synthesis was lower compared to the untreated cultures. The synthesis of heat shock proteins (100, 90, 84, 70, 68 kDa and some of lower MW) reached a maximum 6 h after heat shock. Parallel changes in the phosphorylation state of proteins were observed in an in vitro assay. Four proteins (100, 89, 67, and 15 kDa) increased and two proteins (97, 73 kDa) decreased their phosphorylation state significantly. Six days after heat shock two proteins (89, 55 kDa) increased their phosphorylation state; the 55-kDa phosphoprotein was identified as tubulin. The effect of heat shock on the intracellular calcium level was determined by measuring Fura 2 fluorescence. Six hours after shock, the Ca2+ level increased to a maximum (about three times the control value) and then dropped during the following days below the control values. We conclude from these results that a decrease in the calcium level may be causally involved in the differentiation process. The calcium effect is probably mediated by changes in the activity of different kinases. This assumption is compatible with the results of experiments with cyclic nucleotides when 10(-5) M cAMP and cGMP were added to in vitro assays of protein phosphorylation. They had different stimulating effects in heat-shocked, differentiating, and growing (control) cells.

  13. Mechanisms of stress-induced cellular HSP72 release: implications for exercise-induced increases in extracellular HSP72.

    PubMed

    Lancaster, Graeme I; Febbraio, Mark A

    2005-01-01

    The heat shock proteins are a family of highly conserved proteins with critical roles in maintaining cellular homeostasis and in protecting the cell from stressful conditions. While the critical intracellular roles of heat shock proteins are undisputed, evidence suggests that the cell possess the necessary machinery to actively secrete specific heat shock proteins in response to cellular stress. In this review, we firstly discuss the evidence that physical exercise induces the release of heat shock protein 72 from specific tissues in humans. Importantly, it appears as though this release is the result of an active secretory process, as opposed to non-specific processes such as cell lysis. Next we discuss recent in vitro evidence that has identified a mechanistic basis for the observation that cellular stress induces the release of a specific subset of heat shock proteins. Importantly, while the classical protein secretory pathway does not seem to be involved in the stress-induced release of HSP72, we discuss the evidence that lipid-rafts and exosomes are important mediators of the stress-induced release of HSP72.

  14. Sickle Cell Vaso-occlusive Crisis Induces the Release of Circulating Serum Heat Shock Protein-70

    PubMed Central

    Adewoye, Adeboye H.; Klings, Elizabeth S.; Farber, Harrison W.; Palaima, Elizabeth; Bausero, Maria A.; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H.; Asea, Alexzander

    2006-01-01

    Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P < 0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P < 0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD. PMID:15726596

  15. Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70.

    PubMed

    Adewoye, Adeboye H; Klings, Elizabeth S; Farber, Harrison W; Palaima, Elizabeth; Bausero, Maria A; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H; Asea, Alexzander

    2005-03-01

    Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD.

  16. Heat Shock Proteins Promote Cancer: It's a Protection Racket.

    PubMed

    Calderwood, Stuart K; Gong, Jianlin

    2016-04-01

    Heat shock proteins (HSP) are expressed at high levels in cancer and form a fostering environment that is essential for tumor development. Here, we review the recent data in this area, concentrating mainly on Hsp27, Hsp70, and Hsp90. The overriding role of HSPs in cancer is to stabilize the active functions of overexpressed and mutated cancer genes. Thus, elevated HSPs are required for many of the traits that underlie the morbidity of cancer, including increased growth, survival, and formation of secondary cancers. In addition, HSPs participate in the evolution of cancer treatment resistance. HSPs are also released from cancer cells and influence malignant properties by receptor-mediated signaling. Current data strongly support efforts to target HSPs in cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Multiple independent regulatory pathways control UBI4 expression after heat shock in Saccharomyces cerevisiae.

    PubMed

    Simon, J R; Treger, J M; McEntee, K

    1999-02-01

    Transcription of the polyubiquitin gene UBI4 of Saccharomyces cerevisiae is strongly induced by a variety of environmental stresses, such as heat shock, nutrient depletion and exposure to DNA-damaging agents. This transcriptional response of UBI4 is likely to be the primary mechanism for increasing the pool of ubiquitin for degradation of stress-damaged proteins. Deletion and promoter fusion studies of the 5' regulatory sequences indicated that two different elements, heat shock elements (HSEs) and stress response element (STREs), contributed independently to heat shock regulation of the UBI4 gene. In the absence of HSEs, STRE sequences localized to the intervals -264 to -238 and -215 to -183 were needed for stress control of transcription after heat shock. Site-directed mutagenesis of the STRE (AG4) at -252 to -248 abolished heat shock induction of UBI4 transcription. Northern analysis demonstrated that cells containing either a temperature-sensitive HSF or non-functional Msn2p/Msn4p transcription factors induced high levels of UBI4 transcripts after heat shock. In cells deficient in both heat stress pathways, heat-induced UBI4 transcript levels were considerably lower but not abolished, suggesting a role for another factor(s) in stress control of its expression.

  18. Heating a plasma by a broadband stream of fast electrons: Fast ignition, shock ignition, and Gbar shock wave applications

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

    Gus’kov, S. Yu., E-mail: guskov@sci.lebedev.ru; Nicolai, Ph.; Ribeyre, X.

    2015-09-15

    An exact analytic solution is found for the steady-state distribution function of fast electrons with an arbitrary initial spectrum irradiating a planar low-Z plasma with an arbitrary density distribution. The solution is applied to study the heating of a material by fast electrons of different spectra such as a monoenergetic spectrum, a step-like distribution in a given energy range, and a Maxwellian spectrum, which is inherent in laser-produced fast electrons. The heating of shock- and fast-ignited precompressed inertial confinement fusion (ICF) targets as well as the heating of a target designed to generate a Gbar shock wave for equation ofmore » state (EOS) experiments by laser-produced fast electrons with a Maxwellian spectrum is investigated. A relation is established between the energies of two groups of Maxwellian fast electrons, which are responsible for generation of a shock wave and heating the upstream material (preheating). The minimum energy of the fast and shock igniting beams as well as of the beam for a Gbar shock wave generation increases with the spectral width of the electron distribution.« less

  19. Shock-wave initiation of heated plastified TATB detonation

    NASA Astrophysics Data System (ADS)

    Kuzmitsky, Igor; Rudenko, Vladimir; Gatilov, Leonid; Koshelev, Alexandr

    1999-06-01

    Explosive, plastified TATB, attracts attention with its weak sensitivity to shock loads and high temperature stability ( Pthreshold ? 6.5 GPa and Tcrit ? 250 0Q). However, at its cooling to T 250 0Q plastified TATB becomes as sensitive to shock load as octogen base HE: the excitation threshold reduces down to Pthreshold 2.0 GPa. The main physical reason for the HE sensitivity change is reduction in density at heating and, hence, higher porosity of the product (approximately from 2Moreover, increasing temperature increases the growth rate of uhotf spots which additionally increases the shock sensitivity [1]. Heated TATB experiments are also conducted at VNIIEF. The detonation excitation was computed within 1D program system MAG using EOS JWL for HE and EP and LLNL kinetics [1,2,3]. Early successful results of using this kinetics to predict detonation excitation in heated plastified TATB in VNIIEF experiments with short and long loading pulses are presented. Parameters of the chemical zone of the stationary detonation wave in plastified TATB (LX-17) were computed with the data from [1]. Parameters Heated In shell Cooled Unheated ?0 , g/cm3 1.70 1.81 1.84 1.905 D , km/s 7.982 7.764 7.686 7.517 PN, GPa 45.4 45.8 35.7 32.9 PJ, GPa 27.0 27.3 27.2 26.4 ?x , mm 0.504 0.843 1.041 2.912 ?t , ns 63.1 108.6 135.5 387.4 [1] Effect of Confinement and Thermal Cycling on the Shock Initiation of LX-17 P.A. Urtiew, C.M. Tarver, J.L. Maienschein, and W.C. Tao. LLNL. Combustion and Flame 105: 43-53 (1996) [2] C.M. Tarver, P.A. Urtiew and W.C. Tao (LLNL) Effects of tandem and colliding shock waves on initiation of triaminotrinitrobenzene. J.Appl. Phys. 78(5), September 1995 [3] Craig M. Tarver, John W. Kury and R. Don Breithaupt Detonation waves in triaminotrinitrobenzene J. Appl. Phys. 82(8) , 15 October 1997.

  20. Non-specific protein modifications by a phytochemical induce heat shock response for self-defense.

    PubMed

    Ohnishi, Kohta; Ohkura, Shinya; Nakahata, Erina; Ishisaka, Akari; Kawai, Yoshichika; Terao, Junji; Mori, Taiki; Ishii, Takeshi; Nakayama, Tsutomu; Kioka, Noriyuki; Matsumoto, Shinya; Ikeda, Yasutaka; Akiyama, Minoru; Irie, Kazuhiro; Murakami, Akira

    2013-01-01

    Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.

  1. Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense

    PubMed Central

    Ohnishi, Kohta; Ohkura, Shinya; Nakahata, Erina; Ishisaka, Akari; Kawai, Yoshichika; Terao, Junji; Mori, Taiki; Ishii, Takeshi; Nakayama, Tsutomu; Kioka, Noriyuki; Matsumoto, Shinya; Ikeda, Yasutaka; Akiyama, Minoru; Irie, Kazuhiro; Murakami, Akira

    2013-01-01

    Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities. PMID:23536805

  2. Heat shock response and mammal adaptation to high elevation (hypoxia).

    PubMed

    Wang, Xiaolin; Xu, Cunshuan; Wang, Xiujie; Wang, Dongjie; Wang, Qingshang; Zhang, Baochen

    2006-10-01

    The mammal's high elevation (hypoxia) adaptation was studied by using the immunological and the molecular biological methods to understand the significance of Hsp (hypoxia) adaptation in the organic high elevation, through the mammal heat shock response. (1) From high elevation to low elevation (natural hypoxia): Western blot and conventional RT-PCR and real-time fluorescence quota PCR were adopted. Expression difference of heat shock protein of 70 (Hsp70) and natural expression of brain tissue of Hsp70 gene was determined in the cardiac muscle tissue among the different elevation mammals (yak). (2) From low elevation to high elevation (hypoxia induction): The mammals (domestic rabbits) from the low elevation were sent directly to the areas with different high elevations like 2300, 3300 and 5000 m above sea level to be raised for a period of 3 weeks before being slaughtered and the genetic inductive expression of the brain tissue of Hsp70 was determined with RT-PCR. The result indicated that all of the mammals at different elevations possessed their heat shock response gene. Hsp70 of the high elevation mammal rose abruptly under stress and might be induced to come into being by high elevation (hypoxia). The speedy synthesis of Hsp70 in the process of heat shock response is suitable to maintain the cells' normal physiological functions under stress. The Hsp70 has its threshold value. The altitude of 5000 m above sea level is the best condition for the heat shock response, and it starts to reduce when the altitude is over 6000 m above sea level. The Hsp70 production quantity and the cell hypoxia bearing capacity have their direct ratio.

  3. Analysis of the Bacterial Heat Shock Response to Photodynamic Therapy-Mediated Oxidative Stress

    PubMed Central

    St. Denis, Tyler G.; Huang, Liyi; Dai, Tianhong; Hamblin, Michael R.

    2011-01-01

    Antimicrobial photodynamic therapy (PDT) has recently emerged as an effective modality for the selective destruction of bacteria and other pathogenic microorganisms. We investigated whether PDT induced protective responses such as heat shock proteins in bacteria. Using the photosensitizer Toluidine Blue O (TBO) at sub-lethal PDT conditions, a 7-fold increase in bacterial heat shock protein GroEL and a 3-fold increase in heat shock protein DnaK were observed in Escherichia coli post PDT. Pretreatment with 50o C heat for 30 minutes reduced PDT killing in both E. coli and in Enterococcus faecalis, with the most pronounced inhibition occurring at 50-μM TBO with 5-J/cm2 635 nm light, where E. coli killing was reduced by 2- log10 and E. faecalis killing was reduced by 4-log10. Finally, inhibition of the highly conserved chaperone DnaK using a small molecule benzylidene lactam heat shock protein inhibitor potentiated (but not significantly) the effect of PDT at a TBO concentration of 2.5 μM in E. faecalis; however, this effect was not observed in E. coli presumably because inhibitor could not gain access due to Gram-negative permeability barrier. Induction of heat shock proteins may be a mechanism whereby bacteria could become resistant to PDT and warrants the need for further study in the application of dual PDT-heat shock protein-inhibition therapies. PMID:21261628

  4. Magnetic/NIR-thermally responsive hybrid nanogels for optical temperature sensing, tumor cell imaging and triggered drug release

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Yi, Jinhui; Mukherjee, Sumit; Banerjee, Probal; Zhou, Shuiqin

    2014-10-01

    The paper demonstrates a class of multifunctional core-shell hybrid nanogels with fluorescent and magnetic properties, which have been successfully developed for simultaneous optical temperature sensing, tumor cell imaging and magnetic/NIR-thermally responsive drug carriers. The as-synthesized hybrid nanogels were designed by coating bifunctional nanoparticles (BFNPs, fluorescent carbon dots embedded in the porous carbon shell and superparamagnetic iron oxide nanocrystals clustered in the core) with a thermo-responsive poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)]-based hydrogel as the shell. The BFNPs in hybrid nanogels not only demonstrate excellent photoluminescence (PL) and photostability due to the fluorescent carbon dots embedded in the porous carbon shell, but also has targeted drug accumulation potential and a magnetic-thermal conversion ability due to the superparamagnetic iron oxide nanocrystals clustered in the core. The thermo-responsive poly(NIPAM-AAm)-based gel shell can not only modify the physicochemical environment of the BFNPs core to manipulate the fluorescence intensity for sensing the variation of the environmental temperature, but also regulate the release rate of the loaded anticancer drug (curcumin) by varying the local temperature of environmental media. In addition, the carbon layer of BFNPs can adsorb and convert the NIR light to heat, leading to a promoted drug release under NIR irradiation and improving the therapeutic efficacy of drug-loaded hybrid nanogels. Furthermore, the superparamagnetic iron oxide nanocrystals in the core of BFNPs can trigger localized heating using an alternating magnetic field, leading to a phase change in the polymer gel to trigger the release of loaded drugs. Finally, the multifunctional hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells. The demonstrated hybrid nanogels would be an ideal system for the biomedical

  5. Test of a new heat-flow equation for dense-fluid shock waves.

    PubMed

    Holian, Brad Lee; Mareschal, Michel; Ravelo, Ramon

    2010-09-21

    Using a recently proposed equation for the heat-flux vector that goes beyond Fourier's Law of heat conduction, we model shockwave propagation in the dense Lennard-Jones fluid. Disequilibrium among the three components of temperature, namely, the difference between the kinetic temperature in the direction of a planar shock wave and those in the transverse directions, particularly in the region near the shock front, gives rise to a new transport (equilibration) mechanism not seen in usual one-dimensional heat-flow situations. The modification of the heat-flow equation was tested earlier for the case of strong shock waves in the ideal gas, which had been studied in the past and compared to Navier-Stokes-Fourier solutions. Now, the Lennard-Jones fluid, whose equation of state and transport properties have been determined from independent calculations, allows us to study the case where potential, as well as kinetic contributions are important. The new heat-flow treatment improves the agreement with nonequilibrium molecular-dynamics simulations under strong shock wave conditions, compared to Navier-Stokes.

  6. Lysosomal responses to heat-shock of seasonal temperature extremes in Cd-exposed mussels.

    PubMed

    Múgica, M; Izagirre, U; Marigómez, I

    2015-07-01

    The present study was aimed at determining the effect of temperature extremes on lysosomal biomarkers in mussels exposed to a model toxic pollutant (Cd) at different seasons. For this purpose, temperature was elevated 10°C (from 12°C to 22°C in winter and from 18°C to 28°C in summer) for a period of 6h (heat-shock) in control and Cd-exposed mussels, and then returned back to initial one. Lysosomal membrane stability and lysosomal structural changes in digestive gland were investigated. In winter, heat-shock reduced the labilisation period (LP) of the lysosomal membrane, especially in Cd-exposed mussels, and provoked transient lysosomal enlargement. LP values recovered after the heat-shock cessation but lysosomal enlargement prevailed in both experimental groups. In summer, heat-shock induced remarkable reduction in LP and lysosomal enlargement (more markedly in Cd-exposed mussels), which recovered within 3 days. Besides, whilst heat-shock effects on LP were practically identical for Cd-exposed mussels in winter and summer, the effects were longer-lasting in summer than in winter for control mussels. Thus, lysosomal responsiveness after heat-shock was higher in summer than in winter but recovery was faster as well, and therefore the consequences of the heat shock seem to be more decisive in winter. In contrast, inter-season differences were attenuated in the presence of Cd. Consequently, mussels seem to be better prepared in summer than in winter to stand short periods of abrupt temperature change; this is, however, compromised when mussels are exposed to pollutants such as Cd. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson’s Disease

    PubMed Central

    McDonald, Louise M.; Griffin, Harry J.; Angeli, Aikaterini; Torkamani, Mariam; Georgiev, Dejan; Jahanshahi, Marjan

    2015-01-01

    Background Paradoxical kinesis has been observed in bradykinetic people with Parkinson’s disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson’s disease tested on medication and in age-matched controls. Methods Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant’s performance on previous trials using a staircase tracking procedure. Results On trials with threat of shock, both patients with Parkinson’s disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings. Conclusions When motivated to avoid mild electric shock, patients with Parkinson’s disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of

  8. The 70 kDa Heat Shock Protein Assists during the Repair of Chilling Injury in the Insect, Pyrrhocoris apterus

    PubMed Central

    Koštál, Vladimír; Tollarová-Borovanská, Michaela

    2009-01-01

    Background The Pyrrhocoris apterus (Insecta: Heteroptera) adults attain high levels of cold tolerance during their overwintering diapause. Non-diapause reproducing adults, however, lack the capacity to express a whole array of cold-tolerance adaptations and show relatively low survival when exposed to sub-zero temperatures. We assessed the competence of non-diapause males of P. apterus for responding to heat- and cold-stresses by up-regulation of 70 kDa heat shock proteins (Hsps) and the role of Hsps during repair of heat- and cold-induced injury. Principal Findings The fragments of P. apterus homologues of Hsp70 inducible (PaHsp70) and cognate forms (PaHsc70) were cloned and sequenced. The abundance of mRNA transcripts for the inducible form (qPCR) and corresponding protein (Western blotting) were significantly up-regulated in response to high and low temperature stimuli. In the cognate form, mRNA was slightly up-regulated in response to both stressors but very low or no up-regulation of protein was apparent after heat- or cold-stress, respectively. Injection of 695 bp-long Pahsp70 dsRNA (RNAi) caused drastic suppression of the heat- and cold-stress-induced Pahsp70 mRNA response and the up-regulation of corresponding protein was practically eliminated. Our RNAi predictably prevented recovery from heat shock and, in addition, negatively influenced repair of chilling injuries caused by cold stress. Cold tolerance increased when the insects were first exposed to a mild heat shock, in order to trigger the up-regulation of PaHsp70, and subsequently exposed to cold stress. Conclusion Our results suggest that accumulation of PaHsp70 belongs to a complex cold tolerance adaptation in the insect Pyrrhocoris apterus. PMID:19229329

  9. Changes in the transcriptome of morula-stage bovine embryos caused by heat shock: relationship to developmental acquisition of thermotolerance

    PubMed Central

    2013-01-01

    Background While initially sensitive to heat shock, the bovine embryo gains thermal resistance as it progresses through development so that physiological heat shock has little effect on development to the blastocyst stage by Day 5 after insemination. Here, experiments using 3’ tag digital gene expression (3’DGE) and real-time PCR were conducted to determine changes in the transcriptome of morula-stage bovine embryos in response to heat shock (40 degrees C for 8 h) that could be associated with thermotolerance. Results Using 3’DGE, expression of 173 genes were modified by heat shock, with 94 genes upregulated by heat shock and 79 genes downregulated by heat shock. A total of 38 differentially-regulated genes were associated with the ubiquitin protein, UBC. Heat shock increased expression of one heat shock protein gene, HSPB11, and one heat shock protein binding protein, HSPBP1, tended to increase expression of HSPA1A and HSPB1, but did not affect expression of 64 other genes encoding heat shock proteins, heat shock transcription factors or proteins interacting with heat shock proteins. Moreover, heat shock increased expression of five genes associated with oxidative stress (AKR7A2, CBR1, GGH, GSTA4, and MAP2K5), decreased expression of HIF3A, but did not affect expression of 42 other genes related to free radical metabolism. Heat shock also had little effect on genes involved in embryonic development. Effects of heat shock for 2, 4 and 8 h on selected heat shock protein and antioxidant genes were also evaluated by real-time PCR. Heat shock increased steady-state amounts of mRNA for HSPA1A (P<0.05) and tended to increase expression of HSP90AA1 (P<0.07) but had no effect on expression of SOD1 or CAT. Conclusions Changes in the transcriptome of the heat-shocked bovine morula indicate that the embryo is largely resistant to effects of heat shock. As a result, transcription of genes involved in thermal protection is muted and there is little disruption of gene

  10. Risk analysis for dry snow slab avalanche release by skier triggering

    NASA Astrophysics Data System (ADS)

    McClung, David

    2013-04-01

    Risk analysis is of primary importance for skier triggering of avalanches since human triggering is responsible for about 90% of deaths from slab avalanches in Europe and North America. Two key measureable quantities about dry slab avalanche release prior to initiation are the depth to the weak layer and the slope angle. Both are important in risk analysis. As the slope angle increases, the probability of avalanche release increases dramatically. As the slab depth increases, the consequences increase if an avalanche releases. Among the simplest risk definitions is (Vick, 2002): Risk = (Probability of failure) x (Consequences of failure). Here, these two components of risk are the probability or chance of avalanche release and the consequences given avalanche release. In this paper, for the first time, skier triggered avalanches were analyzed from probability theory and its relation to risk for both the D and . The data consisted of two quantities : (,D) taken from avalanche fracture line profiles after an avalanche has taken place. Two data sets from accidentally skier triggered avalanches were considered: (1) 718 for and (2) a set of 1242 values of D which represent average values along the fracture line. The values of D were both estimated (about 2/3) and measured (about 1/3) by ski guides from Canadian Mountain Holidays CMH). I also analyzed 1231 accidentally skier triggered avalanches reported by CMH ski guides for avalanche size (representing destructive potential) on the Canadian scale. The size analysis provided a second analysis of consequences to verify that using D. The results showed that there is an intermediate range of both D and with highest risk. ForD, the risk (product of consequences and probability of occurrence) is highest for D in the approximate range 0.6 m - 1.0 m. The consequences are low for lower values of D and the chance of release is low for higher values of D. Thus, the highest product is in the intermediate range. For slope angles

  11. Outcomes of percutaneous trigger finger release with concurrent steroid injection.

    PubMed

    Liu, Wen-Chih; Lu, Chun-Kuan; Lin, Yu-Chuan; Huang, Peng-Ju; Lin, Gau-Tyan; Fu, Yin-Chih

    2016-12-01

    Percutaneous release (PR) of the A1 pulley is a quick, safe, and minimally invasive procedure for treating trigger fingers. The purpose of this study is to identify if PR with additional steroid injections can shorten the recovery to reach unlimited range of motion. Between January 2013 and December 2013, we included 432 trigger fingers with actively correctable triggering or severer symptoms without previous surgical release or steroid injections from two hand clinic offices (A and B). The same experienced surgeon performed PR at the office. Patients from Clinic A received PR with steroid injections and those from Clinic B received PR without steroid injections. Patients returned for follow-up 1 week, 6 weeks, and 12 weeks after the procedure. Between the steroid group and the nonsteroid group, there is no significant difference in the mean time for patients to return to normal work and the rate of residual extensor lag. Middle fingers showed a 5.09-fold chance of having a residual extensor lag over that of the other fingers. High grade trigger fingers recovered more slowly than low grade ones. The success rate of a 12-week follow-up was 98.4%. There was no significant difference between the steroid group (97.5%) and the nonsteroid group (99.1%). PR can treat trigger fingers effectively, but additional steroid injection does not provide more benefit. Some fingers showed temporary extensor lag, especially in middle fingers and high grade trigger fingers, but 85% of those will eventually reach full recovery after self-rehabilitation without another surgical release. Copyright © 2016. Published by Elsevier Taiwan.

  12. Heat release rate of wood-plastic composites

    Treesearch

    N. M. Stark; R. H. White; C. M. Clemons

    1997-01-01

    Wood-plastic composites are becoming more important as a material that fulfills recycling needs. In this study, fire performance tests were conducted on several compositions of wood and plastic materials using the Ohio State University rate of heat release apparatus. Test results included five-minute average heat release rate in kW/m2 (HRR avg) and maximum heat release...

  13. Cardioprotective effects of 70-kDa heat shock protein in transgenic mice.

    PubMed

    Radford, N B; Fina, M; Benjamin, I J; Moreadith, R W; Graves, K H; Zhao, P; Gavva, S; Wiethoff, A; Sherry, A D; Malloy, C R; Williams, R S

    1996-03-19

    Heat shock proteins are proposed to limit injury resulting from diverse environmental stresses, but direct metabolic evidence for such a cytoprotective function in vertebrates has been largely limited to studies of cultured cells. We generated lines of transgenic mice to express human 70-kDa heat shock protein constitutively in the myocardium. Hearts isolated from these animals demonstrated enhanced recovery of high energy phosphate stores and correction of metabolic acidosis following brief periods of global ischemia sufficient to induce sustained abnormalities of these variables in hearts from nontransgenic littermates. These data demonstrate a direct cardioprotective effect of 70-kDa heat shock protein to enhance postischemic recovery of the intact heart.

  14. Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound

    PubMed Central

    Cao, Yang; Chen, Yuli; Yu, Tao; Guo, Yuan; Liu, Fengqiu; Yao, Yuanzhi; Li, Pan; Wang, Dong; Wang, Zhigang; Chen, Yu; Ran, Haitao

    2018-01-01

    Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets. By triggering LIFU, the nanodroplets could be converted into microbubbles locally in tumor tissues for acoustic imaging and the loaded anticancer drug (doxorubicin) was released after the microbubble collapse. Based on the acoustic property of shell materials, such as shell stiffness, two types of nanodroplets (lipid-based nanodroplets and PLGA-based nanodroplets) were activated by different acoustic pressure levels. Ultrasound irradiation duration and power of LIFU were tested and selected to monitor and control the drug release from nanodroplets. Various ultrasound energies were introduced to induce the phase transition and microbubble collapse of nanodroplets in vitro (3 W/3 min for lipid nanodroplets; 8 W/3 min for PLGA nanodroplets). Results: We detected three steps in the drug-releasing profiles exhibiting the programmable patterns. Importantly, the intratumoral accumulation and distribution of the drug with LIFU exposure were significantly enhanced, and tumor proliferation was substantially inhibited. Co-delivery of two drug-loaded nanodroplets could overcome the physical barriers of tumor tissues during chemotherapy. Conclusion: Our study provides a new strategy for the efficient ultrasound-triggered chemotherapy by nanocarriers with programmable LIFU capable of achieving the on-demand drug release. PMID:29507623

  15. Temperature responsive porous silicon nanoparticles for cancer therapy - spatiotemporal triggering through infrared and radiofrequency electromagnetic heating.

    PubMed

    Tamarov, Konstantin; Xu, Wujun; Osminkina, Liubov; Zinovyev, Sergey; Soininen, Pasi; Kudryavtsev, Andrey; Gongalsky, Maxim; Gaydarova, Azha; Närvänen, Ale; Timoshenko, Victor; Lehto, Vesa-Pekka

    2016-11-10

    One critical functionality of the carrier system utilized in targeted drug delivery is its ability to trigger the release of the therapeutic cargo once the carrier has reached its target. External triggering is an alluring approach as it can be applied in a precise spatiotemporal manner. In the present study, we achieved external triggering through the porous silicon (PSi) nanoparticles (NPs) by providing a pulse of infrared or radiofrequency radiation. The NPs were grafted with a temperature responsive polymer whose critical temperature was tailored to be slightly above 37°C. The polymer coating improved the biocompatibility of the NPs significantly in comparison with their uncoated counterparts. Radiation induced a rapid temperature rise, which resulted in the collapse of the polymer chains facilitating the cargo release. Both infrared and radiofrequency radiation were able to efficiently trigger the release of the encapsulated drug in vitro and induce significant cell death in comparison to the control groups. Radiofrequency radiation was found to be more efficient in vitro, and the treatment efficacy was verified in vivo in a lung carcinoma (3LL) mice model. After a single intratumoral administration of the carrier system combined with radiofrequency radiation, there was clear suppression of the growth of the carcinoma and a prolongation of the survival time of the animals. The temperature responsive (TR) polymer grafted on the surface of porous silicon nanoparticles (PSi NPs) changes its conformation in response to the heating induced by infrared or radiofrequency radiation. The conformation change allows the loaded doxorubicin to escape from the pores, achieving controlled drug release from TR PSi NPs, which displayed efficacy against malignant cells both in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Transcription Regulation of HYPK by Heat Shock Factor 1

    PubMed Central

    Das, Srijit; Bhattacharyya, Nitai Pada

    2014-01-01

    HYPK (Huntingtin Yeast Partner K) was originally identified by yeast two-hybrid assay as an interactor of Huntingtin, the protein mutated in Huntington's disease. HYPK was characterized earlier as an intrinsically unstructured protein having chaperone-like activity in vitro and in vivo. HYPK has the ability of reducing rate of aggregate formation and subsequent toxicity caused by mutant Huntingtin. Further investigation revealed that HYPK is involved in diverse cellular processes and required for normal functioning of cells. In this study we observed that hyperthermia increases HYPK expression in human and mouse cells in culture. Expression of exogenous Heat Shock Factor 1 (HSF1), upon heat treatment could induce HYPK expression, whereas HSF1 knockdown reduced endogenous as well as heat-induced HYPK expression. Putative HSF1-binding site present in the promoter of human HYPK gene was identified and validated by reporter assay. Chromatin immunoprecipitation revealed in vivo interaction of HSF1 and RNA polymerase II with HYPK promoter sequence. Additionally, acetylation of histone H4, a known epigenetic marker of inducible HSF1 binding, was observed in response to heat shock in HYPK gene promoter. Overexpression of HYPK inhibited cells from lethal heat-induced death whereas knockdown of HYPK made the cells susceptible to lethal heat shock-induced death. Apart from elevated temperature, HYPK was also upregulated by hypoxia and proteasome inhibition, two other forms of cellular stress. We concluded that chaperone-like protein HYPK is induced by cellular stress and under transcriptional regulation of HSF1. PMID:24465598

  17. A minimal titration model of the mammalian dynamical heat shock response

    NASA Astrophysics Data System (ADS)

    Sivéry, Aude; Courtade, Emmanuel; Thommen, Quentin

    2016-12-01

    Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene regulatory network of the HSR that reproduces quantitatively different heat shock experiments both on heat shock factor 1 (HSF1) and HSPs activities. This model, which is based on chemical kinetics laws, is kept with a low dimensionality without altering the biological interpretation of the model dynamics. This simplistic model highlights the titration of HSF1 by chaperones as the guiding line of the network. Moreover, by a steady states analysis of the network, three different temperature stress regimes appear: normal, acute, and chronic, where normal stress corresponds to pseudo thermal adaption. The protein triage that governs the fate of damaged proteins or the different stress regimes are consequences of the titration mechanism. The simplicity of the present model is of interest in order to study detailed modelling of cross regulation between the HSR and other major genetic networks like the cell cycle or the circadian clock.

  18. Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response.

    PubMed

    Perez, Felipe P; Zhou, Ximing; Morisaki, Jorge; Jurivich, Donald

    2008-04-01

    Hormesis may result when mild repetitive stress increases cellular defense against diverse injuries. This process may also extend in vitro cellular proliferative life span as well as delay and reverse some of the age-dependent changes in both replicative and non-replicative cells. This study evaluated the potential hormetic effect of non-thermal repetitive electromagnetic field shock (REMFS) and its impact on cellular aging and mortality in primary human T lymphocytes and fibroblast cell lines. Unlike previous reports employing electromagnetic radiation, this study used a long wave length, low energy, and non-thermal REMFS (50MHz/0.5W) for various therapeutic regimens. The primary outcomes examined were age-dependent morphological changes in cells over time, cellular death prevention, and stimulation of the heat shock response. REMFS achieved several biological effects that modified the aging process. REMFS extended the total number of population doublings of mouse fibroblasts and contributed to youthful morphology of cells near their replicative lifespan. REMFS also enhanced cellular defenses of human T cells as reflected in lower cell mortality when compared to non-treated T cells. To determine the mechanism of REMFS-induced effects, analysis of the cellular heat shock response revealed Hsp90 release from the heat shock transcription factor (HSF1). Furthermore, REMFS increased HSF1 phosphorylation, enhanced HSF1-DNA binding, and improved Hsp70 expression relative to non-REMFS-treated cells. These results show that non-thermal REMFS activates an anti-aging hormetic effect as well as reduces cell mortality during lethal stress. Because the REMFS configuration employed in this study can potentially be applied to whole body therapy, prospects for translating these data into clinical interventions for Alzheimer's disease and other degenerative conditions with aging are discussed.

  19. pH-Triggered Echogenicity and Contents Release from Liposomes

    PubMed Central

    2015-01-01

    Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%). PMID:25271780

  20. pH-triggered echogenicity and contents release from liposomes.

    PubMed

    Nahire, Rahul; Hossain, Rayat; Patel, Rupa; Paul, Shirshendu; Meghnani, Varsha; Ambre, Avinash H; Gange, Kara N; Katti, Kalpana S; Leclerc, Estelle; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku

    2014-11-03

    Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%).

  1. Release Path Temperatures of Shock-Compressed Tin from Dynamic Reflectance and Radiance Measurements

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

    La Lone, B. M.; Stevens, G. D.; Turley, W. D.

    2013-08-01

    Dynamic reflectance and radiance measurements were conducted for tin samples shock compressed to 35 GPa and released to 15 GPa using high explosives. We determined the reflectance of the tin samples glued to lithium fluoride windows using an integrating sphere with an internal xenon flashlamp as an illumination source. The dynamic reflectance (R) was determined at near normal incidence in four spectral bands with coverage in visible and near-infrared spectra. Uncertainties in R/R0 are < 2%, and uncertainties in absolute reflectance are < 5%. In complementary experiments, thermal radiance from the tin/glue/lithium fluoride interface was recorded with similar shock stressmore » and spectral coverage as the reflectance measurements. The two sets of experiments were combined to obtain the temperature history of the tin surface with an uncertainty of < 2%. The stress at the interface was determined from photonic Doppler velocimetry and combined with the temperatures to obtain temperature-stress release paths for tin. We discuss the relationship between the experimental release paths and release isentropes that begin on the principal shock Hugoniot.« less

  2. Cardioprotective effects of 70-kDa heat shock protein in transgenic mice.

    PubMed Central

    Radford, N B; Fina, M; Benjamin, I J; Moreadith, R W; Graves, K H; Zhao, P; Gavva, S; Wiethoff, A; Sherry, A D; Malloy, C R; Williams, R S

    1996-01-01

    Heat shock proteins are proposed to limit injury resulting from diverse environmental stresses, but direct metabolic evidence for such a cytoprotective function in vertebrates has been largely limited to studies of cultured cells. We generated lines of transgenic mice to express human 70-kDa heat shock protein constitutively in the myocardium. Hearts isolated from these animals demonstrated enhanced recovery of high energy phosphate stores and correction of metabolic acidosis following brief periods of global ischemia sufficient to induce sustained abnormalities of these variables in hearts from nontransgenic littermates. These data demonstrate a direct cardioprotective effect of 70-kDa heat shock protein to enhance postischemic recovery of the intact heart. Images Fig. 1 Fig. 3 PMID:8637874

  3. Heat shock increases oxidative stress to modulate growth and physico-chemical attributes in diverse maize cultivars

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    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.

  4. HSP70 gene expression in Mytilus galloprovincialis hemocytes is triggered by moderate heat shock and Vibrio anguillarum, but not by V. splendidus or Micrococcus lysodeikticus.

    PubMed

    Cellura, Cinzia; Toubiana, Mylène; Parrinello, Nicolo; Roch, Philippe

    2006-01-01

    Complete sequence of HSP70 cDNA from the mussel, Mytilus galloprovincialis was established before quantifying its expression following moderate heat shock or injection of heat-killed bacteria. HSP70 cDNA is comprised of 2378 bp including one ORF of 654 aa, with a predicted 70 bp 5'-UTR and a 343 bp 3'-UTR (GenBank, 18 Jan 05, AY861684). Alignment identity ranged from 89% for Crassostrea ariakensis to 72% for C. virginica. Curiously, HSP70 gene and cDNA sequences from M. galloprovincialis, deposited later (03 and 27 May), show only 73% identity with the present sequence. Meanwhile, characteristic motifs of the HSP70 family were located in conserved positions. Expression of HSP70 gene was quantified on circulating hemocyte mRNA using Q-PCR after RT using random hexaprimers. Housekeeping gene was 28S rRNA. Four stresses were applied: heat shock that consisted of immersing mussels for 90 min at 30 degrees C and returning them to 20 degrees C sea water, one injection of heat-killed Gram-negative bacteria, Vibrio splendidus LGP32, one injection of heat-killed Gram-negative bacteria Vibrio anguillarum, one injection of heat-killed Gram-positive bacteria Micrococcus lysodeikticus. We found no significant modification of 28S rRNA gene expression. Significant increase of 5.2 +/- 0.4 fold the ratio HSP70/28S rRNA was observed 6 h after heat shock and was maximum at 15 h (6.1 +/- 1.1), and still significant after 24 h (1.7 +/- 0.03). Similarly, injecting V. anguillarum resulted in a significant increase of 2.7 +/- 0.1 after 12 h. Expression was maximum after 48 h (5.2 +/- 0.05) and returned to baseline after 72 h. In contrast, injecting V. splendidus or M. lysodeikticus failed to significantly modulate HSP70 gene expression at least during the first 3 days post-injection. Consequently, mussel hemocytes appeared to discriminate between pathogenic and non-pathogenic Vibrios, as well as between Gram-negative and Gram-positive bacteria.

  5. Heat shock suppresses mating and sperm transfer in the rice leaf folder Cnaphalocrocis medinalis.

    PubMed

    Liao, H J; Qian, Q; Liu, X D

    2014-06-01

    Temperature is a key environmental factor in determining the population size of Cnaphalocrocis medinalis in summer. High temperatures inhibit survival, development and fecundity of this insect. However, biological responses of female and male adults to heat shock, and physiological mechanism of high temperature suppressing population development are still ambiguous. We experimentally tested the impact of heat shock (5 h day-1) on biological traits, spermatogenesis and sperm transfer of adults of C. medinalis. The result showed that heat exposure to 39 and 40 °C for 5 h reduced longevity and copulation frequency of adults, and hatchability of eggs. Immediate survival rate of males was lower than that of females after 3 days of exposure to 41 °C. The oviposition period, copulation frequency, fecundity of adults and hatchability of eggs were significantly lower when male adults were exposed to 40 or 41 °C for 3 days. Heat shock decreased frequency and success rate of mating when males were exposed, and it also resulted in postponement of mating behaviour and prolongation of mating duration as both the female and male adults were exposed. Heat shock did not affect spermatogenesis, but significantly inhibited sperms maturation. Moreover, males could not ejaculate sperm into females during copulation when these male moths received heat shock. Heat shock remarkably suppressed mating behaviour and sperm transfer, which led to a dramatic decline of rice leaf folder populations.

  6. Interferometric and schlieren characterization of the plasmas and shock wave dynamics during laser-triggered discharge in atmospheric air

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

    Wei, Wenfu; Li, Xingwen, E-mail: xwli@mail.xjtu.edu.cn; Wu, Jian

    2014-08-15

    This paper describes our efforts to reveal the underlying physics of laser-triggered discharges in atmospheric air using a Mach-Zehnder interferometer and schlieren photography. Unlike the hemispherical shock waves that are produced by laser ablation, bell-like morphologies are observed during laser-triggered discharges. Phase shifts are recovered from the interferograms at a time of 1000 ns by the 2D fast Fourier transform method, and then the values of the refractive index are deduced using the Abel inversion. An abundance of free electrons is expected near the cathode surface. The schlieren photographs visualize the formation of stagnation layers at ∼600 ns in the interaction zonesmore » of the laser- and discharge-produced plasmas. Multiple reflected waves are observed at later times with the development of shock wave propagations. Estimations using the Taylor-Sedov self-similar solution indicated that approximately 45.8% and 51.9% of the laser and electrical energies are transferred into the gas flow motions, respectively. Finally, numerical simulations were performed, which successfully reproduced the main features of the experimental observations, and provided valuable insights into the plasma and shock wave dynamics during the laser-triggered discharge.« less

  7. Function and regulation of heat shock factor 2 during mouse embryogenesis

    PubMed Central

    Rallu, M.; Loones, Mt.; Lallemand, Y.; Morimoto, R.; Morange, M.; Mezger, V.

    1997-01-01

    The spontaneous expression of heat shock genes during development is well documented in many animal species, but the mechanisms responsible for this developmental regulation are only poorly understood. In vertebrates, additional heat shock transcription factors, distinct from the heat shock factor 1 (HSF1) involved in the stress response, were suggested to be involved in this developmental control. In particular, the mouse HSF2 has been found to be active in testis and during preimplantation development. However, the role of HSF2 and its mechanism of activation have remained elusive due to the paucity of data on its expression during development. In this study, we have examined HSF2 expression during the postimplantation phase of mouse development. Our data show a developmental regulation of HSF2, which is expressed at least until 15.5 days of embryogenesis. It becomes restricted to the central nervous system during the second half of gestation. It is expressed in the ventricular layer of the neural tube which contains mitotically active cells but not in postmitotic neurons. Parallel results were obtained for mRNA, protein, and activity levels, demonstrating that the main level of control was transcriptional. The detailed analysis of the activity of a luciferase reporter gene under the control of the hsp70.1 promoter, as well as the description of the protein expression patterns of the major heat shock proteins in the central nervous system, show that HSF2 and heat shock protein expression domains do not coincide. This result suggests that HFS2 might be involved in other regulatory developmental pathways and paves the way to new functional approaches. PMID:9122205

  8. Triggering collapse of the presolar dense cloud core and injecting short-lived radioisotopes with a shock wave. III. Rotating three-dimensional cloud cores

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

    Boss, Alan P.; Keiser, Sandra A., E-mail: boss@dtm.ciw.edu

    2014-06-10

    A key test of the supernova triggering and injection hypothesis for the origin of the solar system's short-lived radioisotopes is to reproduce the inferred initial abundances of these isotopes. We present here the most detailed models to date of the shock wave triggering and injection process, where shock waves with varied properties strike fully three-dimensional, rotating, dense cloud cores. The models are calculated with the FLASH adaptive mesh hydrodynamics code. Three different outcomes can result: triggered collapse leading to fragmentation into a multiple protostar system; triggered collapse leading to a single protostar embedded in a protostellar disk; or failure tomore » undergo dynamic collapse. Shock wave material is injected into the collapsing clouds through Rayleigh-Taylor fingers, resulting in initially inhomogeneous distributions in the protostars and protostellar disks. Cloud rotation about an axis aligned with the shock propagation direction does not increase the injection efficiency appreciably, as the shock parameters were chosen to be optimal for injection even in the absence of rotation. For a shock wave from a core-collapse supernova, the dilution factors for supernova material are in the range of ∼10{sup –4} to ∼3 × 10{sup –4}, in agreement with recent laboratory estimates of the required amount of dilution for {sup 60}Fe and {sup 26}Al. We conclude that a type II supernova remains as a promising candidate for synthesizing the solar system's short-lived radioisotopes shortly before their injection into the presolar cloud core by the supernova's remnant shock wave.« less

  9. Shock compression and flash-heating of molecular adsorbates on the picosecond time scale

    NASA Astrophysics Data System (ADS)

    Berg, Christopher Michael

    An ultrafast nonlinear coherent laser spectroscopy termed broadband multiplex vibrational sum-frequency generation (SFG) with nonresonant suppression was employed to monitor vibrational transitions of molecular adsorbates on metallic substrates during laser-driven shock compression and flash-heating. Adsorbates were in the form of well-ordered self-assembled monolayers (SAMs) and included molecular explosive simulants, such as nitroaromatics, and long chain-length alkanethiols. Based on reflectance measurements of the metallic substrates, femtosecond flash-heating pulses were capable of producing large-amplitude temperature jumps with DeltaT = 500 K. Laser-driven shock compression of SAMs produced pressures up to 2 GPa, where 1 GPa ≈ 1 x 104 atm. Shock pressures were estimated via comparison with frequency shifts observed in the monolayer vibrational transitions during hydrostatic pressure measurements in a SiC anvil cell. Molecular dynamics during flash-heating and shock loading were probed with vibrational SFG spectroscopy with picosecond temporal resolution and sub-nanometer spatial resolution. Flash-heating studies of 4-nitrobenzenethiolate (NBT) on Au provided insight into effects from hot-electron excitation of the molecular adsorbates at early pump-probe delay times. At longer delay times, effects from the excitation of SAM lattice modes and lower-energy NBT vibrations were shown. In addition, flash-heating studies of alkanethiolates demonstrated chain disordering behaviors as well as interface thermal conductances across the Au-SAM junction, which was of specific interest within the context of molecular electronics. Shock compression studies of molecular explosive simulants, such as 4-nitrobenzoate (NBA), demonstrated the proficiency of this technique to observe shock-induced molecular dynamics, in this case orientational dynamics, on the picosecond time scale. Results validated the utilization of these refined shock loading techniques to probe the shock

  10. Interspecific- and acclimation-induced variation in levels of heat-shock proteins 70 (hsp70) and 90 (hsp90) and heat-shock transcription factor-1 (HSF1) in congeneric marine snails (genus Tegula): implications for regulation of hsp gene expression.

    PubMed

    Tomanek, Lars; Somero, George N

    2002-03-01

    In our previous studies of heat-shock protein (hsp) expression in congeneric marine gastropods of the genus Tegula, we observed interspecific and acclimation-induced variation in the temperatures at which heat-shock gene expression is induced (T(on)). To investigate the factors responsible for these inter- and intraspecific differences in T(on), we tested the predictions of the 'cellular thermometer' model for the transcriptional regulation of hsp expression. According to this model, hsps not active in chaperoning unfolded proteins bind to a transcription factor, heat-shock factor-1 (HSF1), thereby reducing the levels of free HSF1 that are available to bind to the heat-shock element, a regulatory element upstream of hsp genes. Under stress, hsps bind to denatured proteins, releasing HSF1, which can now activate hsp gene transcription. Thus, elevated levels of heat-shock proteins of the 40, 70 and 90 kDa families (hsp 40, hsp70 and hsp90, respectively) would be predicted to elevate T(on). Conversely, elevated levels of HSF1 would be predicted to decrease T(on). Following laboratory acclimation to 13, 18 and 23 degrees C, we used solid-phase immunochemistry (western analysis) to quantify endogenous levels of two hsp70 isoforms (hsp74 and hsp72), hsp90 and HSF1 in the low- to mid-intertidal species Tegula funebralis and in two subtidal to low-intertidal congeners, T. brunnea and T. montereyi. We found higher endogenous levels of hsp72 (a strongly heat-induced isoform) at 13 and 18 degrees C in T. funebralis in comparison with T. brunnea and T. montereyi. However, T. funebralis also had higher levels of HSF1 than its congeners. The higher levels of HSF1 in T. funebralis cannot, within the framework of the cellular thermometer model, account for the higher T(on) observed for this species, although they may explain why T. funebralis is able to induce the heat-shock response more rapidly than T. brunnea. However, the cellular thermometer model does appear to explain the

  11. Examine the Correlation between Heat Shock Protein IbpA and Heat Tolerance in Cronobacter sakazakii.

    PubMed

    Zhao, Zhi Jing; Wang, Bin; Yuan, Jing; Liang, Hao Yu; Dong, Si Guo; Zeng, Ming

    2017-08-01

    We used a proteomic approach to identify IbpA in Cronobacter sakazakii (C. sakazaki), which is related to heat tolerance in this strain. The abundance of IbpA in C. sakazakii strains strongly increased after heat shock. C. sakazakii CMCC 45402 ibpA deletion mutants were successfully constructed. The C. sakazakii CMCC 45402 ΔibpA and wild-type strains could not be distinguished based on colony morphology on LB agar plates or biochemical assays. The growth of the C. sakazakii CMCC 45402 ΔibpA mutant in heat shock conditions was indistinguishable from that of the isogenic wild-type, but showed greater heat resistance than E. coli O157:H7 strain CMCC 44828. This study suggests that the absence of a single ibpA gene has no obvious effect on the phenotype or heat resistance of the strain C. sakazakii CMCC 45402. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  12. Shock-Bubble Heating of the Intracluster Medium

    NASA Astrophysics Data System (ADS)

    Friedman, Samuel H.; Heinz, S.; Churazov, E.

    2011-01-01

    Active galactic nuclei (AGN) Feedback via extragalactic jets requires a thermalization of the energy injected into the intracluster medium (ICM) in order for energy feedback to occur. Heinz and Churazov (2005) proposed a method using shock waves and previously inflated bubbles in the ICM to extract energy from the shock waves and turn the energy into rotational kinetic energy. This energy would decay and allow heating to occur elsewhere throughout the galaxy cluster. In this paper, we extend to three dimensions (3D) the previous work using hydrodynamic simulations. We also compare our results to previous related work done performed experimentally.

  13. OLA1 protects cells in heat shock by stabilizing HSP70

    PubMed Central

    Mao, R-F; Rubio, V; Chen, H; Bai, L; Mansour, O C; Shi, Z-Z

    2013-01-01

    The heat-shock response is an evolutionarily conserved cellular defense mechanism against environmental stresses, characterized by the rapid synthesis of heat-shock proteins (HSPs). HSP70, a highly inducible molecular chaperone, assists in refolding or clearance of damaged proteins, thereby having a central role in maintaining intracellular homeostasis and thermotolerance. To date, induction of HSP70 expression has been described extensively at the transcriptional level. However, post-translational regulation of HSP70, such as protein stability, is only partially understood. In this study, we investigated the role of OLA1 (Obg-like ATPase 1), a previously uncharacterized cytosolic ATPase, in regulating the turnover of HSP70. Downregulation of OLA1 in mammalian cells by either RNAi or targeted gene disruption results in reduced steady-state levels of HSP70, impaired HSP70 induction by heat, and functionally, increased cellular sensitivity to heat shock. Conversely, overexpression of OLA1 correlates with elevated HSP70 protein levels and improved thermal resistance. Protein–protein interaction assays demonstrated that binding of OLA1 to the HSP70 carboxyl terminus variable domain hinders the recruitment of CHIP (C-terminus of Hsp70-binding protein), an E3 ubiquitin ligase for HSP70, and thus prevents HSP70 from the CHIP-mediated ubiquitination. These findings suggest a novel molecular mechanism by which OLA1 stabilizes HSP70, leading to upregulation of HSP70 as well as increased survival during heat shock. PMID:23412384

  14. Reversible electron heating vs. wave-particle interactions in quasi-perpendicular shocks

    NASA Technical Reports Server (NTRS)

    Veltri, P.; Mangeney, A.; Scudder, J. D.

    1992-01-01

    The energy necessary to explain the electron heating in quasi-perpendicular collisionless shocks can be derived either from the electron acceleration in the d.c. cross shock electric potential, or by the interactions between the electrons and the waves existing in the shock. A Monte Carlo simulation has been performed to study the electron distribution function evolution through the shock structure, with and without particle diffusion on waves. This simulation has allowed us to clarify the relative importance of the two possible energy sources; in particular it has been shown that the electron parallel temperature is determined by the d.c. electromagnetic field and not by any wave-particle-induced heating. Wave particle interactions are effective in smoothing out the large gradients in phase space produced by the 'reversible' motion of the electrons, thus producing a 'cooling' of the electrons.

  15. Efficient electron heating in relativistic shocks and gamma-ray-burst afterglow.

    PubMed

    Gedalin, M; Balikhin, M A; Eichler, D

    2008-02-01

    Electrons in shocks are efficiently energized due to the cross-shock potential, which develops because of differential deflection of electrons and ions by the magnetic field in the shock front. The electron energization is necessarily accompanied by scattering and thermalization. The mechanism is efficient in both magnetized and nonmagnetized relativistic electron-ion shocks. It is proposed that the synchrotron emission from the heated electrons in a layer of strongly enhanced magnetic field is responsible for gamma-ray-burst afterglows.

  16. Molecular changes associated with heat-shock treatment in avian mononuclear and lymphoid lineage cells.

    PubMed

    Miller, L; Qureshi, M A

    1992-03-01

    The induction of heat-shock protein (HSP) synthesis in avian cells of the mononuclear phagocytic system (MPS) and lymphoid system (LS) lineage was investigated by exposure to in vitro heat-shock conditions. In addition, the kinetics of HSP90 mRNA expression was examined in chicken peritoneal macrophages (PM) as well as heat-shock-induced HSP synthesis in PM from chickens, turkeys, quail, and ducks. Each MPS and LS cell type expressed three major (23, 70, and 90 kDa) HSP following a 1-h heat shock at 45 C. However, a unique heat-induced 32-kDa protein (P32) was expressed only by cells of MPS lineage. The expression of HSP90 mRNA in chicken PM was temperature- and time-dependent. These findings imply that avian PM undergo molecular changes in response to elevated environmental temperatures and that the pattern of HSP expression appears to be distinct for cells of the MPS and LS lineages in chickens.

  17. Heat shock protein 70 in the rat nasal cavity: localisation and response to hyperthermia.

    PubMed

    Simpson, Sharon A; Alexander, David J; Reed, Celia J

    2004-06-01

    Heat shock proteins (HSPs) are a group of proteins that are rapidly induced in response to physiological stress, including hyperthermia and exposure to toxicants. Thus they may provide a useful index of toxicity in in vitro systems for screening for toxicity. We have recently developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to localise HSP70 within the rat nasal cavity and to characterise its response to hyperthermia. Constitutively, HSP70 was found to be predominantly localised to the sustentacular cells, basal cells and Bowman's glands of the olfactory epithelium (OE), with the most intense immunohistochemical staining at levels 3 and 4 of the posterior of the rat nasal cavity. Ethmoturbinates (ETs) and liver slices were exposed to heat shock (37 degrees and 43 degrees C, respectively) for 45 min and then returned to normal culture temperatures (31 degrees and 37 degrees C, respectively) for 24 h. In ETs, HSP72 was maximally induced 4-fold at 4 h after heat shock, and levels then returned to those of control tissue. ATP concentrations were markedly decreased up to 4 h after heat shock and then returned to control levels. In contrast, HSP72 levels in liver slices increased and ATP levels decreased steadily throughout the 24 h culture period. ETs were also able to withstand a 45-min heat shock at 43 degrees C, that is 12 degrees C above normal culture temperature. Incubation of ETs with cycloheximide prior to heat shock reduced the ability of the OE to recover from heat shock at 37 degrees C. Thus the OE of the rat nasal cavity expresses HSP72, and this protein appears to play an important role in the ability of the tissue to withstand hyperthermia.

  18. Electron heating in a Monte Carlo model of a high Mach number, supercritical, collisionless shock

    NASA Technical Reports Server (NTRS)

    Ellison, Donald C.; Jones, Frank C.

    1987-01-01

    Preliminary work in the investigation of electron injection and acceleration at parallel shocks is presented. A simple model of electron heating that is derived from a unified shock model which includes the effects of an electrostatic potential jump is described. The unified shock model provides a kinetic description of the injection and acceleration of ions and a fluid description of electron heating at high Mach number, supercritical, and parallel shocks.

  19. Anti-apoptotic effect of heat shock protein 90 on hypoxia-mediated cardiomyocyte damage is mediated via the phosphatidylinositol 3-kinase/AKT pathway.

    PubMed

    Wang, Wei; Peng, Yizhi; Wang, Yuanyuan; Zhao, Xiaohui; Yuan, Zhiqiang

    2009-09-01

    1. Hypoxia-induced cardiomyocyte apoptosis contributes significantly to cardiac dysfunction following trauma, shock and burn injury. There is evidence that heat shock protein (HSP) 90 is anti-apoptotic in cardiomyocytes subjected to a variety of apoptotic stimuli. Because HSP90 acts as an upstream regulator of the serine/threonine protein kinase Akt survival pathway during cellular stress, we hypothesized that HSP90 exerts a cardioprotective effect via the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. 2. Neonatal rat cardiomyocytes were subjected to normoxia or hypoxia in the absence or presence of the HSP90 inhibitor geldanamycin (1 μg/mL). Cardiomyocyte apoptosis was assessed by release of lactate dehydrogenase (LDH), terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) staining and caspase 3 activity. Expression of HSP90, Akt, Bad and cytochrome c release was determined by western blot analysis. 3. Following exposure of cells to hypoxia, HSP90 was markedly elevated in a time-dependent manner, reaching a peak at 6 h (eightfold increase). Geldanamycin significantly increased hypoxia-induced release of LDH by 114%, the percentage of apoptotic cardiomyocytes by 102% and caspase 3 activity by 78%. Pretreatment of cells with geldanamycin also suppressed phosphorylation of both Akt and its downstream target Bad, but promoted the mitochondrial release of cytochrome c. 4. In conclusion, HSP90 activity is enhanced in cardiomyocytes following hypoxic insult. The anti-apoptotic effect of HSP90 on cardiomyocytes subjected to hypoxia is mediated, at least in part, by the PI3-K/Akt pathway. Key words: apoptosis, cardiomyocyte, heart failure, heat shock protein 90, hypoxia, phosphatidylinositol 3-kinase/Akt signalling pathway, serine/threonine protein kinase Akt.

  20. Heat shock modulates the subcellular localization, stability, and activity of HIPK2

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

    Upadhyay, Mamta; Bhadauriya, Pratibha; Ganesh, Subramaniam, E-mail: sganesh@iitk.ac.in

    2016-04-15

    The homeodomain-interacting protein kinase-2 (HIPK2) is a highly conserved serine/threonine kinase and is involved in transcriptional regulation. HIPK2 is a highly unstable protein, and is kept at a low level under normal physiological conditions. However, exposure of cells to physiological stress – such as hypoxia, oxidative stress, or UV damage – is known to stabilize HIPK2, leading to the HIPK2-dependent activation of p53 and the cell death pathway. Therefore HIPK2 is also known as a stress kinase and as a stress-activated pro-apoptotic factor. We demonstrate here that exposure of cells to heat shock results in the stabilization of HIPK2 andmore » the stabilization is mediated via K63-linked ubiquitination. Intriguingly, a sub-lethal heat shock (42 °C, 1 h) results in the cytoplasmic localization of HIPK2, while a lethal heat shock (45 °C, 1 h) results in its nuclear localization. Cells exposed to the lethal heat shock showed significantly higher levels of the p53 activity than those exposed to the sub-lethal thermal stress, suggesting that both the level and the nuclear localization are essential for the pro-apoptotic activity of HIPK2 and that the lethal heat shock could retain the HIPK2 in the nucleus to promote the cell death. Taken together our study underscores the importance of HIPK2 in stress mediated cell death, and that the HIPK2 is a generic stress kinase that gets activated by diverse set of physiological stressors.« less

  1. Alternative Mechanism by which IFN-γ Enhances Tumor Recognition: Active Release of Heat Shock Protein 721

    PubMed Central

    Bausero, Maria A.; Gastpar, Robert; Multhoff, Gabriele; Asea, Alexzander

    2006-01-01

    IFN-γ exhibits differential effects depending on the target and can induce cellular activation and enhance survival or mediate cell death via activation of apoptotic pathways. In this study, we demonstrate an alternative mechanism by which IFN-γ enhances tumor recognition, mediated by the active release of Hsp72. We demonstrate that stimulation of 4T1 breast adenocarcinoma cells and K562 erythroleukemic cells with IFN-γ triggers the cellular stress response, which results in the enhanced expression of total Hsp72 expression without a significant increase in cell death. Intracellular expression of Hsp72 was abrogated in cells stably transfected with a mutant hsf-1 gene. IFN-γ-induced Hsp72 expression correlated with enhanced surface expression and consequent release of Hsp72 into the culture medium. Pretreatment of tumors with compounds known to the block the classical protein transport pathway, including monensin, brefeldin A, tunicamycin, and thapsigargin, did not significantly block Hsp72 release. However, pretreatment with intracellular calcium chelator BAPTA-AM or disruption of lipid rafts using methyl β-cyclodextrin completely abrogated IFN-γ-induced Hsp72 release. Biochemical characterization revealed that Hsp72 is released within exosomes and has the ability to up-regulate CD83 expression and stimulate IL-12 release by naive dendritic cells. Pretreatment with neutralizing mAb or depletion of Hsp72 completely abrogated its chaperokine function. Taken together, these findings are indicative of an additional previously unknown mechanism by which IFN-γ promotes tumor surveillance and furthers our understanding of the central role of extracellular Hsp72 as an endogenous adjuvant and danger signal. PMID:16116176

  2. Alternative mechanism by which IFN-gamma enhances tumor recognition: active release of heat shock protein 72.

    PubMed

    Bausero, Maria A; Gastpar, Robert; Multhoff, Gabriele; Asea, Alexzander

    2005-09-01

    IFN-gamma exhibits differential effects depending on the target and can induce cellular activation and enhance survival or mediate cell death via activation of apoptotic pathways. In this study, we demonstrate an alternative mechanism by which IFN-gamma enhances tumor recognition, mediated by the active release of Hsp72. We demonstrate that stimulation of 4T1 breast adenocarcinoma cells and K562 erythroleukemic cells with IFN-gamma triggers the cellular stress response, which results in the enhanced expression of total Hsp72 expression without a significant increase in cell death. Intracellular expression of Hsp72 was abrogated in cells stably transfected with a mutant hsf-1 gene. IFN-gamma-induced Hsp72 expression correlated with enhanced surface expression and consequent release of Hsp72 into the culture medium. Pretreatment of tumors with compounds known to the block the classical protein transport pathway, including monensin, brefeldin A, tunicamycin, and thapsigargin, did not significantly block Hsp72 release. However, pretreatment with intracellular calcium chelator BAPTA-AM or disruption of lipid rafts using methyl beta-cyclodextrin completely abrogated IFN-gamma-induced Hsp72 release. Biochemical characterization revealed that Hsp72 is released within exosomes and has the ability to up-regulate CD83 expression and stimulate IL-12 release by naive dendritic cells. Pretreatment with neutralizing mAb or depletion of Hsp72 completely abrogated its chaperokine function. Taken together, these findings are indicative of an additional previously unknown mechanism by which IFN-gamma promotes tumor surveillance and furthers our understanding of the central role of extracellular Hsp72 as an endogenous adjuvant and danger signal.

  3. Rate of Heat Release in Diesel Engines

    DOT National Transportation Integrated Search

    1977-10-01

    In this report, the concept of heat release in diesel engines is compared with reaction rates in petrol engines as a means of describing combustion. The intimate relationships between heat release, cylinder pressure development and cylinder pressure ...

  4. The heat shock response and major heat shock proteins of Tritrichomonas mobilensis and Tritrichomonas augusta.

    PubMed

    Bozner, P

    1996-02-01

    The responses to heat shock in Tritrichomonas mobilensis, a squirrel monkey parasite and Tritrichomonas augusta, an amphibian trichomonad, were evaluated by means of metabolic labeling with [35S]methionine. Electrophoretically separated trichomonad proteins synthesized at different temperatures were visualized by autoradiography and the label incorporation quantitated by a trichloroacetic acid precipitation procedure. A considerable difference in thermotolerance between the two species was found as the protein synthesis reached a maximum at 41 C in T. mobilensis and 37 C in T. augusta. The latter tolerated temperature increases 13 C above normal cultivation temperatures as compared to only 4 C thermotolerance range above normal in T. mobilensis. Major heat shock proteins (Hsps) were expressed in both T. mobilensis (with apparent Mr 94, 72, and 58 kDa) and T. augusta (Mr 94, 70, and 56 kDa) as revealed by autoradiography. Western blot analysis with polyclonal antibody against DnaK of Escherichia coli showed the presence of antigenic Hsp70 homologs in both trichomonads. Similarly, a polyclonal antibody against Hsp60 with broad interspecies cross-reactivity detected Hsp60 homologs in both T. mobilensis and T. augusta. The anti-DnaK antibody cross-reacted with a T. mobilensis protein localized in Golgi apparatus as demonstrated by immunoelectron microscopy. Immunocytochemistry on trichomonad frozen sections revealed the presence of the Hsp60 homolog in light-microscopic granules corresponding to hydrogenosomes.

  5. Heat shock protein-70 neutralizes apoptosis inducing factor in Bcr/Abl expressing cells.

    PubMed

    Wang, Fang; Dai, An-Ya; Tao, Kun; Xiao, Qing; Huang, Zheng-Lan; Gao, Miao; Li, Hui; Wang, Xin; Cao, Wei-Xi; Feng, Wen-Li

    2015-10-01

    Bcr/Abl fusion protein is a hallmark of human chronic myeloid leukemia (CML). The protein can activate various signaling pathways to make normal cells transform malignantly and thus to facilitate tumorigenesis. It has been reported that heat shock protein-70 (HSP-70) can be served as an anti-apoptotic protein that suppresses Bax and Apo-2L/TRAIL. But it is unclear whether HSP-70 affects AIF-initiated apoptosis in Bcr/Abl expressing cells considering that HSP-70 is coincidentally over-regulated in these cells. Our findings supported that abundant HSP-70 in Bcr/Abl cells neutralizes AIF by segregating it from nucleus via direct interaction, leading to the failure of AIF initiating cell death and the silence of caspase-independent apoptotic pathway upon apoptotic induction. Moderate inhibition of HSP-70 expression by siRNA leads to Vp-16 triggered re-distribution of AIF in nucleus. In addition, AIF bears a HSP-70 binding domain allowing association with HSP-70. Therefore, disruption of the association using an AIF mutant lacking this domain can restore the potential of AIF importing into nucleus, and finally triggers cell death in a time dependent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. RSK2 represses HSF1 activation during heat shock

    PubMed Central

    Wang, Xiaozhe; Asea, Alexzander; Xie, Yue; Kabingu, Edith; Stevenson, Mary Ann; Calderwood, Stuart K.

    2000-01-01

    Heat shock transcription factor 1(HSF1) activation is a multistep process. The conversion of a latent cytoplasmic form to a nuclear, DNA binding state appears to be activated by nonsteroidal anti-inflammatory drugs. In previous studies, we showed that HSF 1 is phosphorylated by the protein kinase RSK2 in vitro and that this effect is inhibited by nonsteroidal anti-inflammatory drugs at the concentration that leads to the activation of HSF1 in vivo (Stevenson et al 1999). In the present study, using cells from a patient with Coffin-Lowry syndrome (deficient in RSK2), we demonstrate that RSK2 slightly represses activation of HSF1 in vivo at 37°C. In Coffin-Lowry syndrome cells, HSF1-HSE DNA binding activity after treatment with sodium salicylate was slightly higher than that in untreated cells, indicating that although RSK2 is involved in HSF1 regulation, it is not the unique protein kinase that suppresses HSF1-HSE binding activity at 37°C. However, heat shock treatment resulted in significantly higher HSF1-HSE binding activity in Coffin-Lowry syndrome cells as compared with normal controls, suggesting that RSK2 represses HSF1-HSE binding activity during heat shock. PMID:11189448

  7. RSK2 represses HSF1 activation during heat shock.

    PubMed

    Wang, X; Asea, A; Xie, Y; Kabingu, E; Stevenson, M A; Calderwood, S K

    2000-11-01

    Heat shock transcription factor 1(HSF1) activation is a multistep process. The conversion of a latent cytoplasmic form to a nuclear, DNA binding state appears to be activated by nonsteroidal anti-inflammatory drugs. In previous studies, we showed that HSF 1 is phosphorylated by the protein kinase RSK2 in vitro and that this effect is inhibited by nonsteroidal anti-inflammatory drugs at the concentration that leads to the activation of HSF1 in vivo (Stevenson et al 1999). In the present study, using cells from a patient with Coffin-Lowry syndrome (deficient in RSK2), we demonstrate that RSK2 slightly represses activation of HSF1 in vivo at 37 degrees C. In Coffin-Lowry syndrome cells, HSF1-HSE DNA binding activity after treatment with sodium salicylate was slightly higher than that in untreated cells, indicating that although RSK2 is involved in HSF1 regulation, it is not the unique protein kinase that suppresses HSF1-HSE binding activity at 37 degrees C. However, heat shock treatment resulted in significantly higher HSF1-HSE binding activity in Coffin-Lowry syndrome cells as compared with normal controls, suggesting that RSK2 represses HSF1-HSE binding activity during heat shock.

  8. Complete annular and partial oblique pulley release for pediatric locked trigger thumb

    PubMed Central

    Kuo, Meiying

    2010-01-01

    Purpose To report the surgical treatment outcome of pediatric locked trigger thumb by sequential release of the annular pulley and partial release of the oblique pulley. Materials and Methods A retrospective review was undertaken on 28 operative thumbs in 24 patients with an average follow-up of 79 months. Intraoperative observations focused on the pathology of the pulley system. Surgical technique involved complete release of the annular pulley, which alone was insufficient in relieving the deformity, along with release of the proximal 50% of the oblique pulley in all patients. Postoperative parameters of bowstringing, resolution of Notta's node, thumb interphalangeal motion, and patient/parent satisfaction were assessed. Results The oblique pulley appeared stenotic, whereas the annular pulley was observed to be membranous and nearly indistinguishable from the tendon sheath. No patients had recurrence of thumb locking or triggering. No bowstringing was detected, and Notta’s node resolved fully in 19 of 20 thumbs. Five thumbs had an average of 12o less active IP joint motion without flexion contracture (i.e., less flexion). All patients or families expressed overall satisfaction with the procedure. Conclusion The annular pulley was attenuated in the majority of cases and the proximal half of the oblique pulley was stenotic in all patients. Releasing 50% of the oblique pulley after complete annular pulley release was necessary in all thumbs to achieve full FPL excursion. Mistaking the constricted proximal oblique pulley for an annular pulley may encourage releasing the entire oblique pulley, leading to an adverse result. Satisfactory outcome was achieved after surgical treatment of pediatric locked trigger thumbs. Type of Study/Level of Evidence Therapeutic IV. PMID:22131924

  9. Experimental Study of Shock Wave Interference Heating on a Cylindrical Leading Edge. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Wieting, Allan R.

    1987-01-01

    An experimental study of shock wave interference heating on a cylindrical leading edge representative of the cowl of a rectangular hypersonic engine inlet at Mach numbers of 6.3, 6.5, and 8.0 is presented. Stream Reynolds numbers ranged from 0.5 x 106 to 4.9 x 106 per ft. and stream total temperature ranged from 2100 to 3400 R. The model consisted of a 3" dia. cylinder and a shock generation wedge articulated to angles of 10, 12.5, and 15 deg. A fundamental understanding was obtained of the fluid mechanics of shock wave interference induced flow impingement on a cylindrical leading edge and the attendant surface pressure and heat flux distributions. The first detailed heat transfer rate and pressure distributions for two dimensional shock wave interference on a cylinder was provided along with insight into the effects of specific heat variation with temperature on the phenomena. Results show that the flow around a body in hypersonic flow is altered significantly by the shock wave interference pattern that is created by an oblique shock wave from an external source intersecting the bow shock wave produced in front of the body.

  10. A study of 60 patients with percutaneous trigger finger releases: clinical and ultrasonographic findings.

    PubMed

    Gulabi, D; Cecen, G S; Bekler, H I; Saglam, F; Tanju, N

    2014-09-01

    We present the clinical results and ultrasonographic findings of 61 trigger digits treated with percutaneous A1 pulley release. An endoscopic carpal tunnel knife was used for the release in the outpatient department. The mean follow-up period was 3.5 months. A total of 55 digits (90%) had complete relief of their triggering postoperatively. Six digits (10%) had Grade 2 triggering clinically in the early postoperative period.The complications included six cases of insufficient release (10%), scar sensitivity in one patient, short-term hypoaesthesia in three digits (5%), and flexor tendon laceration noted on postoperative ultrasonography in eight digits (13%). No neurovascular damage was noted on the postoperative ultrasonography. Ultrasonograpy provides information about tendon laceration and changes in thickness of the pulleys and confirm A1 pulley release after surgery, but it does not alter clinical decision-making. We believe that pre- and postoperative ultrasonograpy does not need to be included as a routine examination. © The Author(s) 2014.

  11. Arctigenin from Fructus Arctii is a novel suppressor of heat shock response in mammalian cells

    PubMed Central

    Ishihara, Keiichi; Yamagishi, Nobuyuki; Saito, Youhei; Takasaki, Midori; Konoshima, Takao; Hatayama, Takumi

    2006-01-01

    Because heat shock proteins (Hsps) are involved in protecting cells and in the pathophysiology of diseases such as inflammation, cancer, and neurodegenerative disorders, the use of regulators of the expression of Hsps in mammalian cells seems to be useful as a potential therapeutic modality. To identify compounds that modulate the response to heat shock, we analyzed several natural products using a mammalian cell line containing an hsp promoter-regulated reporter gene. In this study, we found that an extract from Fructus Arctii markedly suppressed the expression of Hsp induced by heat shock. A component of the extract arctigenin, but not the component arctiin, suppressed the response at the level of the activation of heat shock transcription factor, the induction of mRNA, and the synthesis and accumulation of Hsp. Furthermore, arctigenin inhibited the acquisition of thermotolerance in mammalian cells, including cancer cells. Thus, arctigenin seemed to be a new suppressive regulator of heat shock response in mammalian cells, and may be useful for hyperthermia cancer therapy. PMID:16817321

  12. Controlled release of bupivacaine using hybrid thermoresponsive nanoparticles activated via photothermal heating.

    PubMed

    Alejo, Teresa; Andreu, Vanesa; Mendoza, Gracia; Sebastian, Victor; Arruebo, Manuel

    2018-08-01

    Near-infrared (NIR) responsive nanoparticles are of great interest in the biomedical field as antennas for photothermal therapy and also as triggers for on-demand drug delivery. The present work reports the preparation of hollow gold nanoparticles (HGNPs) with plasmonic absorption in the NIR region covalently bound to a thermoresponsive polymeric shell that can be used as an on-demand drug delivery system for the release of analgesic drugs. The photothermal heating induced by the nanoparticles is able to produce the collapse of the polymeric shell thus generating the release of the local anesthetic bupivacaine in a spatiotemporally controlled way. Those HGNPs contain a 10 wt.% of polymer and present excellent reversible heating under NIR light excitation. Bupivacaine released at physiological temperature (37 °C) showed a pseudo-zero order release that could be spatiotemporally modified on-demand after applying several pulses of light/temperature above and below the lower critical solution temperature (LCST) of the polymeric shell. Furthermore, the nanomaterials obtained did not displayed detrimental effects on four mammalian cell lines at doses up to 0.2 mg/mL. From the results obtained it can be concluded than this type of hybrid thermoresponsive nanoparticle can be used as an externally activated on-demand drug delivery system. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

    PubMed Central

    Nardoni, Martina; della Valle, Elena; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

    2018-01-01

    Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects. PMID:29584700

  14. Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

    PubMed

    Nardoni, Martina; Della Valle, Elena; Liberti, Micaela; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

    2018-03-27

    Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

  15. Heat-induced ribosome pausing triggers mRNA co-translational decay in Arabidopsis thaliana

    PubMed Central

    Merret, Rémy; Nagarajan, Vinay K.; Carpentier, Marie-Christine; Park, Sunhee; Favory, Jean-Jacques; Descombin, Julie; Picart, Claire; Charng, Yee-yung; Green, Pamela J.; Deragon, Jean-Marc; Bousquet-Antonelli, Cécile

    2015-01-01

    The reprogramming of gene expression in heat stress is a key determinant to organism survival. Gene expression is downregulated through translation initiation inhibition and release of free mRNPs that are rapidly degraded or stored. In mammals, heat also triggers 5′-ribosome pausing preferentially on transcripts coding for HSC/HSP70 chaperone targets, but the impact of such phenomenon on mRNA fate remains unknown. Here, we provide evidence that, in Arabidopsis thaliana, heat provokes 5′-ribosome pausing leading to the XRN4-mediated 5′-directed decay of translating mRNAs. We also show that hindering HSC/HSP70 activity at 20°C recapitulates heat effects by inducing ribosome pausing and co-translational mRNA turnover. Strikingly, co-translational decay targets encode proteins with high HSC/HSP70 binding scores and hydrophobic N-termini, two characteristics that were previously observed for transcripts most prone to pausing in animals. This work suggests for the first time that stress-induced variation of translation elongation rate is an evolutionarily conserved process leading to the polysomal degradation of thousands of ‘non-aberrant’ mRNAs. PMID:25845591

  16. Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation

    PubMed Central

    Shinkawa, Toyohide; Tan, Ke; Fujimoto, Mitsuaki; Hayashida, Naoki; Yamamoto, Kaoru; Takaki, Eiichi; Takii, Ryosuke; Prakasam, Ramachandran; Inouye, Sachiye; Mezger, Valerie; Nakai, Akira

    2011-01-01

    Heat shock response is characterized by the induction of heat shock proteins (HSPs), which facilitate protein folding, and non-HSP proteins with diverse functions, including protein degradation, and is regulated by heat shock factors (HSFs). HSF1 is a master regulator of HSP expression during heat shock in mammals, as is HSF3 in avians. HSF2 plays roles in development of the brain and reproductive organs. However, the fundamental roles of HSF2 in vertebrate cells have not been identified. Here we find that vertebrate HSF2 is activated during heat shock in the physiological range. HSF2 deficiency reduces threshold for chicken HSF3 or mouse HSF1 activation, resulting in increased HSP expression during mild heat shock. HSF2-null cells are more sensitive to sustained mild heat shock than wild-type cells, associated with the accumulation of ubiquitylated misfolded proteins. Furthermore, loss of HSF2 function increases the accumulation of aggregated polyglutamine protein and shortens the lifespan of R6/2 Huntington's disease mice, partly through αB-crystallin expression. These results identify HSF2 as a major regulator of proteostasis capacity against febrile-range thermal stress and suggest that HSF2 could be a promising therapeutic target for protein-misfolding diseases. PMID:21813737

  17. Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging.

    PubMed

    Barna, János; Princz, Andrea; Kosztelnik, Mónika; Hargitai, Balázs; Takács-Vellai, Krisztina; Vellai, Tibor

    2012-11-01

    Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins) that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta) ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

  18. Heat shock protein expression enhances heat tolerance of reptile embryos

    PubMed Central

    Gao, Jing; Zhang, Wen; Dang, Wei; Mou, Yi; Gao, Yuan; Sun, Bao-Jun; Du, Wei-Guo

    2014-01-01

    The role of heat shock proteins (HSPs) in heat tolerance has been demonstrated in cultured cells and animal tissues, but rarely in whole organisms because of methodological difficulties associated with gene manipulation. By comparing HSP70 expression patterns among representative species of reptiles and birds, and by determining the effect of HSP70 overexpression on embryonic development and hatchling traits, we have identified the role of HSP70 in the heat tolerance of amniote embryos. Consistent with their thermal environment, and high incubation temperatures and heat tolerance, the embryos of birds have higher onset and maximum temperatures for induced HSP70 than do reptiles, and turtles have higher onset and maximum temperatures than do lizards. Interestingly, the trade-off between benefits and costs of HSP70 overexpression occurred between life-history stages: when turtle embryos developed at extreme high temperatures, HSP70 overexpression generated benefits by enhancing embryo heat tolerance and hatching success, but subsequently imposed costs by decreasing heat tolerance of surviving hatchlings. Taken together, the correlative and causal links between HSP70 and heat tolerance provide, to our knowledge, the first unequivocal evidence that HSP70 promotes thermal tolerance of embryos in oviparous amniotes. PMID:25080340

  19. Immunogenic apoptosis in human acute myeloid leukemia (AML): primary human AML cells expose calreticulin and release heat shock protein (HSP) 70 and HSP90 during apoptosis.

    PubMed

    Fredly, Hanne; Ersvær, Elisabeth; Gjertsen, Bjørn-Tore; Bruserud, Oystein

    2011-06-01

    Several previous studies have demonstrated that both conventional cytotoxic drugs as well as targeted therapeutics can induce apoptosis in primary human acute myelogenous leukemia (AML) cells. However, the apoptotic phenotype of dying AML cells has been less extensively characterized. Even though specific antileukemic immune reactivity is important in AML, especially for allotransplanted patients, it has not been investigated whether dying primary human AML cells show phenotypic characteristics consistent with immunogenic apoptosis [calreticulin exposure, heat shock protein (HSP) release]. We therefore investigated whether in vitro cultured primary human acute myeloid leukemia (AML) cells show calreticulin exposure and HSP70/HSP90 release during spontaneous (stress-induced) apoptosis when cultured in medium alone and when cultured in the presence of antileukemic drugs. Both surface exposure of calreticulin and release of HSP70 and HSP90 was detected but showed a wide variation between patients. This variation was also maintained when the AML cells were cultured in the presence of cytotoxic drugs (cytarabine, daunorubicin, mitomycin), all-trans retinoic acid (ATRA) and valproic acid. Finally, AML cells collected during in vivo ATRA therapy showed increased calreticulin exposure during spontaneous in vitro apoptosis, suggesting that in vivo pharmacotherapy can modulate the apoptotic phenotype. To conclude, apoptotic AML cells can show phenotypic characteristics consistent with immunogenic apoptosis, but there is a wide variation between patients and the level of calreticulin exposure/HSP release seems to depend on individual patient characteristics rather than the apoptosis-inducing agent.

  20. The role of heat shock proteins in kidney disease

    PubMed Central

    2016-01-01

    Abstract Heat Shock Proteins (HSP) belong to the family of intracellular proteins that are constitutively expressed and are upregulated by various stressors including heat, oxidative and chemical stress. HSP helps in reparative processes, including the refolding of damaged proteins and the removal of irreparably damaged proteins that would initiate cellular death or apoptosis. A growing body of evidence has expanded the role of HSP and defined their role in diseases such as neurodegenerative disorders, cancer, ischemic heart disease and kidney diseases. The protective role of HSP in ischemic renal injury has been described and HSP impairment has been noted in other forms of kidney injuries including post-transplant situation. Further research into the role of HSP in prevention of kidney injury is crucial if translation from the laboratory to patient bedside has to occur. This article aims to be a review of heat shock protein, and its relevance to kidney diseases. PMID:28191532

  1. Interference heating from interactions of shock waves with turbulent boundary layers at Mach 6

    NASA Technical Reports Server (NTRS)

    Johnson, C. B.; Kaufman, L. G., II

    1974-01-01

    An experimental investigation of interference heating resulting from interactions of shock waves and turbulent boundary layers was conducted. Pressure and heat-transfer distributions were measured on a flat plate in the free stream and on the wall of the test section of the Langley Mach 6 high Reynolds number tunnel for Reynolds numbers ranging from 2 million to 400 million. Various incident shock strengths were obtained by varying a wedge-shock generator angle (from 10 deg to 15 deg) and by placing a spherical-shock generator at different vertical positions above the instrumented flat plate and tunnel wall. The largest heating-rate amplification factors obtained for completely turbulent boundary layers were 22.1 for the flat plate and 11.6 for the tunnel wall experiments. Maximum heating correlated with peak pressures using a power law with a 0.85 exponent. Measured pressure distributions were compared with those calculated using turbulent free-interaction pressure rise theories, and separation lengths were compared with values calculated by using different methods.

  2. Effect of wall heat transfer on shock-tube test temperature at long times

    NASA Astrophysics Data System (ADS)

    Frazier, C.; Lamnaouer, M.; Divo, E.; Kassab, A.; Petersen, E.

    2011-02-01

    When performing chemical kinetics experiments behind reflected shock waves at conditions of lower temperature (<1,000 K), longer test times on the order of 10-20 ms may be required. The integrity of the test temperature during such experiments may be in question, because heat loss to the tube walls may play a larger role than is generally seen in shock-tube kinetics experiments that are over within a millisecond or two. A series of detailed calculations was performed to estimate the effect of longer test times on the temperature uniformity of the post-shock test gas. Assuming the main mode of heat transfer is conduction between the high-temperature gas and the colder shock-tube walls, a comprehensive set of calculations covering a range of conditions including test temperatures between 800 and 1,800 K, pressures between 1 and 50 atm, driven-tube inner diameters between 3 and 16.2 cm, and test gases of N2 and Ar was performed. Based on the results, heat loss to the tube walls does not significantly reduce the area-averaged temperature behind the reflected shock wave for test conditions that are likely to be used in shock-tube studies for test times up to 20 ms (and higher), provided the shock-tube inner diameter is sufficiently large (>8cm). Smaller diameters on the order of 3 cm or less can experience significant temperature loss near the reflected-shock region. Although the area-averaged gas temperature decreases due to the heat loss, the main core region remains spatially uniform so that the zone of temperature change is limited to only the thermal layer adjacent to the walls. Although the heat conduction model assumes the gas and wall to behave as solid bodies, resulting in a core gas temperature that remains constant at the initial temperature, a two-zone gas model that accounts for density loss from the core to the colder thermal layer indicates that the core temperature and gas pressure both decrease slightly with time. A full CFD solution of the shock

  3. Hormetic heat shock and HSF-1 overexpression improve C. elegans survival and proteostasis by inducing autophagy.

    PubMed

    Kumsta, Caroline; Hansen, Malene

    2017-06-03

    The cellular recycling process of macroautophagy/autophagy is an essential homeostatic system induced by various stresses, but it remains unclear how autophagy contributes to organismal stress resistance. In a recent study, we report that a mild and physiologically beneficial ("hormetic") heat shock as well as overexpression of the heat-shock responsive transcription factor HSF-1 systemically increases autophagy in C. elegans. Accordingly, we found HSF-1- and heat stress-inducible autophagy to be required for C. elegans thermoresistance and longevity. Moreover, a hormetic heat shock or HSF-1 overexpression alleviated PolyQ protein aggregation in an autophagy-dependent manner. Collectively, we demonstrate a critical role for autophagy in C. elegans stress resistance and hormesis, and reveal a requirement for autophagy in HSF-1 regulated functions in the heat-shock response, proteostasis, and aging.

  4. Shock and Release Response of Unreacted Epon 828: Shot 2s-905

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

    Pisa, Matthew Alexander; Fredenburg, David A.; Dattelbaum, Dana M.

    This document summarizes the shock and release response of Epon 828 measured in the dynamic impact experiment 2s-905. Experimentally, a thin Kel-F impactor backed by a low impedance foam impacted an Epon 828 target with embedded electromagnetic gauges. Computationally, a one dimensional simulation of the impact event was performed, and tracer particles were located at the corresponding electromagnetic gauge locations. The experimental configuration was such that the Epon 828 target was initially shocked, and then allowed to release from the high-pressure state. Comparisons of the experimental gauge and computational tracer data were made to assess the performance of equation ofmore » state (EOS) 7603, a SESAME EOS for Epon 828, on and off the principal shock Hugoniot. Results indicate that while EOS 7603 can capture the Hugoniot response to better that 1%, while the sound speeds at pressure are under-predicted by 6 - 7%.« less

  5. Polymer Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

    PubMed Central

    Nahire, Rahul; Haldar, Manas K.; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H.; Katti, Kalpana S.; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

    2013-01-01

    Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 minutes simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging. PMID:23394107

  6. Ion Thermalization and Electron Heating across Quasi-Perpendicular Shocks Observed by the MMS Mission

    NASA Astrophysics Data System (ADS)

    Chen, L.-J.; Wilson, L. B., III; Wang, S.; Bessho, N.; Viñas, A. F.-; Lai, H.; Russell, C. T.; Schwartz, S. J.; Hesse, M.; Moore, T. E.; Burch, J. L.; Gershman, D. J.; Giles, B. L.; Torbert, R. B.; Ergun, R. E.; Dorelli, J.; Strangeway, R. J.; Paterson, W. R.; Lavraud, B.; Khotyaintsev, Yu. V.

    2017-12-01

    Collisionless shocks often involve intense plasma heating in space and astrophysical systems. Despite decades of research, a number of key questions concerning electron and ion heating across collisionless shocks remain unanswered. We 'image' 20 supercritical quasi-perpendicular bow shocks encountered by the Magnetospheric Multiscale (MMS) spacecraft with electron and ion distribution functions to address how ions are thermalized and how electrons are heated. The continuous burst measurements of 3D plasma distribution functions from MMS reveal that the primary thermalization phase of ions occurs concurrently with the main temperature increase of electrons as well as large-amplitude wave fluctuations. Approaching the shock from upstream, the ion temperature (Ti) increases due to the reflected ions joining the incoming solar wind population, as recognized by prior studies, and the increase of Ti precedes that of the electrons. Thermalization in the form of merging between the decelerated solar wind ions and the reflected component often results in a decrease in Ti. In most cases, the Ti decrease is followed by a gradual increase further downstream. Anisotropic, energy-dependent, and/or nongyrotropic electron energization are observed in association with large electric field fluctuations in the main electron temperature (Te) gradient, motivating a renewed scrutiny of the effects from the electrostatic cross-shock potential and wave fluctuations on electron heating. Particle-in-cell (PIC) simulations are carried out to assist interpretations of the MMS observations. We assess the roles of instabilities and the cross-shock potential in thermalizing ions and heating electrons based on the MMS measurements and PIC simulation results. Challenges will be posted for future computational studies and laboratory experiments on collisionless shocks.

  7. Ion Thermalization and Electron Heating across Quasi-Perpendicular Shocks Observed by the MMS Mission

    NASA Astrophysics Data System (ADS)

    Chen, L. J.; Wilson, L. B., III; Wang, S.; Bessho, N.; Figueroa-Vinas, A.; Lai, H.; Russell, C. T.; Schwartz, S. J.; Hesse, M.; Moore, T. E.; Burch, J.; Gershman, D. J.; Giles, B. L.; Torbert, R. B.; Ergun, R.; Dorelli, J.; Strangeway, R. J.; Paterson, W. R.; Lavraud, B.; Khotyaintsev, Y. V.

    2017-12-01

    Collisionless shocks often involve intense plasma heating in space and astrophysical systems. Despite decades of research, a number of key questions concerning electron and ion heating across collisionless shocks remain unanswered. We `image' 20 supercritical quasi-perpendicular bow shocks encountered by the Magnetospheric Multiscale (MMS) spacecraft with electron and ion distribution functions to address how ions are thermalized and how electrons are heated. The continuous burst measurements of 3D plasma distribution functions from MMS reveal that the primary thermalization phase of ions occurs concurrently with the main temperature increase of electrons as well as large-amplitude wave fluctuations. Approaching the shock from upstream, the ion temperature (Ti) increases due to the reflected ions joining the incoming solar wind population, as recognized by prior studies, and the increase of Ti precedes that of the electrons. Thermalization in the form of merging between the decelerated solar wind ions and the reflected component often results in a decrease in Ti. In most cases, the Ti decrease is followed by a gradual increase further downstream. Anisotropic, energy-dependent, and/or nongyrotropic electron energization are observed in association with large electric field fluctuations in the main electron temperature (Te) gradient, motivating a renewed scrutiny of the effects from the electrostatic cross-shock potential and wave fluctuations on electron heating. Particle-in-cell (PIC) simulations are carried out to assist interpretations of the MMS observations. We assess the roles of instabilities and the cross-shock potential in thermalizing ions and heating electrons based on the MMS measurements and PIC simulation results. Challenges will be posted for future computational studies and laboratory experiments on collisionless shocks.

  8. Recombinant HSP70 and mild heat shock stimulate growth of aged mesenchymal stem cells.

    PubMed

    Andreeva, N V; Zatsepina, O G; Garbuz, D G; Evgen'ev, M B; Belyavsky, A V

    2016-07-01

    Heat shock proteins including the major stress protein HSP70 support intracellular homeostasis and prevent protein damage after a temperature increase and other stressful environmental stimuli, as well as during aging. We have shown earlier that prolonged administration of recombinant human HSP70 to mice exhibiting Alzheimer's-like neurodegeneration as well as during sepsis reduces the clinical manifestations of these pathologies. Herein, we studied the action of recombinant human HSP70 on young and aged mouse mesenchymal stem cells (MSCs) in culture. The results obtained indicate that HSP70 at concentrations of 2 μg/ml and higher significantly stimulates growth of aged but not young MSCs. A similar effect is produced by application of a mild heat shock (42 °C 5 min) to the cells. Importantly, responses of young and aged MSCs to heat shock treatment of various durations differed drastically, and aged MSCs were significantly more sensitive to higher heat stress exposures than the young cells. Western blotting and protein labeling experiments demonstrated that neither mild heat shock nor exogenous HSP70 administration resulted in significant endogenous HSP70 induction in young and aged MSCs, whereas mild heat shock increased HSC70 levels in aged MSCs. The results of this study suggest that the administration of exogenous HSP70 and the application of mild heat stress may produce a certain "rejuvenating" effect on MSCs and possibly other cell types in vivo, and these interventions may potentially be used for life extension by delaying various manifestations of aging at the molecular and cellular level.

  9. Effects of dietary zinc on gene expression of antioxidant enzymes and heat shock proteins in hepatopancreas of abalone Haliotis discus hannai.

    PubMed

    Wu, Chenglong; Zhang, Wenbing; Mai, Kangsen; Xu, Wei; Zhong, Xiaoli

    2011-06-01

    The expression patterns of different genes encoding antioxidant enzymes and heat shock proteins were investigated, in present study, by real-time quantitative PCR in the hepatopancreas of abalone Haliotis discus hannai fed with different levels of dietary zinc (6.69, 33.8, 710.6 and 3462.5 mg/kg) for 20 weeks. The antioxidant enzymes include Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase (CAT), mu-glutathione-s-transferase (mu-GST) and thioredoxin peroxidase (TPx). The results showed that the mRNA expression of these antioxidant enzymes increased and reached the maximum at the dietary zinc level of 33.8 mg/kg, and then dropped progressively. Expression levels of the heat shock proteins (HSP26, HSP70 and HSP90) firstly increased at 33.8 mg/kg dietary Zn level, and reached to the maximum at 710.6 mg/kg, then dropped at 3462.5 mg/kg (p<0.05). Excessive dietary Zn (710.6 and 3462.5 mg/kg) significantly increases the Zn content and significantly decreases the total antioxidant capacity (T-AOC) in hepatopancreas (p<0.05). These findings showed that dietary Zn (33.8 mg/kg) could highly trigger the expression levels of antioxidant enzymes and heat shock proteins, but excessive dietary Zn (710.6 and 3462.5 mg/kg) induces a high oxidative stress in abalone. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

    PubMed

    Wu, Daocheng; Wan, Mingxi

    2008-01-01

    Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

  11. Epigallocatechin-3-gallate suppressed the over-expression of HSP 70 and MDR1 induced by heat shock in SGC 7901.

    PubMed

    Tang, Xiao-Yan; Zhu, You-Qing

    2008-06-01

    This study investigated the effects of epigallocatechin-3-gallate (EGCG) on the expression of HSP 70 and MDR 1. SGC-7901 cells were cultured with RPMI 1640 medium. The single or combined effects of EGCG (0.1, 1, 10, 20, and 40 micromol/L) and heat shock were examined by MTT assay. The expression of HSP 70 and MDR 1 was semi-quantified by the reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry method (SP staining). EGCG suppressed cell proliferation at a time- and dose-dependent manner. The effects of combined treatment with EGCG and heat shock on the growth of SGC-7901 cells were stronger than single effects of EGCG. After using EGCG for 24 h, 48 h and 72 h, the IC50s were 112.5 micromol/l, 21.41 micromol/l and 5.24 micromol/l, respectively. Heat shock stimulated the over-expression of HSP 70, especially after heat shock for 8 h, as well as MDR1 after heat shock for 24 h. But EGCG suppressed the over-expression induced by heat shock. The authors conclude that EGCG inhibited the proliferation of SGC-7901, and EGCG combined with heat shock strengthened the effects. Heat shock weakened the over-expression of HSP 70 and MDR1; however, EGCG suppressed the over-expression of HSP 70 and MDR1 induced by heat shock. EGCG combined with heat shock may enhance the sensitivity of drugs to tumors.

  12. Molecular and Physiological Analysis of a Heat-Shock Response in Wheat 1

    PubMed Central

    McElwain, Elizabeth F.; Spiker, Steven

    1992-01-01

    We have isolated two cDNA clones from wheat (Triticum aestivum L. var Stephens), designated WHSP16.8 and WHSP16.9, that are highly similar in sequence to the low molecular weight heat-shock protein genes previously isolated from soybean. RNA blot analysis confirms that these sequences are present in heat-shocked wheat seedlings, but not in control tissues. The WHSP16.8 and WHSP16.9 cDNAs were isolated by screening a lambda gt11 expression library with antibodies to HMGc (a chromosomal protein of wheat). Immunoblot analysis has demonstrated that the antibodies raised against HMGc also recognize a group of proteins that are induced by heat shock and have molecular weights (estimated by sodium dodecyl sulfate electrophoresis) consistent with the molecular weights of the proteins deduced from the sequences of the cDNAs. ImagesFigure 3Figure 4Figure 5 PMID:16669058

  13. Kinetics of plasma heat shock protein HSP-70 release in coronary artery surgery: on-pump versus off-pump.

    PubMed

    Pizon, M T; Gburek, T; Pizon, M; Sztefko, K

    2006-12-01

    Heat shock protein HSP-70 is known as protective chaperone molecule synthetized in response following ischemia and stress agents. It is detected in the myocardium and endothelium as well as in the circulation. Damaged as well as viable but exposed to stress cells contribute to the release of HSP-70 into the circulation. The aim of the study was to investigate if cardiopulmonary bypss (CPB) leads to more circulating HSP-70, on the basis of comparison dynamics of plasma concentration HSP-70 in 8 men undergoing procedures with the use of CPB (coronary artery bypass grafting, CABG group) and 8 men undergoing off-pump surgery (OPCAB group). Blood samples were taken preoperatively, twice intraoperatively, immediately after surgical procedure (1 h) and 24-hours thereafter. The concentration of plasma HSP-70 was measured by means of immunoassay. The derived results were compared statistically with the frequency of incidence postoperative atrial fibrillation (AF). In CABG group was observed continuous gradual increase of plasma HSP-70 concentration during the operation with the peak 1 h after surgery (P<0.01), in striking contrast to OPCAB group, in which was detected small, but non statistically significant increase of HSP-70 1 h after operation. Significantly more of circulating HSP-70 it was detected in CABG group during the operation and 1 h after surgery (CABG vs OPCAB, respectively P<0.015 and P<0.028). In both groups among patients witch AF it was found higher postoperative values of circulating HSP-70 compared with the non-AF group (P=0.0415). The use of CPB leads to significant more release of HSP-70 into the circulation. According to our findings high plasma concentration of HSP-70 may be the measure of operative cellular stress, ischemia or injury and may be related with greater onset of postoperative AF. High circulating HSP-70 levels is connected with higher incidence of postoperative AF after open heart surgery.

  14. Skin test performed with highly purified Mycobacterium tuberculosis recombinant protein triggers tuberculin shock in infected guinea pigs.

    PubMed

    Reece, Stephen T; Stride, Nicole; Ovendale, Pamela; Reed, Steven G; Campos-Neto, Antonio

    2005-06-01

    Tuberculin shock due to inoculation of Mycobacterium tuberculosis antigens in patients with tuberculosis is a serious syndrome originally described over 100 years ago by Robert Koch. Here, we present experimental evidence that a single M. tuberculosis recombinant protein, CFP-10, triggers this syndrome. Intradermal inoculation of CFP-10 elicits in M. tuberculosis-infected mice high levels of serum tumor necrosis factor alpha and causes tuberculin shock in infected guinea pigs characterized by hypothermia and death within 6 to 48 h after the antigen inoculation. Autopsies of these animals revealed intense polycythemia and hemorrhagic patches in the lung parenchyma, a pathological observation consistent with tuberculin shock. These results point to the possible occurrence of tuberculin shock in sensitive individuals inoculated with highly purified M. tuberculosis recombinant proteins as vaccine candidates or skin test reagents.

  15. Blast shock wave mitigation using the hydraulic energy redirection and release technology.

    PubMed

    Chen, Yun; Huang, Wei; Constantini, Shlomi

    2012-01-01

    A hydraulic energy redirection and release technology has been developed for mitigating the effects of blast shock waves on protected objects. The technology employs a liquid-filled plastic tubing as a blast overpressure transformer to transfer kinetic energy of blast shock waves into hydraulic energy in the plastic tubings. The hydraulic energy is redirected through the plastic tubings to the openings at the lower ends, and then is quickly released with the liquid flowing out through the openings. The samples of the specifically designed body armor in which the liquid-filled plastic tubings were installed vertically as the outer layer of the body armor were tested. The blast test results demonstrated that blast overpressure behind the body armor samples was remarkably reduced by 97% in 0.2 msec after the liquid flowed out of its appropriate volume through the openings. The results also suggested that a volumetric liquid surge might be created when kinetic energy of blast shock wave was transferred into hydraulic energy to cause a rapid physical movement or displacement of the liquid. The volumetric liquid surge has a strong destructive power, and can cause a noncontact, remote injury in humans (such as blast-induced traumatic brain injury and post-traumatic stress disorder) if it is created in cardiovascular system. The hydraulic energy redirection and release technology can successfully mitigate blast shock waves from the outer surface of the body armor. It should be further explored as an innovative approach to effectively protect against blast threats to civilian and military personnel.

  16. Blast Shock Wave Mitigation Using the Hydraulic Energy Redirection and Release Technology

    PubMed Central

    Chen, Yun; Huang, Wei; Constantini, Shlomi

    2012-01-01

    A hydraulic energy redirection and release technology has been developed for mitigating the effects of blast shock waves on protected objects. The technology employs a liquid-filled plastic tubing as a blast overpressure transformer to transfer kinetic energy of blast shock waves into hydraulic energy in the plastic tubings. The hydraulic energy is redirected through the plastic tubings to the openings at the lower ends, and then is quickly released with the liquid flowing out through the openings. The samples of the specifically designed body armor in which the liquid-filled plastic tubings were installed vertically as the outer layer of the body armor were tested. The blast test results demonstrated that blast overpressure behind the body armor samples was remarkably reduced by 97% in 0.2 msec after the liquid flowed out of its appropriate volume through the openings. The results also suggested that a volumetric liquid surge might be created when kinetic energy of blast shock wave was transferred into hydraulic energy to cause a rapid physical movement or displacement of the liquid. The volumetric liquid surge has a strong destructive power, and can cause a noncontact, remote injury in humans (such as blast-induced traumatic brain injury and post-traumatic stress disorder) if it is created in cardiovascular system. The hydraulic energy redirection and release technology can successfully mitigate blast shock waves from the outer surface of the body armor. It should be further explored as an innovative approach to effectively protect against blast threats to civilian and military personnel. PMID:22745740

  17. Unrestrained AMPylation targets cytosolic chaperones and activates the heat shock response

    PubMed Central

    Truttmann, Matthias C.; Zheng, Xu; Hanke, Leo; Damon, Jadyn R.; Grootveld, Monique; Krakowiak, Joanna; Pincus, David; Ploegh, Hidde L.

    2017-01-01

    Protein AMPylation is a conserved posttranslational modification with emerging roles in endoplasmic reticulum homeostasis. However, the range of substrates and cell biological consequences of AMPylation remain poorly defined. We expressed human and Caenorhabditis elegans AMPylation enzymes—huntingtin yeast-interacting protein E (HYPE) and filamentation-induced by cyclic AMP (FIC)-1, respectively—in Saccharomyces cerevisiae, a eukaryote that lacks endogenous protein AMPylation. Expression of HYPE and FIC-1 in yeast induced a strong cytoplasmic Hsf1-mediated heat shock response, accompanied by attenuation of protein translation, massive protein aggregation, growth arrest, and lethality. Overexpression of Ssa2, a cytosolic heat shock protein (Hsp)70, was sufficient to partially rescue growth. In human cell lines, overexpression of active HYPE similarly induced protein aggregation and the HSF1-dependent heat shock response. Excessive AMPylation also abolished HSP70-dependent influenza virus replication. Our findings suggest a mode of Hsp70 inactivation by AMPylation and point toward a role for protein AMPylation in the regulation of cellular protein homeostasis beyond the endoplasmic reticulum. PMID:28031489

  18. Chaos and ion heating in a slow shock

    NASA Technical Reports Server (NTRS)

    Lin, Y.; Lee, L. C.

    1991-01-01

    An ion heating mechanism is proposed of slow shocks, which is associated with the chaotic motion of particles in the downstream wave field. For a coherent electromagnetic wave propagating along the downstream magnetic field, corresponding to switch-off shocks, the particle motions are not chaotic. For an oblique wave, the interaction between the particles and the wave field may lead to chaotic particle motions. Such particles may be greatly thermalized within one wavelength after they are incident into the downstream wave field. The results can be used to explain the existence of the critical intermediate Mach number observed in the hybrid simulations.

  19. Time-resolved diffraction of shock-released SiO 2 and diaplectic glass formation

    DOE PAGES

    Gleason, A. E.; Bolme, C. A.; Lee, H. J.; ...

    2017-11-14

    Understanding how rock-forming minerals transform under shock loading is critical for modeling collisions between planetary bodies, interpreting the significance of shock features in minerals and for using them as diagnostic indicators of impact conditions, such as shock pressure. To date, our understanding of the formation processes experienced by shocked materials is based exclusively on ex situ analyses of recovered samples. Formation mechanisms and origins of commonly observed mesoscale material features, such as diaplectic (i.e., shocked) glass, remain therefore controversial and unresolvable. Here in this paper we show in situ pump-probe X-ray diffraction measurements on fused silica crystallizing to stishovite onmore » shock compression and then converting to an amorphous phase on shock release in only 2.4 ns from 33.6 GPa. Recovered glass fragments suggest permanent densification. These observations of real-time diaplectic glass formation attest that it is a back-transformation product of stishovite with implications for revising traditional shock metamorphism stages.« less

  20. Time-resolved diffraction of shock-released SiO 2 and diaplectic glass formation

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

    Gleason, A. E.; Bolme, C. A.; Lee, H. J.

    Understanding how rock-forming minerals transform under shock loading is critical for modeling collisions between planetary bodies, interpreting the significance of shock features in minerals and for using them as diagnostic indicators of impact conditions, such as shock pressure. To date, our understanding of the formation processes experienced by shocked materials is based exclusively on ex situ analyses of recovered samples. Formation mechanisms and origins of commonly observed mesoscale material features, such as diaplectic (i.e., shocked) glass, remain therefore controversial and unresolvable. Here in this paper we show in situ pump-probe X-ray diffraction measurements on fused silica crystallizing to stishovite onmore » shock compression and then converting to an amorphous phase on shock release in only 2.4 ns from 33.6 GPa. Recovered glass fragments suggest permanent densification. These observations of real-time diaplectic glass formation attest that it is a back-transformation product of stishovite with implications for revising traditional shock metamorphism stages.« less

  1. Ultrasound Enhanced Matrix Metalloproteinase-9 Triggered Release of Contents from Echogenic Liposomes

    PubMed Central

    Nahire, Rahul; Paul, Shirshendu; Scott, Michael D.; Singh, Raushan K.; Muhonen, Wallace W.; Shabb, John; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

    2012-01-01

    The extracellular enzyme matrix metalloproteinase-9 (MMP-9) is overexpressed in atherosclerotic plaques and in metastatic cancers. The enzyme is responsible for rupture of the plaques and for the invasion and metastasis of a large number of cancers. The ability of ultrasonic excitation to induce thermal and mechanical effects has been used to release drugs from different carriers. However, majority of these studies were performed with low frequency ultrasound (LFUS) at kHz frequencies. Clinical usage of LFUS excitations will be limited due to harmful biological effects. Herein, we report our results on the release of encapsulated contents from substrate lipopeptide incorporated echogenic liposomes triggered by recombinant human MMP-9. The contents release was further enhanced by the application of diagnostic frequency (3 MHz) ultrasound. The echogenic liposomes were successfully imaged employing a medical ultrasound transducer (4 – 15 MHz). The conditioned cell culture media from cancer cells (secreting MMP-9) released the encapsulated dye from the liposomes (30 – 50%) and this release is also increased (50 – 80%) by applying diagnostic frequency ultrasound (3 MHz) for 3 minutes. With further developments, these liposomes have the potential to serve as multimodal carriers for triggered release and simultaneous ultrasound imaging. PMID:22849291

  2. Heat shock protein expression enhances heat tolerance of reptile embryos.

    PubMed

    Gao, Jing; Zhang, Wen; Dang, Wei; Mou, Yi; Gao, Yuan; Sun, Bao-Jun; Du, Wei-Guo

    2014-09-22

    The role of heat shock proteins (HSPs) in heat tolerance has been demonstrated in cultured cells and animal tissues, but rarely in whole organisms because of methodological difficulties associated with gene manipulation. By comparing HSP70 expression patterns among representative species of reptiles and birds, and by determining the effect of HSP70 overexpression on embryonic development and hatchling traits, we have identified the role of HSP70 in the heat tolerance of amniote embryos. Consistent with their thermal environment, and high incubation temperatures and heat tolerance, the embryos of birds have higher onset and maximum temperatures for induced HSP70 than do reptiles, and turtles have higher onset and maximum temperatures than do lizards. Interestingly, the trade-off between benefits and costs of HSP70 overexpression occurred between life-history stages: when turtle embryos developed at extreme high temperatures, HSP70 overexpression generated benefits by enhancing embryo heat tolerance and hatching success, but subsequently imposed costs by decreasing heat tolerance of surviving hatchlings. Taken together, the correlative and causal links between HSP70 and heat tolerance provide, to our knowledge, the first unequivocal evidence that HSP70 promotes thermal tolerance of embryos in oviparous amniotes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  3. Trigger chemistries for better industrial formulations.

    PubMed

    Wang, Hsuan-Chin; Zhang, Yanfeng; Possanza, Catherine M; Zimmerman, Steven C; Cheng, Jianjun; Moore, Jeffrey S; Harris, Keith; Katz, Joshua S

    2015-04-01

    In recent years, innovations and consumer demands have led to increasingly complex liquid formulations. These growing complexities have provided industrial players and their customers access to new markets through product differentiation, improved performance, and compatibility/stability with other products. One strategy for enabling more complex formulations is the use of active encapsulation. When encapsulation is employed, strategies are required to effect the release of the active at the desired location and time of action. One particular route that has received significant academic research effort is the employment of triggers to induce active release upon a specific stimulus, though little has translated for industrial use to date. To address emerging industrial formulation needs, in this review, we discuss areas of trigger release chemistries and their applications specifically as relevant to industrial use. We focus the discussion on the use of heat, light, shear, and pH triggers as applied in several model polymeric systems for inducing active release. The goal is that through this review trends will emerge for how technologies can be better developed to maximize their value through industrial adaptation.

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

    PubMed Central

    2010-01-01

    Background Aspergillus fumigatus is a thermotolerant human-pathogenic mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. Its predominance is based on several factors most of which are still unknown. The thermotolerance of A. fumigatus is one of the traits which have been assigned to pathogenicity. It allows the fungus to grow at temperatures up to and above that of a fevered human host. To elucidate the mechanisms of heat resistance, we analyzed the change of the A. fumigatus proteome during a temperature shift from 30°C to 48°C by 2D-fluorescence difference gel electrophoresis (DIGE). To improve 2D gel image analysis results, protein spot quantitation was optimized by missing value imputation and normalization. Differentially regulated proteins were compared to previously published transcriptome data of A. fumigatus. The study was augmented by bioinformatical analysis of transcription factor binding sites (TFBSs) in the promoter region of genes whose corresponding proteins were differentially regulated upon heat shock. Results 91 differentially regulated protein spots, representing 64 different proteins, were identified by mass spectrometry (MS). They showed a continuous up-, down- or an oscillating regulation. Many of the identified proteins were involved in protein folding (chaperones), oxidative stress response, signal transduction, transcription, translation, carbohydrate and nitrogen metabolism. A correlation between alteration of transcript levels and corresponding proteins was detected for half of the differentially regulated proteins. Interestingly, some previously undescribed putative targets for the heat shock regulator Hsf1 were identified. This provides evidence for Hsf1-dependent regulation of mannitol biosynthesis, translation, cytoskeletal dynamics and cell division in A. fumigatus. Furthermore, computational analysis of promoters revealed putative binding sites for an AP-2alpha-like transcription factor

  5. Reduction-Responsive Polymeric Micelles and Vesicles for Triggered Intracellular Drug Release

    PubMed Central

    Sun, Huanli; Cheng, Ru; Deng, Chao

    2014-01-01

    Abstract Significance: The therapeutic effects of current micellar and vesicular drug formulations are restricted by slow and inefficient drug release at the pathological site. The development of smart polymeric nanocarriers that release drugs upon arriving at the target site has received a tremendous amount of attention for cancer therapy. Recent Advances: Taking advantage of a high reducing potential in the tumor tissues and in particular inside the tumor cells, various reduction-sensitive polymeric micelles and vesicles have been designed and explored for triggered anticancer drug release. These reduction-responsive nanosystems have demonstrated several unique features, such as good stability under physiological conditions, fast response to intracellular reducing environment, triggering drug release right in the cytosol and cell nucleus, and significantly improved antitumor activity, compared to traditional reduction-insensitive counterparts. Critical Issues: Although reduction-sensitive micelles and polymersomes have accomplished rapid intracellular drug release and enhanced in vitro antitumor effect, their fate inside the cells including the mechanism, site, and rate of reduction reaction remains unclear. Moreover, the systemic fate and performance of reduction-sensitive polymeric drug formulations have to be investigated. Future Directions: Biophysical studies should be carried out to gain insight into the degradation and drug release behaviors of reduction-responsive nanocarriers inside the tumor cells. Furthermore, novel ligand-decorated reduction-sensitive nanoparticulate drug formulations should be designed and explored for targeted cancer therapy in vivo. Antioxid. Redox Signal. 21, 755–767. PMID:24279980

  6. Remote modulation of neural activities via near-infrared triggered release of biomolecules.

    PubMed

    Li, Wei; Luo, Rongcong; Lin, Xudong; Jadhav, Amol D; Zhang, Zicong; Yan, Li; Chan, Chung-Yuan; Chen, Xianfeng; He, Jufang; Chen, Chia-Hung; Shi, Peng

    2015-10-01

    The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically

  7. Global gene expression analysis of the heat shock response in the phytopathogen Xylella fastidiosa.

    PubMed

    Koide, Tie; Vêncio, Ricardo Z N; Gomes, Suely L

    2006-08-01

    Xylella fastidiosa is a phytopathogenic bacterium that is responsible for diseases in many economically important crops. Although different strains have been studied, little is known about X. fastidiosa stress responses. One of the better characterized stress responses in bacteria is the heat shock response, which induces the expression of specific genes to prevent protein misfolding and aggregation and to promote degradation of the irreversibly denatured polypeptides. To investigate X. fastidiosa genes involved in the heat shock response, we performed a whole-genome microarray analysis in a time course experiment. Globally, 261 genes were induced (9.7%) and 222 genes were repressed (8.3%). The expression profiles of the differentially expressed genes were grouped, and their expression patterns were validated by quantitative reverse transcription-PCR experiments. We determined the transcription start sites of six heat shock-inducible genes and analyzed their promoter regions, which allowed us to propose a putative consensus for sigma(32) promoters in Xylella and to suggest additional genes as putative members of this regulon. Besides the induction of classical heat shock protein genes, we observed the up-regulation of virulence-associated genes such as vapD and of genes for hemagglutinins, hemolysin, and xylan-degrading enzymes, which may indicate the importance of heat stress to bacterial pathogenesis. In addition, we observed the repression of genes related to fimbriae, aerobic respiration, and protein biosynthesis and the induction of genes related to the extracytoplasmic stress response and some phage-related genes, revealing the complex network of genes that work together in response to heat shock.

  8. Non-Lethal Heat Shock Increased Hsp70 and Immune Protein Transcripts but Not Vibrio Tolerance in the White-Leg Shrimp

    PubMed Central

    Loc, Nguyen Hong; MacRae, Thomas H.; Musa, Najiah; Bin Abdullah, Muhd Danish Daniel; Abdul Wahid, Mohd. Effendy; Sung, Yeong Yik

    2013-01-01

    Non-lethal heat shock boosts bacterial and viral disease tolerance in shrimp, possibly due to increases in endogenous heat shock protein 70 (Hsp70) and/or immune proteins. To further understand the mechanisms protecting shrimp against infection, Hsp70 and the mRNAs encoding the immune-related proteins prophenoloxidase (proPO), peroxinectin, penaeidin, crustin and hemocyanin were studied in post-larvae of the white-leg shrimp Litopenaeus vannamei, following a non-lethal heat shock. As indicated by RT-qPCR, a 30 min abrupt heat shock increased Hsp70 mRNA in comparison to non-heated animals. Immunoprobing of western blots and quantification by ELISA revealed that Hsp70 production after heat shock was correlated with enhanced Hsp70 mRNA. proPO and hemocyanin mRNA levels were augmented, whereas peroxinectin and crustin mRNA levels were unchanged following non-lethal heat shock. Penaeidin mRNA was decreased by all heat shock treatments. Thirty min abrupt heat shock failed to improve survival of post-larvae in a standardized challenge test with Vibrio harveyi, indicating that under the conditions of this study, L. vannamei tolerance to Vibrio infection was influenced neither by Hsp70 accumulation nor the changes in the immune-related proteins, observations dissimilar to other shrimp species examined. PMID:24039886

  9. Effect of patchouli alcohol on the regulation of heat shock-induced oxidative stress in IEC-6 cells.

    PubMed

    Liu, Xiaoxi; Jiang, Linshu; Liu, Fenghua; Chen, Yuping; Xu, Lei; Li, Deyin; Ma, Yunfei; Li, Huanrong; Xu, Jianqin

    2016-08-01

    Purpose Patchouli alcohol (PA) is used to treat gastrointestinal dysfunction. The purpose of this study was to ascertain the function of PA in the regulated process of oxidative stress in rat intestinal epithelial cells (IEC-6). Materials and methods Oxidative stress was stimulated by exposing IEC-6 cells to heat shock (42 °C for 3 h). IEC-6 cells in treatment groups were pretreated with various concentrations of PA (10, 40, and 80 ng/mL) for 3 h before heat shock. Results Heat shock caused damage to the morphology of IEC-6 cells, and increased reactive oxygen species (ROS) level and malondialdehyde (MDA) content. Moreover, mRNA and protein expression by target genes related to oxidative stress in heat shock were also altered. Specifically, the mRNA expression by HSP70, HSP90, GSH-px, NRF2 nd HO-1were all increased, and Nrf2 and Keap1 protein expression were increased after heat shock. However, pretreatment with PA weakened the level of damage to the cellular morphology, and decreased the MDA content caused by heat shock, indicating PA had cytoprotective activities. Pretreatment with PA at high dose significantly increased generation of intracellular ROS. Compared with the heat shock group alone, PA pretreatment significantly decreased the mRNA expression by HSP70, HSP90, SOD, CAT, GSH-px, KEAP1 and HO-1. Furthermore, the high dose of PA significantly increased Nrf2 protein expression, while both the intermediate and high dose of PA significantly increased HO-1 protein expression. Conclusion Heat-shock-induced oxidative stress in IEC-6 cells, and PA could alleviate the Nrf2-Keap1 cellular oxidative stress responses.

  10. Proper Heat Shock Pretreatment Reduces Acute Liver Injury Induced by Carbon Tetrachloride and Accelerates Liver Repair in Mice

    PubMed Central

    Li, San-Qiang; Wang, Dong-Mei; Shu, You-Ju; Wan, Xue-Dong; Xu, Zheng-Shun; Li, En-Zhong

    2013-01-01

    Whether proper heat shock preconditioning can reduce liver injury and accelerate liver repair after acute liver injury is worth study. So mice received heat shock preconditioning at 40°C for 10 minutes (min), 20 min or 30 min and recovered at room temperature for 8 hours (h) under normal feeding conditions. Then acute liver injury was induced in the heat shock-pretreated mice and unheated control mice by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4). Hematoxylin and eosin (H&E) staining, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the expression levels of heat shock protein 70 (HSP70), cytochrome P450 1A2 (CYP1A2) and proliferating cell nuclear antigen (PCNA) were detected in the unheated control mice and heat shock-pretreated mice after CCl4 administration. Our results showed that heat shock preconditioning at 40°C for 20 min remarkably improved the mice’s survival rate (P<0.05), lowered the levels of serum AST and ALT (P<0.05), induced HSP70 (P<0.01), CYP1A2 (P<0.01) and PCNA (P<0.05) expression, effectively reduced liver injury (P<0.05) and accelerated the liver repair (P<0.05) compared with heat shock preconditioning at 40°C for 10 min or 30 min in the mice after acute liver injury induced by CCl4 when compared with the control mice. Our results may be helpful in further investigation of heat shock pretreatment as a potential clinical approach to target liver injury PMID:24526809

  11. Heat shock factor 1 upregulates transcription of Epstein-Barr Virus nuclear antigen 1 by binding to a heat shock element within the BamHI-Q promoter

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

    Wang, Feng-Wei; Wu, Xian-Rui; Liu, Wen-Ju

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for maintenance of the episome and establishment of latency. In this study, we observed that heat treatment effectively induced EBNA1 transcription in EBV-transformed B95-8 and human LCL cell lines. Although Cp is considered as the sole promoter used for the expression of EBNA1 transcripts in the lymphoblastoid cell lines, the RT-PCR results showed that the EBNA1 transcripts induced by heat treatment arise from Qp-initiated transcripts. Using bioinformatics, a high affinity and functional heat shock factor 1 (HSF1)-binding element within the - 17/+4 oligonucleotide of the Qp was found, and was determinedmore » by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Moreover, heat shock and exogenous HSF1 expression induced Qp activity in reporter assays. Further, RNA interference-mediated HSF1 gene silencing attenuated heat-induced EBNA1 expression in B95-8 cells. These results provide evidence that EBNA1 is a new target for the transcription factor HSF1.« less

  12. Whole-Genome Analysis Reveals That Active Heat Shock Factor Binding Sites Are Mostly Associated with Non-Heat Shock Genes in Drosophila melanogaster

    PubMed Central

    Gonsalves, Sarah E.; Moses, Alan M.; Razak, Zak; Robert, Francois; Westwood, J. Timothy

    2011-01-01

    During heat shock (HS) and other stresses, HS gene transcription in eukaryotes is up-regulated by the transcription factor heat shock factor (HSF). While the identities of the major HS genes have been known for more than 30 years, it has been suspected that HSF binds to numerous other genes and potentially regulates their transcription. In this study, we have used a chromatin immunoprecipitation and microarray (ChIP-chip) approach to identify 434 regions in the Drosophila genome that are bound by HSF. We have also performed a transcript analysis of heat shocked Kc167 cells and third instar larvae and compared them to HSF binding sites. The heat-induced transcription profiles were quite different between cells and larvae and surprisingly only about 10% of the genes associated with HSF binding sites show changed transcription. There were also genes that showed changes in transcript levels that did not appear to correlate with HSF binding sites. Analysis of the locations of the HSF binding sites revealed that 57% were contained within genes with approximately 2/3rds of these sites being in introns. We also found that the insulator protein, BEAF, has enriched binding prior to HS to promoters of genes that are bound by HSF upon HS but that are not transcriptionally induced during HS. When the genes associated with HSF binding sites in promoters were analyzed for gene ontology terms, categories such as stress response and transferase activity were enriched whereas analysis of genes having HSF binding sites in introns identified those categories plus ones related to developmental processes and reproduction. These results suggest that Drosophila HSF may be regulating many genes besides the known HS genes and that some of these genes may be regulated during non-stress conditions. PMID:21264254

  13. Whole-genome analysis reveals that active heat shock factor binding sites are mostly associated with non-heat shock genes in Drosophila melanogaster.

    PubMed

    Gonsalves, Sarah E; Moses, Alan M; Razak, Zak; Robert, Francois; Westwood, J Timothy

    2011-01-14

    During heat shock (HS) and other stresses, HS gene transcription in eukaryotes is up-regulated by the transcription factor heat shock factor (HSF). While the identities of the major HS genes have been known for more than 30 years, it has been suspected that HSF binds to numerous other genes and potentially regulates their transcription. In this study, we have used a chromatin immunoprecipitation and microarray (ChIP-chip) approach to identify 434 regions in the Drosophila genome that are bound by HSF. We have also performed a transcript analysis of heat shocked Kc167 cells and third instar larvae and compared them to HSF binding sites. The heat-induced transcription profiles were quite different between cells and larvae and surprisingly only about 10% of the genes associated with HSF binding sites show changed transcription. There were also genes that showed changes in transcript levels that did not appear to correlate with HSF binding sites. Analysis of the locations of the HSF binding sites revealed that 57% were contained within genes with approximately 2/3rds of these sites being in introns. We also found that the insulator protein, BEAF, has enriched binding prior to HS to promoters of genes that are bound by HSF upon HS but that are not transcriptionally induced during HS. When the genes associated with HSF binding sites in promoters were analyzed for gene ontology terms, categories such as stress response and transferase activity were enriched whereas analysis of genes having HSF binding sites in introns identified those categories plus ones related to developmental processes and reproduction. These results suggest that Drosophila HSF may be regulating many genes besides the known HS genes and that some of these genes may be regulated during non-stress conditions.

  14. 27-Hydroxycholesterol upregulates the production of heat shock protein 60 of monocytic cells.

    PubMed

    Kim, Bo-Young; Son, Yonghae; Choi, Jeongyoon; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

    2017-09-01

    Investigating differentially expressed proteins in a milieu rich in cholesterol oxidation products, we found via mass spectrometry-based proteomics that surface levels of heat shock protein 60 (HSP60) were upregulated on monocytic cells in the presence of 27-hydroxycholesterol (27OHChol). The elevated levels of cytoplasmic membrane HSP60 were verified via Western blot analysis and visualized by confocal microscopy. Treatment with 27OHChol also resulted in increased levels of cellular HSP60 without altering its transcription. Cholesterol, however, did not affect cell-surface levels and cellular amount of HSP60. GSK 2033, an LXR antagonist, inhibited expression of live X receptor α, but not of HSP60, induced by 27OHChol. Treatment with 27OHChol also resulted in increased release of HSP60 from monocytic cells, but the release was significantly reduced by inhibitors of endoplasmic reticulum-Golgi protein trafficking, brefeldin A and monensin. Results of the current study indicate that 27OHChol upregulates not only cell-surface and cellular levels of HSP60 but also its release from monocytic cells, thereby contributing to activation of the immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The formation of massive molecular filaments and massive stars triggered by a magnetohydrodynamic shock wave

    NASA Astrophysics Data System (ADS)

    Inoue, Tsuyoshi; Hennebelle, Patrick; Fukui, Yasuo; Matsumoto, Tomoaki; Iwasaki, Kazunari; Inutsuka, Shu-ichiro

    2018-05-01

    Recent observations suggest an that intensive molecular cloud collision can trigger massive star/cluster formation. The most important physical process caused by the collision is a shock compression. In this paper, the influence of a shock wave on the evolution of a molecular cloud is studied numerically by using isothermal magnetohydrodynamics simulations with the effect of self-gravity. Adaptive mesh refinement and sink particle techniques are used to follow the long-time evolution of the shocked cloud. We find that the shock compression of a turbulent inhomogeneous molecular cloud creates massive filaments, which lie perpendicularly to the background magnetic field, as we have pointed out in a previous paper. The massive filament shows global collapse along the filament, which feeds a sink particle located at the collapse center. We observe a high accretion rate \\dot{M}_acc> 10^{-4} M_{⊙}yr-1 that is high enough to allow the formation of even O-type stars. The most massive sink particle achieves M > 50 M_{⊙} in a few times 105 yr after the onset of the filament collapse.

  16. SPERM MOTILITY IN HSF1 KNOCKOUT MICE AFTER HEAT SHOCK IS ASSOCIATED WITH FERTILITY DEFICITS

    EPA Science Inventory

    SPERM MOTILITY IN HSF1 KNOCKOUT MICE AFTER HEAT SHOCK IS ASSOCIATED WITH FERTILITY DEFICITS. L.F. Strader*, S.D. Perreault, J.C. Luft*, and D.J. Dix*. US EPA/ORD, Reproductive Toxicology Div., Research Triangle Park, NC
    Heat shock proteins (HSPs) protect cells from environm...

  17. Prediction and measurement of heat transfer rates for the shock-induced unsteady laminar boundary layer on a flat plate

    NASA Technical Reports Server (NTRS)

    Cook, W. J.

    1972-01-01

    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.

  18. The Effects of Calcitonin on the Development of and Ca2+ Levels in Heat-shocked Bovine Preimplantation Embryos In Vitro

    PubMed Central

    KAMANO, Shumpei; IKEDA, Shuntaro; SUGIMOTO, Miki; KUME, Shinichi

    2014-01-01

    Intracellular calcium homeostasis is essential for proper cell function. We investigated the effects of heat shock on the development of and the intracellular Ca2+ levels in bovine preimplantation embryos in vitro and the effects of calcitonin (CT), a receptor-mediated Ca2+ regulator, on heat shock-induced events. Heat shock (40.5 C for 10 h between 20 and 30 h postinsemination) of in vitro-produced bovine embryos did not affect the cleavage rate; however, it significantly decreased the rates of development to the 5- to 8-cell and blastocyst stages as compared with those of the control cultured for the entire period at 38.5 C (P < 0.05). The relative intracellular Ca2+ levels at the 1-cell stage (5 h after the start of heat shock), as assessed by Fluo-8 AM, a fluorescent probe for Ca2+, indicated that heat shock significantly lowered the Ca2+ level as compared with the control level. Semiquantitative reverse transcription PCR and western blot analyses revealed the expression of CT receptor in bovine preimplantation embryos. The addition of CT (10 nM) to the culture medium ameliorated the heat shock-induced impairment of embryonic development beyond the 5- to 8-cell stage. The Ca2+ level in the heat-shocked embryos cultured with CT was similar to that of the control embryos, suggesting that heat shock lowers the Ca2+ level in fertilized embryos in vitro and that a lower Ca2+ level is implicated in heat shock-induced impairment of embryonic development. Intracellular Ca2+-mobilizing agents, e.g., CT, may effectively circumvent the detrimental effects of heat shock on early embryonic development. PMID:24899099

  19. Self similar flow behind an exponential shock wave in a self-gravitating, rotating, axisymmetric dusty gas with heat conduction and radiation heat flux

    NASA Astrophysics Data System (ADS)

    Bajargaan, Ruchi; Patel, Arvind

    2018-04-01

    One-dimensional unsteady adiabatic flow behind an exponential shock wave propagating in a self-gravitating, rotating, axisymmetric dusty gas with heat conduction and radiation heat flux, which has exponentially varying azimuthal and axial fluid velocities, is investigated. The shock wave is driven out by a piston moving with time according to an exponential law. The dusty gas is taken to be a mixture of a non-ideal gas and small solid particles. The density of the ambient medium is assumed to be constant. The equilibrium flow conditions are maintained and energy is varying exponentially, which is continuously supplied by the piston. The heat conduction is expressed in the terms of Fourier's law, and the radiation is assumed of diffusion type for an optically thick grey gas model. The thermal conductivity and the absorption coefficient are assumed to vary with temperature and density according to a power law. The effects of the variation of heat transfer parameters, gravitation parameter and dusty gas parameters on the shock strength, the distance between the piston and the shock front, and on the flow variables are studied out in detail. It is interesting to note that the similarity solution exists under the constant initial angular velocity, and the shock strength is independent from the self gravitation, heat conduction and radiation heat flux.

  20. Genetic variation in resistance of the preimplantation bovine embryo to heat shock.

    PubMed

    Hansen, Peter J

    2014-12-01

    Reproduction is among the physiological functions in mammals most susceptible to disruption by hyperthermia. Many of the effects of heat stress on function of the oocyte and embryo involve direct effects of elevated temperature (i.e. heat shock) on cellular function. Mammals limit the effects of heat shock by tightly regulating body temperature. This ability is genetically controlled: lines of domestic animals have been developed with superior ability to regulate body temperature during heat stress. Through experimentation in cattle, it is also evident that there is genetic variation in the resistance of cells to the deleterious effects of elevated temperature. Several breeds that were developed in hot climates, including Bos indicus (Brahman, Gir, Nelore and Sahiwal) and Bos taurus (Romosinuano and Senepol) are more resistant to the effects of elevated temperature on cellular function than breeds that evolved in cooler climates (Angus, Holstein and Jersey). Genetic differences are expressed in the preimplantation embryo by Day 4-5 of development (after embryonic genome activation). It is not clear whether genetic differences are expressed in cells in which transcription is repressed (oocytes >100 µm in diameter or embryos at stages before embryonic genome activation). The molecular basis for cellular thermotolerance has also not been established, although there is some suggestion for involvement of heat shock protein 90 and the insulin-like growth factor 1 system. Given the availability of genomic tools for genetic selection, identification of genes controlling cellular resistance to elevated temperature could be followed by progress in selection for those genes within the populations in which they exist. It could also be possible to introduce genes from thermotolerant breeds into thermally sensitive breeds. The ability to edit the genome makes it possible to design new genes that confer protection of cells from stresses like heat shock.

  1. Spatially resolved heat release rate measurements in turbulent premixed flames

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

    Ayoola, B.O.; Kaminski, C.F.; Balachandran, R.

    Heat release rate is a fundamental property of great importance for the theoretical and experimental elucidation of unsteady flame behaviors such as combustion noise, combustion instabilities, and pulsed combustion. Investigations of such thermoacoustic interactions require a reliable indicator of heat release rate capable of resolving spatial structures in turbulent flames. Traditionally, heat release rate has been estimated via OH or CH radical chemiluminescence; however, chemiluminescence suffers from being a line-of-sight technique with limited capability for resolving small-scale structures. In this paper, we report spatially resolved two-dimensional measurements of a quantity closely related to heat release rate. The diagnostic technique usesmore » simultaneous OH and CH{sub 2}O planar laser-induced fluorescence (PLIF), and the pixel-by-pixel product of the OH and CH{sub 2}O PLIF signals has previously been shown to correlate well with local heat release rates. Results from this diagnostic technique, which we refer to as heat release rate imaging (HR imaging), are compared with traditional OH chemiluminescence measurements in several flames. Studies were performed in lean premixed ethylene flames stabilized between opposed jets and with a bluff body. Correlations between bulk strain rates and local heat release rates were obtained and the effects of curvature on heat release rate were investigated. The results show that the heat release rate tends to increase with increasing negative curvature for the flames investigated for which Lewis numbers are greater than unity. This correlation becomes more pronounced as the flame gets closer to global extinction.« less

  2. Rapid Light-Triggered Drug Release in Liposomes Containing Small Amounts of Unsaturated and Porphyrin-Phospholipids.

    PubMed

    Luo, Dandan; Li, Nasi; Carter, Kevin A; Lin, Cuiyan; Geng, Jumin; Shao, Shuai; Huang, Wei-Chiao; Qin, Yueling; Atilla-Gokcumen, G Ekin; Lovell, Jonathan F

    2016-06-01

    Prompt membrane permeabilization is a requisite for liposomes designed for local stimuli-induced intravascular release of therapeutic payloads. Incorporation of a small amount (i.e., 5 molar percent) of an unsaturated phospholipid, such as dioleoylphosphatidylcholine (DOPC), accelerates near infrared (NIR) light-triggered doxorubicin release in porphyrin-phospholipid (PoP) liposomes by an order of magnitude. In physiological conditions in vitro, the loaded drug can be released in a minute under NIR irradiation, while liposomes maintain serum stability otherwise. This enables rapid laser-induced drug release using remarkably low amounts of PoP (i.e., 0.3 molar percent). Light-triggered drug release occurs concomitantly with DOPC and cholesterol oxidation, as detected by mass spectrometry. In the presence of an oxygen scavenger or an antioxidant, light-triggered drug release is inhibited, suggesting that the mechanism is related to singlet oxygen mediated oxidization of unsaturated lipids. Despite the irreversible modification of lipid composition, DOPC-containing PoP liposome permeabilization is transient. Human pancreatic xenograft growth in mice is significantly delayed with a single chemophototherapy treatment following intravenous administration of 6 mg kg(-1) doxorubicin, loaded in liposomes containing small amounts of DOPC and PoP. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Development of a non-explosive release actuator using shape memory alloy wire.

    PubMed

    Yoo, Young Ik; Jeong, Ju Won; Lim, Jae Hyuk; Kim, Kyung-Won; Hwang, Do-Soon; Lee, Jung Ju

    2013-01-01

    We have developed a newly designed non-explosive release actuator that can replace currently used release devices. The release mechanism is based on a separation mechanism, which relies on segmented nuts and a shape memory alloy (SMA) wire trigger. A quite fast and simple trigger operation is made possible through the use of SMA wire. This actuator is designed to allow a high preload with low levels of shock for the solar arrays of medium-size satellites. After actuation, the proposed device can be easily and instantly reset. Neither replacement, nor refurbishment of any components is necessary. According to the results of a performance test, the release time, preload capacity, and maximum shock level are 50 ms, 15 kN, and 350 G, respectively. In order to increase the reliability of the actuator, more than ten sets of performance tests are conducted. In addition, the proposed release actuator is tested under thermal vacuum and extreme vibration environments. No degradation or damage was observed during the two environment tests, and the release actuator was able to operate successfully. Considering the test results as a whole, we conclude that the proposed non-explosive release actuator can be applied reliably to intermediate-size satellites to replace existing release systems.

  4. The role of heat shock proteins in protection and pathophysiology of the arterial wall.

    PubMed

    Xu, Q; Wick, G

    1996-09-01

    The arterial wall is an integrated functional component of the circulatory system that is continually remodelling in response to various stressors, including localized injury, toxins, smoking and hypercholesterolaemia. These stimuli directly or indirectly cause changes in blood pressure and damage to the vessel wall, and eventually induce arterial stiffness and obstruction. To maintain the homeostasis of the vessel wall, the vascular cells produce a high level of stress proteins, also known as heat shock proteins, which protect against damage during haemodynamic stress. However, an immune reaction to heat shock proteins might contribute to the development of atherosclerosis. We hypothesize that the induction of heat shock proteins is beneficial in the arterial wall's response to stress but is harmful in certain other circumstances.

  5. Antarctic marine molluscs do have an HSP70 heat shock response

    PubMed Central

    Fraser, Keiron P. P.; Peck, Lloyd S.

    2008-01-01

    The success of any organism depends not only on niche adaptation but also the ability to survive environmental perturbation from homeostasis, a situation generically described as stress. Although species-specific mechanisms to combat “stress” have been described, the production of heat shock proteins (HSPs), such as HSP70, is universally described across all taxa. Members of the HSP70 gene family comprising the constitutive (HSC70) and inducible (HSP70) members, plus GRP78 (glucose-regulated protein, 78 kDa), a related HSP70 family member, were cloned using degenerate polymerase chain reaction (PCR) from two evolutionary divergent Antarctic marine molluscs (Laternula elliptica and Nacella concinna), a bivalve and a gastropod, respectively. The expression of the HSP70 family members was surveyed via quantitative PCR after an acute 2-h heat shock experiment. Both species demonstrated significant up-regulation of HSP70 gene expression in response to increased temperatures. However, the temperature level at which these responses were induced varied with the species (+6–8°C for L. elliptica and +8–10°C for N. concinna) compared to their natural environmental temperature). L. elliptica also showed tissue-specific expression of the genes under study. Previous work on Antarctic fish has shown that they lack the classical heat shock response, with the inducible form of HSP70 being permanently expressed with an expression not further induced under higher temperature regimes. This study shows that this is not the case for other Antarctic animals, with the two molluscs showing an inducible heat shock response, at a level probably set during their temperate evolutionary past. PMID:18347940

  6. Antarctic marine molluscs do have an HSP70 heat shock response.

    PubMed

    Clark, Melody S; Fraser, Keiron P P; Peck, Lloyd S

    2008-01-01

    The success of any organism depends not only on niche adaptation but also the ability to survive environmental perturbation from homeostasis, a situation generically described as stress. Although species-specific mechanisms to combat "stress" have been described, the production of heat shock proteins (HSPs), such as HSP70, is universally described across all taxa. Members of the HSP70 gene family comprising the constitutive (HSC70) and inducible (HSP70) members, plus GRP78 (glucose-regulated protein, 78 kDa), a related HSP70 family member, were cloned using degenerate polymerase chain reaction (PCR) from two evolutionary divergent Antarctic marine molluscs (Laternula elliptica and Nacella concinna), a bivalve and a gastropod, respectively. The expression of the HSP70 family members was surveyed via quantitative PCR after an acute 2-h heat shock experiment. Both species demonstrated significant up-regulation of HSP70 gene expression in response to increased temperatures. However, the temperature level at which these responses were induced varied with the species (+6-8 degrees C for L. elliptica and +8-10 degrees C for N. concinna) compared to their natural environmental temperature). L. elliptica also showed tissue-specific expression of the genes under study. Previous work on Antarctic fish has shown that they lack the classical heat shock response, with the inducible form of HSP70 being permanently expressed with an expression not further induced under higher temperature regimes. This study shows that this is not the case for other Antarctic animals, with the two molluscs showing an inducible heat shock response, at a level probably set during their temperate evolutionary past.

  7. Nickel (II) nitrate hexahydrate triggered canine neutrophil extracellular traps release in vitro.

    PubMed

    Wei, Zhengkai; Zhang, Xu; Wang, Yanan; Wang, Jingjing; Fu, Yunhe; Yang, Zhengtao

    2018-05-30

    Nickel (II) nitrate hexahydrate (Ni) is a common heavy metal material in battery manufacturing, electroplating alloy parts and ceramic staining, therefore we frequently contact with Ni-related products in daily life. In this study, we aimed to investigate the effects of Ni on neutrophils extracellular traps (NETs) release by canine polymorphonuclear neutrophils (PMNs). The structure of Ni-induced NETs was observed by fluorescence confocal microscopy. Ni-triggered NETs release was quantified by Pico Green ® and fluorescence microplate reader. In addition, the inhibitors of NADPH oxidase, ERK1/2-, p38 - signaling pathways were used for preliminary inquiry into the potential mechanism of this process. The results showed that Ni markedly triggered the formation of NETs-like structures, and these structures were mainly consisted of DNA decorated with NE and MPO. Furthermore, quantification experiments showed that Ni significantly increased NETs formation compared to control groups. These results forcefully confirmed that nickel nitrate possesses the ability to induce NETs formation. However, inhibiting the NADPH oxidase, ERK1/2- and p38 MAPK-signaling pathways did not significantly change the quantitation of Ni-induced NETs release. To our knowledge, this study is the first report of Ni-triggered NETs release in vitro, which might provide an entirely new mechanism of several diseases and health issues induced by nickel overexposure. Copyright © 2018. Published by Elsevier Ltd.

  8. Temporal patterns of cardiac performance and genes encoding heat shock proteins and metabolic sensors of an intertidal limpet Cellana toreuma during sublethal heat stress.

    PubMed

    Zhang, Shu; Han, Guo-dong; Dong, Yun-wei

    2014-04-01

    Intertidal invertebrates develop effective physiological adaptations to cope with the rapidly changing thermal environment in the intertidal zone. In the present study, the temporal patterns of heart rate, protein carbonyl groups, and genes encoding heat shock proteins (hsp70 and hsp90) and metabolic sensors (ampkα, ampkβ and sirt1) were measured to study the effect of sublethal heat stress on the cardiac function, oxidative stress, heat shock response and cellular metabolism of an intertidal limpet Cellana toreuma. All the physiological parameters are sensitive to temperature and duration of heat stress. Spearman correlation analysis revealed that the correlations between heart rate and levels of heat shock proteins mRNA and metabolic sensors mRNA were statistically significant. These results further suggest that cardiac function plays crucial roles in cellular energy metabolism and heat shock responses. The significant increase of protein carbonyl groups at 34°C after 4h exposure indicated that the failure of cardiac function and the increase of anaerobic metabolism partly leads to the increase of protein carbonyl groups. Generally, the physiological responses to heat stress are sensitive to temperature and are energy-consumptive, as indicated by the upregulation of metabolic sensors mRNA. However, the upregulation of heat shock proteins and metabolic sensors at the post-transcriptional level and related functions need to be confirmed in further experiments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Mechanisms of HSP72 release.

    PubMed

    Asea, Alexzander

    2007-04-01

    Currently two mechanisms are recognized by which heat shock proteins (HSP) are released from cells; a passive release mechanism, including necrotic cell death, severe blunt trauma, surgery and following infection with lytic viruses, and an active release mechanism which involves the non classical protein release pathway. HSPs are released both as free HSP and within exosomes. This review covers recent findings on the mechanism by which stress induces the release of HSP72 into the circulation and the biological significance of circulating HSP72 to host defense against disease.

  10. Shock-darkening in ordinary chondrites: Determination of the pressure-temperature conditions by shock physics mesoscale modeling

    NASA Astrophysics Data System (ADS)

    Moreau, J.; Kohout, T.; Wünnemann, K.

    2017-11-01

    We determined the shock-darkening pressure range in ordinary chondrites using the iSALE shock physics code. We simulated planar shock waves on a mesoscale in a sample layer at different nominal pressures. Iron and troilite grains were resolved in a porous olivine matrix in the sample layer. We used equations of state (Tillotson EoS and ANEOS) and basic strength and thermal properties to describe the material phases. We used Lagrangian tracers to record the peak shock pressures in each material unit. The post-shock temperatures (and the fractions of the tracers experiencing temperatures above the melting point) for each material were estimated after the passage of the shock wave and after the reflections of the shock at grain boundaries in the heterogeneous materials. The results showed that shock-darkening, associated with troilite melt and the onset of olivine melt, happened between 40 and 50 GPa with 52 GPa being the pressure at which all tracers in the troilite material reach the melting point. We demonstrate the difficulties of shock heating in iron and also the importance of porosity. Material impedances, grain shapes, and the porosity models available in the iSALE code are discussed. We also discuss possible not-shock-related triggers for iron melt.

  11. Corequake and shock heating model of the 5 March 1979 gamma ray burst

    NASA Technical Reports Server (NTRS)

    Ellison, D. C.; Kazanas, D.

    1983-01-01

    Ramatry, et al. proposed a model to account for the 5 March 1979 gamma ray burst in terms of a neutron star corequake and subsequent shock heating of the neutron star atmosphere. This model is extended by examining the overall energetics and characteristics of these shocks, taking into account the e(+)-e(-) pair production behind the shock. The effects of a dipole magnetic field in the shock jump conditions are also examined and it is concluded that the uneven heating produced by such a field can account for the temperature difference between pole and equator implied by the pulsating phase of the burst. The overall energetics and distribution of energy between e(+)-(-) pairs and photons appears to be in agreement with observations if this event is at a distance of 55 kpc as implied by its association with the Large Magellanic Cloud.

  12. The 60 kDa heat shock proteins in the hyperthermophilic archaeon Sulfolobus shibatae.

    PubMed

    Kagawa, H K; Osipiuk, J; Maltsev, N; Overbeek, R; Quaite-Randall, E; Joachimiak, A; Trent, J D

    1995-11-10

    One of the most abundant proteins in the hyperthermophilic archaeon Sulfolobus shibatae is the 59 kDa heat shock protein (TF55) that is believed to form a homo-oligomeric double ring complex structurally similar to the bacterial chaperonins. We discovered a second protein subunit in the S. shibatae ring complex (referred to as alpha) that is stoichiometric with TF55 (renamed beta). The gene and flanking regions of alpha were cloned and sequenced and its inferred amino acid sequence has 54.4% identity and 74.4% similarity to beta. Transcription start sites for both alpha and beta were mapped and three potential transcription regulatory regions were identified. Northern analyses of cultures shifted from normal growth temperatures (70 to 75 degrees C) to heat shock temperatures (85 to 90 degrees C) indicated that the levels of alpha and beta mRNAs increased during heat shock, but at all temperatures their relative proportions remained constant. Monitoring protein synthesis by autoradiography of total proteins from cultures pulse labeled with L(-)[35S]methionine at normal and heat shock temperatures indicated significant increases in alpha and beta synthesis during heat shock. Under extreme heat shock conditions (> or = 90 degrees C) alpha and beta appeared to be the only two proteins synthesized. The purified alpha and beta subunits combined to form high molecular mass complexes with similar mobilities on native polyacrylamide gels to the complexes isolated directly from cells. Equal proportions of the two subunits gave the greatest yield of the complex, which we refer to as a "rosettasome". It is argued that the rosettasome consists of two homo-oligomeric rings; one of alpha and the other of beta. Polyclonal antibodies against alpha and beta from S. shibatae cross-reacted with proteins of similar molecular mass in 10 out of the 17 archaeal species tested, suggesting that the two rosettasome proteins are highly conserved among the archaea. The archaeal sequences were

  13. Wind Observations of Wave Heating and/or Particle Energization at Supercritical Interplanetary Shocks

    NASA Technical Reports Server (NTRS)

    Wilson, Lynn Bruce, III; Szabo, Adam; Koval, Andriy; Cattell, Cynthia A.; Kellogg, Paul J.; Goetz, Keith; Breneman, Aaron; Kersten, Kris; Kasper, Justin C.; Pulupa, Marc

    2011-01-01

    We present the first observations at supercritical interplanetary shocks of large amplitude (> 100 mV/m pk-pk) solitary waves, approx.30 mV/m pk-pk waves exhibiting characteristics consistent with electron Bernstein waves, and > 20 nT pk-pk electromagnetic lower hybrid-like waves, with simultaneous evidence for wave heating and particle energization. The solitary waves and the Bernstein-like waves were likely due to instabilities driven by the free energy provided by reflected ions [Wilson III et al., 2010]. They were associated with strong particle heating in both the electrons and ions. We also show a case example of parallel electron energization and perpendicular ion heating due to a electromagnetic lower hybrid-like wave. Both studies provide the first experimental evidence of wave heating and/or particle energization at interplanetary shocks. Our experimental results, together with the results of recent Vlasov [Petkaki and Freeman, 2008] and PIC [Matsukyo and Scholer, 2006] simulations using realistic mass ratios provide new evidence to suggest that the importance of wave-particle dissipation at shocks may be greater than previously thought.

  14. WATER LEVEL DRAWDOWN TRIGGERS SYSTEM-WIDE BUBBLE RELEASE FROM RESERVOIR SEDIMENTS

    EPA Science Inventory

    Reservoirs are an important anthropogenic source of methane and ebullition is a key pathway by which methane stored in reservoir sediments can be released to the atmosphere. Changes in hydrostatic pressure during periods of falling water levels can trigger bubbling events, sugge...

  15. Hierarchical functional specificity of cytosolic heat shock protein 70 (Hsp70) nucleotide exchange factors in yeast.

    PubMed

    Abrams, Jennifer L; Verghese, Jacob; Gibney, Patrick A; Morano, Kevin A

    2014-05-09

    Heat shock protein 70 (Hsp70) molecular chaperones play critical roles in protein homeostasis. In the budding yeast Saccharomyces cerevisiae, cytosolic Hsp70 interacts with up to three types of nucleotide exchange factors (NEFs) homologous to human counterparts: Sse1/Sse2 (Heat shock protein 110 (Hsp110)), Fes1 (HspBP1), and Snl1 (Bag-1). All three NEFs stimulate ADP release; however, it is unclear why multiple distinct families have been maintained throughout eukaryotic evolution. In this study we investigate NEF roles in Hsp70 cell biology using an isogenic combinatorial collection of NEF deletion mutants. Utilizing well characterized model substrates, we find that Sse1 participates in most Hsp70-mediated processes and is of particular importance in protein biogenesis and degradation, whereas Fes1 contributes to a minimal extent. Surprisingly, disaggregation and resolubilization of thermally denatured firefly luciferase occurred independently of NEF activity. Simultaneous deletion of SSE1 and FES1 resulted in constitutive activation of heat shock protein expression mediated by the transcription factor Hsf1, suggesting that these two factors are important for modulating stress response. Fes1 was found to interact in vivo preferentially with the Ssa family of cytosolic Hsp70 and not the co-translational Ssb homolog, consistent with the lack of cold sensitivity and protein biogenesis phenotypes for fes1Δ cells. No significant consequence could be attributed to deletion of the minor Hsp110 SSE2 or the Bag homolog SNL1. Together, these lines of investigation provide a comparative analysis of NEF function in yeast that implies Hsp110 is the principal NEF for cytosolic Hsp70, making it an ideal candidate for therapeutic intervention in human protein folding disorders.

  16. Regulation of protein turnover by heat shock proteins.

    PubMed

    Bozaykut, Perinur; Ozer, Nesrin Kartal; Karademir, Betul

    2014-12-01

    Protein turnover reflects the balance between synthesis and degradation of proteins, and it is a crucial process for the maintenance of the cellular protein pool. The folding of proteins, refolding of misfolded proteins, and also degradation of misfolded and damaged proteins are involved in the protein quality control (PQC) system. Correct protein folding and degradation are controlled by many different factors, one of the most important of which is the heat shock protein family. Heat shock proteins (HSPs) are in the class of molecular chaperones, which may prevent the inappropriate interaction of proteins and induce correct folding. On the other hand, these proteins play significant roles in the degradation pathways, including endoplasmic reticulum-associated degradation (ERAD), the ubiquitin-proteasome system, and autophagy. This review focuses on the emerging role of HSPs in the regulation of protein turnover; the effects of HSPs on the degradation machineries ERAD, autophagy, and proteasome; as well as the role of posttranslational modifications in the PQC system. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Effects of heat shocks on microbial community structure and microbial activity of a methanogenic enrichment degrading benzoate.

    PubMed

    Mei, R; Narihiro, T; Nobu, M K; Liu, W-T

    2016-11-01

    In anaerobic digesters, temperature fluctuation could lead to process instability and failure. It is still not well understood how digester microbiota as a whole respond to heat shock, and what specific organisms are vulnerable to perturbation or responsible for process recovery after perturbation. To address these questions, a mesophilic benzoate-degrading methanogenic culture enriched from digester was subjected to different levels of heat shock. Three types of methane production profiles after perturbation were observed in comparison to the control: uninhibited, inhibited with later recovery, and inhibited without recovery. These responses were correlated with the microbial community compositions based on the analyses of 16S rRNA and 16S rRNA gene. Specifically, the primary benzoate-degrading syntroph was highly affected by heat shock, and its abundance and activity were both crucial to the restoration of benzoate degradation after heat shock. In contrast, methanogens were stable regardless whether methane production was inhibited. Populations related to 'Candidatus Cloacimonetes' and Firmicutes showed stimulated growth. These observations indicated distinct physiological traits and ecological niches associated with individual microbial groups. The results obtained after exposure to heat shock can be critical to more comprehensive characterization of digester ecology under perturbations. Anaerobic digestion is an essential step in municipal wastewater treatment owing to its striking capacity of reducing wasted sludge and recovering energy. However, as an elaborate microbial process, it requires constant temperature control and is sensitive to heat shock. In this study, we explored the microbial response to heat shock of a methanogenic culture enriched from anaerobic digester sludge. Microorganisms that were vulnerable to perturbation or responsible for process recovery after perturbation were identified. © 2016 The Society for Applied Microbiology.

  18. Al 1s-2p Absorption Spectroscopy of Shock-Wave Heating and Compression in Laser-Driven Planar Foil

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

    Sawada, H.; Regan, S.P.; Radha, P.B.

    Time-resolved Al 1s-2p absorption spectroscopy is used to diagnose direct-drive, shock-wave heating and compression of planar targets having nearly Fermi-degenerate plasma conditions (Te ~ 10–40 eV, rho ~ 3–11 g/cm^3) on the OMEGA Laser System [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. A planar plastic foil with a buried Al tracer layer was irradiated with peak intensities of 10^14–10^15 W/cm^2 and probed with the pseudocontinuum M-band emission from a point-source Sm backlighter in the range of 1.4–1.7 keV. The laser ablation process launches 10–70 Mbar shock waves into the CH/Al/CH target. The Al 1s-2p absorption spectra weremore » analyzed using the atomic physic code PRISMSPECT to infer Te and rho in the Al layer, assuming uniform plasma conditions during shock-wave heating, and to determine when the heat front penetrated the Al layer. The drive foils were simulated with the one-dimensional hydrodynamics code LILAC using a flux-limited (f =0.06 and f =0.1) and nonlocal thermal-transport model [V. N. Goncharov et al., Phys. Plasmas 13, 012702 (2006)]. The predictions of simulated shock-wave heating and the timing of heat-front penetration are compared to the observations. The experimental results for a wide variety of laser-drive conditions and buried depths have shown that the LILAC predictions using f = 0.06 and the nonlocal model accurately model the shock-wave heating and timing of the heat-front penetration while the shock is transiting the target. The observed discrepancy between the measured and simulated shock-wave heating at late times of the drive can be explained by the reduced radiative heating due to lateral heat flow in the corona.« less

  19. Heat shock protein 70 as a biomarker of heat stress in a simulated hot cockpit.

    PubMed

    Kumar, Yadunanda; Chawla, Anuj; Tatu, Utpal

    2003-07-01

    Fighter pilots are frequently exposed to high temperatures during high-speed low-level flight. Heat strain can result in temporary impairment of cognitive functions and when severe, loss of consciousness and consequent loss of life and equipment. Induction of stress proteins is a highly conserved stress response mechanism from bacteria to humans. Induced stress protein levels are known to be cytoprotective and have been correlated with stress tolerance. Although many studies on the heat shock response mechanisms have been performed in cell culture and animal model systems, there is very limited information on stress protein induction in human subjects. Heat shock proteins (Hsp), especially Hsp70, may be induced in human subjects exposed to high temperatures in a hot cockpit designed to simulate heat stress experienced in low flying sorties. Six healthy volunteers were subjected to heat stress at 55 degrees C in a high temperature cockpit simulator for a period of 1 h at 30% humidity. Physiological parameters such as oral and skin temperatures, heart rate, and sweat rate were monitored regularly during this time. The level of Hsp70 in leukocytes was examined before and after the heat exposure in each subject. Hsp70 was found to be significantly induced in all the six subjects exposed to heat stress. The level of induced Hsp70 appears to correlate with other strain indicators such as accumulative circulatory strain and Craig's modified index. The usefulness of Hsp70 as a molecular marker of heat stress in humans is discussed.

  20. Dietary Nutrients and Bioactive Substances Modulate Heat Shock Protein (HSP) Expression: A Review.

    PubMed

    Moura, Carolina Soares; Lollo, Pablo Christiano Barboza; Morato, Priscila Neder; Amaya-Farfan, Jaime

    2018-05-28

    Interest in the heat shock proteins (HSPs), as a natural physiological toolkit of living organisms, has ranged from their chaperone function in nascent proteins to the remedial role following cell stress. As part of the defence system, HSPs guarantee cell tolerance against a variety of stressors, including exercise, oxidative stress, hyper and hypothermia, hyper and hypoxia and improper diets. For the past couple of decades, research on functional foods has revealed a number of substances likely to trigger cell protection through mechanisms that involve the induction of HSP expression. This review will summarize the occurrence of the most easily inducible HSPs and describe the effects of dietary proteins, peptides, amino acids, probiotics, high-fat diets and other food-derived substances reported to induce HSP response in animals and humans studies. Future research may clarify the mechanisms and explore the usefulness of this natural alternative of defense and the modulating mechanism of each substance.

  1. [Triptolide reverses apatinib resistance in gastric cancer cell line MKN45 via inhibition of heat shock protein 70].

    PubMed

    Teng, F; Xu, Z Y; Lyu, H; Wang, Y P; Wang, L J; Huang, T; Sun, J C; Zhu, H T; Ni, Y X; Cheng, X D

    2018-02-23

    Objective: To investigate the effect of triptolide, a specific inhibitor of heat shock protein 70 (HSP70), on apatinib resistance in gastric cancer cells line MKN45. Methods: The apatinib-resistant cells (MKN45/AR) and MKN45 parental cells were treated with apatinib, triptolide and apatinib combined with triptolide, respectively. CCK-8 assay was performed to determine the half maximal inhibitory concentration (IC(50)) of MKN45/AR and MKN45 cells in the presence of different treatment. The mRNA expression of heat shock protein gene (HSPA1A and HSPA1B) was detected by RT-PCR, while the protein expression of heat shock protein 70 was analyzed using Western blot in MKN45/AR and MKN45 cells. Results: The IC(50) values of apatinib-sensitive and apatinib-resistant MKN45 cells were 10.411 μmol/L and 70.527 μmol/L, respectively, showing a significant difference ( P <0.05). The mRNA expression of HSPA1A and HSPA1B in MKN45/AR cells was significantly higher than that in MKN45 cells ( P <0.001). The protein expression of heat shock protein 70 was significantly decreased after 0.25 μmol/L triptolide treatment in MKN45/AR cells ( P <0.01). When heat shock protein 70 was inhibited by triptolide, the IC(50) value of apatinib in MKN45/AR cells was reduced to 11.679 μmol/L, which was significantly lower than cells treated with apatinib alone ( P <0.05). Conclusions: The apatinib-resistant MKN45 cells have high levels of heat shock protein 70. Low doses of triptolide can significantly inhibit heat shock protein 70, leading to reverse the resistance phenotype of MKN45/AR cells. Therefore, inhibition of heat shock protein 70 provides a new therapy strategy for patients with apatinib resistance.

  2. Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.

    PubMed

    Zhang, Lingling; Hou, Rui; Su, Hailin; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2012-01-01

    Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes.

  3. Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: increased HSP70-glucocorticoid receptor heterocomplex.

    PubMed

    Bei, E S; Salpeas, V; Alevizos, B; Anagnostara, C; Pappa, D; Moutsatsou, P

    2013-11-01

    Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p < 0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p ≤ 0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis. Copyright © 2013. Published by Elsevier Ltd.

  4. Photolysis of Caged Ca2+ But Not Receptor-Mediated Ca2+ Signaling Triggers Astrocytic Glutamate Release

    PubMed Central

    Smith, Nathan A.; Xu, Qiwu; Goldman, Siri; Peng, Weiguo; Huang, Jason H.; Takano, Takahiro; Nedergaard, Maiken

    2013-01-01

    Astrocytes in hippocampal slices can dynamically regulate synaptic transmission in a process mediated by increases in intracellular Ca2+. However, it is debated whether astrocytic Ca2+ signals result in release of glutamate. We here compared astrocytic Ca2+ signaling triggered by agonist exposure versus photolysis side by side. Using transgenic mice in which astrocytes selectively express the MrgA1 receptor, we found that receptor-mediated astrocytic Ca2+ signaling consistently triggered neuronal hyperpolarization and decreased the frequency of miniature excitatory postsynaptic currents (EPSCs). In contrast, photolysis of caged Ca2+ (o-nitrophenyl–EGTA) in astrocytes led to neuronal depolarization and increased the frequency of mEPSCs through a metabotropic glutamate receptor-mediated pathway. Analysis of transgenic mice in which astrocytic vesicular release is suppressed (dominant-negative SNARE mice) and pharmacological manipulations suggested that glutamate is primarily released by opening of anion channels rather than exocytosis. Combined, these studies show that photolysis but not by agonists induced astrocytic Ca2+ signaling triggers glutamate release. PMID:24174673

  5. Mechanistic Studies on the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9

    PubMed Central

    Elegbede, Adekunle I.; Banerjee, Jayati; Hanson, Andrea J.; Tobwala, Shakila; Ganguli, Bratati; Wang, Rongying; Lu, Xiaoning; Srivastava, D. K.; Mallik, Sanku

    2009-01-01

    Matrix metalloproteinases (MMPs) are a class of extracellular matrix degrading enzymes over-expressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report our results on the mechanistic studies of the MMP-9 triggered release of the liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing Circular Dichroism spectroscopy, we demonstrate that the lipopeptides, when incorporated in liposomes, are de-mixed in the lipid bilayers and generate triple helical structures. MMP-9 cleaves the triple helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple helical peptides, failed to release the contents from the liposomes. We also observed that the rate and the extent of release of the liposomal contents depend on the mismatch between acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. Circular Dichroism spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides. PMID:18642903

  6. Glutamine's protection against cellular injury is dependent on heat shock factor-1.

    PubMed

    Morrison, Angela L; Dinges, Martin; Singleton, Kristen D; Odoms, Kelli; Wong, Hector R; Wischmeyer, Paul E

    2006-06-01

    Glutamine (GLN) has been shown to protect cells, tissues, and whole organisms from stress and injury. Enhanced expression of heat shock protein (HSP) has been hypothesized to be responsible for this protection. To date, there are no clear mechanistic data confirming this relationship. This study tested the hypothesis that GLN-mediated activation of the HSP pathway via heat shock factor-1 (HSF-1) is responsible for cellular protection. Wild-type HSF-1 (HSF-1(+/+)) and knockout (HSF-1(-/-)) mouse fibroblasts were used in all experiments. Cells were treated with GLN concentrations ranging from 0 to 16 mM and exposed to heat stress injury in a concurrent treatment model. Cell viability was assayed with phenazine methosulfate plus tetrazolium salt, HSP-70, HSP-25, and nuclear HSF-1 expression via Western blot analysis, and HSF-1/heat shock element (HSE) binding via EMSA. GLN significantly attenuated heat-stress induced cell death in HSF-1(+/+) cells in a dose-dependent manner; however, the survival benefit of GLN was lost in HSF-1(-/-) cells. GLN led to a dose-dependent increase in HSP-70 and HSP-25 expression after heat stress. No inducible HSP expression was observed in HSF-1(-/-) cells. GLN increased unphosphorylated HSF-1 in the nucleus before heat stress. This was accompanied by a GLN-mediated increase in HSF-1/HSE binding and nuclear content of phosphorylated HSF-1 after heat stress. This is the first demonstration that GLN-mediated cellular protection after heat-stress injury is related to HSF-1 expression and cellular capacity to activate an HSP response. Furthermore, the mechanism of GLN-mediated protection against injury appears to involve an increase in nuclear HSF-1 content before stress and increased HSF-1 promoter binding and phosphorylation.

  7. Lipoic Acid Exerts Antioxidant and Anti-inflammatory Effects in Response to Heat Shock in C2C12 Myotubes.

    PubMed

    Lee, Cheng-Tse; Chang, Li-Ching; Wu, Pei-Fung

    2016-06-01

    This study explored that lipoic acid treatment for 24 h significantly upregulated and promoted heat shock-induced catalase expression and downregulated GPx1 messenger RNA (mRNA) expression, indicating that lipoic acid exhibits antioxidant activity in the decomposition of hydrogen peroxide by upregulating catalase expression. Moreover, lipoic acid treatment for 3 h increased and promoted heat shock-induced interleukin (IL)-6 mRNA and protein levels and that for 24 h downregulated IL-6 mRNA expression, suggesting a dual effect of lipoic acid on IL-6 regulation. Lipoic acid alone failed to increase or reduce tumor necrosis factor (TNF)-α mRNA and protein levels, whereas heat shock alone downregulated TNF-α mRNA and protein expression. These data suggest that lipoic acid does not have a proinflammatory role and that heat shock acts as an anti-inflammatory agent by downregulating TNF-α expression in C2C12 myotubes. Moreover, lipoic acid or heat shock alone upregulated the IL-6 receptor (IL-6R-α) and glycoprotein 130 (gp130) mRNA expression followed by IL-6 expression; these data indicate that the regulation of lipoic acid or heat shock is mediated by IL-6R signaling, thus suggesting that C2C12 myotubes possesses a mechanism for regulating IL-6R and gp130 expression following lipoic acid treatment or heat shock.

  8. Laser-triggered release of encapsulated molecules from polylactic-co-glycolic acid microcapsules

    NASA Astrophysics Data System (ADS)

    Ariyasu, Kazumasa; Ishii, Atsuhiro; Umemoto, Taiga; Terakawa, Mitsuhiro

    2016-08-01

    The controlled release of encapsulated molecules from a microcapsule is a promising method of targeted drug delivery. Laser-triggered methods for the release of encapsulated molecules have the advantage of spatial and temporal controllability. In this study, we demonstrated the release of encapsulated molecules from biodegradable polymer-based microcapsules using near-infrared femtosecond laser pulses. The polylactic-co-glycolic acid microcapsules encapsulating fluorescein isothiocyanate-dextran molecules were fabricated using a dual-coaxial nozzle system. Irradiation of femtosecond laser pulses enhanced the release of the molecules from the microcapsules, which was accompanied by a decrease in the residual ratio of the microcapsules. The laser-induced modification of the surface of the shell of the microcapsules indicated the potential for sustained release as well as burst release.

  9. Modification of embryonic resistance to heat shock in cattle by melatonin and genetic variation in HSPA1L.

    PubMed

    Ortega, M Sofia; Rocha-Frigoni, Nathália A S; Mingoti, Gisele Zoccal; Roth, Zvi; Hansen, Peter J

    2016-11-01

    The objectives were to test whether (1) melatonin blocks inhibition of embryonic development caused by heat shock at the zygote stage, and (2) the frequency of a thermoprotective allele for HSPA1L is increased in blastocysts formed from heat-shocked zygotes as compared with blastocysts from control zygotes. It was hypothesized that melatonin prevents effects of heat shock on development by reducing accumulation of reactive oxygen species (ROS) and that embryos inheriting the thermoprotective allele of HSPA1L would be more likely to survive heat shock. Effects of 1 µM melatonin on ROS were determined in experiments 1 and 2. Zygotes were cultured at 38.5 or 40°C for 3 h in the presence of CellROX reagent (ThermoFisher Scientific, Waltham, MA). Culture was in a low [5% (vol/vol)] oxygen (experiment 1) or low or high [21% (vol/vol)] oxygen environment (experiment 2). Heat shock and high oxygen increased ROS; melatonin decreased ROS. Development was assessed in experiments 3 and 4. In experiment 3, zygotes were cultured in low oxygen ± 1 µM melatonin and exposed to 38.5 or 40°C for 12 h (experiment 1) beginning 8 h after fertilization. Melatonin did not protect the embryo from heat shock. Experiment 4 was performed similarly except that temperature treatments (38.5 or 40°C, 24 h) were performed in a low or high oxygen environment (2×2 × 2 factorial design with temperature, melatonin, and oxygen concentration as main effects), and blastocysts were genotyped for a deletion (D) mutation (C→D) in the promoter region of HSPA1L associated with thermotolerance. Heat shock decreased percent of zygotes developing to the blastocyst stage independent of melatonin or oxygen concentration. Frequency of genotypes for HSPA1L was affected by oxygen concentration and temperature, with an increase in the D allele for blastocysts that developed in high oxygen and following heat shock. It was concluded that (1) lack of effect of melatonin or oxygen concentration on embryonic

  10. Genomic Heat Shock Element Sequences Drive Cooperative Human Heat Shock Factor 1 DNA Binding and Selectivity*

    PubMed Central

    Jaeger, Alex M.; Makley, Leah N.; Gestwicki, Jason E.; Thiele, Dennis J.

    2014-01-01

    The heat shock transcription factor 1 (HSF1) activates expression of a variety of genes involved in cell survival, including protein chaperones, the protein degradation machinery, anti-apoptotic proteins, and transcription factors. Although HSF1 activation has been linked to amelioration of neurodegenerative disease, cancer cells exhibit a dependence on HSF1 for survival. Indeed, HSF1 drives a program of gene expression in cancer cells that is distinct from that activated in response to proteotoxic stress, and HSF1 DNA binding activity is elevated in cycling cells as compared with arrested cells. Active HSF1 homotrimerizes and binds to a DNA sequence consisting of inverted repeats of the pentameric sequence nGAAn, known as heat shock elements (HSEs). Recent comprehensive ChIP-seq experiments demonstrated that the architecture of HSEs is very diverse in the human genome, with deviations from the consensus sequence in the spacing, orientation, and extent of HSE repeats that could influence HSF1 DNA binding efficacy and the kinetics and magnitude of target gene expression. To understand the mechanisms that dictate binding specificity, HSF1 was purified as either a monomer or trimer and used to evaluate DNA-binding site preferences in vitro using fluorescence polarization and thermal denaturation profiling. These results were compared with quantitative chromatin immunoprecipitation assays in vivo. We demonstrate a role for specific orientations of extended HSE sequences in driving preferential HSF1 DNA binding to target loci in vivo. These studies provide a biochemical basis for understanding differential HSF1 target gene recognition and transcription in neurodegenerative disease and in cancer. PMID:25204655

  11. DNA transformation via local heat shock

    NASA Astrophysics Data System (ADS)

    Li, Sha; Meadow Anderson, L.; Yang, Jui-Ming; Lin, Liwei; Yang, Haw

    2007-07-01

    This work describes transformation of foreign DNA into bacterial host cells by local heat shock using a microfluidic system with on-chip, built-in platinum heaters. Plasmid DNA encoding ampicillin resistance and a fluorescent protein can be effectively transformed into the DH5α chemically competent E. coli using this device. Results further demonstrate that only one-thousandth of volume is required to obtain transformation efficiencies as good as or better than conventional practices. As such, this work complements other lab-on-a-chip technologies for potential gene cloning/therapy and protein expression applications.

  12. EFFECTS OF HEAT AND BROMOCHLOROACETIC ACID ON MALE REPRODUCTION IN HEAT SHOCK FACTOR-1 GENE KNOCKOUT MICE

    EPA Science Inventory

    Effects of heat and bromochloroacetic acid on male reproduction in heat shock factor-1 gene knockout mice.
    Luft JC1, IJ Benjamin2, JB Garges1 and DJ Dix1. 1Reproductive Toxicology Division, USEPA, RTP, NC, 27711 and 2Dept of Internal Medicine, Univ.of Texas Southwestern Med C...

  13. Focal gene misexpression in zebrafish embryos induced by local heat shock using a modified soldering iron.

    PubMed

    Hardy, Melissa E; Ross, Louis V; Chien, Chi-Bin

    2007-11-01

    Misexpression of genes in a temporally and spatially controlled fashion is an important tool for assessing gene function during development. Because few tissue-specific promoters have been identified in zebrafish, inducible systems such as the Cre/LoxP and Tet repressor systems are of limited utility. Here we describe a new method of misexpression: local heat shock using a modified soldering iron. Zebrafish carrying transgenes under the control of a heat shock promoter (hsp70) are focally heated with the soldering iron to induce gene expression in a small area of the embryo. We have validated this method in three stable transgenic lines and at three developmental timepoints. Local heat shock is a fast, easy, and inexpensive method for gene misexpression. Copyright 2007 Wiley-Liss, Inc.

  14. Asymmetric shock heating and the terrestrial magma ocean origin of the Moon.

    PubMed

    Karato, Shun-ichiro

    2014-01-01

    One of the difficulties of the current giant impact model for the origin of the Moon is to explain the marked similarity in the isotopic compositions and the substantial differences in the major element chemistry. Physics of shock heating is analyzed to show that the degree of heating is asymmetric between the impactor and the target, if the target (the proto-Earth) had a magma-ocean but the impactor did not. The magma ocean is heated much more than the solid impactor and the vapor-rich jets come mainly from the magma-ocean from which the Moon might have been formed. In this scenario, the similarity and differences in the composition between the Moon and Earth would be explained as a natural consequence of a collision in the later stage of planetary formation. Including the asymmetry in shock heating is the first step toward explaining the chemical composition of the Moon.

  15. Genetic variation in heat shock protein 70 is associated with septic shock: narrowing the association to a specific haplotype.

    PubMed

    Kee, C; Cheong, K Y; Pham, K; Waterer, G W; Temple, S E L

    2008-12-01

    Heat shock protein 70 (HSP70) plays a major role in immune responses. Polymorphisms within the gene have been associated with development of septic shock. This study refines the region of the HSP70 gene associated with development of septic shock and confirms its functionality. Subjects (n = 31) were grouped into one of three haplotypes based on their HSPA1B-179C>T and HSPA1B1267A>G genotypes. Mononuclear cells from these subjects were stimulated with heat-killed bacteria (10(7 )colony-forming units/mL Escherichia coli or Streptococcus pneumoniae) for 8 and 21 h. HSP70 and tumour necrosis factor (TNF) mRNA and protein levels were measured by reverse transcriptase-polymerase chain reaction and ELISA, respectively. The HSPA1B-179*C:1267*A haplotype was associated with significantly lower levels of HSPA1B mRNA and protein and higher production of TNF mRNA and protein compared to the other haplotypes. Induction of HSP70 was TNF independent. These results suggest that the HSPA1B-179C>T:1267A>G haplotype is functional and may explain the association of the HSP70 gene with development of septic shock.

  16. Recruitment of phosphorylated small heat shock protein Hsp27 to nuclear speckles without stress

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

    Bryantsev, A.L.; Chechenova, M.B.; Shelden, E.A.

    During stress, the mammalian small heat shock protein Hsp27 enters cell nuclei. The present study examines the requirements for entry of Hsp27 into nuclei of normal rat kidney (NRK) renal epithelial cells, and for its interactions with specific nuclear structures. We find that phosphorylation of Hsp27 is necessary for the efficient entry into nuclei during heat shock but not sufficient for efficient nuclear entry under control conditions. We further report that Hsp27 is recruited to an RNAse sensitive fraction of SC35 positive nuclear speckles, but not other intranuclear structures, in response to heat shock. Intriguingly, Hsp27 phosphorylation, in the absencemore » of stress, is sufficient for recruitment to speckles found in post-anaphase stage mitotic cells. Additionally, pseudophosphorylated Hsp27 fused to a nuclear localization peptide (NLS) is recruited to nuclear speckles in unstressed interphase cells, but wildtype and nonphosphorylatable Hsp27 NLS fusion proteins are not. The expression of NLS-Hsp27 mutants does not enhance colony forming abilities of cells subjected to severe heat shock, but does regulate nuclear speckle morphology. These data demonstrate that phosphorylation, but not stress, mediates Hsp27 recruitment to an RNAse soluble fraction of nuclear speckles and support a site-specific role for Hsp27 within the nucleus.« less

  17. Hydrodynamic modelling of accretion impacts in classical T Tauri stars: radiative heating of the pre-shock plasma

    NASA Astrophysics Data System (ADS)

    Costa, G.; Orlando, S.; Peres, G.; Argiroffi, C.; Bonito, R.

    2017-01-01

    Context. It is generally accepted that, in classical T Tauri stars, the plasma from the circumstellar disc accretes onto the stellar surface with free-fall velocity and the impact generates a shock. The impact region is expected to contribute to emission in different spectral bands; many studies have confirmed that the X-rays arise from the post-shock plasma but, otherwise, there are no studies in the literature investigating the origin of the observed UV emission which is apparently correlated to accretion. Aims: We investigated the effect of radiative heating of the infalling material by the post-shock plasma at the base of the accretion stream, with the aim to identify in which region a significant part of the UV emission originates. Methods: We developed a one-dimensional hydrodynamic model describing the impact of an accretion stream onto the stellar surface; the model takes into account the gravity, the radiative cooling of an optically thin plasma, the thermal conduction, and the heating due to absorption of X-ray radiation. The latter term represents the heating of the infalling plasma due to the absorption of X-rays emitted from the post-shock region. Results: We found that the radiative heating of the pre-shock plasma plays a non-negligible role in the accretion phenomenon. In particular, the dense and cold plasma of the pre-shock accretion column is gradually heated up to a few 105K due to irradiation of X-rays arising from the shocked plasma at the impact region. This heating mechanism does not affect significantly the dynamics of the post-shock plasma. On the other hand, a region of radiatively heated gas (that we consider a precursor) forms in the unshocked accretion column and contributes significantly to UV emission. Our model naturally reproduces the luminosity of UV emission lines correlated to accretion and shows that most of the UV emission originates from the precursor.

  18. Electron Heating in Low Mach Number Perpendicular Shocks. II. Dependence on the Pre-shock Conditions

    NASA Astrophysics Data System (ADS)

    Guo, Xinyi; Sironi, Lorenzo; Narayan, Ramesh

    2018-05-01

    Recent X-ray observations of merger shocks in galaxy clusters have shown that the post-shock plasma is two-temperature, with the protons being hotter than the electrons. In this work, the second of a series, we investigate the efficiency of irreversible electron heating in perpendicular low Mach number shocks, by means of two-dimensional particle-in-cell simulations. We consider values of plasma beta (the ratio of thermal and magnetic pressures) in the range 4 ≲ β p0 ≲ 32, and sonic Mach number (the ratio of shock speed to pre-shock sound speed) in the range 2 ≲ M s ≲ 5, as appropriate for galaxy cluster shocks. As shown in Paper I, magnetic field amplification—induced by shock compression of the pre-shock field, or by strong proton cyclotron and mirror modes accompanying the relaxation of proton temperature anisotropy—can drive the electron temperature anisotropy beyond the threshold of the electron whistler instability. The growth of whistler waves breaks the electron adiabatic invariance, and allows for efficient entropy production. We find that the post-shock electron temperature T e2 exceeds the adiabatic expectation {T}e2,{ad} by an amount ({T}e2-{T}e2,{ad})/{T}e0≃ 0.044 {M}s({M}s-1) (here, T e0 is the pre-shock temperature), which depends only weakly on the plasma beta over the range 4 ≲ β p0 ≲ 32 that we have explored, as well as on the proton-to-electron mass ratio (the coefficient of ≃0.044 is measured for our fiducial {m}i/{m}e=49, and we estimate that it will decrease to ≃0.03 for the realistic mass ratio). Our results have important implications for current and future observations of galaxy cluster shocks in the radio band (synchrotron emission and Sunyaev–Zel’dovich effect) and at X-ray frequencies.

  19. Low-dose chemotherapy of hepatocellular carcinoma through triggered-release from bilayer-decorated magnetoliposomes.

    PubMed

    Chen, Yanjing; Chen, Yuan; Xiao, Da; Bose, Arijit; Deng, Ruitang; Bothun, Geoffrey D

    2014-04-01

    Low-dose (LD) chemotherapy is a promising treatment strategy that may be improved by controlled delivery. Polyethylene glycol-stabilized bilayer-decorated magnetoliposomes (dMLs) have been designed as a stimuli-responsive LD chemotherapy drug delivery system and tested in vitro using Huh-7 hepatocellular carcinoma cell line. The dMLs contained hydrophobic superparamagnetic iron oxide nanoparticles within the lipid bilayer and doxorubicin hydrochloride (DOX, 2 μM) within the aqueous core. Structural analysis by cryogenic transmission electron microscopy and dynamic light scattering showed that the assemblies were approximately 120 nm in diameter. Furthermore, the samples consisted of a mixture of dMLs and bare liposomes (no nanoparticles), which provided dual burst and spontaneous DOX release profiles, respectively. Cell viability results show that the cytotoxicity of DOX-loaded dMLs was similar to that of bare dMLs (∼10%), which indicates that spontaneous DOX leakage had little cytotoxic effect. However, when subjected to a physiologically acceptable radiofrequency (RF) electromagnetic field, cell viability was reduced up to 40% after 8h and significant cell death (>90%) was observed after 24h. The therapeutic mechanism was intracellular RF-triggered DOX release from the dMLs and not intracellular hyperthermia due to nanoparticle heating via magnetic losses. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Low-Dose Chemotherapy of Hepatocellular Carcinoma through Triggered-Release from Bilayer-Decorated Magnetoliposomes

    PubMed Central

    Chen, Yanjing; Chen, Yuan; Xiao, Da; Bose, Arijit; Deng, Ruitang; Bothun, Geoffrey D.

    2014-01-01

    Low-dose (LD) chemotherapy is a promising treatment strategy that may be improved by controlled delivery. Polyethylene glycol-stabilized bilayer-decorated magnetoliposomes (dMLs) have been designed as a stimuli-responsive LD chemotherapy drug delivery system and tested in vitro using Huh-7 hepatocellular carcinoma cell line. The dMLs contained hydrophobic superparamagnetic iron oxide nanoparticles within the lipid bilayer and doxorubicin hydrochloride (DOX, 2 µM) within the aqueous core. Structural analysis by cryogenic transmission electron microscopy and dynamic light scattering showed that the assemblies were approximately 120 nm in diameter. Furthermore, the samples consisted of a mixture of dMLs and bare liposomes (no nanoparticles), which provided dual burst and spontaneous DOX release profiles, respectively. Cell viability results show that the cytotoxicity of DOX-loaded dMLs was similar to that of bare dMLs (~10%), which indicates that spontaneous DOX leakage had little cytotoxic effect. However, when subjected to a physiologically acceptable radiofrequency (RF) electromagnetic field, cell viability was reduced up to 40% after 8 h and complete cell death was observed after 24 h. The therapeutic mechanism was intracellular RF-triggered DOX release from the dMLs and not intracellular hyperthermia due to nanoparticle heating via magnetic losses. PMID:24549047

  1. Cooption of heat shock regulatory system for anhydrobiosis in the sleeping chironomid Polypedilum vanderplanki

    PubMed Central

    Shagimardanova, Elena; Kozlova, Olga; Cherkasov, Alexander; Sutormin, Roman; Stepanova, Vita V.; Stupnikov, Alexey; Logacheva, Maria; Penin, Aleksey; Sogame, Yoichiro; Cornette, Richard; Tokumoto, Shoko; Miyata, Yugo; Gelfand, Mikhail S.; Gusev, Oleg

    2018-01-01

    Polypedilum vanderplanki is a striking and unique example of an insect that can survive almost complete desiccation. Its genome and a set of dehydration–rehydration transcriptomes, together with the genome of Polypedilum nubifer (a congeneric desiccation-sensitive midge), were recently released. Here, using published and newly generated datasets reflecting detailed transcriptome changes during anhydrobiosis, as well as a developmental series, we show that the TCTAGAA DNA motif, which closely resembles the binding motif of the Drosophila melanogaster heat shock transcription activator (Hsf), is significantly enriched in the promoter regions of desiccation-induced genes in P. vanderplanki, such as genes encoding late embryogenesis abundant (LEA) proteins, thioredoxins, or trehalose metabolism-related genes, but not in P. nubifer. Unlike P. nubifer, P. vanderplanki has double TCTAGAA sites upstream of the Hsf gene itself, which is probably responsible for the stronger activation of Hsf in P. vanderplanki during desiccation compared with P. nubifer. To confirm the role of Hsf in desiccation-induced gene activation, we used the Pv11 cell line, derived from P. vanderplanki embryo. After preincubation with trehalose, Pv11 cells can enter anhydrobiosis and survive desiccation. We showed that Hsf knockdown suppresses trehalose-induced activation of multiple predicted Hsf targets (including P. vanderplanki-specific LEA protein genes) and reduces the desiccation survival rate of Pv11 cells fivefold. Thus, cooption of the heat shock regulatory system has been an important evolutionary mechanism for adaptation to desiccation in P. vanderplanki. PMID:29463761

  2. Shock Heating of the Merging Galaxy Cluster A521

    NASA Technical Reports Server (NTRS)

    Bourdin, H.; Mazzotta, P.; Markevitch, M.; Giacintucci, S.; Brunetti, G.

    2013-01-01

    A521 is an interacting galaxy cluster located at z = 0.247, hosting a low-frequency radio halo connected to an eastern radio relic. Previous Chandra observations hinted at the presence of an X-ray brightness edge at the position of the relic, which may be a shock front. We analyze a deep observation of A521 recently performed with XMM-Newton in order to probe the cluster structure up to the outermost regions covered by the radio emission. The cluster atmosphere exhibits various brightness and temperature anisotropies. In particular, two cluster cores appear to be separated by two cold fronts. We find two shock fronts, one that was suggested by Chandra and that is propagating to the east, and another to the southwestern cluster outskirt. The two main interacting clusters appear to be separated by a shock-heated region, which exhibits a spatial correlation with the radio halo. The outer edge of the radio relic coincides spatially with a shock front, suggesting that this shock is responsible for the generation of cosmic-ray electrons in the relic. The propagation direction and Mach number of the shock front derived from the gas density jump, M = 2.4 +/- 0.2, are consistent with expectations from the radio spectral index, under the assumption of Fermi I acceleration mechanism.

  3. Heat Shock Partially Dissociates the Overlapping Modules of the Yeast Protein-Protein Interaction Network: A Systems Level Model of Adaptation

    PubMed Central

    Mihalik, Ágoston; Csermely, Peter

    2011-01-01

    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

  4. Heat release effects in a turbulent, reacting shear layer

    NASA Astrophysics Data System (ADS)

    Hermanson, James Carl

    The effects of heat release were studied in a planar, gaseous reacting mixing layer formed between free streams containing hydrogen and fluorine in inert diluents. Sufficiently high concentrations of reactants were employed to produce adiabatic flame temperature rises of up to 940 K (1240 K absolute). The Reynolds number at the measuring station, based on velocity difference, 1% temperature thickness and cold kinematic viscosity was approximately 6x10^4. The temperature field was measured with cold wire resistance thermometers and thermocouples. Flow visualization was accomplished by schlieren spark and motion picture photography. Mean velocity information was extracted from mean pitot probe dynamic pressure measurements.Though the displacement thickness of the layer, for zero streamwise pressure gradient, increased with increasing heat release, the actual growth rate of the layer did not increase, but instead decreased slightly. The overall entrainment into the layer was seen to be substantially reduced as a consequence of heat release. Calculations showed that the decrease in layer growth rate can be accounted for by a corresponding reduction in turbulent shear stress.The mean temperature rise profiles, normalized by the adiabatic flame temperature rise, were not greatly changed in shape by heat release. A small decrease in normalized mean temperature rise with heat release was observed. Large scale coherent structures were observed to persist at all levels of heat release in this investigation. The mean structure spacing decreased with increasing temperature. This decrease exceeded the rate of layer growth rate reduction, and suggests that the mechanisms of vortex amalgamation were, to some extent, inhibited by heat release.Imposition of a favorable pressure gradient resulted in additional thinning of the layer, and caused a slight increase in the mixing and amount of chemical product formation. The change in layer growth rate can be shown to be related to a

  5. Shock-induced heating and millisecond boiling in gels and tissue due to high intensity focused ultrasound

    PubMed Central

    Canney, Michael S.; Khokhlova, Vera A.; Bessonova, Olga V.; Bailey, Michael R.; Crum, Lawrence A.

    2009-01-01

    Nonlinear propagation causes high intensity ultrasound waves to distort and generate higher harmonics, which are more readily absorbed and converted to heat than the fundamental frequency. Although such nonlinear effects have previously been investigated and found not to significantly alter high intensity focused ultrasound (HIFU) treatments, two results reported here change this paradigm. One is that at clinically relevant intensity levels, HIFU waves not only become distorted but form shock waves in tissue. The other is that the generated shock waves heat the tissue to boiling in much less time than predicted for undistorted or weakly distorted waves. In this study, a 2-MHz HIFU source operating at peak intensities up to 25,000 W/cm2 was used to heat transparent tissue-mimicking phantoms and ex vivo bovine liver samples. Initiation of boiling was detected using high-speed photography, a 20-MHz passive cavitation detector, and fluctuation of the drive voltage at the HIFU source. The time to boil obtained experimentally was used to quantify heating rates and was compared to calculations using weak shock theory and the shock amplitudes obtained from nonlinear modeling and from measurements with a fiber optic hydrophone. As observed experimentally and predicted by calculations, shocked focal waveforms produced boiling in as little as 3 ms and the time to initiate boiling was sensitive to small changes in HIFU output. Nonlinear heating due to shock waves is therefore important to HIFU and clinicians should be aware of the potential for very rapid boiling since it alters treatments. PMID:20018433

  6. Al 1s-2p absorption spectroscopy of shock-wave heating and compression in laser-driven planar foil

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

    Sawada, H.; Regan, S. P.; Radha, P. B.

    Time-resolved Al 1s-2p absorption spectroscopy is used to diagnose direct-drive, shock-wave heating and compression of planar targets having nearly Fermi-degenerate plasma conditions (T{sub e}{approx}10-40 eV, {rho}{approx}3-11 g/cm{sup 3}) on the OMEGA Laser System [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. A planar plastic foil with a buried Al tracer layer was irradiated with peak intensities of 10{sup 14}-10{sup 15} W/cm{sup 2} and probed with the pseudocontinuum M-band emission from a point-source Sm backlighter in the range of 1.4-1.7 keV. The laser ablation process launches 10-70 Mbar shock waves into the CH/Al/CH target. The Al 1s-2p absorption spectramore » were analyzed using the atomic physic code PRISMSPECT to infer T{sub e} and {rho} in the Al layer, assuming uniform plasma conditions during shock-wave heating, and to determine when the heat front penetrated the Al layer. The drive foils were simulated with the one-dimensional hydrodynamics code LILAC using a flux-limited (f=0.06 and f=0.1) and nonlocal thermal-transport model [V. N. Goncharov et al., Phys. Plasmas 13, 012702 (2006)]. The predictions of simulated shock-wave heating and the timing of heat-front penetration are compared to the observations. The experimental results for a wide variety of laser-drive conditions and buried depths have shown that the LILAC predictions using f=0.06 and the nonlocal model accurately model the shock-wave heating and timing of the heat-front penetration while the shock is transiting the target. The observed discrepancy between the measured and simulated shock-wave heating at late times of the drive can be explained by the reduced radiative heating due to lateral heat flow in the corona.« less

  7. Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows.

    PubMed

    Min, Li; Cheng, Jian-bo; Shi, Bao-lu; Yang, Hong-jian; Zheng, Nan; Wang, Jia-qi

    2015-06-01

    Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperature-humidity index (THI) is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines (leptin and adiponectin), AMP-activated protein kinase (AMPK), and heat shock signal molecules (heat shock transcription factor (HSF) and heat shock proteins (HSP)) in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment: eighteen lactating Holstein dairy cows were used. The treatments were: heat stress (HS, THI average=81.7, n=9) and cooling (CL, THI average=53.4, n=9). Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment: HS treatment cows (n=9) from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90 (P<0.05). Adiponectin is strongly associated with AMPK. The increases of adiponectin and AMPK may be one of the mechanisms to maintain homeostasis in heat-stressed dairy cows. When heat stress treatment lasted 8 weeks, a higher expression of HSF and HSP70 was observed under moderate heat stress. Serum HSF and HSP70 are sensitive and accurate in heat stress and they could be potential indicators of animal response to heat stress. We recommend serum HSF and HSP70 as meaningful biomarkers to supplement the THI and evaluate moderate heat

  8. Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows*

    PubMed Central

    Min, Li; Cheng, Jian-bo; Shi, Bao-lu; Yang, Hong-jian; Zheng, Nan; Wang, Jia-qi

    2015-01-01

    Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperature-humidity index (THI) is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines (leptin and adiponectin), AMP-activated protein kinase (AMPK), and heat shock signal molecules (heat shock transcription factor (HSF) and heat shock proteins (HSP)) in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment: eighteen lactating Holstein dairy cows were used. The treatments were: heat stress (HS, THI average=81.7, n=9) and cooling (CL, THI average=53.4, n=9). Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment: HS treatment cows (n=9) from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90 (P<0.05). Adiponectin is strongly associated with AMPK. The increases of adiponectin and AMPK may be one of the mechanisms to maintain homeostasis in heat-stressed dairy cows. When heat stress treatment lasted 8 weeks, a higher expression of HSF and HSP70 was observed under moderate heat stress. Serum HSF and HSP70 are sensitive and accurate in heat stress and they could be potential indicators of animal response to heat stress. We recommend serum HSF and HSP70 as meaningful biomarkers to supplement the THI and evaluate moderate heat

  9. Differential expression of hsp70 stress proteins in human endothelial cells exposed to heat shock and hydrogen peroxide.

    PubMed

    Jornot, L; Mirault, M E; Junod, A F

    1991-09-01

    The potential role of oxidative stress conditions in the induction of heat shock proteins was studied in human umbilical vein endothelial cells. We compared the effects of temperature (43 to 45 degrees C), exposure to hydrogen peroxide (H2O2) and oxygen metabolites generated by the enzyme system hypoxanthine-xanthine oxidase (O2- plus H2O2), as well as exposure to 95% O2, on the expression of the major 70-kD heat shock proteins (hsp70). Northern blot analysis indicated that: (1) heat shock induced a rapid and marked increase in hsp70 mRNA levels that reached a maximum during recovery from a 30-min exposure to 45 degrees C; (2) treatment with a 5-mM H2O2 bolus or 50 mU/ml xanthine oxidase also increased hsp70 mRNA levels but to a lesser extent than heat shock (about 10 and 25 times less, respectively); (3) no change was detected after a 5-day exposure to 95% O2. Nuclear run on transcription data and kinetics of mRNA decay in the presence of actinomycin D indicated that the observed increase in hsp70 mRNA levels in both heat-shocked and H2O2-treated cells was mainly due to a transcriptional induction. The kinetics of hsp70 synthesis correlated with the accumulation of hsp70 mRNA. Two-dimensional gel electrophoresis and immunologic analysis of these heat shock proteins revealed a series of at least five distinct hsp70 isoforms induced in heat-shocked cells, whereas only a specific subset of these proteins, mainly one acidic isoform, was induced in very low amounts in response to H2O2 treatment. These results clearly indicate that the endothelial cell responses to oxidative stress and heat shock differ in both qualitative and quantitative terms in respect to hsp70 induction. They also suggest that the intensity of this response to oxidative stress conditions may vary depending on the nature of the oxidative challenge.

  10. Asymmetric shock heating and the terrestrial magma ocean origin of the Moon

    PubMed Central

    KARATO, Shun-ichiro

    2014-01-01

    One of the difficulties of the current giant impact model for the origin of the Moon is to explain the marked similarity in the isotopic compositions and the substantial differences in the major element chemistry. Physics of shock heating is analyzed to show that the degree of heating is asymmetric between the impactor and the target, if the target (the proto-Earth) had a magma-ocean but the impactor did not. The magma ocean is heated much more than the solid impactor and the vapor-rich jets come mainly from the magma-ocean from which the Moon might have been formed. In this scenario, the similarity and differences in the composition between the Moon and Earth would be explained as a natural consequence of a collision in the later stage of planetary formation. Including the asymmetry in shock heating is the first step toward explaining the chemical composition of the Moon. PMID:24621956

  11. Expressed sequence tags from heat-shocked seagrass Zostera noltii (Hornemann) from its southern distribution range.

    PubMed

    Massa, Sónia I; Pearson, Gareth A; Aires, Tânia; Kube, Michael; Olsen, Jeanine L; Reinhardt, Richard; Serrão, Ester A; Arnaud-Haond, Sophie

    2011-09-01

    Predicted global climate change threatens the distributional ranges of species worldwide. We identified genes expressed in the intertidal seagrass Zostera noltii during recovery from a simulated low tide heat-shock exposure. Five Expressed Sequence Tag (EST) libraries were compared, corresponding to four recovery times following sub-lethal temperature stress, and a non-stressed control. We sequenced and analyzed 7009 sequence reads from 30min, 2h, 4h and 24h after the beginning of the heat-shock (AHS), and 1585 from the control library, for a total of 8594 sequence reads. Among 51 Tentative UniGenes (TUGs) exhibiting significantly different expression between libraries, 19 (37.3%) were identified as 'molecular chaperones' and were over-expressed following heat-shock, while 12 (23.5%) were 'photosynthesis TUGs' generally under-expressed in heat-shocked plants. A time course analysis of expression showed a rapid increase in expression of the molecular chaperone class, most of which were heat-shock proteins; which increased from 2 sequence reads in the control library to almost 230 in the 30min AHS library, followed by a slow decrease during further recovery. In contrast, 'photosynthesis TUGs' were under-expressed 30min AHS compared with the control library, and declined progressively with recovery time in the stress libraries, with a total of 29 sequence reads 24h AHS, compared with 125 in the control. A total of 4734 TUGs were screened for EST-Single Sequence Repeats (EST-SSRs) and 86 microsatellites were identified. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. dFOXO Activates Large and Small Heat Shock Protein Genes in Response to Oxidative Stress to Maintain Proteostasis in Drosophila.

    PubMed

    Donovan, Marissa R; Marr, Michael T

    2016-09-02

    Maintaining protein homeostasis is critical for survival at the cellular and organismal level (Morimoto, R. I. (2011) Cold Spring Harb. Symp. Quant. Biol. 76, 91-99). Cells express a family of molecular chaperones, the heat shock proteins, during times of oxidative stress to protect against proteotoxicity. We have identified a second stress responsive transcription factor, dFOXO, that works alongside the heat shock transcription factor to activate transcription of both the small heat shock protein and the large heat shock protein genes. This expression likely protects cells from protein misfolding associated with oxidative stress. Here we identify the regions of the Hsp70 promoter essential for FOXO-dependent transcription using in vitro methods and find a physiological role for FOXO-dependent expression of heat shock proteins in vivo. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Inertial cavitation to non-invasively trigger and monitor intratumoral release of drug from intravenously delivered liposomes.

    PubMed

    Graham, Susan M; Carlisle, Robert; Choi, James J; Stevenson, Mark; Shah, Apurva R; Myers, Rachel S; Fisher, Kerry; Peregrino, Miriam-Bazan; Seymour, Len; Coussios, Constantin C

    2014-03-28

    The encapsulation of cytotoxic drugs within liposomes enhances pharmacokinetics and allows passive accumulation within tumors. However, liposomes designed to achieve good stability during the delivery phase often have compromised activity at the target site. This problem of inefficient and unpredictable drug release is compounded by the present lack of low-cost, non-invasive methods to measure such release. Here we show that focused ultrasound, used at pressures similar to those applied during diagnostic ultrasound scanning, can be utilised to both trigger and monitor release of payload from liposomes. Notably, drug release was influenced by liposome composition and the presence of SonoVue® microbubbles, which provided the nuclei for the initiation of an event known as inertial cavitation. In vitro studies demonstrated that liposomes formulated with a high proportion of 1,2 distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) released up to 30% of payload following ultrasound exposure in the presence of SonoVue®, provided that the exposure created sufficient inertial cavitation events, as characterised by violent bubble collapse and the generation of broadband acoustic emissions. In contrast a 'Doxil'-like liposome formulation gave no such triggered release. In pre-clinical studies, ultrasound was used as a non-invasive, targeted stimulus to trigger a 16-fold increase in the level of payload release within tumors following intravenous delivery. The inertial cavitation events driving this release could be measured remotely in real-time and were a reliable predictor of drug release. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Expression of Small Heat-Shock Proteins at Low Temperatures1

    PubMed Central

    Sabehat, Adnan; Lurie, Susan; Weiss, David

    1998-01-01

    We previously reported that short exposure of tomato (Lycopersicon esculentum L.) fruits to high temperature protects them from chilling injury. To study the involvement of heat-shock proteins (HSPs) in the acquisition of low-temperature tolerance, we cloned two heat-shock-induced genes that are also expressed at low temperatures. The cloned cDNAs belong to the small HSP group. Sequence analyses of the clones showed perfect homology to the tomato-ripening gene tom66 and to the tomato chloroplastic HSP21 gene tom111. The expression of both genes was induced by high temperature in fruits, flowers, leaves, and stems, but not by low or ambient temperatures or by other stresses such as drought and anaerobic conditions. When the heated fruits were transferred to low temperature, tom66 and tom111 mRNA levels first decreased but were then reinduced. Induction was not observed in nonheated fruits at low temperature. Immunodetection of tom111-encoded protein indicated that this protein is present at low temperatures in the heated fruits. The results of this study show that the expression of tom66 and tom111 is correlated with protection against some, but not all, symptoms of chilling injury. PMID:9625718

  15. Involvement of heat shock proteins in gluten-sensitive enteropathy

    PubMed Central

    Sziksz, Erna; Pap, Domonkos; Veres, Gábor; Fekete, Andrea; Tulassay, Tivadar; Vannay, Ádám

    2014-01-01

    Gluten-sensitive enteropathy, also known as coeliac disease (CD), is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nutrients. As it is triggered by dietary gluten and related prolamins present in wheat, rye and barley, the accepted treatment for CD is a strict gluten-free diet. However, a complete exclusion of gluten-containing cereals from the diet is often difficult, and new therapeutic strategies are urgently needed. A class of proteins that have already emerged as drug targets for other autoimmune diseases are the heat shock proteins (HSPs), which are highly conserved stress-induced chaperones that protect cells against harmful extracellular factors. HSPs are expressed in several tissues, including the gastrointestinal tract, and their levels are significantly increased under stress circumstances. HSPs exert immunomodulatory effects, and also play a crucial role in the maintenance of epithelial cell structure and function, as they are responsible for adequate protein folding, influence the degradation of proteins and cell repair processes after damage, and modulate cell signalling, cell proliferation and apoptosis. The present review discusses the involvement of HSPs in the pathophysiology of CD. Furthermore, HSPs may represent a useful therapeutic target for the treatment of CD due to the cytoprotective, immunomodulatory, and anti-apoptotic effects in the intestinal mucosal barrier. PMID:24914370

  16. Seasonal effects of heat shock on bacterial populations, including artificial Vibrio parahaemolyticus exposure, in the Pacific oyster, Crassostrea gigas.

    PubMed

    Aagesen, Alisha M; Häse, Claudia C

    2014-04-01

    During the warmer summer months, oysters are conditioned to spawn, resulting in massive physiological efforts for gamete production. Moreover, the higher temperatures during the summer typically result in increased bacteria populations in oysters. We hypothesized that these animals are under multiple stresses that lead to possible immune system impairments during the summer months that can possibly lead to death. Here we show that in the summer and the fall animals exposed to a short heat stress respond similarly, resulting in a general trend of more bacteria being found in heat shocked animals than their non-heat shocked counterparts. We also show that naturally occurring bacterial populations are effected by a heat shock. In addition, oysters artificially contaminated with Vibrio parahaemolyticus were also affected by a heat shock. Heat shocked animals contained higher concentrations of V. parahaemolyticus in their tissues and hemolymph than control animals and this was consistent for animals examined during summer and fall. Finally, oyster hemocyte interactions with V. parahaemolyticus differed based on the time of the year. Overall, these findings demonstrate that seasonal changes and/or a short heat shock is sufficient to impact bacterial retention, particularly V. parahaemolyticus, in oysters and this line of research might lead to important considerations for animal harvesting procedures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. TRIGGERING COLLAPSE OF THE PRESOLAR DENSE CLOUD CORE AND INJECTING SHORT-LIVED RADIOISOTOPES WITH A SHOCK WAVE. II. VARIED SHOCK WAVE AND CLOUD CORE PARAMETERS

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

    Boss, Alan P.; Keiser, Sandra A., E-mail: boss@dtm.ciw.edu, E-mail: keiser@dtm.ciw.edu

    2013-06-10

    A variety of stellar sources have been proposed for the origin of the short-lived radioisotopes that existed at the time of the formation of the earliest solar system solids, including Type II supernovae (SNe), asymptotic giant branch (AGB) and super-AGB stars, and Wolf-Rayet star winds. Our previous adaptive mesh hydrodynamics models with the FLASH2.5 code have shown which combinations of shock wave parameters are able to simultaneously trigger the gravitational collapse of a target dense cloud core and inject significant amounts of shock wave gas and dust, showing that thin SN shocks may be uniquely suited for the task. However,more » recent meteoritical studies have weakened the case for a direct SN injection to the presolar cloud, motivating us to re-examine a wider range of shock wave and cloud core parameters, including rotation, in order to better estimate the injection efficiencies for a variety of stellar sources. We find that SN shocks remain as the most promising stellar source, though planetary nebulae resulting from AGB star evolution cannot be conclusively ruled out. Wolf-Rayet (WR) star winds, however, are likely to lead to cloud core shredding, rather than to collapse. Injection efficiencies can be increased when the cloud is rotating about an axis aligned with the direction of the shock wave, by as much as a factor of {approx}10. The amount of gas and dust accreted from the post-shock wind can exceed that injected from the shock wave, with implications for the isotopic abundances expected for a SN source.« less

  18. Remote shock sensing and notification system

    DOEpatents

    Muralidharan, Govindarajan [Knoxville, TN; Britton, Charles L [Alcoa, TN; Pearce, James [Lenoir City, TN; Jagadish, Usha [Knoxville, TN; Sikka, Vinod K [Oak Ridge, TN

    2010-11-02

    A low-power shock sensing system includes at least one shock sensor physically coupled to a chemical storage tank to be monitored for impacts, and an RF transmitter which is in a low-power idle state in the absence of a triggering signal. The system includes interface circuitry including or activated by the shock sensor, wherein an output of the interface circuitry is coupled to an input of the RF transmitter. The interface circuitry triggers the RF transmitter with the triggering signal to transmit an alarm message to at least one remote location when the sensor senses a shock greater than a predetermined threshold. In one embodiment the shock sensor is a shock switch which provides an open and a closed state, the open state being a low power idle state.

  19. Remote shock sensing and notification system

    DOEpatents

    Muralidharan, Govindarajan; Britton, Charles L.; Pearce, James; Jagadish, Usha; Sikka, Vinod K.

    2008-11-11

    A low-power shock sensing system includes at least one shock sensor physically coupled to a chemical storage tank to be monitored for impacts, and an RF transmitter which is in a low-power idle state in the absence of a triggering signal. The system includes interference circuitry including or activated by the shock sensor, wherein an output of the interface circuitry is coupled to an input of the RF transmitter. The interface circuitry triggers the RF transmitting with the triggering signal to transmit an alarm message to at least one remote location when the sensor senses a shock greater than a predetermined threshold. In one embodiment the shock sensor is a shock switch which provides an open and a closed state, the open state being a low power idle state.

  20. Heating the polar corona by collisionless shocks: an example of cross-fertilization in space physics

    NASA Astrophysics Data System (ADS)

    Zimbardo, Gaetano; Nistico, Giuseppe

    We propose a new model for explaining the observations of preferential heating of heavy ions in the polar solar corona. We consider that a large number of small scale shock waves can be present in the solar corona, as suggested by recent observations of polar coronal jets. The heavy ion energization mechanism is, essentially, the ion reflection off supercritical quasi-perpendicular collisionless shocks in the corona and the subsequent acceleration by the motional electric field E = -V × B. The mechanism of heavy ion reflection is based on ion gyration in the magnetic overshoot of the shock. The acceleration due to E is perpendicular to the magnetic field, giving rise to large temperature anisotropy with T⊥ T , in agreement with observations. Also, heating is more than mass proportional with respect to protons, because the heavy ion orbit is mostly upstream of the quasi-perpendicular shock foot. The observed temperature ratios between O5+ ions and protons in the polar corona, and between α particles and protons in the solar wind are easily recovered. Results of numerical simulations reproducing the heavy ion reflection will be presented. This work is an interesting example of cross-fertilization in space plasma physics: the non adiabatic heating of heavy ions comes from Speiser orbits in the magnetotail, observations of preferential heating of heavy ions at shocks comes from Ulysses data on corotating interaction regions shocks, heavy ion reflecton from a magnetic barrier is akin to the ion orbits in the Ferraro-Rosenbluth sheath considered for the magnetopause, the formation of shocks in the reconnection outflow regions comes from solar flare models, and evidence of reconnection and fast flows in the polar corona comes from Hinode and STEREO observations of coronal hole jets.

  1. New Evidence for Efficient Collisionless Heating of Electrons at the Reverse Shock of a Young Supernova Remnant

    NASA Technical Reports Server (NTRS)

    Yamaguchi, Hiroya; Eriksen, Kristoffer A.; Badenes, Carles; Hughes, John P.; Brickhouse, Nancy S.; Foster, Adam R.; Patnaude, Daniel J.; Petre, Robert; Slane, Patrick O.; Smith, Randall K.

    2013-01-01

    Although collisionless shocks are ubiquitous in astrophysics, certain key aspects of them are not well understood. In particular, the process known as collisionless electron heating, whereby electrons are rapidly energized at the shock front, is one of the main open issues in shock physics. Here, we present the first clear evidence for efficient collisionless electron heating at the reverse shock of Tycho's supernova remnant (SNR), revealed by Fe K diagnostics using high-quality X-ray data obtained by the Suzaku satellite. We detect K beta (3p yields 1s) fluorescence emission from low-ionization Fe ejecta excited by energetic thermal electrons at the reverse shock front, which peaks at a smaller radius than Fe K alpha (2p yields 1s) emission dominated by a relatively highly ionized component. Comparisons with our hydrodynamical simulations imply instantaneous electron heating to a temperature 1000 times higher than expected from Coulomb collisions alone. The unique environment of the reverse shock, which is propagating with a high Mach number into rarefied ejecta with a low magnetic field strength, puts strong constraints on the physical mechanism responsible for this heating and favors a cross-shock potential created by charge deflection at the shock front. Our sensitive observation also reveals that the reverse shock radius of this SNR is about 10% smaller than the previous measurement using the Fe K alpha morphology from the Chandra observations. Since strong Fe K beta fluorescence is expected only from low-ionization plasma where Fe ions still have many 3p electrons, this feature is key to diagnosing the plasma state and distribution of the immediate postshock ejecta in a young SNR.

  2. Translational control of small heat shock genes in mesophilic and thermophilic cyanobacteria by RNA thermometers

    PubMed Central

    Cimdins, Annika; Klinkert, Birgit; Aschke-Sonnenborn, Ursula; Kaiser, Friederike M; Kortmann, Jens; Narberhaus, Franz

    2014-01-01

    Cyanobacteria constitute a heterogeneous phylum of oxygen-producing, photosynthetic prokaryotes. They are susceptible to various stress conditions like heat, salt, or light stress, all inducing the cyanobacterial heat shock response (HSR). Cyanobacterial small heat shock proteins (sHsps) are known to preserve thylakoid membrane integrity under stress conditions, thereby protecting the photosynthesis machinery. In Synechocystis sp PCC 6803, synthesis of the sHsp Hsp17 is regulated by an RNA thermometer (RNAT) in the 5′-untranslated region (5′-UTR) of the hsp17 mRNA. RNATs are direct temperature sensors that control expression of many bacterial heat shock and virulence genes. They hinder translation at low temperatures by base pairing, thus blocking ribosome access to the mRNA.   To explore the temperature range in which RNATs act, we studied various RNAT candidates upstream of sHsp genes from mesophilic and thermophilic cyanobacteria. The mesophilic cyanobacteria Anabaena variabilis and Nostoc sp chromosomally encode two sHsps each. Reporter gene studies suggested RNAT-mediated post-transcriptional regulation of shsp expression in both organisms. Detailed structural analysis of the two A. variabilis candidates revealed two novel RNAT types. The first, avashort, regulates translation primarily by masking of the AUG translational start codon. The second, featuring an extended initial hairpin, thus named avalong, presumably makes use of complex tertiary interaction. The 5′-UTR of the small heat shock gene hspA in the thermophile Thermosynechococcus elongatus is predicted to adopt an extended secondary structure. Structure probing revealed that the ribosome binding site was blocked at temperatures below 55 °C. The results of this study demonstrate that cyanobacteria commonly use RNATs to control expression of their small heat shock genes. PMID:24755616

  3. Radiative cooling in shock-heated hydrogen-helium plasmas. [for planetary entry probe heat shields

    NASA Technical Reports Server (NTRS)

    Poon, P. T. Y.; Stickford, G. H., Jr.

    1978-01-01

    Axial and off-axis radiative cooling of cylindrical shock-heated hydrogen-helium plasmas is investigated theoretically and experimentally. The coupled fluid dynamic-radiative transfer equations are solved by a combination of approximation techniques aimed at simplifying the computation of the flux divergence term, namely, the quasi-isothermal approximation and the exponential approximation developed for the solid angle integration. The accuracy of the approximation schemes has been assessed and found acceptable for applying the methods to the rapid computation of the radiatively coupled flow problem. Radiative cooling experiments were conducted in a 6-inch annular arc accelerator shock tube (ANAA) for an initial pressure of 1 torr and shock speeds from 35 to 45 Km/sec. The results indicate that the lateral cooling is small compared with the axial cooling, and that better agreement is achieved between the data and the theoretical results by inclusion of the lateral temperature gradient.

  4. Lipogels responsive to near-infrared light for the triggered release of therapeutic agents.

    PubMed

    Martín-Saavedra, Francisco; Ruiz-Hernández, Eduardo; Escudero-Duch, Clara; Prieto, Martín; Arruebo, Manuel; Sadeghi, Negar; Deckers, Roel; Storm, Gert; Hennink, Wim E; Santamaría, Jesús; Vilaboa, Nuria

    2017-10-01

    Here we report a composite system based on fibrin hydrogels that incorporate in their structure near-infrared (NIR) responsive nanomaterials and thermosensitive liposomes (TSL). Polymerized fibrin networks entrap simultaneously gold-based nanoparticles (NPs) capable of transducing NIR photon energy into heat, and lysolipid-incorporated TSL (LTSL) loaded with doxorubicin hydrochloride (DOX). NIR irradiation of the resulting hydrogels (referred to as "lipogels") with 808nm laser light increased the temperature of the illuminated areas, leading to the release of the liposomal cargo. Levels of DOX that release from the "smart" composites were dependent on the concentration of NIR nanotransducers loaded in the lipogel, the intensity of the electromagnetic energy deposited and the irradiation regime. Released DOX retained its bioactivity, as shown in cultures of epithelial carcinoma cells. Finally, the developed drug delivery platform was refined by using NIR-photoabsorbers based on copper sulfide NPs to generate completely biodegradable composites as well as through the incorporation of cholesterol (Ch) in LTSL formulation, which lessens leakiness of the liposomal cargo at physiological temperature. This remotely controlled system may suit well for those therapies that require precise control over the dose of delivered drug in a defined spatiotemporal framework. Hydrogels composed of fibrin embedding nanoparticles responsive to near infrared (NIR) energy and thermosensitive liposomes loaded with doxorubicin hydrochloride (DOX), were prepared by in situ polymerization. NIR-light irradiation of these constructs, referred to as "NIR responsive lipogels", results in the controlled release of DOX to the surrounding medium. This technology may use fully degradable components and can preserve the bioactivity of liposomal cargo after remote triggering to finely regulate the dose and bioavailability of delivered payloads. NIR responsive lipogels technology overcomes the

  5. Extracellular small heat shock proteins: exosomal biogenesis and function.

    PubMed

    Reddy, V Sudhakar; Madala, Satish K; Trinath, Jamma; Reddy, G Bhanuprakash

    2018-05-01

    Small heat shock proteins (sHsps) belong to the family of heat shock proteins (Hsps): some are induced in response to multiple stressful events to protect the cells while others are constitutively expressed. Until now, it was believed that Hsps, including sHsps, are present inside the cells and perform intracellular functions. Interestingly, several groups recently reported the extracellular presence of Hsps, and sHsps have also been detected in sera/cerebrospinal fluids in various pathological conditions. Secretion into the extracellular milieu during many pathological conditions suggests additional or novel functions of sHsps in addition to their intracellular properties. Extracellular sHsps are implicated in cell-cell communication, activation of immune cells, and promoting anti-inflammatory and anti-platelet responses. Interestingly, exogenous administration of sHsps showed therapeutic effects in multiple disease models implying that extracellular sHsps are beneficial in pathological conditions. sHsps do not possess signal sequence and, hence, are not exported through the classical Endoplasmic reticulum-Golgi complex (ER-Golgi) secretory pathway. Further, export of sHsps is not inhibited by ER-Golgi secretory pathway inhibitors implying the involvement of a nonclassical secretory pathway in sHsp export. In lieu, lysoendosomal and exosomal pathways have been proposed for the export of sHsps. Heat shock protein 27 (Hsp27), αB-crystallin (αBC), and Hsp20 are shown to be exported by exosomes. Exosomes packaged with sHsps have beneficial effects in in vivo disease models. However, secretion mechanisms and therapeutic use of sHsps have not been elucidated in detail. Therefore, this review aimed at highlighting the current understanding of sHsps (Hsp27, αBC, and Hsp20) in the extracellular medium.

  6. Analysis of compaction shock interactions during DDT of low density HMX

    NASA Astrophysics Data System (ADS)

    Rao, Pratap T.; Gonthier, Keith A.

    2017-01-01

    Deflagration-to-Detonation Transition (DDT) in confined, low density granular HMX occurs by a complex mechanism that involves compaction shock interactions within the material. Piston driven DDT experiments indicate that detonation is abruptly triggered by the interaction of a strong combustion-supported secondary shock and a piston-supported primary (input) shock, where the nature of the interaction depends on initial packing density and primary shock strength. These interactions influence transition by affecting dissipative heating within the microstructure during pore collapse. Inert meso-scale simulations of successive shock loading of low density HMX are performed to examine how dissipation and hot-spot formation are affected by the initial density, and the primary and secondary shock strengths. This information is used to formulate an ignition and burn model for low density HMX that accounts for the effect of shock densensitization on burn. Preliminary DDT predictions are presented that illustrate how primary shock strength affects the transition mechanism.

  7. Transcriptome Profiling of Selectively Bred Pacific Oyster Crassostrea gigas Families that Differ in Tolerance of Heat Shock

    PubMed Central

    Bayne, Christopher J.; Camara, Mark D.; Cunningham, Charles; Jenny, Matthew J.; Langdon, Christopher J.

    2010-01-01

    Sessile inhabitants of marine intertidal environments commonly face heat stress, an important component of summer mortality syndrome in the Pacific oyster Crassostrea gigas. Marker-aided selection programs would be useful for developing oyster strains that resist summer mortality; however, there is currently a need to identify candidate genes associated with stress tolerance and to develop molecular markers associated with those genes. To identify candidate genes for further study, we used cDNA microarrays to test the hypothesis that oyster families that had high (>64%) or low (<29%) survival of heat shock (43°C, 1 h) differ in their transcriptional responses to stress. Based upon data generated by the microarray and by real-time quantitative PCR, we found that transcription after heat shock increased for genes putatively encoding heat shock proteins and genes for proteins that synthesize lipids, protect against bacterial infection, and regulate spawning, whereas transcription decreased for genes for proteins that mobilize lipids and detoxify reactive oxygen species. RNAs putatively identified as heat shock protein 27, collagen, peroxinectin, S-crystallin, and two genes with no match in Genbank had higher transcript concentrations in low-surviving families than in high-surviving families, whereas concentration of putative cystatin B mRNA was greater in high-surviving families. These ESTs should be studied further for use in marker-aided selection programs. Low survival of heat shock could result from a complex interaction of cell damage, opportunistic infection, and metabolic exhaustion. PMID:19205802

  8. HEAT SHOCK FACTOR 1-MEDIATED THERMOTOLERANCE PREVENTS CELL DEATH AND RESULTS IN G2/M CELL CYCLE ARREST

    EPA Science Inventory

    Mammalian cells respond to stress by activating heat shock transcription factors (e.g., HSF1) that regulate increased synthesis of heat shock proteins (HSPs). HSPs mediate protection from deleterious effects of stress by preventing permanent disruption of normal cellular mitosis...

  9. α-Crystallins Are Small Heat Shock Proteins: Functional and Structural Properties.

    PubMed

    Tikhomirova, T S; Selivanova, O M; Galzitskaya, O V

    2017-02-01

    During its life cycle, a cell can be subjected to various external negative effects. Many proteins provide cell protection, including small heat shock proteins (sHsp) that have chaperone-like activity. These proteins have several important functions involving prevention of apoptosis and retention of cytoskeletal integrity; also, sHsp take part in the recovery of enzyme activity. The action mechanism of sHsp is based on the binding of hydrophobic regions exposed to the surface of a molten globule. α-Crystallins presented in chordate cells as two αA- and αB-isoforms are the most studied small heat shock proteins. In this review, we describe the main functions of α-crystallins, features of their secondary and tertiary structures, and examples of their partners in protein-protein interactions.

  10. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27.

    PubMed

    Gan, Nanqin; Wu, Yu-Chieh; Brunet, Mathilde; Garrido, Carmen; Chung, Fung-Lung; Dai, Chengkai; Mi, Lixin

    2010-11-12

    It is conceivable that stimulating proteasome activity for rapid removal of misfolded and oxidized proteins is a promising strategy to prevent and alleviate aging-related diseases. Sulforaphane (SFN), an effective cancer preventive agent derived from cruciferous vegetables, has been shown to enhance proteasome activities in mammalian cells and to reduce the level of oxidized proteins and amyloid β-induced cytotoxicity. Here, we report that SFN activates heat shock transcription factor 1-mediated heat shock response. Specifically, SFN-induced expression of heat shock protein 27 (Hsp27) underlies SFN-stimulated proteasome activity. SFN-induced proteasome activity was significantly enhanced in Hsp27-overexpressing cells but absent in Hsp27-silenced cells. The role of Hsp27 in regulating proteasome activity was further confirmed in isogenic REG cells, in which SFN-induced proteasome activation was only observed in cells stably overexpressing Hsp27, but not in the Hsp27-free parental cells. Finally, we demonstrated that phosphorylation of Hsp27 is irrelevant to SFN-induced proteasome activation. This study provides a novel mechanism underlying SFN-induced proteasome activity. This is the first report to show that heat shock response by SFN, in addition to the antioxidant response mediated by the Keap1-Nrf2 pathway, may contribute to cytoprotection.

  11. Inducing Heat Shock Proteins Enhances the Stemness of Frozen-Thawed Adipose Tissue-Derived Stem Cells.

    PubMed

    Shaik, Shahensha; Hayes, Daniel; Gimble, Jeffrey; Devireddy, Ram

    2017-04-15

    Extensive research has been performed to determine the effect of freezing protocol and cryopreservation agents on the viability of adipose tissue-derived stromal/stem cells (ASCs) as well as other cells. Unfortunately, the conclusion one may draw after decades of research utilizing fundamentally similar cryopreservation techniques is that a barrier exists, which precludes full recovery. We hypothesize that agents capable of inducing a subset of heat shock proteins (HSPs) and chaperones will reduce the intrinsic barriers to the post-thaw recovery of ASCs. ASCs were exposed to 43°C for 1 h to upregulate HSPs, and the temporal HSP expression profile postheat shock was determined by performing quantitative polymerase chain reaction (PCR) and western blotting assays. The expression levels of HSP70 and HSP32 were found to be maximum at 3 h after the heat shock, whereas HSP90 and HSP27 remain unchanged. The heat shocked ASCs cryopreserved during maximal HSPs expression exhibited increased post-thaw viability than the nonheat shocked samples. Histochemical staining and quantitative reverse transcription-PCR indicated that the ASC differentiation potential was retained. Thus, suggesting that the upregulation of HSPs before a freezing insult is beneficial to ASCs and a potential alternative to the use of harmful cryoprotective agents.

  12. Translation Regulation and RNA Granule Formation after Heat Shock of Procyclic Form Trypanosoma brucei: Many Heat-Induced mRNAs Are also Increased during Differentiation to Mammalian-Infective Forms.

    PubMed

    Minia, Igor; Merce, Clementine; Terrao, Monica; Clayton, Christine

    2016-09-01

    African trypanosome procyclic forms multiply in the midgut of tsetse flies, and are routinely cultured at 27°C. Heat shocks of 37°C and above result in general inhibition of translation, and severe heat shock (41°C) results in sequestration of mRNA in granules. The mRNAs that are bound by the zinc-finger protein ZC3H11, including those encoding refolding chaperones, escape heat-induced translation inhibition. At 27°C, ZC3H11 mRNA is predominantly present as an untranslated cytosolic messenger ribonucleoprotein particle, but after heat shocks of 37°C-41°C, the ZC3H11 mRNA moves into the polysomal fraction. To investigate the scope and specificities of heat-shock translational regulation and granule formation, we analysed the distributions of mRNAs on polysomes at 27°C and after 1 hour at 39°C, and the mRNA content of 41°C heat shock granules. We found that mRNAs that bind to ZC3H11 remained in polysomes at 39°C and were protected from sequestration in granules at 41°C. As previously seen for starvation stress granules, the mRNAs that encode ribosomal proteins were excluded from heat-shock granules. 70 mRNAs moved towards the polysomal fraction after the 39°C heat shock, and 260 increased in relative abundance. Surprisingly, many of these mRNAs are also increased when trypanosomes migrate to the tsetse salivary glands. It therefore seems possible that in the wild, temperature changes due to diurnal variations and periodic intake of warm blood might influence the efficiency with which procyclic forms develop into mammalian-infective forms.

  13. Enzymatic triggered release of an HIV-1 entry inhibitor from prostate specific antigen degradable microparticles.

    PubMed

    Clark, Meredith R; Aliyar, Hyder A; Lee, Chang-won; Jay, Julie I; Gupta, Kavita M; Watson, Karen M; Stewart, Russell J; Buckheit, Robert W; Kiser, Patrick F

    2011-07-15

    This paper describes the design, construction and characterization of the first anti-HIV drug delivery system that is triggered to release its contents in the presence of human semen. Microgel particles were synthesized with a crosslinker containing a peptide substrate for the seminal serine protease prostate specific antigen (PSA) and were loaded with the HIV-1 entry inhibitor sodium poly(styrene-4-sulfonate) (pSS). The particles were composed of N-2-hydroxyproplymethacrylamide and bis-methacrylamide functionalized peptides based on the PSA substrates GISSFYSSK and GISSQYSSK. Exposure to human seminal plasma (HSP) degraded the microgel network and triggered the release of the entrapped antiviral polymer. Particles with the crosslinker composed of the substrate GISSFYSSK showed 17 times faster degradation in seminal plasma than that of the crosslinker composed of GISSQYSSK. The microgel particles containing 1 mol% GISSFYSSK peptide crosslinker showed complete degradation in 30 h in the presence of HSP at 37°C and pSS released from the microgels within 30 min reached a concentration of 10 μg/mL, equivalent to the published IC(90) for pSS. The released pSS inactivated HIV-1 in the presence of HSP. The solid phase synthesis of the crosslinkers, preparation of the particles by inverse microemulsion polymerization, HSP-triggered release of pSS and inactivation of HIV-1 studies are described. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Effects of heat shock protein 90 expression on pectoralis major oxidation in broilers exposed to acute heat stress.

    PubMed

    Hao, Y; Gu, X H

    2014-11-01

    This study was conducted to determine the effects of heat shock protein 90 (HSP90) expression on pH, lipid peroxidation, heat shock protein 70 (HSP70), and glucocorticoid receptor (GR) expression of pectoralis major in broilers exposed to acute heat stress. In total, 90 male broilers were randomly allocated to 3 groups: control (CON), heat stress (HS), or geldanamycin treatment (GA). On d 41, the broilers in the GA group were injected intraperitoneally with GA (5 μg/kg of BW), and the broilers in the CON and HS groups were injected intraperitoneally with saline. Twenty-four hours later, the broilers in the CON group were moved to environmental chambers controlled at 22°C for 2 h, and the broilers in the HS and GA groups were moved to environmental chambers controlled at 40°C for 2 h. The pH values of the pectoralis major after 30 min and 24 h of chilling after slaughter of HS and GA broilers were significantly lower (P < 0.01) than those of the CON broilers. Heat stress caused significant increases in sera corticosterone and lactic dehydrogenase, the activity of malondialdehyde and superoxide dismutase, the expression of HSP90 and HSP70, and nuclear expression of GR protein in the pectoralis major (P < 0.05). Heat stress induced a significant decrease in GR protein expression in the cytoplasm and GR mRNA expression. Furthermore, the low expression of HSP90 significantly increased levels of lactic dehydrogenase and malondialdehyde and GR protein expression in the cytoplasm under heat stress (P < 0.01), and significantly decreased nuclear GR protein expression (P < 0.01). Heat shock protein 90 was positively correlated with corticosterone and superoxide dismutase activities (P < 0.01), and HSP90 mRNA was negatively correlated with pH after chilling for 24 h. The results demonstrated that HSP90 plays a pivotal role in protecting cells from oxidation. ©2014 Poultry Science Association Inc.

  15. An artificial HSE promoter for efficient and selective detection of heat shock pathway activity.

    PubMed

    Ortner, Viktoria; Ludwig, Alfred; Riegel, Elisabeth; Dunzinger, Sarah; Czerny, Thomas

    2015-03-01

    Detection of cellular stress is of major importance for the survival of cells. During evolution, a network of stress pathways developed, with the heat shock (HS) response playing a major role. The key transcription factor mediating HS signalling activity in mammalian cells is the HS factor HSF1. When activated it binds to the heat shock elements (HSE) in the promoters of target genes like heat shock protein (HSP) genes. They are induced by HSF1 but in addition they integrate multiple signals from different stress pathways. Here, we developed an artificial promoter consisting only of HSEs and therefore selectively reacting to HSF-mediated pathway activation. The promoter is highly inducible but has an extreme low basal level. Direct comparison with the HSPA1A promoter activity indicates that heat-dependent expression can be fully recapitulated by isolated HSEs in human cells. Using this sensitive reporter, we measured the HS response for different temperatures and exposure times. In particular, long heat induction times of 1 or 2 h were compared with short heat durations down to 1 min, conditions typical for burn injuries. We found similar responses to both long and short heat durations but at completely different temperatures. Exposure times of 2 h result in pathway activation at 41 to 44 °C, whereas heat pulses of 1 min lead to a maximum HS response between 47 and 50 °C. The results suggest that the HS response is initiated by a combination of temperature and exposure time but not by a certain threshold temperature.

  16. Linking physiological and cellular responses to thermal stress: β-adrenergic blockade reduces the heat shock response in fish.

    PubMed

    Templeman, Nicole M; LeBlanc, Sacha; Perry, Steve F; Currie, Suzanne

    2014-08-01

    When faced with stress, animals use physiological and cellular strategies to preserve homeostasis. We were interested in how these high-level stress responses are integrated at the level of the whole animal. Here, we investigated the capacity of the physiological stress response, and specifically the β-adrenergic response, to affect the induction of the cellular heat shock proteins, HSPs, following a thermal stress in vivo. We predicted that blocking β-adrenergic stimulation during an acute heat stress in the whole animal would result in reduced levels of HSPs in red blood cells (RBCs) of rainbow trout compared to animals where adrenergic signaling remained intact. We first determined that a 1 h heat shock at 25 °C in trout acclimated to 13 °C resulted in RBC adrenergic stimulation as determined by a significant increase in cell swelling, a hallmark of the β-adrenergic response. A whole animal injection with the β2-adrenergic antagonist, ICI-118,551, successfully reduced this heat-induced RBC swelling. The acute heat shock caused a significant induction of HSP70 in RBCs of 13 °C-acclimated trout as well as a significant increase in plasma catecholamines. When heat-shocked fish were treated with ICI-118,551, we observed a significant attenuation of the HSP70 response. We conclude that circulating catecholamines influence the cellular heat shock response in rainbow trout RBCs, demonstrating physiological/hormonal control of the cellular stress response.

  17. Electron heating in quasi-perpendicular shocks - A Monte Carlo simulation

    NASA Technical Reports Server (NTRS)

    Veltri, Pierluigi; Mangeney, Andre; Scudder, Jack D.

    1990-01-01

    To study the problem of electron heating in quasi-perpendicular shocks, under the combined effects of 'reversible' motion, in the shock electric potential and magnetic field, and wave-particle interactions a diffusion equation was derived, in the drift (adiabatic) approximation and it was solved by using a Monte Carlo method. The results show that most of the observations can be explained within this framework. The simulation has also definitively shown that the electron parallel temperature is determined by the dc electromagnetic field and not by any wave particle induced heating. Wave-particle interactions are effective in smoothing out the large gradients in phase space produced by the 'reversible' motion of the electrons, thus producing a 'cooling' of the electrons. Some constraints on the wave-particle interaction process may be obtained from a detailed comparison between the simulation and observations. In particular, it appears that the adiabatic approximation must be violated in order to explain the observed evolution of the perpendicular temperature.

  18. Effect of temperature shock and inventory surprises on natural gas and heating oil futures returns.

    PubMed

    Hu, John Wei-Shan; Hu, Yi-Chung; Lin, Chien-Yu

    2014-01-01

    The aim of this paper is to examine the impact of temperature shock on both near-month and far-month natural gas and heating oil futures returns by extending the weather and storage models of the previous study. Several notable findings from the empirical studies are presented. First, the expected temperature shock significantly and positively affects both the near-month and far-month natural gas and heating oil futures returns. Next, significant temperature shock has effect on both the conditional mean and volatility of natural gas and heating oil prices. The results indicate that expected inventory surprises significantly and negatively affects the far-month natural gas futures returns. Moreover, volatility of natural gas futures returns is higher on Thursdays and that of near-month heating oil futures returns is higher on Wednesdays than other days. Finally, it is found that storage announcement for natural gas significantly affects near-month and far-month natural gas futures returns. Furthermore, both natural gas and heating oil futures returns are affected more by the weighted average temperature reported by multiple weather reporting stations than that reported by a single weather reporting station.

  19. Effect of Temperature Shock and Inventory Surprises on Natural Gas and Heating Oil Futures Returns

    PubMed Central

    Hu, John Wei-Shan; Lin, Chien-Yu

    2014-01-01

    The aim of this paper is to examine the impact of temperature shock on both near-month and far-month natural gas and heating oil futures returns by extending the weather and storage models of the previous study. Several notable findings from the empirical studies are presented. First, the expected temperature shock significantly and positively affects both the near-month and far-month natural gas and heating oil futures returns. Next, significant temperature shock has effect on both the conditional mean and volatility of natural gas and heating oil prices. The results indicate that expected inventory surprises significantly and negatively affects the far-month natural gas futures returns. Moreover, volatility of natural gas futures returns is higher on Thursdays and that of near-month heating oil futures returns is higher on Wednesdays than other days. Finally, it is found that storage announcement for natural gas significantly affects near-month and far-month natural gas futures returns. Furthermore, both natural gas and heating oil futures returns are affected more by the weighted average temperature reported by multiple weather reporting stations than that reported by a single weather reporting station. PMID:25133233

  20. Different mechanisms are involved in the transcriptional activation by yeast heat shock transcription factor through two different types of heat shock elements.

    PubMed

    Hashikawa, Naoya; Yamamoto, Noritaka; Sakurai, Hiroshi

    2007-04-06

    The hydrophobic repeat is a conserved structural motif of eukaryotic heat shock transcription factor (HSF) that enables HSF to form a homotrimer. Homotrimeric HSF binds to heat shock elements (HSEs) consisting of three inverted repeats of the sequence nGAAn. Sequences consisting of four or more nGAAn units are bound cooperatively by two HSF trimers. We show that in Saccharomyces cerevisiae cells oligomerization-defective Hsf1 is not able to bind HSEs with three units and is not extensively phosphorylated in response to stress; it is therefore unable to activate genes containing this type of HSE. Several lines of evidence indicate that oligomerization is a prerequisite for stress-induced hyperphosphorylation of Hsf1. In contrast, oligomerization and hyperphosphorylation are not necessary for gene activation via HSEs with four units. Intragenic suppressor screening of oligomerization-defective hsf1 showed that an interface between adjacent DNA-binding domains is important for the binding of Hsf1 to the HSE. We suggest that Saccharomyces cerevisiae HSEs with different structures are regulated differently; HSEs with three units require Hsf1 to be both oligomerized and hyperphosphorylated, whereas HSEs with four or more units do not require either.

  1. Targeted gene expression without a tissue-specific promoter: creating mosaic embryos using laser-induced single-cell heat shock

    NASA Technical Reports Server (NTRS)

    Halfon, M. S.; Kose, H.; Chiba, A.; Keshishian, H.

    1997-01-01

    We have developed a method to target gene expression in the Drosophila embryo to a specific cell without having a promoter that directs expression in that particular cell. Using a digitally enhanced imaging system to identify single cells within the living embryo, we apply a heat shock to each cell individually by using a laser microbeam. A 1- to 2-min laser treatment is sufficient to induce a heat-shock response but is not lethal to the heat-shocked cells. Induction of heat shock was measured in a variety of cell types, including neurons and somatic muscles, by the expression of beta-galactosidase from an hsp26-lacZ reporter construct or by expression of a UAS target gene after induction of hsGAL4. We discuss the applicability of this technique to ectopic gene expression studies, lineage tracing, gene inactivation studies, and studies of cells in vitro. Laser heat shock is a versatile technique that can be adapted for use in a variety of research organisms and is useful for any studies in which it is desirable to express a given gene in only a distinct cell or clone of cells, either transiently or constitutively, at a time point of choice.

  2. Isoform composition and stoichiometry of the approx. 90-kDa heat shock protein associated with glucocorticoid receptors

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

    Mendel, D.B.; Orti, E.

    1988-05-15

    The authors observed that the approx. 90-kDa non-steroid-binding component of nonactivated glucocorticoid receptors purified from WEHI-7 mouse thymoma cells (which has been identified as the approx. 90-kDa heat shock protein) consistently migrates as a doublet during polyacrylamide gel electrophoresis under denaturing and reducing conditions. It has recently been reported that murine Meth A cells contain a tumor-specific transplantation antigen (TSTA) which is related or identical to the approx. 90-kDa heat shock protein. The observation that TSTA and the approx. 90-kDa heat shock protein isolated from these cells exists as two isoforms of similar molecular mass and charge has suggested thatmore » the doublet observed is also due to the existence of two isoforms. They have therefore conducted this study to determine whether TSTA and the approx. 90-kDa component of glucocorticoid receptors are indeed related, to establish whether the receptor preferentially binds one isoform of the approx. 90-kDa heat shock protein, and to investigate the stoichiometry of the nonactivated receptor complex. They used the BuGr1 and AC88 monoclonal antibodies to purify, respectively, receptor-associated and free approx. 90-kDa heat shock protein from WEHI-7 cells grown for 48 h with (/sup 35/S)methionine to metabolically label proteins to steady state. The long-term metabolic labeling approach has also enabled them to directly determine that the purified non-activated glucocorticoid receptor contains a single steroid-binding protein and two approx. 90-kDa non-steroid-binding subunits. The consistency with which a approx. 1:2 stoichiometric ratio of steroid binding to approx. 90-kDa protein is observed supports the view that the approx. 90-kDa heat shock protein is a true component of nonactivated glucocorticoid-receptor complexes.« less

  3. Proteome changes in rainbow trout (Oncorhynchus mykiss) fertilized eggs as an effect of triploidization heat-shock treatment.

    PubMed

    Babaheydari, Samad Bahrami; Keyvanshokooh, Saeed; Dorafshan, Salar; Johari, Seyed Ali

    2016-03-01

    The aim of the present study was to explore proteome changes in rainbow trout (Oncorhynchus mykiss) fertilized eggs as an effect of triploidization heat-shock treatment. Eggs and milt were taken from eight females and six males. The gametes were pooled to minimize the individual differences. After insemination, the eggs were incubated at 10°C for 10min. Half of the fertilized eggs were then subjected to heat shock for 10min submerged in a 28°C water bath to induce triploidy. The remainder were incubated normally and used as diploid controls. Three batches of eggs were randomly selected from each group and were incubated at 10-11°C under the same environmental conditions in hatchery troughs until the fry stage. Triplicate samples of 30 eggs (10 eggs per trough) from each group were randomly selected 1.5h post-fertilization for proteome extraction. Egg proteins were analyzed using two-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF mass spectrometry. Based on the results from the statistical analyses, 15 protein spots were found to decrease significantly in abundance in heat-shock treated group and were selected for identification. Out of 15 protein spots showing altered abundance, 14 spots were successfully identified. All of the egg proteins identified in our study were related to vitellogenin (vtg). Decreased abundance of vitellogenin in heat-shock treated eggs in our study may either be explained by (i) higher utilization of vtg as an effect of increased cell size in triploids or (ii) changed metabolism in response to heat-shock stress and (iii) diffusion of vtg through chorion due to incidence of egg shell damage. Decreased abundance of vitellogenin in heat-shock treated eggs was associated with reduced early survival rates and lowered growth performance of triploid fish. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Simulation of stimuli-triggered release of molecular species from halloysite nanotubes

    NASA Astrophysics Data System (ADS)

    Elumalai, Divya Narayan; Tully, Joshua; Lvov, Yuri; Derosa, Pedro A.

    2016-10-01

    A Monte Carlo model is used to study the effect of environmental variables (pH and temperature) on the transport and release of dexamethasone molecules from Halloysite Nanotubes (HNTs) in a dielectric fluid medium. The model used for this study was introduced elsewhere and it is based on basic physics interactions without experimental parameters for these interactions. An intermediate phase between the burst and saturation phase is found and explained. Molecules experience a 1-D diffusion process that is different from the diffusion in the burst phase or the surface diffusion experienced by molecules attached to the wall. It is predicted that this phase exists when the molecule-wall interaction is attractive but not always noticeable in the release profile. In this work, it is shown that an agreement with the experiment better than previously reported is obtained when simulated delivery curves are produced by the weighted average of the release profiles from a collection of HNTs with diameters and lengths distributed according to the experimental sample, highlighting the relevance of HNTs' morphology in the release. HNTs are suitable for environment-triggered release and thus the effect of temperature, molecule zeta potential, and pH is studied. It is observed that for temperatures that significantly differ from room temperature (by 100's of degrees), the release profile changes significantly, increasing the delivery speed at high temperature and reducing that speed at low temperature. Finally, it is observed that as the pH becomes more acidic, both the molecule and inner wall surface become more positive (or less negative) with both eventually becoming positive leading to a repulsive interaction; thus, molecules are pushed out by electrostatic repulsion. On the contrary, as the pH becomes more basic, positive molecules become more positive while the wall becomes less negative, but even at pH 12, the wall remains negative and the interaction is attractive. Changes

  5. Changes in the regulation of heat shock gene expression in neuronal cell differentiation.

    PubMed

    Oza, Jay; Yang, Jingxian; Chen, Kuang Yu; Liu, Alice Y-C

    2008-01-01

    Neuronal differentiation of the NG108-15 neuroblastoma-glioma hybrid cells is accompanied by a marked attenuation in the heat shock induction of the Hsp70-firefly luciferase reporter gene activity. Analysis of the amount and activation of heat shock factor 1, induction of mRNA(hsp), and the synthesis and accumulation of heat shock proteins (HSPs) in the undifferentiated and differentiated cells suggest a transcriptional mechanism for this attenuation. Concomitant with a decreased induction of the 72-kDa Hsp70 protein in the differentiated cells, there is an increased abundance of the constitutive 73-kDa Hsc70, a protein known to function in vesicle trafficking. Assessment of sensitivity of the undifferentiated and differentiated cells against stress-induced cell death reveals a significantly greater vulnerability of the differentiated cells toward the cytotoxic effects of arsenite and glutamate/glycine. This study shows that changes in regulation of the HSP and HSC proteins are components of the neuronal cell differentiation program and that the attenuated induction of HSPs likely contributes to neuronal vulnerability whereas the increased expression of Hsc70 likely has a role in neural-specific functions.

  6. Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

    PubMed

    Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

    2013-03-01

    New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

  7. Heat shock and prolonged heat stress attenuate neurotoxin and sporulation gene expression in group I Clostridium botulinum strain ATCC 3502

    PubMed Central

    Selby, Katja; Mascher, Gerald; Somervuo, Panu; Korkeala, Hannu

    2017-01-01

    Foodborne pathogenic bacteria are exposed to a number of environmental stresses during food processing, storage, and preparation, and in the human body. In order to improve the safety of food, the understanding of molecular stress response mechanisms foodborne pathogens employ is essential. Many response mechanisms that are activated during heat shock may cross-protect bacteria against other environmental stresses. To better understand the molecular mechanisms Clostridium botulinum, the causative agent of botulism, utilizes during acute heat stress and during adaptation to stressfully high temperature, the C. botulinum Group I strain ATCC 3502 was grown in continuous culture at 39°C and exposed to heat shock at 45°C, followed by prolonged heat stress at 45°C to allow adaptation of the culture to the high temperature. Growth in continuous culture was performed to exclude secondary growth phase effects or other environmental impacts on bacterial gene transcription. Changes in global gene expression profiles were studied using DNA microarray hybridization. During acute heat stress, Class I and III heat shock genes as well as members of the SOS regulon were activated. The neurotoxin gene botA and genes encoding the neurotoxin-associated proteins were suppressed throughout the study. Prolonged heat stress led to suppression of the sporulation machinery whereas genes related to chemotaxis and motility were activated. Induced expression of a large proportion of prophage genes was detected, suggesting an important role of acquired genes in the stress resistance of C. botulinum. Finally, changes in the expression of a large number of genes related to carbohydrate and amino acid metabolism indicated remodeling of the cellular metabolism. PMID:28464023

  8. Heat shock and prolonged heat stress attenuate neurotoxin and sporulation gene expression in group I Clostridium botulinum strain ATCC 3502.

    PubMed

    Selby, Katja; Mascher, Gerald; Somervuo, Panu; Lindström, Miia; Korkeala, Hannu

    2017-01-01

    Foodborne pathogenic bacteria are exposed to a number of environmental stresses during food processing, storage, and preparation, and in the human body. In order to improve the safety of food, the understanding of molecular stress response mechanisms foodborne pathogens employ is essential. Many response mechanisms that are activated during heat shock may cross-protect bacteria against other environmental stresses. To better understand the molecular mechanisms Clostridium botulinum, the causative agent of botulism, utilizes during acute heat stress and during adaptation to stressfully high temperature, the C. botulinum Group I strain ATCC 3502 was grown in continuous culture at 39°C and exposed to heat shock at 45°C, followed by prolonged heat stress at 45°C to allow adaptation of the culture to the high temperature. Growth in continuous culture was performed to exclude secondary growth phase effects or other environmental impacts on bacterial gene transcription. Changes in global gene expression profiles were studied using DNA microarray hybridization. During acute heat stress, Class I and III heat shock genes as well as members of the SOS regulon were activated. The neurotoxin gene botA and genes encoding the neurotoxin-associated proteins were suppressed throughout the study. Prolonged heat stress led to suppression of the sporulation machinery whereas genes related to chemotaxis and motility were activated. Induced expression of a large proportion of prophage genes was detected, suggesting an important role of acquired genes in the stress resistance of C. botulinum. Finally, changes in the expression of a large number of genes related to carbohydrate and amino acid metabolism indicated remodeling of the cellular metabolism.

  9. Heat Shock Protein 70 Modulates Influenza A Virus Polymerase Activity*

    PubMed Central

    Manzoor, Rashid; Kuroda, Kazumichi; Yoshida, Reiko; Tsuda, Yoshimi; Fujikura, Daisuke; Miyamoto, Hiroko; Kajihara, Masahiro; Kida, Hiroshi; Takada, Ayato

    2014-01-01

    The role of heat shock protein 70 (Hsp70) in virus replication has been discussed for many viruses. The known suppressive role of Hsp70 in influenza virus replication is based on studies conducted in cells with various Hsp70 expression levels. In this study, we determined the role of Hsp70 in influenza virus replication in HeLa and HEK293T cells, which express Hsp70 constitutively. Co-immunoprecipitation and immunofluorescence studies revealed that Hsp70 interacted with PB2 or PB1 monomers and PB2/PB1 heterodimer but not with the PB1/PA heterodimer or PB2/PB1/PA heterotrimer and translocated into the nucleus with PB2 monomers or PB2/PB1 heterodimers. Knocking down Hsp70 resulted in reduced virus transcription and replication activities. Reporter gene assay, immunofluorescence assay, and Western blot analysis of nuclear and cytoplasmic fractions from infected cells demonstrated that the increase in viral polymerase activity during the heat shock phase was accompanied with an increase in Hsp70 and viral polymerases levels in the nuclei, where influenza virus replication takes place, whereas a reduction in viral polymerase activity was accompanied with an increase in cytoplasmic relocation of Hsp70 along with viral polymerases. Moreover, significantly higher levels of viral genomic RNA (vRNA) were observed during the heat shock phase than during the recovery phase. Overall, for the first time, these findings suggest that Hsp70 may act as a chaperone for influenza virus polymerase, and the modulatory effect of Hsp70 appears to be a sequel of shuttling of Hsp70 between nuclear and cytoplasmic compartments. PMID:24474693

  10. Increased temperature, not cardiac load, activates heat shock transcription factor 1 and heat shock protein 72 expression in the heart.

    PubMed

    Staib, Jessica L; Quindry, John C; French, Joel P; Criswell, David S; Powers, Scott K

    2007-01-01

    The expression of myocardial heat shock protein 72 (HSP72) postexercise is initiated by the activation of heat shock transcription factor 1 (HSF1). However, it remains unknown which physiological stimuli govern myocardial HSF1 activation during exercise. These experiments tested the hypothesis that thermal stress and mechanical load, concomitant with simulated exercise, provide independent stimuli for HSF1 activation and ensuing cardiac HSP72 gene expression. To elucidate the independent roles of increased temperature and cardiac workload in the exercise-mediated upregulation of left-ventricular HSP72, hearts from adult male Sprague-Dawley rats were randomly assigned to one of five simulated exercise conditions. Upon reaching a surgical plane of anesthesia, each experimental heart was isolated and perfused using an in vitro working heart model, while independently varying temperatures (i.e., 37 degrees C vs. 40 degrees C) and cardiac workloads (i.e., low preload and afterload vs. high preload and afterload) to mimic exercise responses. Results indicate that hyperthermia, independent of cardiac workload, promoted an increase in nuclear translocation and phosphorylation of HSF1 compared with normothermic left ventricles. Similarly, hyperthermia, independent of workload, resulted in significant increases in cardiac levels of HSP72 mRNA. Collectively, these data suggest that HSF1 activation and HSP72 gene transcriptional competence during simulated exercise are linked to elevated heart temperature and are not a direct function of increased cardiac workload.

  11. Suppression of polyglutamine protein toxicity by co-expression of a heat-shock protein 40 and a heat-shock protein 110

    PubMed Central

    Kuo, Y; Ren, S; Lao, U; Edgar, B A; Wang, T

    2013-01-01

    A network of heat-shock proteins mediates cellular protein homeostasis, and has a fundamental role in preventing aggregation-associated neurodegenerative diseases. In a Drosophila model of polyglutamine (polyQ) disease, the HSP40 family protein, DNAJ-1, is a superior suppressor of toxicity caused by the aggregation of polyQ containing proteins. Here, we demonstrate that one specific HSP110 protein, 70 kDa heat-shock cognate protein cb (HSC70cb), interacts physically and genetically with DNAJ-1 in vivo, and that HSC70cb is necessary for DNAJ-1 to suppress polyglutamine-induced cell death in Drosophila. Expression of HSC70cb together with DNAJ-1 significantly enhanced the suppressive effects of DNAJ-1 on polyQ-induced neurodegeneration, whereas expression of HSC70cb alone did not suppress neurodegeneration in Drosophila models of either general polyQ disease or Huntington's disease. Furthermore, expression of a human HSP40, DNAJB1, together with a human HSP110, APG-1, protected cells from polyQ-induced neural degeneration in flies, whereas expression of either component alone had little effect. Our data provide a functional link between HSP40 and HSP110 in suppressing the cytotoxicity of aggregation-prone proteins, and suggest that HSP40 and HSP110 function together in protein homeostasis control. PMID:24091676

  12. Role of charred wood, heat-shock and light in germination of postfire phrygana species from the eastern Mediterranean Basin

    USGS Publications Warehouse

    Keeley, Jon E.; Babr-Keeley, Melanie

    1999-01-01

    Seeds of 22 species collected from recently burned phrygana were tested for their response to fire-type cues of charred wood and heat-shock. All Cistus species were stimulated by brief heat-shock, as shown in previous studies; however, none responded to charred wood. Only one of the 22 species was stimulated by charred wood, and only in dark-inhibited seeds, and this response did not occur in the light. The lack of charred-wood-induced germination is in contrast to the substantial proportion of species with this germination response reported for mediterranean-type vegetation in California, the Cape region of South Africa, and Western Australia. Phrygana has many species with heat-shock-stimulated germination, primarily in the Fabaceae and Cistaceae. This germination cue is widespread in these two families, thus, the presence of heat-shock-stimulated germination is a result of homologous, rather than covergent, adaptations in mediterranean-climate ecosystems. Germination response to light was not randomly distributed with respect to fire-type response. Heat-shock-stimulated species were almost uniformly light neutral, in contrast to more opportunistic colonizing species with non-refractory seeds, in which half of the species responded positively or negatively to light.

  13. Development of a liposomal delivery system for temperature-triggered release of a tumor targeting agent, Ln(III)-DOTA-phenylboronate.

    PubMed

    Djanashvili, Kristina; ten Hagen, Timo L M; Blangé, Roy; Schipper, Debby; Peters, Joop A; Koning, Gerben A

    2011-02-01

    Liposomes, capable of temperature-triggered content release at the site of interest, can be of great importance for imaging and therapy of tumors. The delivery of imaging agents or therapeutics can be improved by application of liposomes with a gel-to-liquid phase-transition temperature suitable for mild hyperthermia (41-43°C), and by prolonging their circulation time by incorporation of lipids containing polyethyleneglycol moieties. Still, the rapid wash out of the delivered material from the tumor tissue is a major obstacle for both imaging and therapy. In this study, we developed an optimized temperature sensitive liposomal system to be used with mild hyperthermia: highly stable at physiological temperature and with a sharp transition of the bilayer at 41.5°C, with subsequent rapid release of entrapped compounds such as calcein or tumor cell-targeting contrast agents. Intravital microscopy on calcein/rhodamine containing liposomes was applied to demonstrate the applicability of this system in vivo. The calcein loaded liposomes were injected iv into nude mice with a human BLM melanoma tumor implanted in a dorsal skin-fold window chamber. Arrival of the liposomes at the tumor site and content release after temperature increase were monitored. The results demonstrated not only accumulation of the liposomes at the tumor site, but also a massive release of calcein after increase of the temperature to 41°C. The versatility of the thermosensitive liposomes was further demonstrated by encapsulation of a tumor cell-targeting DOTA-phenylboronate conjugate and its release at elevated temperatures. The DOTA ligand in this system is able to chelate a variety of metals suitable for both diagnostic and therapeutic applications, whereas the phenylboronate function is able to target specifically to tumor cells through a covalent binding with sialic acid moieties over-expressed on their surface upon heat-triggered release from the liposomal carrier. Copyright © 2010 Elsevier

  14. Short-term heat shock affects the course of immune response in Galleria mellonella naturally infected with the entomopathogenic fungus Beauveria bassiana.

    PubMed

    Vertyporokh, Lidiia; Taszłow, Paulina; Samorek-Pieróg, Małgorzata; Wojda, Iwona

    2015-09-01

    We aimed to investigate how exposition of infected insects to short-term heat shock affects the biochemical and molecular aspects of their immune response. Galleria mellonella larvae were exposed to 43°C for 15min, at the seventy second hour after natural infection with entomopathogenic fungus Beauveria bassiana. As a result, both qualitative and quantitative changes in hemolymph protein profiles, and among them infection-induced changes in the amount of apolipophorin III (apoLp-III), were observed. Heat shock differently affects the expression of the tested immune-related genes. It transiently inhibits expression of antifungal peptides gallerimycin and galiomicin in both the fat body and hemocytes of infected larvae. The same, although to a lesser extent, concerned apoLp-III gene expression and was observed directly after heat shock. Nevertheless, in larvae that had recovered from heat shock, apoLp-III expression was higher in comparison to unshocked larvae in the fat body but not in hemocytes, which was consistent with the higher amount of this protein detected in the hemolymph of the infected, shocked larvae. Furthermore, lysozyme-type activity was higher directly after heat shock, while antifungal activity was significantly higher also in larvae that had recovered from heat shock, in comparison to the respective values in their non-shocked, infected counterparts. These results show how changes in the external temperature modulate the immune response of G. mellonella suffering from infection with its natural pathogen B. bassiana. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms.

    PubMed

    Ayers, Lisa; Nieuwland, Rienk; Kohler, Malcolm; Kraenkel, Nicolle; Ferry, Berne; Leeson, Paul

    2015-12-01

    Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies. © 2015 Authors; published by Portland Press Limited.

  16. Thermoprotection of synaptic transmission in a Drosophila heat shock factor mutant is accompanied by increased expression of Hsp83 and DnaJ-1.

    PubMed

    Neal, Scott J; Karunanithi, Shanker; Best, Adrienne; So, Anthony Ken-Choy; Tanguay, Robert M; Atwood, Harold L; Westwood, J Timothy

    2006-05-16

    In Drosophila larvae, acquired synaptic thermotolerance after heat shock has previously been shown to correlate with the induction of heat shock proteins (Hsps) including HSP70. We tested the hypothesis that synaptic thermotolerance would be significantly diminished in a temperature-sensitive strain (Drosophila heat shock factor mutant hsf4), which has been reported not to be able to produce inducible Hsps in response to heat shock. Contrary to our hypothesis, considerable thermoprotection was still observed at hsf4 larval synapses after heat shock. To investigate the cause of this thermoprotection, we conducted DNA microarray experiments to identify heat-induced transcript changes in these organisms. Transcripts of the hsp83, dnaJ-1 (hsp40), and glutathione-S-transferase gstE1 genes were significantly upregulated in hsf4 larvae after heat shock. In addition, increases in the levels of Hsp83 and DnaJ-1 proteins but not in the inducible form of Hsp70 were detected by Western blot analysis. The mode of heat shock administration differentially affected the relative transcript and translational changes for these chaperones. These results indicate that the compensatory upregulation of constitutively expressed Hsps, in the absence of the synthesis of the major inducible Hsp, Hsp70, could still provide substantial thermoprotection to both synapses and the whole organism.

  17. Deep-release of Epon 828 epoxy from the shock-driven reaction product phase

    NASA Astrophysics Data System (ADS)

    Lang, John; Fredenburg, Anthony; Coe, Joshua; Dattelbaum, Dana

    2017-06-01

    A challenge in improving equations-of-state (EOS) for polymers and their product phase is the lack of off-Hugoniot data. Here, we describe a novel experimental approach for obtaining release pathways along isentropes from the shocked products. A series of gas-gun experiments was conducted to obtain release isentropes of the products for 70/30 wt% Epon 828 epoxy resin/Jeffamine T-403 curing agent. Thin epoxy flyers backed by a low-density syntactic foam were impacted into LiF windows at up to 6.3 mm/ μs, creating stresses in excess of those required for reaction ( 25 GPa). Following a sustained shock input, a rarefaction fan from the back of the thin flyer reduced the pressure in the epoxy products along a release isentrope. Optical velocimetry (PDV) was used to measure the particle velocity at the epoxy/LiF interface. Numerical simulations using several different EOS describing the reactant-to-product transformation were conducted, and the results were compared with measured wave profiles. The best agreement with experiment was obtained using separate tabular EOS for the polymer ``reactant'' (e.g. epoxy) and product mixture, suggesting the transition to the products is irreversible.

  18. A multifunctional magnetic nanocarrier bearing fluorescent dye for targeted drug delivery by enhanced two-photon triggered release

    NASA Astrophysics Data System (ADS)

    Banerjee, Shashwat S.; Chen, Dong-Hwang

    2009-05-01

    We report a novel nanoformulation for targeted drug delivery which utilizes nanophotonics through the fusion of nanotechnology with biomedical application. The approach involves an energy-transferring magnetic nanoscopic co-assembly fabricated of rhodamine B (RDB) fluorescent dye grafted gum arabic modified Fe3O4 magnetic nanoparticle and photosensitive linker by which dexamethasone drug is conjugated to the magnetic nano-assembly. The advantage offered by this nanoformulation is the indirect photo-triggered-on-demand drug release by efficient up-converting energy of the near-IR (NIR) light to higher energy and intraparticle energy transfer from the dye grafted magnetic nanoparticle to the linker for drug release by cleavage. The synthesized nanoparticles were found to be of ultra-small size (13.33 nm) and are monodispersed in an aqueous suspension. Dexamethasone (Dexa) drug conjugated to RDB-GAMNP by photosensitive linker showed appreciable release of Dexa by photo-triggered response on exposure to radiation having a wavelength in the NIR region whereas no detectable release was observed in the dark. Photo-triggered response for the nanoformulation not bearing the rhodamine B dye was drastically less as less Dexa was released on exposure to NIR radiation which suggest that the photo-cleavage of linker and release of Dexa mainly originated from the indirect excitation through the uphill energy conversions based on donor-acceptor model FRET. The promising pathway of nanophotonics for the on-demand release of the drug makes this nanocarrier very promising for applications in nanomedicine.

  19. Global Aeroheating Measurements of Shock-Shock Interactions on a Swept Cylinder

    NASA Technical Reports Server (NTRS)

    Mason, Michelle L.; Berry, Scott A.

    2015-01-01

    The effects of fin leading-edge radius and sweep angle on peak heating rates due to shock-shock interactions were investigated in the NASA Langley Research Center 20-Inch Mach 6 Air Tunnel. The cylindrical leading-edge fin models, with radii varied from 0.25 to 0.75 inches, represent wings or struts on hypersonic vehicles. A 9deg wedge generated a planar oblique shock at 16.7deg. to the flow that intersected the fin bow shock, producing a shock-shock interaction that impinged on the fin leading edge. The fin sweep angle was varied from 0deg (normal to the free-stream) to 15deg and 25deg swept forward. These cases were chosen to explore three characterized shock-shock interaction types. Global temperature data were obtained from the surface of the fused silica fins using phosphor thermography. Metal oil flow models with the same geometries as the fused silica models were used to visualize the streamline patterns for each angle of attack. High-speed zoom-schlieren videos were recorded to show the features and any temporal unsteadiness of the shock-shock interactions. The temperature data were analyzed using a one-dimensional semi-infinite method, as well as one- and two-dimensional finite-volume methods. These results were compared to determine the proper heat transfer analysis approach to minimize errors from lateral heat conduction due to the presence of strong surface temperature gradients induced by the shock interactions. The general trends in the leading-edge heat transfer behavior were similar for each explored shock-shock interaction type regardless of the leading-edge radius. However, the dimensional peak heat transfer coefficient augmentation increased with decreasing leading-edge radius. The dimensional peak heat transfer output from the two-dimensional code was about 20% higher than the value from a standard, semi-infinite one-dimensional method.

  20. Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation

    PubMed Central

    Zheng, Xu; Krakowiak, Joanna; Patel, Nikit; Beyzavi, Ali; Ezike, Jideofor; Khalil, Ahmad S; Pincus, David

    2016-01-01

    Heat shock factor (Hsf1) regulates the expression of molecular chaperones to maintain protein homeostasis. Despite its central role in stress resistance, disease and aging, the mechanisms that control Hsf1 activity remain unresolved. Here we show that in budding yeast, Hsf1 basally associates with the chaperone Hsp70 and this association is transiently disrupted by heat shock, providing the first evidence that a chaperone repressor directly regulates Hsf1 activity. We develop and experimentally validate a mathematical model of Hsf1 activation by heat shock in which unfolded proteins compete with Hsf1 for binding to Hsp70. Surprisingly, we find that Hsf1 phosphorylation, previously thought to be required for activation, in fact only positively tunes Hsf1 and does so without affecting Hsp70 binding. Our work reveals two uncoupled forms of regulation - an ON/OFF chaperone switch and a tunable phosphorylation gain - that allow Hsf1 to flexibly integrate signals from the proteostasis network and cell signaling pathways. DOI: http://dx.doi.org/10.7554/eLife.18638.001 PMID:27831465

  1. Extracellular heat shock protein HSP90{beta} secreted by MG63 osteosarcoma cells inhibits activation of latent TGF-{beta}1

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

    Suzuki, Shigeki; Kulkarni, Ashok B., E-mail: ak40m@nih.gov

    2010-07-30

    Transforming growth factor-beta 1 (TGF-{beta}1) is secreted as a latent complex, which consists of latency-associated peptide (LAP) and the mature ligand. The release of the mature ligand from LAP usually occurs through conformational change of the latent complex and is therefore considered to be the first step in the activation of the TGF-{beta} signaling pathway. So far, factors such as heat, pH changes, and proteolytic cleavage are reportedly involved in this activation process, but the precise molecular mechanism is still far from clear. Identification and characterization of the cell surface proteins that bind to LAP are important to our understandingmore » of the latent TGF-{beta} activation process. In this study, we have identified heat shock protein 90 {beta} (HSP90{beta}) from the cell surface of the MG63 osteosarcoma cell line as a LAP binding protein. We have also found that MG63 cells secrete HSP90{beta} into extracellular space which inhibits the activation of latent TGF-{beta}1, and that there is a subsequent decrease in cell proliferation. TGF-{beta}1-mediated stimulation of MG63 cells resulted in the increased cell surface expression of HSP90{beta}. Thus, extracellular HSP90{beta} is a negative regulator for the activation of latent TGF-{beta}1 modulating TGF-{beta} signaling in the extracellular domain. -- Research highlights: {yields} Transforming growth factor-beta 1 (TGF-{beta}1) is secreted as a latent complex. {yields} This complex consists of latency-associated peptide (LAP) and the mature ligand. {yields} The release of the mature ligand from LAP is the first step in TGF-{beta} activation. {yields} We identified for the first time a novel mechanism for this activation process. {yields} Heat shock protein 90 {beta} is discovered as a negative regulator for this process.« less

  2. Triggers and Manifestations of Flare Energy Release in the Low Atmosphere

    NASA Astrophysics Data System (ADS)

    Kosovichev, A. G.; Sharykin, I. N.; Sadykov, V. M.; Vargas, S.; Zimovets, I. V.

    2016-12-01

    The main goal is to understand triggers and manifestations of the flare energy release in the lower layers of the solar atmosphere (the photosphere and chromosphere) using high-resolution optical observations and magnetic field measurements. As a case study we present results for an M-class flare. We analyze optical images, HMI Dopplergrams and vector magnetograms, and use Non-Linear Force-Free Field (NLFFF) extrapolation for reconstruction of the magnetic topology. The NLFFF modelling reveals interaction of oppositely directed magnetic flux-tubes in the Polarity Inversion Line (PIL). These two interacting magnetic flux tubes are observed as a compact sheared arcade along the PIL in the high-resolution broad-band continuum images from New Solar Telescope (NST). In the vicinity of the PIL, the NST H-alpha observations reveal formation of a thin three-ribbon structure corresponding to the small-scale photospheric magnetic arcade. Magnetic reconnection is triggered by two interacting magnetic flux tubes with forming current sheet extended along the PIL. Presented observational results evidence in favor of location of the primary energy release site in the dense chromosphere where plasma is partially ionized in the region of strong electric currents concentrated near the polarity inversion line.

  3. Sodium hydrosulfide induces systemic thermotolerance to strawberry plants through transcriptional regulation of heat shock proteins and aquaporin

    PubMed Central

    2014-01-01

    Background Temperature extremes represent an important limiting factor to plant growth and productivity. The present study evaluated the effect of hydroponic pretreatment of strawberry (Fragaria x ananassa cv. ‘Camarosa’) roots with an H2S donor, sodium hydrosulfide (NaHS; 100 μM for 48 h), on the response of plants to acute heat shock treatment (42°C, 8 h). Results Heat stress-induced phenotypic damage was ameliorated in NaHS-pretreated plants, which managed to preserve higher maximum photochemical PSII quantum yields than stressed plants. Apparent mitigating effects of H2S pretreatment were registered regarding oxidative and nitrosative secondary stress, since malondialdehyde (MDA), H2O2 and nitric oxide (NO) were quantified in lower amounts than in heat-stressed plants. In addition, NaHS pretreatment preserved ascorbate/glutathione homeostasis, as evidenced by lower ASC and GSH pool redox disturbances and enhanced transcription of ASC (GDH) and GSH biosynthetic enzymes (GS, GCS), 8 h after heat stress imposition. Furthermore, NaHS root pretreatment resulted in induction of gene expression levels of an array of protective molecules, such as enzymatic antioxidants (cAPX, CAT, MnSOD, GR), heat shock proteins (HSP70, HSP80, HSP90) and aquaporins (PIP). Conclusion Overall, we propose that H2S root pretreatment activates a coordinated network of heat shock defense-related pathways at a transcriptional level and systemically protects strawberry plants from heat shock-induced damage. PMID:24499299

  4. Heat shock and thermotolerance of Escherichia coli O157:H7 in a model beef gravy system and ground beef.

    PubMed

    Juneja, V K; Klein, P G; Marmer, B S

    1998-04-01

    Duplicate beef gravy or ground beef samples inoculated with a suspension of a four-strain cocktail of Escherichia coli O157:H7 were subjected to sublethal heating at 46 degrees C for 15-30 min, and then heated to a final internal temperature of 60 degrees C. Survivor curves were fitted using a linear model that incorporated a lag period (TL), and D-values and 'time to a 4D inactivation' (T4D) were calculated. Heat-shocking allowed the organism to survive longer than non-heat-shocked cells; the T4D values at 60 degrees C increased 1.56- and 1.50-fold in beef gravy and ground beef, respectively. In ground beef stored at 4 degrees C, thermotolerance was lost after storage for 14 h. However, heat-shocked cells appeared to maintain their thermotolerance for at least 24 h in ground beef held to 15 or 28 degrees C. A 25 min heat shock at 46 degrees C in beef gravy resulted in an increase in the levels of two proteins with apparent molecular masses of 60 and 69 kDa. These two proteins were shown to be immunologically related to GroEL and DnaK, respectively. Increased heat resistance due to heat shock must be considered while designing thermal processes to assure the microbiological safety of thermally processed foods.

  5. Effects of anthropogenic heat release upon the urban climate in a Japanese megacity.

    PubMed

    Narumi, Daisuke; Kondo, Akira; Shimoda, Yoshiyuki

    2009-05-01

    This report presents results of investigations of the influence of anthropogenic heat release in Japanese megacity (Keihanshin district) upon the urban climate, using the energy database [Shimoda et al., 1999. Estimation and evaluation of artificial waste heat in urban area. Selected Papers from the Conference ICB-ICUC'99 WCASP-50 WMO/TD no. 1026] as a part of the land-surface boundary conditions of a mesoscale meteorological simulation model. The calculated results related to atmospheric temperature distribution were similar to observed values not only for daily averages but also for amplitudes and phases of diurnal change. To reproduce accurately, it is essential to reproduce urban characteristics such as an urban canopy and anthropogenic heat release in a fine resolution mesh. We attempted an analysis using current data for anthropogenic heat and under uniform heat release conditions, to investigate temporal and spatial characteristics in relation to the influence of anthropogenic heat release on the urban climate. The results of investigation into the influence of anthropogenic heat release on atmospheric temperature using current data indicate that the amount of heat released is lower at night than during the day, but the temperature rise is nearly 3 times greater. Results of investigation into the influence of anthropogenic heat release on wind systems using current data indicate that the onset of land breezes is delayed, particularly in a coastal area. Investigation into the temporal characteristics related to the influence of anthropogenic heat release under uniform heat release conditions showed a maximum influence on temperature during the predawn period.

  6. Effects of Shock-Breakout Pressure on Ejection of Micron-Scale Material from Shocked Tin Surfaces

    NASA Astrophysics Data System (ADS)

    Zellner, Michael; Hammerberg, James; Hixson, Robert; Morley, Kevin; Obst, Andrew; Olson, Russell; Payton, Jeremy; Rigg, Paulo; Buttler, William; Grover, Michael; Iverson, Adam; Macrum, Gregory; Stevens, Gerald; Turley, William; Veeser, Lynn; Routley, Nathan

    2007-06-01

    Los Alamos National Lab (LANL) is actively engaged in the development of a model to predict the formation of micron-scale fragments ejected (ejecta) from shocked metal surfaces. The LANL ejecta model considers that the amount of ejecta is mainly related to the material's phase on shock release at the free-surface. This effort investigates the relation between ejecta production and shock-breakout pressure for Sn shocked with high explosives to pressures near the solid-on-release/partial-liquid-on-release phase transition region. We found that the amount of ejecta produced for shock-breakout pressures that resulted in partial-liquid-on-release increased significantly compared to that which resulted in solid-on-release. Additionally, we found that the amount of ejecta remained relatively constant within the partial-liquid-on-release, regardless of shock-breakout pressure.

  7. Hsp72 release: mechanisms and methodologies.

    PubMed

    Asea, Alexzander

    2007-11-01

    To date there are two mechanisms that are recognized by which heat shock proteins (HSP) are released from cells; a passive release mechanism, including necrotic cell death, severe blunt trauma, surgery and following infection with lytic viruses, and an active release mechanism which involves the non classical protein release pathway in which HSPs are released within highly immunologically potent exosomes and as free HSP. This chapter describes the experimental procedures that have been developed to study the mechanism by which stress induces the release of HSP72 into the circulation and addresses the biological significance of circulating HSP72 to host defense against disease.

  8. The stress protein heat shock cognate 70 (Hsc70) inhibits the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel.

    PubMed

    Iftinca, Mircea; Flynn, Robyn; Basso, Lilian; Melo, Helvira; Aboushousha, Reem; Taylor, Lauren; Altier, Christophe

    2016-01-01

    Specialized cellular defense mechanisms prevent damage from chemical, biological, and physical hazards. The heat shock proteins have been recognized as key chaperones that maintain cell survival against a variety of exogenous and endogenous stress signals including noxious temperature. However, the role of heat shock proteins in nociception remains poorly understood. We carried out an expression analysis of the constitutively expressed 70 kDa heat-shock cognate protein, a member of the stress-induced HSP70 family in lumbar dorsal root ganglia from a mouse model of Complete Freund's Adjuvant-induced chronic inflammatory pain. We used immunolabeling of dorsal root ganglion neurons, behavioral analysis and patch clamp electrophysiology in both dorsal root ganglion neurons and HEK cells transfected with Hsc70 and Transient Receptor Potential Channels to examine their functional interaction in heat shock stress condition. We report an increase in protein levels of Hsc70 in mouse dorsal root ganglia, 3 days post Complete Freund's Adjuvant injection in the hind paw. Immunostaining of Hsc70 was observed in most of the dorsal root ganglion neurons, including the small size nociceptors immunoreactive to the TRPV1 channel. Standard whole-cell patch-clamp technique was used to record Transient Receptor Potential Vanilloid type 1 current after exposure to heat shock. We found that capsaicin-evoked currents are inhibited by heat shock in dorsal root ganglion neurons and transfected HEK cells expressing Hsc70 and TRPV1. Blocking Hsc70 with matrine or spergualin compounds prevented heat shock-induced inhibition of the channel. We also found that, in contrast to TRPV1, both the cold sensor channels TRPA1 and TRPM8 were unresponsive to heat shock stress. Finally, we show that inhibition of TRPV1 depends on the ATPase activity of Hsc70 and involves the rho-associated protein kinase. Our work identified Hsc70 and its ATPase activity as a central cofactor of TRPV1 channel function

  9. Cold Heat Release Characteristics of Solidified Oil Droplet-Water Solution Latent Heat Emulsion by Air Bubbles

    NASA Astrophysics Data System (ADS)

    Inaba, Hideo; Morita, Shin-Ichi

    The present work investigates the cold heat-release characteristics of the solidified oil droplets (tetradecane, C14H30, freezing point 278.9 K)/water solution emulsion as a latent heat-storage material having a low melting point. An air bubbles-emulsion direct-contact heat exchange method is selected for the cold heat-results from the solidified oil droplet-emulsion layer. This type of direct-contact method results in the high thermal efficiency. The diameter of air bubbles in the emulsion increases as compared with that in the pure water. The air bubbles blown from a nozzle show a strong mixing behavior during rising in the emulsion. The temperature effectiveness, the sensible heat release time and the latent heat release time have been measured as experimental parameters. The useful nondimensional emulsion level equations for these parameters have been derived in terms of the nondimensional emalsion level expressed the emulsion layer dimensions, Reynolds number for air flow, Stefan number and heat capacity ratio.

  10. Analysis of transactivation potential of rice (Oryza sativa L.) heat shock factors.

    PubMed

    Lavania, Dhruv; Dhingra, Anuradha; Grover, Anil

    2018-06-01

    Based on yeast one-hybrid assays, we show that the presence of C-terminal AHA motifs is not a prerequisite for transactivation potential in rice heat shock factors. Transcriptional activation or transactivation (TA) of heat stress responsive genes takes place by binding of heat shock factors (Hsfs) to heat shock elements. Analysis of TA potential of thirteen rice (Oryza sativa L.) Hsfs (OsHsfs) carried out in this study by yeast one-hybrid assay showed that OsHsfsA3 possesses strong TA potential while OsHsfs A1a, A2a, A2b, A4a, A4d, A5, A7b, B1, B2a, B2b, B2c and B4d lack TA potential. From a near complete picture of TA potential of the OsHsf family (comprising of 25 members) emerging from this study and an earlier report from our group (Mittal et al. in FEBS J 278(17):3076-3085, 2011), it is concluded that (1) overall, six OsHsfs, namely A3, A6a, A6b, A8, C1a and C1b possess TA potential; (2) four class A OsHsfs, namely A3, A6a, A6b and A8 have TA potential out of which A6a and A6b contain AHA motifs while A3 and A8 lack AHA motifs; (3) nine class A OsHsfs, namely A1a, A2a, A2b, A2e, A4a, A4d, A5, A7a and A7b containing AHA motif(s) lack TA function in the yeast assay system; (4) all class B OsHsfs lack AHA motifs and TA potential (B4a not analyzed) and (5) though all class C OsHsf members lack AHA motifs, two members C1a and C1b possess TA function, while one member C2a lacks TA potential (C2b not analyzed). Thus, the presence or absence of AHA motif is possibly not the only factor determining TA potential of OsHsfs. Our findings will help to identify the transcriptional activators of rice heat shock response.

  11. Shock compression and release of a-axis magnesium single crystals: Anisotropy and time dependent inelastic response

    DOE PAGES

    Renganathan, P.; Winey, J. M.; Gupta, Y. M.

    2017-01-19

    Here, to gain insight into inelastic deformation mechanisms for shocked hexagonal close-packed (hcp) metals, particularly the role of crystal anisotropy, magnesium (Mg) single crystals were subjected to shock compression and release along the a-axis to 3.0 and 4.8 GPa elastic impact stresses. Wave profiles measured at several thicknesses, using laser interferometry, show a sharply peaked elastic wave followed by the plastic wave. Additionally, a smooth and featureless release wave is observed following peak compression. When compared to wave profiles measured previously for c-axis Mg, the elastic wave amplitudes for a-axis Mg are lower for the same propagation distance, and less attenuation of elastic wave amplitude is observed for a given peak stress. The featureless release wave for a-axis Mg is in marked contrast to the structured features observed for c-axis unloading. Numerical simulations, using a time-dependent anisotropic modeling framework, showed that the wave profiles calculated using prismatic slip or (10more » $$\\bar{1}$$2) twinning, individually, do not match the measured compression profiles for a-axis Mg. However, a combination of slip and twinning provides a good overall match to the measured compression profiles. In contrast to compression,prismatic slip alone provides a reasonable match to the measured release wave profiles; (10$$\\bar{1}$$2) twinning due to its uni-directionality is not activated during release. The experimental results and wave profile simulations for a-axis Mg presented here are quite different from the previously published c-axis results, demonstrating the important role of crystal anisotropy on the time-dependent inelastic deformation of Mg single crystals under shock compression and release.« less

  12. Shock compression and release of a-axis magnesium single crystals: Anisotropy and time dependent inelastic response

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

    Renganathan, P.; Winey, J. M.; Gupta, Y. M.

    Here, to gain insight into inelastic deformation mechanisms for shocked hexagonal close-packed (hcp) metals, particularly the role of crystal anisotropy, magnesium (Mg) single crystals were subjected to shock compression and release along the a-axis to 3.0 and 4.8 GPa elastic impact stresses. Wave profiles measured at several thicknesses, using laser interferometry, show a sharply peaked elastic wave followed by the plastic wave. Additionally, a smooth and featureless release wave is observed following peak compression. When compared to wave profiles measured previously for c-axis Mg, the elastic wave amplitudes for a-axis Mg are lower for the same propagation distance, and less attenuation of elastic wave amplitude is observed for a given peak stress. The featureless release wave for a-axis Mg is in marked contrast to the structured features observed for c-axis unloading. Numerical simulations, using a time-dependent anisotropic modeling framework, showed that the wave profiles calculated using prismatic slip or (10more » $$\\bar{1}$$2) twinning, individually, do not match the measured compression profiles for a-axis Mg. However, a combination of slip and twinning provides a good overall match to the measured compression profiles. In contrast to compression,prismatic slip alone provides a reasonable match to the measured release wave profiles; (10$$\\bar{1}$$2) twinning due to its uni-directionality is not activated during release. The experimental results and wave profile simulations for a-axis Mg presented here are quite different from the previously published c-axis results, demonstrating the important role of crystal anisotropy on the time-dependent inelastic deformation of Mg single crystals under shock compression and release.« less

  13. Small interfering RNA mediated Poly (ADP-ribose) Polymerase-1 inhibition upregulates the heat shock response in a murine fibroblast cell line

    PubMed Central

    2011-01-01

    Poly (ADP-ribose) polymerase-1 (PARP-1) is a highly conserved multifunctional enzyme, and its catalytic activity is stimulated by DNA breaks. The activation of PARP-1 and subsequent depletion of nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP) contributes to significant cytotoxicity in inflammation of various etiologies. On the contrary, induction of heat shock response and production of heat shock protein 70 (HSP-70) is a cytoprotective defense mechanism in inflammation. Recent data suggests that PARP-1 modulates the expression of a number of cellular proteins at the transcriptional level. In this study, small interfering RNA (siRNA) mediated PARP-1 knockdown in murine wild-type fibroblasts augmented heat shock response as compared to untreated cells (as evaluated by quantitative analysis of HSP-70 mRNA and HSP-70 protein expression). These events were associated with increased DNA binding of the heat shock factor-1 (HSF-1), the major transcription factor of the heat shock response. Co-immunoprecipitation experiments in nuclear extracts of the wild type cells demonstrated that PARP-1directly interacted with HSF-1. These data demonstrate that, in wild type fibroblasts, PARP-1 plays a pivotal role in modulating the heat shock response both through direct interaction with HSF-1 and poly (ADP-ribosylation). PMID:21345219

  14. τ kinases in the rat heat shock model: Possible implications for Alzheimer disease

    PubMed Central

    Shanavas, Alikunju; Papasozomenos, Sozos Ch.

    2000-01-01

    We have previously shown, by using the phosphate-dependent anti-τ antibodies Tau-1 and PHF-1, that heat shock induces rapid dephosphorylation of τ followed by hyperphosphorylation in female rats. In this study, we analyzed in forebrain homogenates from female Sprague–Dawley rats the activities of extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (Cdk5), cAMP-dependent protein kinase A (PKA), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) at 0 (n = 5), 3 (n = 4), 6 (n = 5), and 12 (n = 5) h after heat shock and in non-heat-shocked controls (n = 5). Immunoprecipitation kinase assays at 0 h showed suppression of the activities of all kinases except of GSK-3β, which showed increased activity. At 3–6 h, the activities of ERK1/2, JNK, Cdk5, and GSK-3β toward selective substrates were increased; however, only JNK, Cdk5, and GSK-3β but not ERK1/2 were overactivated toward purified bovine τ. At 3–6 h, kinase assays specific for PKA and CaMKII showed no increased activity toward either τ or selective substrates. All of eight anti-τ antibodies tested showed dephosphorylation at 0 h and hyperphosphorylation at 3–6 h, except for 12E8, which showed hyperphosphorylation also at 0 h. Immunoblot analysis using activity-dependent antibodies against ERK1/2, JNK, and GSK-3β confirmed the above data. Increased activation and inhibition of kinases after heat shock were statistically significant in comparison with controls. Because τ is hyperphosphorylated in Alzheimer disease these findings suggest that JNK, GSK-3β, and Cdk5 may play a role in its pathogenesis. PMID:11121021

  15. Heat Shock Protein Augmentation of Angelica gigas Nakai Root Hot Water Extract on Adipogenic Differentiation in Murine 3T3-L1 Preadipocytes

    PubMed Central

    Lumbera, Wenchie Marie L.; dela Cruz, Joseph; Yang, Seung-Hak; Hwang, Seong Gu

    2016-01-01

    There is a high association of heat shock on the alteration of energy and lipid metabolism. The alterations associated with thermal stress are composed of gene expression changes and adaptation through biochemical responses. Previous study showed that Angelica gigas Nakai (AGN) root extract promoted adipogenic differentiation in murine 3T3-L1 preadipocytes under the normal temperature condition. However, its effect in heat shocked 3T3-L1 cells has not been established. In this study, we investigated the effect of AGN root hot water extract in the adipogenic differentiation of murine 3T3-L1 preadipocytes following heat shock and its possible mechanism of action. Thermal stress procedure was executed within the same stage of preadipocyte confluence (G0) through incubation at 42°C for one hour and then allowed to recover at normal incubation temperature of 37°C for another hour before AGN treatment for both cell viability assay and Oil Red O. Cell viability assay showed that AGN was able to dose dependently (0 to 400 μg/mL) increase cell proliferation under normal incubation temperature and also was able to prevent cytotoxicity due to heat shock accompanied by cell proliferation. Confluent preadipocytes were subjected into heat shock procedure, recovery and then AGN treatment prior to stimulation with the differentiation solution. Heat shocked preadipocytes exhibited reduced differentiation as supported by decreased amount of lipid accumulation in Oil Red O staining and triglyceride measurement. However, those heat shocked preadipocytes that then were given AGN extract showed a dose dependent increase in lipid accumulation as shown by both evaluation procedures. In line with these results, real-time polymerase chain reaction (RT-PCR) and Western blot analysis showed that AGN increased adipogenic differentiation by upregulating heat shock protection related genes and proteins together with the adipogenic markers. These findings imply the potential of AGN in heat

  16. Heat Shock Protein Augmentation of Angelica gigas Nakai Root Hot Water Extract on Adipogenic Differentiation in Murine 3T3-L1 Preadipocytes.

    PubMed

    Lumbera, Wenchie Marie L; Dela Cruz, Joseph; Yang, Seung-Hak; Hwang, Seong Gu

    2016-03-01

    There is a high association of heat shock on the alteration of energy and lipid metabolism. The alterations associated with thermal stress are composed of gene expression changes and adaptation through biochemical responses. Previous study showed that Angelica gigas Nakai (AGN) root extract promoted adipogenic differentiation in murine 3T3-L1 preadipocytes under the normal temperature condition. However, its effect in heat shocked 3T3-L1 cells has not been established. In this study, we investigated the effect of AGN root hot water extract in the adipogenic differentiation of murine 3T3-L1 preadipocytes following heat shock and its possible mechanism of action. Thermal stress procedure was executed within the same stage of preadipocyte confluence (G0) through incubation at 42°C for one hour and then allowed to recover at normal incubation temperature of 37°C for another hour before AGN treatment for both cell viability assay and Oil Red O. Cell viability assay showed that AGN was able to dose dependently (0 to 400 μg/mL) increase cell proliferation under normal incubation temperature and also was able to prevent cytotoxicity due to heat shock accompanied by cell proliferation. Confluent preadipocytes were subjected into heat shock procedure, recovery and then AGN treatment prior to stimulation with the differentiation solution. Heat shocked preadipocytes exhibited reduced differentiation as supported by decreased amount of lipid accumulation in Oil Red O staining and triglyceride measurement. However, those heat shocked preadipocytes that then were given AGN extract showed a dose dependent increase in lipid accumulation as shown by both evaluation procedures. In line with these results, real-time polymerase chain reaction (RT-PCR) and Western blot analysis showed that AGN increased adipogenic differentiation by upregulating heat shock protection related genes and proteins together with the adipogenic markers. These findings imply the potential of AGN in heat

  17. EFFECT OF EXPOSURE PROTOCOL AND HEAT SHOCK PROTEIN EXPRESSION ON ARSENITE INDUCED GENOTOXICITY IN MCF-7 BREAST CANCER CELLS

    EPA Science Inventory


    Effect of exposure protocol and heat shock protein expression on arsenite induced genotoxicity in MCF-7 breast cancer cells

    The genotoxic effects of arsenic (As) are well accepted, yet its mechanism of action is not clearly defined. Heat-shock proteins (HSPs) protect...

  18. Effects of wake and shock passing on the heat transfer to a film cooled transonic turbine blade

    NASA Astrophysics Data System (ADS)

    Rigby, M. J.

    An attempt is made to further the understanding of film cooling process in an engine environment. The environment in a gas turbine is unsteady. A source of unsteadiness, the cutting of nozzle guide vane (NGV) wakes and shock waves by the rotor, was modeled experimentally. The influence of the unsteady wakes and shock waves on the heat transfer to a film cooled rotor blade was studied for five film cooling configurations using a rotating bar apparatus in front of a 2-D cascade. Heat transfer measurements were made using thin film gauges placed at the mid-span of the test blade. Schlieren photography was used to study the behavior of the coolant film and the movement of the unsteady shock waves and wakes. The effect of simulated NGV wake passing observed on the uncooled airfoil is to promote an intermittent transition of the suction surface. The effect of the wake on the turbulent pressure surface is small. With injection on the suction surface, the film acts as a boundary layer trip which offsets the rise in heat transfer due to the wake. The simulated NGV trailing edge shock wave had a dramatic effect on the suction surface heat transfer.

  19. Application of cosmic-ray shock theories to the Cygnus Loop - an alternative model

    NASA Astrophysics Data System (ADS)

    Boulares, Ahmed; Cox, Donald P.

    1988-10-01

    Steady state cosmic-ray shock models are investigated in light of observations of the Cygnus Loop supernova remnant. In this work the authors find that the model of Völk, Drury, and McKenzie, in which the plasma waves are generated by the streaming instability of the cosmic rays and are dissipated into the gas, can be made consistent with some observed characteristics of Cygnus Loop shocks. The waves heat the gas substantially in the cosmic-ray precursor, in addition to the usual heating in the (possibly weak) gas shock. The model is used to deduce upstream densities and shock velocities using known quantities for Cygnus Loop shocks. Compared to the usual pure gas shock interpretation, it is found that lower densities and approximately 3 times higher velocities are required. If the cosmic-ray models are valid, this could significantly alter our understanding of the Cygnus Loop's distance and age and of the energy released during the initial explosion.

  20. Deficiency of heat shock transcription factor 1 suppresses heat stress-associated increase in slow soleus muscle mass of mice.

    PubMed

    Ohno, Y; Egawa, T; Yokoyama, S; Nakai, A; Sugiura, T; Ohira, Y; Yoshioka, T; Goto, K

    2015-12-01

    Effects of heat shock transcription factor 1 (HSF1) deficiency on heat stress-associated increase in slow soleus muscle mass of mice were investigated. Both HSF1-null and wild-type mice were randomly assigned to control and heat-stressed groups. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anaesthesia. Significant increase in wet and dry weights, and protein content of soleus muscle in wild-type mice was observed seven days after the application of the heat stress. However, heat stress had no impact on soleus muscle mass in HSF1-null mice. Neither type of mice exhibited much effect of heat stress on HSF mRNA expression (HSF1, HSF2 and HSF4). On the other hand, heat stress upregulated heat shock proteins (HSPs) at the mRNA (HSP72) and protein (HSP72 and HSP110) levels in wild-type mice, but not in HSF1-null mice. The population of Pax7-positive nuclei relative to total myonuclei of soleus muscle in wild-type mice was significantly increased by heat stress, but not in HSF1-null mice. Furthermore, the absence of HSF1 gene suppressed heat stress-associated phosphorylation of Akt and p70 S6 kinase (p-p70S6K) in soleus muscle. Heat stress-associated increase in skeletal muscle mass may be induced by HSF1 and/or HSF1-mediated stress response that activates muscle satellite cells and Akt/p70S6K signalling pathway. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. Magnetogasdynamic spherical shock wave in a non-ideal gas under gravitational field with conductive and radiative heat fluxes

    NASA Astrophysics Data System (ADS)

    Nath, G.; Vishwakarma, J. P.

    2016-11-01

    Similarity solutions are obtained for the flow behind a spherical shock wave in a non-ideal gas under gravitational field with conductive and radiative heat fluxes, in the presence of a spatially decreasing azimuthal magnetic field. The shock wave is driven by a piston moving with time according to power law. The radiation is considered to be of the diffusion type for an optically thick grey gas model and the heat conduction is expressed in terms of Fourier's law for heat conduction. Similarity solutions exist only when the surrounding medium is of constant density. The gas is assumed to have infinite electrical conductivity and to obey a simplified van der Waals equation of state. It is shown that an increase of the gravitational parameter or the Alfven-Mach number or the parameter of the non-idealness of the gas decreases the compressibility of the gas in the flow-field behind the shock, and hence there is a decrease in the shock strength. The pressure and density vanish at the inner surface (piston) and hence a vacuum is formed at the center of symmetry. The shock waves in conducting non-ideal gas under gravitational field with conductive and radiative heat fluxes can be important for description of shocks in supernova explosions, in the study of a flare produced shock in the solar wind, central part of star burst galaxies, nuclear explosion etc. The solutions obtained can be used to interpret measurements carried out by space craft in the solar wind and in neighborhood of the Earth's magnetosphere.

  2. Absence of Sperm Factors as in the Parthenogenesis Does Not Interfere on Bovine Embryo Sensitiveness to Heat Shock at Pre-Implantation Stage.

    PubMed

    Camargo, L S A; Paludo, F; Pereira, M M; Wohlres-Viana, S; Gioso, M M; Carvalho, B C; Quintao, C C R; Viana, J H M

    2016-02-01

    Oocyte has been considered the major contributor for embryo thermo-tolerance. However, it was shown that sperm factors can be transferred to the oocyte during fertilization, raising the question of whether the absence of such factors could interfere on embryo thermo-tolerance. In this study, we used parthenogenesis to generate bovine embryos without spermatozoa in order to test whether the absence of sperm factors could influence their thermo-sensitiveness at early stages. In vitro fertilized (IVF) and parthenogenetic (PA) embryos at 44 h post-insemination/chemical activation were exposed to 38.5°C (control) or 41°C (heat shock) for 12 h and then developed for 48 h and up to blastocyst stage. Apoptosis index and expression of PRDX1, GLUT1, GLUT5 and IGF1r genes in blastocysts derived from heat-shocked embryos were also evaluated. The heat shock decreased the blastocyst rate at day seven (p < 0.05) for IVF embryos and at day eight (p < 0.01) for both IVF and PA embryos. Total cell number was not affected by heat shock in IVF and PA blastocysts, but there was an increased proportion (p < 0.05) of apoptotic cells in heat-shocked embryos when compared to controls. There was no interaction (p > 0.05) between method of activation (IVF and PA) and temperature (38.5°C or 41.5°C) for all developmental parameters evaluated. Expression of GLUT1 gene was downregulated (p < 0.05) by heat shock in both IVF and PA blastocyst whereas expression of GLUT5 and IGF1r genes was downregulated (p < 0.05) by heat shock in PA blastocysts. Those data show that the heat shock affects negatively the embryo development towards blastocysts stage, increases the apoptotic index and disturbed the expression of some genes in both IVF and PA embryos, indicating that the presence or absence of sperm factors does not influence the sensitivity of the bovine embryo to heat shock. © 2015 Blackwell Verlag GmbH.

  3. Nitric oxide-heat shock protein axis in menopausal hot flushes: neglected metabolic issues of chronic inflammatory diseases associated with deranged heat shock response.

    PubMed

    Miragem, Antônio Azambuja; Homem de Bittencourt, Paulo Ivo

    2017-09-01

    Although some unequivocal underlying mechanisms of menopausal hot flushes have been demonstrated in animal models, the paucity of similar approaches in humans impedes further mechanistic outcomes. Human studies might show some as yet unexpected physiological mechanisms of metabolic adaptation that permeate the phase of decreased oestrogen levels in both symptomatic and asymptomatic women. This is particularly relevant because both the severity and time span of hot flushes are associated with increased risk of chronic inflammatory disease. On the other hand, oestrogen induces the expression of heat shock proteins of the 70 kDa family (HSP70), which are anti-inflammatory and cytoprotective protein chaperones, whose expression is modulated by different types of physiologically stressful situations, including heat stress and exercise. Therefore, lower HSP70 expression secondary to oestrogen deficiency increases cardiovascular risk and predisposes the patient to senescence-associated secretory phenotype (SASP) that culminates in chronic inflammatory diseases, such as obesities, type 2 diabetes, neuromuscular and neurodegenerative diseases. This review focuses on HSP70 and its accompanying heat shock response (HSR), which is an anti-inflammatory and antisenescent pathway whose intracellular triggering is also oestrogen-dependent via nitric oxide (NO) production. The main goal of the manuscript was to show that the vasomotor symptoms that accompany hot flushes may be a disguised clue for important neuroendocrine alterations linking oestrogen deficiency to the anti-inflammatory HSR. Results from our own group and recent evidence on hypothalamic control of central temperature guided a search on PubMed and Google Scholar websites. Oestrogen elicits rapid production of the vasodilatory gas NO, a powerful activator of HSP70 expression. Whence, part of the protective effects of oestrogen over cardiovascular and neuroendocrine systems is tied to its capacity of inducing the NO

  4. The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock in Caenorhabditis elegans.

    PubMed

    Huelgas-Morales, Gabriela; Silva-García, Carlos Giovanni; Salinas, Laura S; Greenstein, David; Navarro, Rosa E

    2016-04-07

    In response to stressful conditions, eukaryotic cells launch an arsenal of regulatory programs to protect the proteome. One major protective response involves the arrest of protein translation and the formation of stress granules, cytoplasmic ribonucleoprotein complexes containing the conserved RNA-binding proteins TIA-1 and TIAR. The stress granule response is thought to preserve mRNA for translation when conditions improve. For cells of the germline-the immortal cell lineage required for sexual reproduction-protection from stress is critically important for perpetuation of the species, yet how stress granule regulatory mechanisms are deployed in animal reproduction is incompletely understood. Here, we show that the stress granule protein TIAR-1 protects the Caenorhabditis elegans germline from the adverse effects of heat shock. Animals containing strong loss-of-function mutations in tiar-1 exhibit significantly reduced fertility compared to the wild type following heat shock. Analysis of a heat-shock protein promoter indicates that tiar-1 mutants display an impaired heat-shock response. We observed that TIAR-1 was associated with granules in the gonad core and oocytes during several stressful conditions. Both gonad core and oocyte granules are dynamic structures that depend on translation; protein synthesis inhibitors altered their formation. Nonetheless, tiar-1 was required for the formation of gonad core granules only. Interestingly, the gonad core granules did not seem to be needed for the germ cells to develop viable embryos after heat shock. This suggests that TIAR-1 is able to protect the germline from heat stress independently of these structures. Copyright © 2016 Huelgas-Morales et al.

  5. The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock in Caenorhabditis elegans

    PubMed Central

    Huelgas-Morales, Gabriela; Silva-García, Carlos Giovanni; Salinas, Laura S.; Greenstein, David; Navarro, Rosa E.

    2016-01-01

    In response to stressful conditions, eukaryotic cells launch an arsenal of regulatory programs to protect the proteome. One major protective response involves the arrest of protein translation and the formation of stress granules, cytoplasmic ribonucleoprotein complexes containing the conserved RNA-binding proteins TIA-1 and TIAR. The stress granule response is thought to preserve mRNA for translation when conditions improve. For cells of the germline—the immortal cell lineage required for sexual reproduction—protection from stress is critically important for perpetuation of the species, yet how stress granule regulatory mechanisms are deployed in animal reproduction is incompletely understood. Here, we show that the stress granule protein TIAR-1 protects the Caenorhabditis elegans germline from the adverse effects of heat shock. Animals containing strong loss-of-function mutations in tiar-1 exhibit significantly reduced fertility compared to the wild type following heat shock. Analysis of a heat-shock protein promoter indicates that tiar-1 mutants display an impaired heat-shock response. We observed that TIAR-1 was associated with granules in the gonad core and oocytes during several stressful conditions. Both gonad core and oocyte granules are dynamic structures that depend on translation; protein synthesis inhibitors altered their formation. Nonetheless, tiar-1 was required for the formation of gonad core granules only. Interestingly, the gonad core granules did not seem to be needed for the germ cells to develop viable embryos after heat shock. This suggests that TIAR-1 is able to protect the germline from heat stress independently of these structures. PMID:26865701

  6. Thermographic Phosphor Measurements of Shock-Shock Interactions on a Swept Cylinder

    NASA Technical Reports Server (NTRS)

    Jones, Michelle L.; Berry, Scott A.

    2013-01-01

    The effects of fin leading-edge radius and sweep angle on peak heating rates due to shock-shock interactions were investigated in the NASA Langley Research Center 20-inch Mach 6 Air Tunnel. The fin model leading edges, which represent cylindrical leading edges or struts on hypersonic vehicles, were varied from 0.25 inches to 0.75 inches in radius. A 9deg wedge generated a planar oblique shock at 16.7deg to the flow that intersected the fin bow shock, producing a shock-shock interaction that impinged on the fin leading edge. The fin angle of attack was varied from 0deg (normal to the free-stream) to 15deg and 25deg swept forward. Global temperature data was obtained from the surface of the fused silica fins using phosphor thermography. Metal oil flow models with the same geometries as the fused silica models were used to visualize the streamline patterns for each angle of attack. High-speed zoom-schlieren videos were recorded to show the features and temporal unsteadiness of the shock-shock interactions. The temperature data were analyzed using one-dimensional semi-infinite as well as one- and two-dimensional finite-volume methods to determine the proper heat transfer analysis approach to minimize errors from lateral heat conduction due to the presence of strong surface temperature gradients induced by the shock interactions. The general trends in the leading-edge heat transfer behavior were similar for the three shock-shock interactions, respectively, between the test articles with varying leading-edge radius. The dimensional peak heat transfer coefficient augmentation increased with decreasing leading-edge radius. The dimensional peak heat transfer output from the two-dimensional code was about 20% higher than the value from a standard, semi-infinite onedimensional method.

  7. Zn(2+)-Triggered Drug Release from Biocompatible Zirconium MOFs Equipped with Supramolecular Gates.

    PubMed

    Tan, Li-Li; Li, Haiwei; Zhou, Yue; Zhang, Yuanyuan; Feng, Xiao; Wang, Bo; Yang, Ying-Wei

    2015-08-01

    A new theranostic nanoplatform, comprising of monodisperse zirconium metal-organic frameworks (MOFs) as drug carriers and carboxylatopillar[5]arene-based supramolecular switches as gating entities, is constructed, and controlled drug release triggered by bio-friendly Zn(2+) ions (abundant in synaptic vesicles) and auxiliary thermal stimulus is realized. This on-command drug delivery system exhibits large pore sizes for drug encapsulation, excellent biodegradability and biocompatibility, extremely low cytotoxicity and premature drug release, and superior dual-stimuli responsiveness, opening a new avenue in targeted drug delivery and controlled release of therapeutic agents, especially in the treatment of central nervous system diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A Novel mouse model of enhanced proteostasis: Full-length human heat shock factor 1 transgenic mice

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

    Pierce, Anson, E-mail: piercea2@uthscsa.edu; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229; The Department of Veteran's Affairs, South Texas Veterans Health Care System, San Antonio, Texas, 78284

    2010-11-05

    Research highlights: {yields} Development of mouse overexpressing native human HSF1 in all tissues including CNS. {yields} HSF1 overexpression enhances heat shock response at whole-animal and cellular level. {yields} HSF1 overexpression protects from polyglutamine toxicity and favors aggresomes. {yields} HSF1 overexpression enhances proteostasis at the whole-animal and cellular level. -- Abstract: The heat shock response (HSR) is controlled by the master transcriptional regulator heat shock factor 1 (HSF1). HSF1 maintains proteostasis and resistance to stress through production of heat shock proteins (HSPs). No transgenic model exists that overexpresses HSF1 in tissues of the central nervous system (CNS). We generated a transgenicmore » mouse overexpressing full-length non-mutant HSF1 and observed a 2-4-fold increase in HSF1 mRNA and protein expression in all tissues studied of HSF1 transgenic (HSF1{sup +/0}) mice compared to wild type (WT) littermates, including several regions of the CNS. Basal expression of HSP70 and 90 showed only mild tissue-specific changes; however, in response to forced exercise, the skeletal muscle HSR was more elevated in HSF1{sup +/0} mice compared to WT littermates and in fibroblasts following heat shock, as indicated by levels of inducible HSP70 mRNA and protein. HSF1{sup +/0} cells elicited a significantly more robust HSR in response to expression of the 82 repeat polyglutamine-YFP fusion construct (Q82YFP) and maintained proteasome-dependent processing of Q82YFP compared to WT fibroblasts. Overexpression of HSF1 was associated with fewer, but larger Q82YFP aggregates resembling aggresomes in HSF1{sup +/0} cells, and increased viability. Therefore, our data demonstrate that tissues and cells from mice overexpressing full-length non-mutant HSF1 exhibit enhanced proteostasis.« less

  9. Analyzing the Possibility of Dynamic Earthquake Triggering in Socorro, New Mexico

    NASA Astrophysics Data System (ADS)

    Morton, E.; Bilek, S. L.

    2011-12-01

    The release of energy during an earthquake changes the stress state and seismicity both locally and remotely. Far-field stress changes can lead to triggered earthquakes coinciding with the arrival of the surface waves. This dynamic triggering is found to occur in a variety of tectonic settings, but in particular magmatic regions. Here we test whether the Socorro Magma Body region in central New Mexico hosts triggered seismicity. Preliminary inspection of continuous network data in central New Mexico suggested a local triggered event with the passage of surface waves from an MW 6.9 event in 2009. For a more comprehensive view, we examine data from 379 earthquakes MW ≥ 6.0 between January 15, 2008 to March 13, 2010 recorded on the EarthScope USArray Transportable Network stations located within New Mexico and providing more dense coverage for better detectability. Waveforms from twenty EarthScope stations were windowed around the time of the large event, high-pass filtered at 5 Hz to remove low frequency signals and analyzed to detect high frequency triggered local earthquakes. For each possible trigger detected, waveforms from nine short-period stations in the Socorro Seismic Network were added to aid in locating the events. In the time period analyzed, twelve triggered events were detected. Only one of these events, on August 30, 2009, corresponded to the arrival of surface waves, occurring about a minute after their arrival. The majority of the triggered events occur well after the arrival of the surface waves, indicating that they are either independent of the main shock or the result of delayed dynamic triggering. Delayed dynamic triggering can occur hours or days after the passage of surface waves, and are marked by an increase in seismicity relative to background. Only one of the events, on September 18, 2009, occurred within the Socorro Magma Body area. The rest of these events occur spread throughout New Mexico. The widely spread distribution of possibly

  10. Numerical simulation of heat fluxes in a two-temperature plasma at shock tube walls

    NASA Astrophysics Data System (ADS)

    Kuznetsov, E. A.; Poniaev, S. A.

    2015-12-01

    Numerical simulation of a two-temperature three-component Xenon plasma flow is presented. A solver based on the OpenFOAM CFD software package is developed. The heat flux at the shock tube end wall is calculated and compared with experimental data. It is shown that the heat flux due to electrons can be as high as 14% of the total heat flux.

  11. Dynamic m(6)A mRNA methylation directs translational control of heat shock response.

    PubMed

    Zhou, Jun; Wan, Ji; Gao, Xiangwei; Zhang, Xingqian; Jaffrey, Samie R; Qian, Shu-Bing

    2015-10-22

    The most abundant mRNA post-transcriptional modification is N(6)-methyladenosine (m(6)A), which has broad roles in RNA biology. In mammalian cells, the asymmetric distribution of m(6)A along mRNAs results in relatively less methylation in the 5' untranslated region (5'UTR) compared to other regions. However, whether and how 5'UTR methylation is regulated is poorly understood. Despite the crucial role of the 5'UTR in translation initiation, very little is known about whether m(6)A modification influences mRNA translation. Here we show that in response to heat shock stress, certain adenosines within the 5'UTR of newly transcribed mRNAs are preferentially methylated. We find that the dynamic 5'UTR methylation is a result of stress-induced nuclear localization of YTHDF2, a well-characterized m(6)A 'reader'. Upon heat shock stress, the nuclear YTHDF2 preserves 5'UTR methylation of stress-induced transcripts by limiting the m(6)A 'eraser' FTO from demethylation. Remarkably, the increased 5'UTR methylation in the form of m(6)A promotes cap-independent translation initiation, providing a mechanism for selective mRNA translation under heat shock stress. Using Hsp70 mRNA as an example, we demonstrate that a single m(6)A modification site in the 5'UTR enables translation initiation independent of the 5' end N(7)-methylguanosine cap. The elucidation of the dynamic features of 5'UTR methylation and its critical role in cap-independent translation not only expands the breadth of physiological roles of m(6)A, but also uncovers a previously unappreciated translational control mechanism in heat shock response.

  12. Pregermination heat shock and seedling growth of fire-following Fabaceae from four Mediterranean-climate regions

    NASA Astrophysics Data System (ADS)

    Hanley, Mick E.; Fenner, Michael; Ne'eman, Gidi

    2001-12-01

    The role of heat-shock in stimulating the germination of soil-stored seeds from fire-following plant species is well known. However, the effects of high pre-germination temperatures on subsequent seedling growth are less well understood. In this study, we examined the effect of pre-germination heat shock at five temperatures (60°, 75°, 90°, 105° and 120°C, each applied for 5 min) on the seedling growth of four, fire-following Fabaceae species from four Mediterranean-type ecosystems; Hippocrepis multisiliquosa (Israel), Gastrolobium villosum (Western Australia), Cyclopia pubescens (South Africa) and Lupinus succulentus (California). Following heat treatment and subsequent germination, seedlings were grown in controlled conditions before being harvested at either 10, 20- or 40 d old. A significant increase in mean dry weight biomass was found at 10 days for Hippocrepis seedlings germinated from seeds pre-heated to 90°C. However, subsequent comparison of mean dry weight biomass for seedlings of this species at 20 and 40 d old showed no significant response to heat shock pre-treatment. Similarly, an initial increase in growth of Gastrolobium seedlings germinated from seeds heated to 90° and 105°C disappeared as the plants matured. Seedling growth of Lupinus and Cyclopia was unaffected by the pre-germination heat treatment of their seeds. Since seedling competition is influenced by the size and growth rates of neighbouring plants, any changes in seedling growth rates as a consequence of the temperature environment experienced by their seeds, may therefore influence patterns of post-fire plant community recovery.

  13. Low heat-shock thresholds in wild Antarctic inter-tidal limpets (Nacella concinna).

    PubMed

    Clark, Melody S; Geissler, Paul; Waller, Catherine; Fraser, Keiron P P; Barnes, David K A; Peck, Lloyd S

    2008-01-01

    Heat shock proteins (HSPs) are a family of genes classically used to measure levels of organism stress. We have previously identified two HSP70 genes (HSP70A and HSP70B) in sub-tidal populations of the Antarctic limpet (Nacella concinna). These genes are up-regulated in response to increased seawater temperatures of 15 degrees C or more during acute heat shock experiments, temperatures that have very little basis when considering the current Antarctic ecology of these animals. Therefore, the question was posed as to whether these animals could express HSP70 genes when subjected to more complex environmental conditions, such as those that occur in the inter-tidal. Inter-tidal limpets were collected on three occasions in different weather conditions at South Cove, Rothera Point, over a complete tidal cycle, and the expression levels of the HSP70 genes were measured. Both genes showed relative up-regulation of gene expression over the period of the tidal cycle. The average foot temperature of these animals was 3.3 degrees C, far below that of the acute heat shock experiments. These experiments demonstrate that the temperature and expression levels of HSP production in wild animals cannot be accurately extrapolated from experimentally induced treatments, especially when considering the complexity of stressors in the natural environment. However, experimental manipulation can provide molecular markers for identifying stress in Antarctic molluscs, provided it is accompanied by environmental validation, as demonstrated here.

  14. Percutaneous Trigger Finger Release: A Cost-effectiveness Analysis.

    PubMed

    Gancarczyk, Stephanie M; Jang, Eugene S; Swart, Eric P; Makhni, Eric C; Kadiyala, Rajendra Kumar

    2016-07-01

    Percutaneous trigger finger releases (TFRs) performed in the office setting are becoming more prevalent. This study compares the costs of in-hospital open TFRs, open TFRs performed in ambulatory surgical centers (ASCs), and in-office percutaneous releases. An expected-value decision-analysis model was constructed from the payer perspective to estimate total costs of the three competing treatment strategies for TFR. Model parameters were estimated based on the best available literature and were tested using multiway sensitivity analysis. Percutaneous TFR performed in the office and then, if needed, revised open TFR performed in the ASC, was the most cost-effective strategy, with an attributed cost of $603. The cost associated with an initial open TFR performed in the ASC was approximately 7% higher. Initial open TFR performed in the hospital was the least cost-effective, with an attributed cost nearly twice that of primary percutaneous TFR. An initial attempt at percutaneous TFR is more cost-effective than an open TFR. Currently, only about 5% of TFRs are performed in the office; therefore, a substantial opportunity exists for cost savings in the future. Decision model level II.

  15. BH3-only proteins trigger cytochrome c release, but how?

    PubMed

    Häcker, Georg; Weber, Arnim

    2007-06-15

    The mitochondrial apoptosis pathway has been neatly ordered. Mitochondrial apoptosis is governed by Bcl-2 family proteins, and their respective contributions determine the release of cytochrome c. It is clear that, among the Bcl-2 family, BH3-only proteins are the triggers: activation of BH3-only proteins by apoptotic stimuli initiates the process. BH3-only proteins cause cytochrome c release by activating Bax and/or Bak, and the anti-apoptotic group of Bcl-2-like proteins prevents this. However, it is curiously uncertain how BH3-only proteins activate Bax/Bak. Current models suggest that this is either through direct interaction--although this interaction is not detectable experimentally--or by the neutralisation of Bcl-2-like proteins. Here we discuss the context in which these models are placed and attempt to weigh the evidence.

  16. Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1.

    PubMed

    Kusumoto, Hiroki; Hirohashi, Yoshihiko; Nishizawa, Satoshi; Yamashita, Masamichi; Yasuda, Kazuyo; Murai, Aiko; Takaya, Akari; Mori, Takashi; Kubo, Terufumi; Nakatsugawa, Munehide; Kanaseki, Takayuki; Tsukahara, Tomohide; Kondo, Toru; Sato, Noriyuki; Hara, Isao; Torigoe, Toshihiko

    2018-03-01

    In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSC)/cancer-initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells. Western blot analysis and qRT-PCR showed that HS increased the expression of DNAJB8 and SOX2. Gene knockdown experiments using siRNAs showed that the increase in SOX2 expression and SP cell ratio depends on DNAJB8 and that the increase in DNAJB8 and SOX2 depend on HSF1. Furthermore, treatment with a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, decreased the expression of DNAJB8 and SOX2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB8 by activation of HSF1 and induces cancer stem-like cells. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Heat shock instructs hESCs to exit from the self-renewal program through negative regulation of OCT4 by SAPK/JNK and HSF1 pathway.

    PubMed

    Byun, Kyunghee; Kim, Taek-Kyun; Oh, Jeehyun; Bayarsaikhan, Enkhjargal; Kim, Daesik; Lee, Min Young; Pack, Chan-Gi; Hwang, Daehee; Lee, Bonghee

    2013-11-01

    Environmental factors affect self-renewal of stem cells by modulating the components of self-renewal networks. Heat shock, an environmental factor, induces heat shock factors (HSFs), which up-regulate stress response-related genes. However, the link of heat shock to self-renewal of stem cells has not been elucidated yet. Here, we present the direct link of heat shock to a core stem cell regulator, OCT4, in the self-renewal network through SAPK/JNK and HSF1 pathway. We first showed that heat shock initiated differentiation of human embryonic stem cells (hESCs). Gene expression analysis revealed that heat shock increased the expression of many genes involved in cellular processes related to differentiation of stem cells. We then examined the effects of HSFs induced by heat shock on core self-renewal factors. Among HSFs, heat shock induced mainly HSF1 in hESCs. The HSF1 repressed the expression of OCT4, leading to the differentiation of hESCs and the above differentiation-related gene expression change. We further examined the effects of the upstream MAP (mitogen-activated protein) kinases of HSF1 on the repression of OCT4 expression by HSF1. Among the MAP kinases, SAPK/JNK controlled predominantly the repression of the OCT4 expression by HSF1. The direct link of heat shock to the core self-renewal regulator through SAPK/JNK and HSF1 provides a fundamental basis for understanding the effect of heat and other stresses involving activation of HSF1 on the self-renewal program and further controlling differentiation of hESCs in a broad spectrum of stem cell applications using these stresses. © 2013.

  18. Molecular characterization and expression analysis of a heat shock protein 90 gene from disk abalone (Haliotis discus).

    PubMed

    Wang, Ning; Whang, Ilson; Lee, Jae-Seong; Lee, Jehee

    2011-06-01

    Heat shock protein 90s (hsp90s) are chaperones that contribute to the proper folding of cellular proteins and help animals cope with the cellular protein damages in stress conditions. In this study, an hsp90 gene was isolated from disc abalone (Haliotis discus). The complete nucleotide sequence of the hsp90 gene contains an open reading frame of 2,184 base pairs, encoding an 84 kDa protein. Disk abalone hsp90 shares high sequence similarity with other hsp90 family proteins. Although the phylogenetic analysis did not classify it into the hsp90α group, the inductivity of this gene was confirmed by heat shock and lipopolysaccharide (LPS) challenge test. Disk abalone hsp90 gene displayed a rapid and reversible induction response to both an exposure of typical heat shock and the LPS challenge. Once given the sublethal heat shock treatment, the transcription of disk abalone hsp90 gene was significantly up-regulated. With a recovery of 12 h, the transcription of disk abalone hsp90 gene gradually attenuated to the control level. These observations reflected the feedback regulation of abalone heat shock responses faithfully. In response to LPS challenge, the transcription of disk abalone hsp90 gene was significantly increased within 2 h and it approached maximum induction at 4 h later and recovered finally the reference level in 24 h. Take all together, the cloning and expression analysis of disk abalone hsp90 gene provided useful molecular information of abalone responses in stress conditions and potential ways to monitor the chronic stressors in abalone culture environments and diagnose the animal health status.

  19. Heat-shock properties in yttrium-oxide films synthesized from metal-ethylenediamine tetraacetic acid complex through flame-spray apparatus

    NASA Astrophysics Data System (ADS)

    Xin, D. Y.; Komatsu, Keiji; Abe, Keita; Costa, Takashi; Ikeda, Yutaka; Nakamura, Atsushi; Ohshio, Shigeo; Saitoh, Hidetoshi

    2017-03-01

    Recently, a new deposition technique using a metal-ethylenediamine tetraacetic acid (EDTA) complex has been developed. In this study, the heat-shock properties of metal-oxide films synthesized from a metal-EDTA complex were investigated. Y2O3 films were synthesized on stainless-steel (SUS) substrate from EDTA•Y•H through the combustion of H2-O2 gas. A cyclic heat-shock test was conducted on the fabricated Y2O3 films through exposure to the H2-O2 flame. The existence of Y2O3 crystals was confirmed. Surface cracks or damages were not observed in the samples after the cyclic thermal test. Although the number of cross-sectional cracks, crack lengths, and cracks per unit area was increased by the heat shock, delaminations were not observed in the Y2O3 films. The results show that the prepared Y2O3 films have high thermal-shock resistance and are suitable for use as thermal barrier coatings.

  20. Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity.

    PubMed

    Pereira, Nigel; Elias, Rony T; Neri, Queenie V; Gerber, Rachel S; Lekovich, Jovana P; Palermo, Gianpiero D; Rosenwaks, Zev

    2016-11-01

    This study investigates whether an adjuvant gonadotrophin-releasing hormone agonist (GnRHa) trigger with human chorionic gonadotrophin (HCG) improves fresh intracytoplasmic sperm injection (ICSI) cycle outcomes in patients with poor fertilization history after standard HCG trigger alone. This study compared 156 patients with <40% fertilization rate in a prior ICSI cycle with standard HCG trigger who underwent another ICSI cycle with a combined 2 mg GnRHa and 1500 IU HCG ovulatory trigger. There was no difference in the baseline demographics, ovarian stimulation outcomes or sperm parameters of the groups. More mature oocytes were retrieved in the combined trigger group compared with the HCG trigger group: 12 (9-14) versus 10 (7-12); P = 0.01. The fertilization rate in the combined trigger group (59.2%) was higher than the HCG group (35.3%); P = 0.01. The odds of clinical pregnancy and live birth were 1.8 and 1.7 times higher, respectively, when comparing the former group to the latter; P = 0.03. The results suggest that combined GnRHa and HCG trigger in ICSI cycles is a reasonable approach to increase oocyte maturity, specifically ooplasmic maturity, thereby increasing fertilization and improving ICSI cycle outcomes in patients with a history of poor fertilization after standard HCG trigger alone. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  1. Controlled release from bilayer-decorated magnetoliposomes via electromagnetic heating.

    PubMed

    Chen, Yanjing; Bose, Arijit; Bothun, Geoffrey D

    2010-06-22

    Nanoscale assemblies that can be activated and controlled through external stimuli represent a next stage in multifunctional therapeutics. We report the formation, characterization, and release properties of bilayer-decorated magnetoliposomes (dMLs) that were prepared by embedding small hydrophobic SPIO nanoparticles at different lipid molecule to nanoparticle ratios within dipalmitoylphosphatidylcholine (DPPC) bilayers. The dML structure was examined by cryogenic transmission electron microscopy and differential scanning calorimetry, and release was examined by carboxyfluorescein leakage. Nanoparticle heating using alternating current electromagnetic fields (EMFs) operating at radio frequencies provided selective release of the encapsulated molecule at low nanoparticle concentrations and under physiologically acceptable EMF conditions. Without radio frequency heating, spontaneous leakage from the dMLs decreased with increasing nanoparticle loading, consistent with greater bilayer stability and a decrease in the effective dML surface area due to aggregation. With radio frequency heating, the initial rate and extent of leakage increased significantly as a function of nanoparticle loading and electromagnetic field strength. The mechanism of release is attributed to a combination of bilayer permeabilization and partial dML rupture.

  2. Heat Tolerance Induction of the Indian Meal Moth (Lepidoptera: Pyralidae) Is Accompanied by Upregulation of Heat Shock Proteins and Polyols.

    PubMed

    Kim, Minhyun; Lee, Seunghee; Chun, Yong Shik; Na, Jahyun; Kwon, Hyeok; Kim, Wook; Kim, Yonggyun

    2017-08-01

    The Indian meal moth, Plodia interpunctella, causes massive damage to stored grains and processed foods. Heat treatment has been widely used to control insect pests infesting stored grains. However, heat treatment may result in unsatisfactory control owing to heat tolerance of target insects. This study quantified the heat tolerance and analyzed its induction in P. interpunctella. Susceptibility of P. interpunctella to different high temperatures was assessed in all developmental stages. Heat treatment at 44 °C for 1 h caused significant mortalities to all developmental stages, with late-instar larvae exhibiting the highest tolerance. However, the survivorship to heat treatment was significantly increased by pre-exposure to 37 °C for 30 min. The induction of heat tolerance was accompanied by upregulation of two heat shock proteins of Hsc70 and Hsp90. Trehalose and glycerol concentrations in the hemolymph also increased after pre-exposure to 37 °C for 30 min. RNA interference (RNAi) by specific double-stranded RNAs effectively suppressed the inducible expressions of both Hsc70 and Hsp90 in response to 37 °C for 30 min. Either RNAi of Hsc70 or Hsp90 significantly impaired the heat tolerance induction of P. interpunctella. These results suggest that the induction of heat tolerance in P. interpunctella involves the upregulation of these heat shock proteins and hemolymph polyol levels. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Ultrathin ZnSe nanowires: one-pot synthesis via a heat-triggered precursor slow releasing route, controllable Mn doping and application in UV and near-visible light detection.

    PubMed

    Li, Dong; Xing, Guanjie; Tang, Shilin; Li, Xiaohong; Fan, Louzhen; Li, Yunchao

    2017-10-12

    We report herein a heat-triggered precursor slow releasing route for the one-pot synthesis of ultrathin ZnSe nanowires (NWs), which relies on the gradual dissolving of Se powder into oleylamine containing a soluble Zn precursor under heating. This route allows the reaction system to maintain a high monomer concentration throughout the entire reaction process, thus enabling the generation of ZnSe NWs with diameter down to 2.1 nm and length approaching 400 nm. The size-dependent optical properties and band-edge energy levels of the ZnSe NWs were then explored in depth by UV-visible spectroscopy and cyclic voltammetry, respectively. Considering their unique absorption properties, these NWs were specially utilized for fabricating photoelectrochemical-type photodetectors (PDs). Impressively, the PDs based on the ZnSe NWs with diameters of 2.1 and 4.5 nm exhibited excellent responses to UVA and near-visible light, respectively: both possessed ultrahigh on/off ratios (5150 for UVA and 4213 for near-visible light) and ultrawide linear response ranges (from 2.0 to 9000 μW cm -2 for UVA and 5.0 to 8000 μW cm -2 for near-visible light). Furthermore, these ZnSe NWs were selectively doped with various amounts of Mn 2+ to tune their emission properties. As a result, ZnSe NW film-based photochromic cards were creatively developed for visually detecting UVA and near-visible radiation.

  4. The 86-kilodalton antigen from Schistosoma mansoni is a heat-shock protein homologous to yeast HSP-90.

    PubMed

    Johnson, K S; Wells, K; Bock, J V; Nene, V; Taylor, D W; Cordingley, J S

    1989-08-01

    We report the sequence of a cDNA clone encoding an 86-kDa polypeptide antigen (p86) from Schistosoma mansoni. Fusion proteins made in Escherichia coli are recognized by human infection sera. The reading frame of this antigen is highly homologous to those of the large heat-shock proteins of Saccharomyces cerevisiae (HSP90) and Drosophila melanogaster (HSP83). mRNA encoding p86 increases in response to heat shock of adult worms, as does HSP70. Comparisons of the sequences of HSP70 and HSP83 homologues show that these two families of heat-shock proteins are not significantly related except for the last four amino acid residues, which are Glu-Glu-Val-Asp in every case. This sequence is not found at the carboxy terminus of any other protein in the current databases.

  5. Developmentally regulated expression of APG-1, a member of heat shock protein 110 family in murine male germ cells.

    PubMed

    Kaneko, Y; Kimura, T; Nishiyama, H; Noda, Y; Fujita, J

    1997-04-07

    Apg-1 encodes a heat shock protein belonging to the heat shock protein 110 family, and is inducible by a 32 degrees C to 39 degrees C heat shock. Northern blot analysis of the testis from immature and adult mice, and of the purified germ cells revealed the quantitative change of the apg-1 transcripts during germ cell development. By in situ hybridization histochemistry the expressions of the apg-1 transcripts were detected in germ cells at specific stages of development including spermatocytes and spermatids. Although heat-induction of the apg-1 transcripts was observed in W/Wv mutant testis lacking germ cells, it was not detected in wild-type testis nor in the purified germ cells. Thus, the apg-1 expression is not heat-regulated but developmentally regulated in germ cells, suggesting that APG-1 plays a role in normal development of germ cells.

  6. Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro.

    PubMed

    Lv, Li-Hong; Wan, Yun-Le; Lin, Yan; Zhang, Wei; Yang, Mei; Li, Guo-Lin; Lin, Hao-Ming; Shang, Chang-Zhen; Chen, Ya-Jin; Min, Jun

    2012-05-04

    Failure of immune surveillance related to inadequate host antitumor immune responses has been suggested as a possible cause of the high incidence of recurrence and poor overall survival outcome of hepatocellular carcinoma. The stress-induced heat shock proteins (HSPs) are known to act as endogenous "danger signals" that can improve tumor immunogenicity and induce natural killer (NK) cell responses. Exosome is a novel secretory pathway for HSPs. In our experiments, the immune regulatory effect of the HSP-bearing exosomes secreted by human hepatocellular carcinoma cells under stress conditions on NK cells was studied. ELISA results showed that the production of HSP60, HSP70, and HSP90 was up-regulated in both cell lines in a stress-specific manner. After exposure to hepatocellular carcinoma cell-resistant or sensitive anticancer drugs (hereafter referred to as "resistant" or "sensitive" anticancer drug), the membrane microvesicles were actively released by hepatocellular carcinoma cells, differing in their ability to present HSPs on the cell surface, which were characterized as exosomes. Acting as a decoy, the HSP-bearing exosomes efficiently stimulated NK cell cytotoxicity and granzyme B production, up-regulated the expression of inhibitory receptor CD94, and down-regulated the expression of activating receptors CD69, NKG2D, and NKp44. Notably, resistant anticancer drugs enhanced exosome release and generated more exosome-carried HSPs, which augmented the activation of the cytotoxic response. In summary, our findings demonstrated that exosomes derived from resistant anticancer drug-treated HepG2 cells conferred superior immunogenicity in inducing HSP-specific NK cell responses, which provided a clue for finding an efficient vaccine for hepatocellular carcinoma immunotherapy.

  7. Structure and function of small heat shock/alpha-crystallin proteins: established concepts and emerging ideas.

    PubMed

    MacRae, T H

    2000-06-01

    Small heat shock/alpha-crystallin proteins are defined by conserved sequence of approximately 90 amino acid residues, termed the alpha-crystallin domain, which is bounded by variable amino- and carboxy-terminal extensions. These proteins form oligomers, most of uncertain quaternary structure, and oligomerization is prerequisite to their function as molecular chaperones. Sequence modelling and physical analyses show that the secondary structure of small heat shock/alpha-crystallin proteins is predominately beta-pleated sheet. Crystallography, site-directed spin-labelling and yeast two-hybrid selection demonstrate regions of secondary structure within the alpha-crystallin domain that interact during oligomer assembly, a process also dependent on the amino terminus. Oligomers are dynamic, exhibiting subunit exchange and organizational plasticity, perhaps leading to functional diversity. Exposure of hydrophobic residues by structural modification facilitates chaperoning where denaturing proteins in the molten globule state associate with oligomers. The flexible carboxy-terminal extension contributes to chaperone activity by enhancing the solubility of small heat shock/alpha-crystallin proteins. Site-directed mutagenesis has yielded proteins where the effect of the change on structure and function depends upon the residue modified, the organism under study and the analytical techniques used. Most revealing, substitution of a conserved arginine residue within the alpha-crystallin domain has a major impact on quaternary structure and chaperone action probably through realignment of beta-sheets. These mutations are linked to inherited diseases. Oligomer size is regulated by a stress-responsive cascade including MAPKAP kinase 2/3 and p38. Phosphorylation of small heat shock/alpha-crystallin proteins has important consequences within stressed cells, especially for microfilaments.

  8. Shocks and Molecules in Protostellar Outflows

    NASA Astrophysics Data System (ADS)

    Arce, Héctor

    2014-06-01

    As protostars form through the gravitational infall of material from their parent molecular cloud, they power energetic bipolar outflows that interact with the surrounding medium. Protostellar outflows are important to the chemical evolution of star forming regions, as the shocks produced by the interaction of the high-velocity protostellar wind and the ambient cloud can heat the surrounding medium and trigger chemical and physical processes that would otherwise not take place in a quiescent molecular cloud. Protostellar outflows, are therefore a great laboratory to study shock physics and shock-induced chemistry. I will present results from millimeter-wave observations of a small sample of outflow shocks. The spectra show clear evidence of the existence of complex organic molecules (e.g., methyl formate, ethanol, acetaldehyde) and high abundance of certain simple molecules (e.g., HCO^+, HCN, H_2O) in outflows. Results indicate that, most likely, the complex species formed on the surface of grains and were then ejected from the grain mantles by the shock. Spectral surveys of shocked regions using ALMA could therefore be used to probe the composition of dust in molecular clouds. Our results demonstrate that outflows modify the chemical composition of the surrounding gaseous environment and that this needs to be considered when using certain species to study active star forming regions.

  9. Thermospheric Nitric Oxide Response to Shock-led Storms

    PubMed Central

    Knipp, D. J.; Pette, D. V.; Kilcommons, L. M.; Isaacs, T. L.; Cruz, A. A.; Mlynczak, M. G.; Hunt, L. A.; Lin, C. Y.

    2017-01-01

    We present a multi-year superposed epoch study of the Sounding of the Atmosphere using Broadband Emission Radiometry nitric oxide (NO) emission data. NO is a trace constituent in the thermosphere that acts as cooling agent via infrared (IR) emissions. The NO cooling competes with storm time thermospheric heating resulting in a thermostat effect. Our study of nearly 200 events reveals that shock-led interplanetary coronal mass ejections (ICMEs) are prone to early and excessive thermospheric NO production and IR emissions. Excess NO emissions can arrest thermospheric expansion by cooling the thermosphere during intense storms. The strongest events curtail the interval of neutral density increase and produce a phenomenon known as thermospheric ‘overcooling’. We use Defense Meteorological Satellite Program particle precipitation data to show that interplanetary shocks and their ICME drivers can more than double the fluxes of precipitating particles that are known to trigger the production of thermospheric NO. Coincident increases in Joule heating likely amplify the effect. In turn, NO emissions more than double. We discuss the roles and features of shock/sheath structures that allow the thermosphere to temper the effects of extreme storm time energy input and explore the implication these structures may have on mesospheric NO. Shock-driven thermospheric NO IR cooling likely plays an important role in satellite drag forecasting challenges during extreme events. PMID:28824340

  10. Thermospheric Nitric Oxide Response to Shock-led Storms.

    PubMed

    Knipp, D J; Pette, D V; Kilcommons, L M; Isaacs, T L; Cruz, A A; Mlynczak, M G; Hunt, L A; Lin, C Y

    2017-02-01

    We present a multi-year superposed epoch study of the Sounding of the Atmosphere using Broadband Emission Radiometry nitric oxide (NO) emission data. NO is a trace constituent in the thermosphere that acts as cooling agent via infrared (IR) emissions. The NO cooling competes with storm time thermospheric heating resulting in a thermostat effect. Our study of nearly 200 events reveals that shock-led interplanetary coronal mass ejections (ICMEs) are prone to early and excessive thermospheric NO production and IR emissions. Excess NO emissions can arrest thermospheric expansion by cooling the thermosphere during intense storms. The strongest events curtail the interval of neutral density increase and produce a phenomenon known as thermospheric 'overcooling'. We use Defense Meteorological Satellite Program particle precipitation data to show that interplanetary shocks and their ICME drivers can more than double the fluxes of precipitating particles that are known to trigger the production of thermospheric NO. Coincident increases in Joule heating likely amplify the effect. In turn, NO emissions more than double. We discuss the roles and features of shock/sheath structures that allow the thermosphere to temper the effects of extreme storm time energy input and explore the implication these structures may have on mesospheric NO. Shock-driven thermospheric NO IR cooling likely plays an important role in satellite drag forecasting challenges during extreme events.

  11. Glucose Starvation Alters Heat Shock Response, Leading to Death of Wild Type Cells and Survival of MAP Kinase Signaling Mutant

    PubMed Central

    Higgins, LeeAnn; Markowski, Todd; Brambl, Robert

    2016-01-01

    A moderate heat shock induces Neurospora crassa to synthesize large quantities of heat shock proteins that are protective against higher, otherwise lethal temperatures. However, wild type cells do not survive when carbohydrate deprivation is added to heat shock. In contrast, a mutant strain defective in a stress-activated protein kinase does survive the combined stresses. In order to understand the basis for this difference in survival, we have determined the relative levels of detected proteins in the mutant and wild type strain during dual stress, and we have identified gene transcripts in both strains whose quantities change in response to heat shock or dual stress. These data and supportive experimental evidence point to reasons for survival of the mutant strain. By using alternative respiratory mechanisms, these cells experience less of the oxidative stress that proves damaging to wild type cells. Of central importance, mutant cells recycle limited resources during dual stress by undergoing autophagy, a process that we find utilized by both wild type and mutant cells during heat shock. Evidence points to inappropriate activation of TORC1, the central metabolic regulator, in wild type cells during dual stress, based upon behavior of an additional signaling mutant and inhibitor studies. PMID:27870869

  12. Elucidation of the molecular mechanism of heat shock proteins and its correlation with K722Q mutations in Lon protease.

    PubMed

    Bhattacharjee, Sanchari; Dasgupta, Rakhi; Bagchi, Angshuman

    2017-09-01

    Cells withstand the effects of temperature change with the help of small heat shock proteins IbpA and IbpB. The IbpAB protein complex interacts with Lon protease in their free form and gets degraded at physiological temperature when there is no temperature stress. However, the proteolytic degradation of IbpAB is diminished when Lon is mutated. The mutation K722Q in Lon brings about some structural changes so that the proteolytic interactions between the heat shock proteins with that of the mutated Lon protease are lost. However, the detailed molecular aspects of the interactions are not yet fully understood. In the present, we made an attempt to analyze the biochemical aspects of the interactions between the small heat shock proteins IbpAB with wild type and mutant Lon protease. We for the first time deciphered the molecular details of the mechanism of interaction of small heat shock proteins with Lon protease bearing K722Q mutation i.e. the interaction pattern of heat shock proteins with mutant Lon protease at physiological temperature in absence of proteolytic machinery. Our study may therefore be useful to elucidate the mechanistic details of the correlation with IbpA, IbpB and Lon protease. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Larvae of related Diptera species from thermally contrasting habitats exhibit continuous up-regulation of heat shock proteins and high thermotolerance.

    PubMed

    Garbuz, David G; Zatsepina, Olga G; Przhiboro, Andrey A; Yushenova, Irina; Guzhova, Irina V; Evgen'ev, Michael B

    2008-11-01

    A population of Stratiomys japonica, a species belonging to the family Stratiomyidae (Diptera), common name 'soldier flies', occurs in a hot volcanic spring, which is apparently among the most inhospitable environments for animals because of chemical and thermal conditions. Larvae of this species, which naturally often experience temperatures more than 40 degrees C, have constitutively high concentrations of the normally inducible heat-shock protein Hsp70, but very low level of corresponding mRNA. Larvae of three other species of the same family, Stratiomys singularior, Nemotelus bipunctatus and Oxycera pardalina, are confined to different type semi-aquatic habitats with contrasting thermal regime. However, all of them shared the same pattern of Hsp70 expression. Interestingly, heat-shock treatment of S. japonica larvae activates heat-shock factor and significantly induces Hsp70 synthesis, whereas larvae of O. pardalina, a species from constant cold environment, produce significantly less Hsp70 in response to heat shock. Adults of the four species also exhibit lower, but detectable levels of Hsp70 without heat shock. Larvae of all species studied have very high tolerance to temperature stress in comparison with other Diptera species investigated, probably representing an inherent adaptive feature of all Stratiomyidae enabling successful colonization of highly variable and extreme habitats.

  14. Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor

    PubMed Central

    Pothi, Radhika; Hesketh, Andrew; Möller-Levet, Carla; Hodgson, David A; Laing, Emma E; Stewart, Graham R; Smith, Colin P

    2018-01-01

    Abstract Stress-induced adaptations require multiple levels of regulation in all organisms to repair cellular damage. In the present study we evaluated the genome-wide transcriptional and translational changes following heat stress exposure in the soil-dwelling model actinomycete bacterium, Streptomyces coelicolor. The combined analysis revealed an unprecedented level of translational control of gene expression, deduced through polysome profiling, in addition to transcriptional changes. Our data show little correlation between the transcriptome and ‘translatome’; while an obvious downward trend in genome wide transcription was observed, polysome associated transcripts following heat-shock showed an opposite upward trend. A handful of key protein players, including the major molecular chaperones and proteases were highly induced at both the transcriptional and translational level following heat-shock, a phenomenon known as ‘potentiation’. Many other transcripts encoding cold-shock proteins, ABC-transporter systems, multiple transcription factors were more highly polysome-associated following heat stress; interestingly, these protein families were not induced at the transcriptional level and therefore were not previously identified as part of the stress response. Thus, stress coping mechanisms at the level of gene expression in this bacterium go well beyond the induction of a relatively small number of molecular chaperones and proteases in order to ensure cellular survival at non-physiological temperatures. PMID:29746664

  15. Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor.

    PubMed

    Bucca, Giselda; Pothi, Radhika; Hesketh, Andrew; Möller-Levet, Carla; Hodgson, David A; Laing, Emma E; Stewart, Graham R; Smith, Colin P

    2018-05-09

    Stress-induced adaptations require multiple levels of regulation in all organisms to repair cellular damage. In the present study we evaluated the genome-wide transcriptional and translational changes following heat stress exposure in the soil-dwelling model actinomycete bacterium, Streptomyces coelicolor. The combined analysis revealed an unprecedented level of translational control of gene expression, deduced through polysome profiling, in addition to transcriptional changes. Our data show little correlation between the transcriptome and 'translatome'; while an obvious downward trend in genome wide transcription was observed, polysome associated transcripts following heat-shock showed an opposite upward trend. A handful of key protein players, including the major molecular chaperones and proteases were highly induced at both the transcriptional and translational level following heat-shock, a phenomenon known as 'potentiation'. Many other transcripts encoding cold-shock proteins, ABC-transporter systems, multiple transcription factors were more highly polysome-associated following heat stress; interestingly, these protein families were not induced at the transcriptional level and therefore were not previously identified as part of the stress response. Thus, stress coping mechanisms at the level of gene expression in this bacterium go well beyond the induction of a relatively small number of molecular chaperones and proteases in order to ensure cellular survival at non-physiological temperatures.

  16. An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

    PubMed

    Sasikala, Arathyram Ramachandra Kurup; Unnithan, Afeesh Rajan; Yun, Yeo-Heung; Park, Chan Hee; Kim, Cheol Sang

    2016-02-01

    The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a p

  17. Encapsulation of NF-κ B Decoy Oligonucleotides within Echogenic Liposomes and Ultrasound-Triggered Release

    PubMed Central

    Buchanan, Kyle D.; Huang, Shao-Ling; Kim, Hyunggun; McPherson, David D.; MacDonald, Robert C.

    2011-01-01

    Echogenic liposomes (ELIP) have additional promise, beyond diagnostic agents, as vehicles for delivering oligonucleotides (ODN), especially if the release of the agent can be triggered and its uptake can be enhanced by ultrasound application at a specific site. The purpose of this study was to co-encapsulate air and NF-κB decoy ODN within ELIP allowing ultrasound to release encapsulated ODN from ELIP, and to accurately quantify release of encapsulated ODN from ELIP upon ultrasound application. FITC-labeled sense ODN (2 mM) was incorporated within ELIP using freeze/thaw method. Encapsulation efficiency of FITC-ODN was spectrofluorometrically analyzed by quenching fluorescence of unencapsulated FITC-ODN using a complementary strand tagged with Iowa Black FQ-ODN. Quenching of FITC-ODN (0.05 μM) with Iowa Black FQ-ODN (0.1 μM) was found to be efficient (92.4 ± 0.2 %), allowing accurate determination of encapsulated ODN. Encapsulation efficiency of ODN was 14.2 ± 2.5 % in DPPC/DOPC/DPPG/CH liposomes and 29.6 ± 1.5 % in DPPC/DOPE/DPPG/CH liposomes. Application of ultrasound (1 MHz continuous wave, 0.26 MPa peak-to-peak pressure amplitude, 60 seconds.) to the latter formulation triggered 41.6 ± 4.3 % release of ODN from ODN-containing ELIP. We have thus demonstrated that ODN can be encapsulated into ELIP and released efficiently upon ultrasound application. These findings suggest potential applications for gene therapy in atherosclerosis treatment. PMID:19804805

  18. Heat shock protein expression as guidance for the therapeutic window of retinal laser therapy

    NASA Astrophysics Data System (ADS)

    Wang, Jenny; Huie, Philip; Dalal, Roopa; Lee, Seungjun; Tan, Gavin; Lee, Daeyoung; Lavinksy, Daniel; Palanker, Daniel

    2016-03-01

    Unlike conventional photocoagulation, non-damaging retinal laser therapy (NRT) limits laser-induced heating to stay below the retinal damage threshold and therefore requires careful dosimetry. Without the adverse effects associated with photocoagulation, NRT can be applied to critical areas of the retina and repeatedly to manage chronic disorders. Although the clinical benefits of NRT have been demonstrated, the mechanism of therapeutic effect and width of the therapeutic window below damage threshold are not well understood. Here, we measure activation of heat shock response via laser-induced hyperthermia as one indication of cellular response. A 577 nm laser is used with the Endpoint Management (EpM) user interface, a titration algorithm, to set experimental pulse energies relative to a barely visible titration lesion. Live/dead staining and histology show that the retinal damage threshold in rabbits is at 40% of titration energy on EpM scale. Heat shock protein 70 (HSP70) expression in the retinal pigment epithelium (RPE) was detected by whole-mount immunohistochemistry after different levels of laser treatment. We show HSP70 expression in the RPE beginning at 25% of titration energy indicating that there is a window for NRT between 25% and 40% with activation of the heat shock protein expression in response to hyperthermia. HSP70 expression is also seen at the perimeter of damaging lesions, as expected based on a computational model of laser heating. Expression area for each pulse energy setting varied between laser spots due to pigmentation changes, indicating the relatively narrow window of non-damaging activation and highlighting the importance of proper titration.

  19. Self-defensive antibiotic-loaded layer-by-layer coatings: Imaging of localized bacterial acidification and pH-triggering of antibiotic release.

    PubMed

    Albright, Victoria; Zhuk, Iryna; Wang, Yuhao; Selin, Victor; van de Belt-Gritter, Betsy; Busscher, Henk J; van der Mei, Henny C; Sukhishvili, Svetlana A

    2017-10-01

    Self-defensive antibiotic-loaded coatings have shown promise in inhibiting growth of pathogenic bacteria adhering to biomaterial implants and devices, but direct proof that their antibacterial release is triggered by bacterially-induced acidification of the immediate environment under buffered conditions remained elusive. Here, we demonstrate that Staphylococcus aureus and Escherichia coli adhering to such coatings generate highly localized acidification, even in buffered conditions, to activate pH-triggered, self-defensive antibiotic release. To this end, we utilized chemically crosslinked layer-by-layer hydrogel coatings of poly(methacrylic acid) with a covalently attached pH-sensitive SNARF-1 fluorescent label for imaging, and unlabeled-antibiotic (gentamicin or polymyxin B) loaded coatings for antibacterial studies. Local acidification of the coatings induced by S. aureus and E. coli adhering to the coatings was demonstrated by confocal-laser-scanning-microscopy via wavelength-resolved imaging. pH-triggered antibiotic release under static, small volume conditions yielded high bacterial killing efficiencies for S. aureus and E. coli. Gentamicin-loaded films retained their antibacterial activity against S. aureus under fluid flow in buffered conditions. Antibacterial activity increased with the number of polymer layers in the films. Altogether, pH-triggered, self-defensive antibiotic-loaded coatings become activated by highly localized acidification in the immediate environment of an adhering bacterium, offering potential for clinical application with minimized side-effects. Polymeric coatings were created that are able to uptake and selectively release antibiotics upon stimulus by adhering bacteria in order to understand the fundamental mechanisms behind pH-triggered antibiotic release as a potential way to prevent biomaterial-associated infections. Through fluorescent imaging studies, this work importantly shows that adhering bacteria produce highly localized p

  20. Heat Stress Modulates Mycelium Growth, Heat Shock Protein Expression, Ganoderic Acid Biosynthesis, and Hyphal Branching of Ganoderma lucidum via Cytosolic Ca2+

    PubMed Central

    Zhang, Xue; Ren, Ang; Li, Meng-Jiao; Cao, Peng-Fei; Chen, Tian-Xi; Zhang, Guang; Shi, Liang; Jiang, Ai-Liang

    2016-01-01

    ABSTRACT Heat stress (HS) influences the growth and development of organisms. Thus, a comprehensive understanding of how organisms sense HS and respond to it is required. Ganoderma lucidum, a higher basidiomycete with bioactive secondary metabolites, has become a potential model system due to the complete sequencing of its genome, transgenic systems, and reliable reverse genetic tools. In this study, we found that HS inhibited mycelium growth, reduced hyphal branching, and induced the accumulation of ganoderic acid biosynthesis and heat shock proteins (HSPs) in G. lucidum. Our data showed that HS induced a significant increase in cytosolic Ca2+ concentration. Further evidence showed that Ca2+ might be a factor in the HS-mediated regulation of hyphal branching, ganoderic acid (GA) biosynthesis, and the accumulation of HSPs. Our results further showed that the calcium-permeable channel gene (cch)-silenced and phosphoinositide-specific phospholipase gene (plc)-silenced strains reduced the HS-induced increase in HSP expression compared with that observed for the wild type (WT). This study demonstrates that cytosolic Ca2+ participates in heat shock signal transduction and regulates downstream events in filamentous fungi. IMPORTANCE Ganoderma lucidum, a higher basidiomycete with bioactive secondary metabolites, has become a potential model system for evaluating how environmental factors regulate the development and secondary metabolism of basidiomycetes. Heat stress (HS) is an important environmental challenge. In this study, we found that HS inhibited mycelium growth, reduced hyphal branching, and induced HSP expression and ganoderic acid biosynthesis in G. lucidum. Further evidence showed that Ca2+ might be a factor in the HS-mediated regulation of hyphal branching, GA biosynthesis, and the accumulation of HSPs. This study demonstrates that cytosolic Ca2+ participates in heat shock signal transduction and regulates downstream events in filamentous fungi. Our research

  1. Heat Stress Modulates Mycelium Growth, Heat Shock Protein Expression, Ganoderic Acid Biosynthesis, and Hyphal Branching of Ganoderma lucidum via Cytosolic Ca2.

    PubMed

    Zhang, Xue; Ren, Ang; Li, Meng-Jiao; Cao, Peng-Fei; Chen, Tian-Xi; Zhang, Guang; Shi, Liang; Jiang, Ai-Liang; Zhao, Ming-Wen

    2016-07-15

    Heat stress (HS) influences the growth and development of organisms. Thus, a comprehensive understanding of how organisms sense HS and respond to it is required. Ganoderma lucidum, a higher basidiomycete with bioactive secondary metabolites, has become a potential model system due to the complete sequencing of its genome, transgenic systems, and reliable reverse genetic tools. In this study, we found that HS inhibited mycelium growth, reduced hyphal branching, and induced the accumulation of ganoderic acid biosynthesis and heat shock proteins (HSPs) in G. lucidum Our data showed that HS induced a significant increase in cytosolic Ca(2+) concentration. Further evidence showed that Ca(2+) might be a factor in the HS-mediated regulation of hyphal branching, ganoderic acid (GA) biosynthesis, and the accumulation of HSPs. Our results further showed that the calcium-permeable channel gene (cch)-silenced and phosphoinositide-specific phospholipase gene (plc)-silenced strains reduced the HS-induced increase in HSP expression compared with that observed for the wild type (WT). This study demonstrates that cytosolic Ca(2+) participates in heat shock signal transduction and regulates downstream events in filamentous fungi. Ganoderma lucidum, a higher basidiomycete with bioactive secondary metabolites, has become a potential model system for evaluating how environmental factors regulate the development and secondary metabolism of basidiomycetes. Heat stress (HS) is an important environmental challenge. In this study, we found that HS inhibited mycelium growth, reduced hyphal branching, and induced HSP expression and ganoderic acid biosynthesis in G. lucidum Further evidence showed that Ca(2+) might be a factor in the HS-mediated regulation of hyphal branching, GA biosynthesis, and the accumulation of HSPs. This study demonstrates that cytosolic Ca(2+) participates in heat shock signal transduction and regulates downstream events in filamentous fungi. Our research offers a new

  2. Detection of the host immune response to Burkholderia mallei heat-shock proteins GroEL and DnaK in a glanders patient and infected mice.

    PubMed

    Amemiya, Kei; Meyers, Jennifer L; Deshazer, David; Riggins, Renaldo N; Halasohoris, Stephanie; England, Marilyn; Ribot, Wilson; Norris, Sarah L; Waag, David M

    2007-10-01

    We examined, by enzyme-linked immunosorbent assay and Western blot analysis, the host immune response to 2 heat-shock proteins (hsps) in a patient and mice previously infected with Burkholderia mallei. The patient was the first reported human glanders case in 50 years in the United States. The expression of the groEL and dnaK operons appeared to be dependent upon a sigma(32) RNA polymerase as suggested by conserved heat-shock promoter sequences, and the groESL operon may be negatively regulated by a controlling invert repeat of chaperone expression (CIRCE) site. In the antisera, the GroEL protein was found to be more immunoreactive than the DnaK protein in both a human patient and mice previously infected with B. mallei. Examination of the supernatant of a growing culture of B. mallei showed that more GroEL protein than DnaK protein was released from the cell. This may occur similarly within an infected host causing an elevated host immune response to the B. mallei hsps.

  3. Precise new shock temperatures in forsterite and in silicate liquids: phase transitions and heat capacity at high pressure

    NASA Astrophysics Data System (ADS)

    Asimow, P. D.; Fat'yanov, O. V.; Su, C.; Ma, X. J.

    2017-12-01

    Shock temperature measurements in transparent samples provide key constraints on the phase transitions and thermodynamic properties of materials at high pressure and temperature. Such measurements are necessary, for example, to allow equation of state measurements taken along the Hugoniot to be translated to P-V-T space. We have recently completed a detailed study of the accuracy and reproducibility of calibration of our 6-channel fast pyrometer. We have also introduced improved analysis procedures of the time-dependent multi-wavelength radiance signal that avoid the need for a greybody assumption and therefore have better precision than earlier results. This has motivated (a) renewed study of the shock temperature of forsterite in the superheating, partial melting, and complete melting regimes, (b) pre-heated diopside-anorthite glass shock temperature experiments for comparison to pre-heated silicate liquid equation of state results, and (c) new soda-lime glass shock temperature experiments. Single-crystal synthetic forsterite samples were shocked along (100) to pressures between 120 and 210 GPa on the Caltech two-stage light gas gun. Uncertainties on most results are 50 K. Results above the onset of partial melting at 130 GPa are consistent with Lyzenga and Ahrens (1980) data and show a low P-T slope consistent with a partial melting interval. Complete melting may occur, given sufficient time, at about 210 GPa. The experiment at 120-130 GPa is anomalous, showing two-wave structure and time- and wavelength-dependent scattering suggesting a subsolidus phase transition behind the shock front. The amount of super-heating, if any, is far smaller than claimed by Holland and Ahrens (1997). Steady radiation profiles, high emissivity, and consistency from channel to channel provide high precision (±40 K) in diopside-anorthite liquid shocked from just above the glass transition to high pressure. Temperatures are colder than expected for a model with constant heat capacity

  4. An alternatively spliced heat shock transcription factor, OsHSFA2dI, functions in the heat stress-induced unfolded protein response in rice.

    PubMed

    Cheng, Q; Zhou, Y; Liu, Z; Zhang, L; Song, G; Guo, Z; Wang, W; Qu, X; Zhu, Y; Yang, D

    2015-03-01

    As sessile organisms, plants have evolved a wide range of defence pathways to cope with environmental stress such as heat shock. However, the molecular mechanism of these defence pathways remains unclear in rice. In this study, we found that OsHSFA2d, a heat shock transcriptional factor, encodes two main splice variant proteins, OsHSFA2dI and OsHSFA2dII in rice. Under normal conditions, OsHSFA2dII is the dominant but transcriptionally inactive spliced form. However, when the plant suffers heat stress, OsHSFA2d is alternatively spliced into a transcriptionally active form, OsHSFA2dI, which participates in the heat stress response (HSR). Further study found that this alternative splicing was induced by heat shock rather than photoperiod. We found that OsHSFA2dI is localised to the nucleus, whereas OsHSFA2dII is localised to the nucleus and cytoplasm. Moreover, expression of the unfolded protein response (UNFOLDED PROTEIN RESPONSE) sensors, OsIRE1, OsbZIP39/OsbZIP60 and the UNFOLDED PROTEIN RESPONSE marker OsBiP1, was up-regulated. Interestingly, OsbZIP50 was also alternatively spliced under heat stress, indicating that UNFOLDED PROTEIN RESPONSE signalling pathways were activated by heat stress to re-establish cellular protein homeostasis. We further demonstrated that OsHSFA2dI participated in the unfolded protein response by regulating expression of OsBiP1. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

  5. Regulation of the heat shock response under anoxia in the turtle, Trachemys scripta elegans.

    PubMed

    Krivoruchko, Anastasia; Storey, Kenneth B

    2010-03-01

    The effects of 20 h of anoxic submergence in cold water and 5 h of aerobic recovery on the heat shock response were analyzed in four organs of the anoxia-tolerant turtle Trachemys scripta elegans. Immunoblotting was used to analyze levels of active and inactive forms of the heat shock transcription factor 1 (HSF1), nuclear translocation of HSF1, and the levels of six heat shock proteins (HSPs). PCR was also used to retrieve the turtle HSF1 nucleotide sequence; its deduced amino acid sequence showed 97% identity with chicken HSF1. White skeletal muscle showed a strong fivefold increase in the amount of active HSF1 under anoxic conditions as well as an 80% increase in nuclear localization. This was accompanied by upregulation of five HSPs by 1.8- to 2.9-fold: Hsp25, Hsp40, Hsp70, Hsc70, and Hsp90, the latter two remained elevated after 5 h of aerobic recovery. Kidney and liver showed little change in active HSF1 content during anoxia and recovery, but a significant increase in the nuclear localization of HSF1 during anoxia. This supported enhanced expression of three HSPs in kidney (Hsp40, Hsc70, and Hsp90) and four in liver (Hsp40, Hsp60, Hsp70, Hsc70). Heart displayed a strong increase in active HSF1 during anoxia and recovery (6.6- to 6.8-fold higher than control) and increased nuclear localization but heart HSP levels did not rise. The data demonstrate organ-specific regulation of HSPs during anoxia exposure and aerobic recovery in T. s. elegans and suggest that the heat shock response is an important aspect of cytoprotection during facultative anaerobiosis, particularly with regard to underwater hibernation of turtles in cold water.

  6. Social Laughter Triggers Endogenous Opioid Release in Humans.

    PubMed

    Manninen, Sandra; Tuominen, Lauri; Dunbar, Robin I; Karjalainen, Tomi; Hirvonen, Jussi; Arponen, Eveliina; Hari, Riitta; Jääskeläinen, Iiro P; Sams, Mikko; Nummenmaa, Lauri

    2017-06-21

    The size of human social networks significantly exceeds the network that can be maintained by social grooming or touching in other primates. It has been proposed that endogenous opioid release after social laughter would provide a neurochemical pathway supporting long-term relationships in humans (Dunbar, 2012), yet this hypothesis currently lacks direct neurophysiological support. We used PET and the μ-opioid-receptor (MOR)-specific ligand [ 11 C]carfentanil to quantify laughter-induced endogenous opioid release in 12 healthy males. Before the social laughter scan, the subjects watched laughter-inducing comedy clips with their close friends for 30 min. Before the baseline scan, subjects spent 30 min alone in the testing room. Social laughter increased pleasurable sensations and triggered endogenous opioid release in thalamus, caudate nucleus, and anterior insula. In addition, baseline MOR availability in the cingulate and orbitofrontal cortices was associated with the rate of social laughter. In a behavioral control experiment, pain threshold-a proxy of endogenous opioidergic activation-was elevated significantly more in both male and female volunteers after watching laughter-inducing comedy versus non-laughter-inducing drama in groups. Modulation of the opioidergic activity by social laughter may be an important neurochemical pathway that supports the formation, reinforcement, and maintenance of human social bonds. SIGNIFICANCE STATEMENT Social contacts are vital to humans. The size of human social networks significantly exceeds the network that can be maintained by social grooming in other primates. Here, we used PET to show that endogenous opioid release after social laughter may provide a neurochemical mechanism supporting long-term relationships in humans. Participants were scanned twice: after a 30 min social laughter session and after spending 30 min alone in the testing room (baseline). Endogenous opioid release was stronger after laughter versus the

  7. Ion Heating and Thermalization in a 3000 km/s Shock

    NASA Astrophysics Data System (ADS)

    Raymond, J. C.; Winkler, P. F.; Blair, W. P.; Laming, J. M.

    2017-12-01

    Collisionless shock waves can leave the plasma far from thermal equilibrium. Each particle species may have a different temperature, and the velocity distributions may be far from Maxwellian. We present HST/COS observations and MAGELLAN/IMACS of a 3000 km/s shock in the supernova remnant SN1006. The UV lines of He, C and N and the Hα profile show that the temperatures of H, He, C and N are mass-proportional to within the observational uncertainties. Thus there is no strong preferential heating and no strong transfer of energy among the ions. The electron temperature is about 0.05 as large as the proton temperature, and the H I distribution is non-Maxwellian. We briefly compare the results with theoretical expectations.

  8. Studies of shock/shock interaction on smooth and transpiration-cooled hemispherical nosetips in hypersonic flow

    NASA Technical Reports Server (NTRS)

    Holden, Michael S.; Rodriguez, Kathleen M.

    1992-01-01

    A program of experimental research and analysis was conducted to examine the heat transfer and pressure distributions in regions of shock/shock interaction over smooth and transpiration-cooled hemispherical noseshapes. The objective of this investigation was to determine whether the large heat transfer generated in regions of shock/shock interaction can be reduced by transpiration cooling. The experimental program was conducted at Mach numbers of 12 to 16 in the Calspan 48-Inch Shock Tunnel. Type 3 and type 4 interaction regions were generated for a range of freestream unit Reynolds numbers to provide shear layer Reynolds numbers from 10 exp 4 to 10 exp 6 to enable laminar and turbulent interaction regions to be studied. Shock/shock interactions were investigated on a smooth hemispherical nosetip and a similar transpiration-cooled nosetip, with the latter configuration being examined for a range of surface blowing rates up to one-third of the freestream mass flux. While the heat transfer measurements on the smooth hemisphere without shock/shock interaction were in good agreement with Fay-Riddell predictions, those on the transpiration-cooled nosetip indicated that its intrinsic roughness caused heating-enhancement factors of over 1.5. In the shock/shock interaction studies on the smooth nosetip, detailed heat transfer and pressure measurements were obtained to map the variation of the distributions with shock-impingement position for a range of type 3 and type 4 interactions. Such sets of measurements were obtained for a range of unit Reynolds numbers and Mach numbers to obtain both laminar and turbulent interactions. The measurements indicated that shear layer transition has a significant influence on the heating rates for the type 4 interaction as well as the anticipated large effects on type 3 interaction heating. In the absence of blowing, the peak heating in the type 3 and type 4 interaction regions, over the transpiration-cooled model, did not appear to be

  9. Evaporation and Accompanying Isotopic Fractionation of Sulfur from FE-S Melt During Shock Wave Heating

    NASA Technical Reports Server (NTRS)

    Tachibana, S.; Huss, G. R.; Miura, H.; Nakamoto, T.

    2004-01-01

    Chondrules probably formed by melting and subsequent cooling of solid precursors. Evaporation during chondrule melting may have resulted in depletion of volatile elements in chondrules. It is known that kinetic evaporation, especially evaporation from a melt, often leads to enrichment of heavy isotopes in an evaporation residue. However, no evidence for a large degree of heavy-isotope enrichment has been reported in chondrules for K, Mg, Si, and Fe (as FeO). The lack of isotopic fractionation has also been found for sulfur in troilites (FeS) within Bishunpur (LL3.1) and Semarkona (LL3.0) chondrules by an ion microprobe study. The largest fractionation, found in only one grain, was 2.7 +/- 1.4 %/amu, while all other troilite grains showed isotopic fractionations of <1 %/amu. The suppressed isotopic fractionation has been interpreted as results of (i) rapid heating of precursors at temperatures below the silicate solidus and (ii) diffusion-controlled evaporation through a surrounding silicate melt at temperatures above the silicate solidus. The kinetic evaporation model suggests that a rapid heating rate of >10(exp 4)-10(exp 6) K/h for a temperature range of 1000-1300 C is required to explain observed isotopic fractionations. Such a rapid heating rate seems to be difficult to be achieved in the X-wind model, but can be achieved in shock wave heating models. In this study, we have applied the sulfur evaporation model to the shock wave heating conditions of to evaluate evaporation of sulfur and accompanying isotopic fractionation during shock wave heating at temperatures below the silicate solidus.

  10. Experimental study of pressure and heating rate on a swept cylindrical leading edge resulting from swept shock wave interference. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Glass, Christopher E.

    1989-01-01

    The effects of cylindrical leading edge sweep on surface pressure and heat transfer rate for swept shock wave interference were investigated. Experimental tests were conducted in the Calspan 48-inch Hypersonic Shock Tunnel at a nominal Mach number of 8, nominal unit Reynolds number of 1.5 x 10 to the 6th power per foot, leading edge and incident shock generator sweep angles of 0, 15, and 30 deg, and incident shock generator angle-of-attack fixed at 12.5 deg. Detailed surface pressure and heat transfer rate on the cylindircal leading edge of a swept shock wave interference model were measured at the region of the maximum surface pressure and heat transfer rate. Results show that pressure and heat transfer rate on the cylindrical leading edge of the shock wave interference model were reduced as the sweep was increased over the range of tested parameters. Peak surface pressure and heat transfer rate on the cylinder were about 10 and 30 times the undisturbed flow stagnation point value, respectively, for the 0 deg sweep test. A comparison of the 15 and 30 deg swept results with the 0 deg swept results showed that peak pressure was reduced about 13 percent and 44 percent, respectively, and peak heat transfer rate was reduced about 7 percent and 27 percent, respectively.

  11. Heat Shock Factor 1: From Fire Chief to Crowd-Control Specialist.

    PubMed

    Triandafillou, Catherine G; Drummond, D Allan

    2016-07-07

    HSF1 is the supposed master regulator of the heat shock response. In this issue of Molecular Cell, Solís et al. reveal that it has a much narrower job description: organizing a small team of molecular chaperones that keep the proteome moving. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Heat release from wood wall assemblies using oxygen consumption method

    Treesearch

    Hao C. Tran; Robert E. White

    1990-01-01

    The concept of heat release rate is gaining acceptance in the evaluation of fire performance of materials and assemblies. However, this concept has not been incorporated into fire endurance testing such as the ASTM E-119 test method. Heat release rate of assemblies can be useful in determining the time at which the assemblies start to contribute to the controlled fire...

  13. MLKL activation triggers NLRP3-mediated processing and release of IL-1β independent of gasdermin-D

    PubMed Central

    Gutierrez, Kimberley D.; Davis, Michael A.; Daniels, Brian P.; Olsen, Tayla M.; Ralli-Jain, Pooja; Tait, Stephen W.G.; Gale, Michael; Oberst, Andrew

    2017-01-01

    Necroptosis is a form of programmed cell death defined by activation of the kinase RIPK3 and its downstream effector, the pseudokinase MLKL. Activated MLKL translocates to the cell membrane and disrupts it, leading to loss of cellular ion homeostasis. Here, we use a system in which this event can be specifically triggered by a small-molecule ligand to show that MLKL activation is sufficient to induce the processing and release of bioactive IL-1β. MLKL activation triggers potassium efflux and assembly of the NLRP3 inflammasome, which is required for the processing and activity of IL-1β released during necroptosis. Notably, MLKL activation also causes cell membrane disruption, which allows efficient release of IL-1β independent of the recently described pyroptotic effector gasdermin-D. Together, our findings indicate that MLKL is an endogenous activator of the NLRP3 inflammasome, and that MLKL activation provides a mechanism for concurrent processing and release of IL-1β independent of gasdermin-D. PMID:28130493

  14. Passive ice freezing-releasing heat pipe

    DOEpatents

    Gorski, Anthony J.; Schertz, William W.

    1982-01-01

    A heat pipe device has been developed which permits completely passive ice formation and periodic release of ice without requiring the ambient temperature to rise above the melting point of water. This passive design enables the maximum amount of cooling capacity to be stored in the tank.

  15. Intra-binary Shock Heating of Black Widow Companions

    NASA Astrophysics Data System (ADS)

    Romani, Roger W.; Sanchez, Nicolas

    2016-09-01

    The low-mass companions of evaporating binary pulsars (black widows and similar) are strongly heated on the side facing the pulsar. However, in high-quality photometric and spectroscopic data, the heating pattern does not match that expected for direct pulsar illumination. Here we explore a model where the pulsar power is intercepted by an intra-binary shock (IBS) before heating the low-mass companion. We develop a simple analytic model and implement it in the popular “ICARUS” light curve code. The model is parameterized by the wind momentum ratio β and the companion wind speed {f}v{v}{{orb}}, and assumes that the reprocessed pulsar wind emits prompt particles or radiation to heat the companion surface. We illustrate an interesting range of light curve asymmetries controlled by these parameters. The code also computes the IBS synchrotron emission pattern, and thus can model black widow X-ray light curves. As a test, we apply the results to the high-quality asymmetric optical light curves of PSR J2215+5135; the resulting fit gives a substantial improvement upon direct heating models and produces an X-ray light curve consistent with that seen. The IBS model parameters imply that at the present loss rate, the companion evaporation has a characteristic timescale of {τ }{{evap}}≈ 150 Myr. Still, the model is not fully satisfactory, indicating that there are additional unmodeled physical effects.

  16. Modification of N6-methyladenosine RNA methylation on heat shock protein expression.

    PubMed

    Yu, Jiayao; Li, Yi; Wang, Tian; Zhong, Xiang

    2018-01-01

    This study was conducted to investigate effect of N6-methyladenosine (m6A) RNA methylation on Heat shock proteins (HSPs) and dissect the profile of HSP RNA methylation. The results showed that m6A methyltransferases METTL3 mRNA was decreased in responses to heat shock stress in HepG2 cells, but m6A-specific binding protein YTHDF2 mRNA was upregulated in a manner similar to HSP70 induction. Immunofluorescence staining showed that the majority of YTHDF2 was present in the cytosol, however, nearly all YTHDF2 translocated from the cytosol into the nucleus after heat shock. METTL3 knockdown significantly changed HSP70, HSP60, and HSP27 mRNA expression in HepG2 cells using siRNA, however, mRNA lifetime was not impacted. Silence of YTHDF2 using siRNA did not change expression of HSP70, but significantly increased HSP90, HSP60, and HSPB1 mRNA expression. In addition, m6A-seq revealed that HSP m6A methylation peaks are mainly enriched on exons and around stop codons, and shows a unique distribution profile in the 5'UTR and 3'UTR. Knockdown of METTL3 changed the methylation patterns of HSPs transcript. In conclusion, m6A RNA methylation regulates HSP gene expression. Differential expression of HSPs modulated by m6A may depend on the m6A site and abundance of the target gene. This finding provides insights into new regulatory mechanisms of HSPs in normal and stress situations.

  17. Serum heat shock protein 70 level as a biomarker of exceptional longevity.

    PubMed

    Terry, Dellara F; Wyszynski, Diego F; Nolan, Vikki G; Atzmon, Gil; Schoenhofen, Emily A; Pennington, JaeMi Y; Andersen, Stacy L; Wilcox, Marsha A; Farrer, Lindsay A; Barzilai, Nir; Baldwin, Clinton T; Asea, Alexzander

    2006-11-01

    Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular heat shock protein 70 (Hsp70) has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes.

  18. Altered phosphorylation of. tau. protein in heat-shocked rats and patients with Alzheimer disease

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

    Papasozomenos, S.C.; Yuan Su

    1991-05-15

    Six hours after heat shocking 2- to 3-month-old male and female Sprague-Dawley rats at 42C for 15 min, the authors analyzed {tau} protein immunoreactivity in SDS extracts of cerebrums and peripheral nerves by using immunoblot analysis and immunohistochemistry with the anti-{tau} monoclonal antibody Tau-1, which recognizes a phosphate-dependent nonphosphorylated epitope, and with {sup 125}I-labeled protein A. In the cerebal extracts, the authors found altered phosphorylation of {tau} in heat-shocked females, characterized by a marked reduction in the amount of nonphosphorylated {tau}, a doubling of the ratio of total (phosphorylated plus nonphosphorylated) {tau} to nonphosphorylated {tau}, and the appearance of themore » slowest moving phosphorylated {tau} polypeptide (68 kDa). Similar, but milder, changes were observed in male rats. Quantitative immunoblot analysis of cortex and the underlying white matter with Tau-1 and {sup 125}I-labeled protein A showed that the amount of phosphorylated {tau} progressively increased in the Alzheimer disease-affected cerebral cortex, while concurrently a proportionally lesser amount of {tau} entered the white matter axons. The similar findings for the rat heat-shock model and Alzheimer disease suggest that life stressors may play a role in the etiopathogenesis of Alzheimer's disease.« less

  19. Triggered metal ion release and oxidation: Ferrocene as new mechanophore in polymers.

    PubMed

    Di Giannantonio, Michela; Ayer, Mathieu A; Verde-Sesto, Ester; Lattuada, Marco; Weder, Christoph; Fromm, Katharina M

    2018-06-13

    The introduction of mechanophores into polymers allows transducing mechanical forces into chemical reactions for e.g. self-healing, catalytic activity, or mechanochromic response. Here, the first example of mechanically induced metal ion release from a polymer is reported. Ferrocene (Fc) was incorporated as an Fe-ion releasing mechanophore into poly(methyl acrylate)s (PMAs) and polyurethanes (PUs). Sonication triggered the preferential cleavage of the polymers at the Fc units over other bonds, as shown by a kinetic study of the molar mass distribution of the cleaved Fc-containing and Fc-free reference polymers. The released and oxidized Fe2+ ions can be detected with KSCN to generate the red-colored [Fe(SCN)n(H2O)6-n)](3-n)+ or reacted with K4[Fe(CN)6] to afford Prussian blue. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Protease-sensitive, polymer-caged liposomes: a method for making highly targeted liposomes using triggered release.

    PubMed

    Basel, Matthew T; Shrestha, Tej B; Troyer, Deryl L; Bossmann, Stefan H

    2011-03-22

    Liposomes have become useful and well-known drug delivery vehicles because of their ability to entrap drugs without chemically modifying them and to deliver them somewhat selectively to tumorous tissue via the enhanced permeation and retention (EPR) effect. Although useful, liposome preparations are still less than ideal because of imperfect specificity, slow release kinetics in the tumor, and leakiness prior to reaching the tumor site. Cancer-associated proteases (CAPs), which are differentially expressed in tumors, have also gained traction recently as a method for tumor targeting and drug delivery. By combining the EPR effect with CAPs sensitivity, a much more specific liposome can be produced. The method described here creates an improved liposome system that can target more specifically, with faster release kinetics and lower general leaking, by deliberately producing a very unstable liposome (loaded with hyperosmotic vehicle) that is subsequently stabilized by a cross-linked polymer shell containing consensus sequences for cancer-associated proteases (protease-triggered, caged liposomes). A cholesterol-anchored, graft copolymer, composed of a short peptide sequence for urokinase plasminogen activator (uPA) and poly(acrylic acid), was synthesized and incorporated into liposomes prepared at high osmolarities. Upon cross-linking of the polymers, the protease-triggered, caged liposomes showed significant resistance to osmotic swelling and leaking of contents. Protease-triggered, caged liposomes also showed significant and substantial differential release of contents in the presence of uPA, while bare liposomes showed no differential effect in the presence of uPA. Thus a protease-sensitive liposome system with fast release kinetics was developed that could be used for more specific targeting to tumors.

  1. Coptidis Rhizoma Prevents Heat Stress-Induced Brain Damage and Cognitive Impairment in Mice

    PubMed Central

    Moon, Minho; Huh, Eugene; Song, Eun Ji; Hwang, Deok-Sang; Lee, Tae Hee; Oh, Myung Sook

    2017-01-01

    Heat stress conditions lead to neuroinflammation, neuronal death, and memory loss in animals. Coptidis Rhizoma (CR) exhibits potent fever-reducing effects and has been used as an important traditional medicinal herb for treating fever. However, to date, the effects of antipyretic CR on heat-induced brain damages have not been investigated. In this study, CR significantly reduced the elevation of ear and rectal temperatures after exposure to heat in mice. Additionally, CR attenuated hyperthermia-induced stress responses, such as release of cortisol into the blood, and upregulation of heat shock protein and c-Fos in the hypothalamus and hippocampus of mice. The administration of CR inhibited gliosis and neuronal loss induced by thermal stress in the hippocampal CA3 region. Treatment with CR also reduced the heat stress-induced expression of nuclear factor kappa β, tumor necrosis factor-α, and interleukin-1β (IL-1β) in the hippocampus. Moreover, CR significantly decreased proinflammatory mediators such as IL-9 and IL-13 in the heat-stressed hypothalamus. Furthermore, CR attenuated cognitive dysfunction triggered by thermal stress. These results indicate that CR protects the brain against heat stress-mediated brain damage via amelioration of hyperthermia and neuroinflammation in mice, suggesting that fever-reducing CR can attenuate thermal stress-induced neuropathology. PMID:28946610

  2. The heat-shock protein/chaperone network and multiple stress resistance.

    PubMed

    Jacob, Pierre; Hirt, Heribert; Bendahmane, Abdelhafid

    2017-04-01

    Crop yield has been greatly enhanced during the last century. However, most elite cultivars are adapted to temperate climates and are not well suited to more stressful conditions. In the context of climate change, stress resistance is a major concern. To overcome these difficulties, scientists may help breeders by providing genetic markers associated with stress resistance. However, multistress resistance cannot be obtained from the simple addition of single stress resistance traits. In the field, stresses are unpredictable and several may occur at once. Consequently, the use of single stress resistance traits is often inadequate. Although it has been historically linked with the heat stress response, the heat-shock protein (HSP)/chaperone network is a major component of multiple stress responses. Among the HSP/chaperone 'client proteins', many are primary metabolism enzymes and signal transduction components with essential roles for the proper functioning of a cell. HSPs/chaperones are controlled by the action of diverse heat-shock factors, which are recruited under stress conditions. In this review, we give an overview of the regulation of the HSP/chaperone network with a focus on Arabidopsis thaliana. We illustrate the role of HSPs/chaperones in regulating diverse signalling pathways and discuss several basic principles that should be considered for engineering multiple stress resistance in crops through the HSP/chaperone network. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  3. Physics of Shock Compression and Release: NEMD Simulations of Tantalum and Silicon

    NASA Astrophysics Data System (ADS)

    Hahn, Eric; Meyers, Marc; Zhao, Shiteng; Remington, Bruce; Bringa, Eduardo; Germann, Tim; Ravelo, Ramon; Hammerberg, James

    2015-06-01

    Shock compression and release allow us to evaluate physical deformation and damage mechanisms occurring in extreme environments. SPaSM and LAMMPS molecular dynamics codes were employed to simulate single and polycrystalline tantalum and silicon at strain rates above 108 s-1. Visualization and analysis was accomplished using OVITO, Crystal Analysis Tool, and a redesigned orientation imaging function implemented into SPaSM. A comparison between interatomic potentials for both Si and Ta (as pertaining to shock conditions) is conducted and the influence on phase transformation and plastic relaxation is discussed. Partial dislocations, shear induced disordering, and metastable phase changes are observed in compressed silicon. For tantalum, the role of grain boundary and twin intersections are evaluated for their role in ductile spallation. Finally, the temperature dependent response of both Ta and Si is investigated.

  4. Picornavirus proteins share antigenic determinants with heat shock proteins 60/65.

    PubMed

    Härkönen, T; Puolakkainen, M; Sarvas, M; Airaksinen, U; Hovi, T; Roivainen, M

    2000-11-01

    Immunological cross-reactions between enteroviruses and islet cell autoantigens have been suggested to play a role in the etiopathogenesis of insulin dependent diabetes mellitus (IDDM). In the nonobese diabetic mouse, an autoimmune model of IDDM, one of the reactive beta cell autoantigens is the heat shock protein 60 (HSP60). These studies were prompted by sequence homology discovered between the immunogenic region in HSP60 and two regions in enterovirus capsid proteins, one in the VP1 protein and the other in the VP0, the precursor of VP2 and VP4 proteins. Possible immunological cross-reactions between enterovirus proteins and heat shock proteins were studied by EIA and immunoblotting by using purified virus preparations, viral expression proteins VP1 and VP0, and recombinant HSP60/65 proteins, and corresponding polyclonal antisera. The HSP60/65 family of proteins is highly conserved and there is a striking degree of homology between bacterial and human heat shock proteins. Rabbit antibodies to HSP65 of Mycobacterium bovis that reacted with human HSP60 were also found to recognise capsid protein VP1 of coxsackievirus A9, VP1, and/or VP2 of coxsackievirus B4. Both viruses were also recognised by antisera raised against HSP60 of Chlamydia pneumoniae. In addition to the capsid proteins derived from native virions, antisera to both bacterial HSP proteins recognised expression protein VP1 of coxsackievirus A9. The cross-reactivity was also demonstrated the other way around; antisera to purified virus particles reacted with the HSP 60/65 proteins to some extent. These results suggest that apart from the well-documented sequence homology between the 2C protein of coxsackieviruses and the beta-cell autoantigen glutamic acid decarboxylase, there are other motifs in picornavirus proteins homologous to islet cell autoantigens, which might induce cross-reacting immune responses during picornavirus infections.

  5. Triggering Collapse of the Presolar Dense Cloud Core and Injecting Short-lived Radioisotopes with a Shock Wave. V. Nonisothermal Collapse Regime

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

    Boss, Alan P., E-mail: aboss@carnegiescience.edu

    Recent meteoritical analyses support an initial abundance of the short-lived radioisotope (SLRI) {sup 60}Fe that may be high enough to require nucleosynthesis in a core-collapse supernova, followed by rapid incorporation into primitive meteoritical components, rather than a scenario where such isotopes were inherited from a well-mixed region of a giant molecular cloud polluted by a variety of supernovae remnants and massive star winds. This paper continues to explore the former scenario, by calculating three-dimensional, adaptive mesh refinement, hydrodynamical code (FLASH 2.5) models of the self-gravitational, dynamical collapse of a molecular cloud core that has been struck by a thin shockmore » front with a speed of 40 km s{sup −1}, leading to the injection of shock front matter into the collapsing cloud through the formation of Rayleigh–Taylor fingers at the shock–cloud intersection. These models extend the previous work into the nonisothermal collapse regime using a polytropic approximation to represent compressional heating in the optically thick protostar. The models show that the injection efficiencies of shock front materials are enhanced compared to previous models, which were not carried into the nonisothermal regime, and so did not reach such high densities. The new models, combined with the recent estimates of initial {sup 60}Fe abundances, imply that the supernova triggering and injection scenario remains a plausible explanation for the origin of the SLRIs involved in the formation of our solar system.« less

  6. Continuous fever-range heat stress induces thermotolerance in odontoblast-lineage cells.

    PubMed

    Morotomi, Takahiko; Kitamura, Chiaki; Okinaga, Toshinori; Nishihara, Tatsuji; Sakagami, Ryuji; Anan, Hisashi

    2014-07-01

    Heat shock during restorative procedures can trigger damage to the pulpodentin complex. While severe heat shock has toxic effects, fever-range heat stress exerts beneficial effects on several cells and tissues. In this study, we examined whether continuous fever-range heat stress (CFHS) has beneficial effects on thermotolerance in the rat clonal dental pulp cell line with odontoblastic properties, KN-3. KN-3 cells were cultured at 41°C for various periods, and the expression level of several proteins was assessed by Western blot analysis. After pre-heat-treatment at 41°C for various periods, KN-3 cells were exposed to lethal severe heat shock (LSHS) at 49°C for 10min, and cell viability was examined using the MTS assay. Additionally, the expression level of odontoblast differentiation makers in surviving cells was examined by Western blot analysis. CFHS increased the expression levels of several heat shock proteins (HSPs) in KN-3 cells, and induced transient cell cycle arrest. KN-3 cells, not pre-heated or exposed to CFHS for 1 or 3h, died after exposure to LSHS. In contrast, KN-3 cells exposed to CFHS for 12h were transiently lower on day 1, but increased on day 3 after LSHS. The surviving cells expressed odontoblast differentiation markers, dentine sialoprotein and dentine matrix protein-1. These results suggest that CFHS for 12h improves tolerance to LSHS by inducing HSPs expression and cell cycle arrest in KN-3 cells. The appropriate pretreatment with continuous fever-range heat stress can provide protection against lethal heat shock in KN-3 cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Crystal structure of a small heat-shock protein from Xylella fastidiosa reveals a distinct high-order structure.

    PubMed

    Fonseca, Emanuella Maria Barreto; Scorsato, Valéria; Dos Santos, Marcelo Leite; Júnior, Atilio Tomazini; Tada, Susely Ferraz Siqueira; Dos Santos, Clelton Aparecido; de Toledo, Marcelo Augusto Szymanski; de Souza, Anete Pereira; Polikarpov, Igor; Aparicio, Ricardo

    2017-04-01

    Citrus variegated chlorosis is a disease that attacks economically important citrus plantations and is caused by the plant-pathogenic bacterium Xylella fastidiosa. In this work, the structure of a small heat-shock protein from X. fastidiosa (XfsHSP17.9) is reported. The high-order structures of small heat-shock proteins from other organisms are arranged in the forms of double-disc, hollow-sphere or spherical assemblies. Unexpectedly, the structure reported here reveals a high-order architecture forming a nearly square cavity.

  8. Translational induction of heat shock transcription factor σ32: evidence for a built-in RNA thermosensor

    PubMed Central

    Morita, Miyo Terao; Tanaka, Yoshiyuki; Kodama, Takashi S.; Kyogoku, Yoshimasa; Yanagi, Hideki; Yura, Takashi

    1999-01-01

    Induction of heat shock proteins in Escherichia coli is primarily caused by increased cellular levels of the heat shock σ-factor σ32 encoded by the rpoH gene. Increased σ32 levels result from both enhanced synthesis and stabilization. Previous work indicated that σ32 synthesis is induced at the translational level and is mediated by the mRNA secondary structure formed within the 5′-coding sequence of rpoH, including the translation initiation region. To understand the mechanism of heat induction of σ32 synthesis further, we analyzed expression of rpoH–lacZ gene fusions with altered stability of mRNA structure before and after heat shock. A clear correlation was found between the stability and expression or the extent of heat induction. Temperature-melting profiles of mRNAs with or without mutations correlated well with the expression patterns of fusion genes carrying the corresponding mutations in vivo. Furthermore, temperature dependence of mRNA–30S ribosome–tRNAfMet complex formation with wild-type or mutant mRNAs in vitro agreed well with that of the expression of gene fusions in vivo. Our results support a novel mechanism in which partial melting of mRNA secondary structure at high temperature enhances ribosome entry and translational initiation without involvement of other cellular components, that is, intrinsic mRNA stability controls synthesis of a transcriptional regulator. PMID:10090722

  9. TRIGGER MECHANISM OF SOLAR SUBFLARES IN A BRAIDED CORONAL MAGNETIC STRUCTURE

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

    Tiwari, Sanjiv K.; Alexander, Caroline E.; Winebarger, Amy R.

    Fine-scale braiding of coronal magnetic loops by continuous footpoint motions may power coronal heating via nanoflares, which are spontaneous fine-scale bursts of internal reconnection. An initial nanoflare may trigger an avalanche of reconnection of the braids, making a microflare or larger subflare. In contrast to this internal triggering of subflares, we observe external triggering of subflares in a braided coronal magnetic field observed by the High-resolution Coronal Imager (Hi-C). We track the development of these subflares using 12 s cadence images acquired by SDO/AIA in 1600, 193, 94 Å, and registered magnetograms of SDO/HMI, over four hours centered on the Hi-Cmore » observing time. These data show numerous recurring small-scale brightenings in transition-region emission happening on polarity inversion lines where flux cancellation is occurring. We present in detail an example of an apparent burst of reconnection of two loops in the transition region under the braided coronal field which is appropriate for releasing a short reconnected loop downward and a longer reconnected loop upward. The short loop presumably submerges into the photosphere, participating in observed flux cancellation. A subflare in the overlying braided magnetic field is apparently triggered by the disturbance of the braided field by the reconnection-released upward loop. At least 10 subflares observed in this braided structure appear to be triggered this way. How common this external trigger mechanism for coronal subflares is in other active regions, and how important it is for coronal heating in general, remain to be seen.« less

  10. Quality of cut lettuce treated by heat shock: prevention of enzymatic browning, repression of phenylalanine ammonia-lyase activity, and improvement on sensory evaluation during storage.

    PubMed

    Murata, Masatsune; Tanaka, Eriko; Minoura, Emiko; Homma, Seiichi

    2004-03-01

    Stored cut lettuce gradually turns brown on the cut section after several days of storage, because cutting induces phenylalanine ammonia-lyase (PAL) activity, the biosynthesis of polyphenol is promoted, and the polyphenols are oxidized by polyphenol oxidase. Here, the effect of heat shock treatment at 50 degrees C for 90 s on the quality of cut lettuce during cold storage was examined. The heat shock treatment significantly repressed the induction of PAL activity and phenolics accumulation in cut lettuce during storage, and prevented the browning of cut lettuce. Ascorbic acid content was not affected by the heat shock treatment. The sensory analysis showed that the organoleptic quality of cut lettuce treated by heat shock was significantly better than that of the control cut lettuce. These results show that heat shock treatment is useful for prolonging the shelf life of cut lettuce.

  11. Metal ions induced heat shock protein response by elevating superoxide anion level in HeLa cells transformed by HSE-SEAP reporter gene.

    PubMed

    Yu, Zhanjiang; Yang, Xiaoda; Wang, Kui

    2006-06-01

    The aim of this work is to define the relationship between heat shock protein (HSP) and reactive oxygen species (ROS) in the cells exposed to different concentrations of metal ions, and to evaluate a new method for tracing the dynamic levels of cellular reactive oxygen species using a HSE-SEAP reporter gene. The expression of heat shock protein was measured using a secreted alkaline phosphatase (SEAP) reporter gene transformed into HeLa cell strain, the levels of superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)) were determined by NBT reduction assay and DCFH staining flow cytometry (FCM), respectively. The experimental results demonstrated that the expression of heat shock protein induced by metal ions was linearly related to the cellular superoxide anion level before cytotoxic effects were observed, but not related to the cellular hydrogen peroxide level. The experimental results suggested that metal ions might induce heat shock protein by elevating cellular superoxide anion level, and thus the expression of heat shock protein indicated by the HSE-SEAP reporter gene can be an effective model for monitoring the dynamic level of superoxide anion and early metal-induced oxidative stress/cytotoxicity.

  12. Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release

    NASA Astrophysics Data System (ADS)

    Shao, Jingxin; Xuan, Mingjun; Si, Tieyan; Dai, Luru; He, Qiang

    2015-11-01

    Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety.Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid

  13. The differential effects of heat-shocking on the viability of spores from Bacillus anthracis, Bacillus subtilis, and Clostridium sporogenes after treatment with peracetic acid- and glutaraldehyde-based disinfectants

    PubMed Central

    March, Jordon K; Pratt, Michael D; Lowe, Chinn-Woan; Cohen, Marissa N; Satterfield, Benjamin A; Schaalje, Bruce; O'Neill, Kim L; Robison, Richard A

    2015-01-01

    This study investigated (1) the susceptibility of Bacillus anthracis (Ames strain), Bacillus subtilis (ATCC 19659), and Clostridium sporogenes (ATCC 3584) spores to commercially available peracetic acid (PAA)- and glutaraldehyde (GA)-based disinfectants, (2) the effects that heat-shocking spores after treatment with these disinfectants has on spore recovery, and (3) the timing of heat-shocking after disinfectant treatment that promotes the optimal recovery of spores deposited on carriers. Suspension tests were used to obtain inactivation kinetics for the disinfectants against three spore types. The effects of heat-shocking spores after disinfectant treatment were also determined. Generalized linear mixed models were used to estimate 6-log reduction times for each spore type, disinfectant, and heat treatment combination. Reduction times were compared statistically using the delta method. Carrier tests were performed according to AOAC Official Method 966.04 and a modified version that employed immediate heat-shocking after disinfectant treatment. Carrier test results were analyzed using Fisher's exact test. PAA-based disinfectants had significantly shorter 6-log reduction times than the GA-based disinfectant. Heat-shocking B. anthracis spores after PAA treatment resulted in significantly shorter 6-log reduction times. Conversely, heat-shocking B. subtilis spores after PAA treatment resulted in significantly longer 6-log reduction times. Significant interactions were also observed between spore type, disinfectant, and heat treatment combinations. Immediately heat-shocking spore carriers after disinfectant treatment produced greater spore recovery. Sporicidal activities of disinfectants were not consistent across spore species. The effects of heat-shocking spores after disinfectant treatment were dependent on both disinfectant and spore species. Caution must be used when extrapolating sporicidal data of disinfectants from one spore species to another. Heat-shocking

  14. Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: loading, enzyme-trigger release and cell uptake.

    PubMed

    Barbieri, Stefano; Sonvico, Fabio; Como, Caterina; Colombo, Gaia; Zani, Franca; Buttini, Francesca; Bettini, Ruggero; Rossi, Alessandra; Colombo, Paolo

    2013-05-10

    Tamoxifen citrate (TAM), an anticancer drug with amphiphilic properties, was loaded in lecithin/chitosan nanoparticles (LCN) with a view to oral administration. The influence of tamoxifen loading on the physico-chemical properties of nanoparticles was studied. Size, surface charge and morphological properties of tamoxifen-loaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAM preparation up to 60 mg/100 ml maintained the positive zeta potential value of about +45 mV. A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20mg. A strong influence of loaded tamoxifen on the structure of lecithin/chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis. A loading of tamoxifen in nanoparticles of around 19% was obtained. The release of the drug from the LCN-TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro-intestinal fluids without enzymes. When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner. Tamoxifen-loaded nanoparticles showed cytotoxicity towards MCF-7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release. Caco-2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Compaction shock dissipation in low density granular explosive

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

    Rao, Pratap T.; Gonthier, Keith A., E-mail: gonthier@me.lsu.edu; Chakravarthy, Sunada

    The microstructure of granular explosives can affect dissipative heating within compaction shocks that can trigger combustion and initiate detonation. Because initiation occurs over distances that are much larger than the mean particle size, homogenized (macroscale) theories are often used to describe local thermodynamic states within and behind shocks that are regarded as the average manifestation of thermodynamic fields at the particle scale. In this paper, mesoscale modeling and simulation are used to examine how the initial packing density of granular HMX (C{sub 4}H{sub 8}N{sub 8}O{sub 8}) C{sub 4}H{sub 8}N{sub 8}O{sub 8} having a narrow particle size distribution influences dissipation withinmore » resolved, planar compaction shocks. The model tracks the evolution of thermomechanical fields within large ensembles of particles due to pore collapse. Effective shock profiles, obtained by averaging mesoscale fields over space and time, are compared with those given by an independent macroscale compaction theory that predicts the variation in effective thermomechanical fields within shocks due to an imbalance between the solid pressure and a configurational stress. Reducing packing density is shown to reduce the dissipation rate within shocks but increase the integrated dissipated work over shock rise times, which is indicative of enhanced sensitivity. In all cases, dissipated work is related to shock pressure by a density-dependent power law, and shock rise time is related to pressure by a power law having an exponent of negative one.« less

  16. BAG3 Is a Modular, Scaffolding Protein that physically Links Heat Shock Protein 70 (Hsp70) to the Small Heat Shock Proteins.

    PubMed

    Rauch, Jennifer N; Tse, Eric; Freilich, Rebecca; Mok, Sue-Ann; Makley, Leah N; Southworth, Daniel R; Gestwicki, Jason E

    2017-01-06

    Small heat shock proteins (sHsps) are a family of ATP-independent molecular chaperones that are important for binding and stabilizing unfolded proteins. In this task, the sHsps have been proposed to coordinate with ATP-dependent chaperones, including heat shock protein 70 (Hsp70). However, it is not yet clear how these two important components of the chaperone network are linked. We report that the Hsp70 co-chaperone, BAG3, is a modular, scaffolding factor to bring together sHsps and Hsp70s. Using domain deletions and point mutations, we found that BAG3 uses both of its IPV motifs to interact with sHsps, including Hsp27 (HspB1), αB-crystallin (HspB5), Hsp22 (HspB8), and Hsp20 (HspB6). BAG3 does not appear to be a passive scaffolding factor; rather, its binding promoted de-oligomerization of Hsp27, likely by competing for the self-interactions that normally stabilize large oligomers. BAG3 bound to Hsp70 at the same time as Hsp22, Hsp27, or αB-crystallin, suggesting that it might physically bring the chaperone families together into a complex. Indeed, addition of BAG3 coordinated the ability of Hsp22 and Hsp70 to refold denatured luciferase in vitro. Together, these results suggest that BAG3 physically and functionally links Hsp70 and sHsps. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The effectiveness of manual versus algometer pressure release techniques for treating active myofascial trigger points of the upper trapezius.

    PubMed

    Abu Taleb, Walaa; Rehan Youssef, Aliaa; Saleh, Amir

    2016-10-01

    Manual pressure release (MPR) is a popular treatment of trigger points. Yet, treatment response may be influenced by inconsistent application of pressure. Further, it may contribute to increased risk of work-related musculoskeletal disorders of the wrist and hand in therapists. Therefore, this study aimed at introducing a novel method to apply pressure using the algometer and to compare its effectiveness to MPR. Forty-five volunteers with active trigger points of the upper trapezius received algometer pressure release (APR), MPR, or sham ultrasound (US). Pain pressure threshold (PPT) and contralateral active and passive neck side-bending ranges were assessed at baseline and immediately after a single session. Results showed no significant differences in post-treatment PPT between the study groups (p > 0.05). The APR group showed a significant increase in passive side-bending range compared with the two other groups, whereas active range improved in the APR compared with the US group (p < 0.05). Our results show that using algometer to apply pressure release to upper trapezius trigger points is more effective compared with manual release and sham US. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Sequence and structure determinants of Drosophila Hsp70 mRNA translation: 5'UTR secondary structure specifically inhibits heat shock protein mRNA translation.

    PubMed Central

    Hess, M A; Duncan, R F

    1996-01-01

    Preferential translation of Drosophila heat shock protein 70 (Hsp70) mRNA requires only the 5'-untranslated region (5'-UTR). The sequence of this region suggests that it has relatively little secondary structure, which may facilitate efficient protein synthesis initiation. To determine whether minimal 5'-UTR secondary structure is required for preferential translation during heat shock, the effect of introducing stem-loops into the Hsp70 mRNA 5'-UTR was measured. Stem-loops of -11 kcal/mol abolished translation during heat shock, but did not reduce translation in non-heat shocked cells. A -22 kcal/mol stem-loop was required to comparably inhibit translation during growth at normal temperatures. To investigate whether specific sequence elements are also required for efficient preferential translation, deletion and mutation analyses were conducted in a truncated Hsp70 5'-UTR containing only the cap-proximal and AUG-proximal segments. Linker-scanner mutations in the cap-proximal segment (+1 to +37) did not impair translation. Re-ordering the segments reduced mRNA translational efficiency by 50%. Deleting the AUG-proximal segment severely inhibited translation. A 5-extension of the full-length leader specifically impaired heat shock translation. These results indicate that heat shock reduces the capacity to unwind 5-UTR secondary structure, allowing only mRNAs with minimal 5'-UTR secondary structure to be efficiently translated. A function for specific sequences is also suggested. PMID:8710519

  19. Human Myocardium Releases Heat Shock Protein 27 (HSP27) after Global Ischemia: The Proinflammatory Effect of Extracellular HSP27 through Toll-like Receptor (TLR)-2 and TLR4

    PubMed Central

    Jin, Chunhua; Cleveland, Joseph C; Ao, Lihua; Li, Jilin; Zeng, Qingchun; Fullerton, David A; Meng, Xianzhong

    2014-01-01

    The myocardial inflammatory response contributes to cardiac functional injury associated with heart surgery obligating global ischemia/reperfusion (I/R). Toll-like receptors (TLRs) play an important role in the mechanism underlying myocardial I/R injury. The aim of this study was to examine the release of small constitutive heat shock proteins (HSPs) from human and mouse myocardium after global ischemia and examine the role of extracellular small HSP in myocardial injury. HSP27 release was assessed by enzyme-linked immunosorbent assay. Anti-HSP27 was applied to evaluate the role of extracellular HSP27 in the postischemic inflammatory response and functional injury in mouse hearts. Isolated hearts and cultured coronary vascular endothelial cells were exposed to recombinant HSP27 to determine its effect on proinflammatory signaling and production of proinflammatory mediators. HSP27 levels were markedly elevated in coronary sinus blood of patients and in coronary effluent of mouse hearts after global ischemia. Neutralizing extracellular HSP27 suppressed myocardial nuclear factor (NF)-κB activation and interleukin (IL)-6 production and improved cardiac function in mouse hearts. Perfusion of HSP27 to mouse hearts induced NF-κB activation and IL-6 production and depressed contractility. Further, recombinant HSP27 induced NF-κB phosphorylation and upregulated monocyte chemoattractant protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1 production in both human and mouse coronary vascular endothelial cells. TLR2 knockout (KO) or TLR4 mutation abolished NF-κB phosphorylation and reduced MCP-1 and ICAM-1 production induced by extracellular HSP27 in endothelial cells. In conclusion, these results show that the myocardium releases HSP27 after global ischemia and that extracellular HSP27 is proinflammatory and contributes to the inflammatory mechanism of myocardial functional injury. Both TLR2 and TLR4 are involved in mediating the proinflammatory effect of

  20. Human myocardium releases heat shock protein 27 (HSP27) after global ischemia: the proinflammatory effect of extracellular HSP27 through toll-like receptor (TLR)-2 and TLR4.

    PubMed

    Jin, Chunhua; Cleveland, Joseph C; Ao, Lihua; Li, Jilin; Zeng, Qingchun; Fullerton, David A; Meng, Xianzhong

    2014-06-09

    The myocardial inflammatory response contributes to cardiac functional injury associated with heart surgery obligating global ischemia/reperfusion (I/R). Toll-like receptors (TLRs) play an important role in the mechanism underlying myocardial I/R injury. The aim of this study was to examine the release of small constitutive heat shock proteins (HSPs) from human and mouse myocardium after global ischemia and examine the role of extracellular small HSP in myocardial injury. HSP27 release was assessed by enzyme-linked immunosorbent assay. Anti-HSP27 was applied to evaluate the role of extracellular HSP27 in the postischemic inflammatory response and functional injury in mouse hearts. Isolated hearts and cultured coronary vascular endothelial cells were exposed to recombinant HSP27 to determine its effect on proinflammatory signaling and production of proinflammatory mediators. HSP27 levels were markedly elevated in coronary sinus blood of patients and in coronary effluent of mouse hearts after global ischemia. Neutralizing extracellular HSP27 suppressed myocardial nuclear factor (NF)-κB activation and interleukin (IL)-6 production and improved cardiac function in mouse hearts. Perfusion of HSP27 to mouse hearts induced NF-κB activation and IL-6 production and depressed contractility. Further, recombinant HSP27 induced NF-κB phosphorylation and upregulated monocyte chemoattractant protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1 production in both human and mouse coronary vascular endothelial cells. TLR2 knockout (KO) or TLR4 mutation abolished NF-κB phosphorylation and reduced MCP-1 and ICAM-1 production induced by extracellular HSP27 in endothelial cells. In conclusion, these results show that the myocardium releases HSP27 after global ischemia and that extracellular HSP27 is proinflammatory and contributes to the inflammatory mechanism of myocardial functional injury. Both TLR2 and TLR4 are involved in mediating the proinflammatory effect of

  1. The effect of trigger point management by positional release therapy on tension type headache.

    PubMed

    Ghanbari, Ali; Rahimijaberi, Abbas; Mohamadi, Marzieh; Abbasi, Leila; Sarvestani, Fahimeh Kamali

    2012-01-01

    The aim of this study was to compare the effectiveness of trigger points' management by Positional Release Therapy (PRT) and routine medical therapy in treatment of Tension Type Headache. Tension Type Headache is the most frequent headache with the basis of myofascial and trigger point disorders. PRT is an indirect technique that treats trigger points. 30 Patients with active trigger points in cervical muscles entered to the study. They were randomly assigned to PRT or medical therapy group. Headache frequency, intensity and duration and tablet count were recorded by use of a daily headache diary. Sensitivity of trigger points was assessed by numeric pain intensity and by use of a digital force gauge (FG 5020). Both groups showed significant reduction in headache frequency and duration and tablet count after treatment phase. However, the reduction of study variables was persisted only in PRT group after follow up phase. There was no significant reduction in headache intensity, neither in PRT and nor in medication group. Sensitivity of trigger points was significantly reduced. In comparison of the two study groups, there was no significant difference in headache frequency, intensity, duration and tablet count (p> 0.05). Both procedures were equally effective according to the study. Thus, PRT can be a treatment choice for patients with T.T.H.

  2. Low heat shock thresholds in wild Antarctic inter-tidal limpets (Nacella concinna)

    PubMed Central

    Geissler, Paul; Waller, Catherine; Fraser, Keiron P. P.; Barnes, David K. A.; Peck, Lloyd S.

    2008-01-01

    Heat shock proteins (HSPs) are a family of genes classically used to measure levels of organism stress. We have previously identified two HSP70 genes (HSP70A and HSP70B) in sub-tidal populations of the Antarctic limpet (Nacella concinna). These genes are up-regulated in response to increased seawater temperatures of 15°C or more during acute heat shock experiments, temperatures that have very little basis when considering the current Antarctic ecology of these animals. Therefore, the question was posed as to whether these animals could express HSP70 genes when subjected to more complex environmental conditions, such as those that occur in the inter-tidal. Inter-tidal limpets were collected on three occasions in different weather conditions at South Cove, Rothera Point, over a complete tidal cycle, and the expression levels of the HSP70 genes were measured. Both genes showed relative up-regulation of gene expression over the period of the tidal cycle. The average foot temperature of these animals was 3.3°C, far below that of the acute heat shock experiments. These experiments demonstrate that the temperature and expression levels of HSP production in wild animals cannot be accurately extrapolated from experimentally induced treatments, especially when considering the complexity of stressors in the natural environment. However, experimental manipulation can provide molecular markers for identifying stress in Antarctic molluscs, provided it is accompanied by environmental validation, as demonstrated here. Electronic supplementary material The online version of this article (doi:10.1007/s12192-008-0015-7) contains supplementary material, which is available to authorized users. PMID:18347941

  3. The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis.

    PubMed

    Chen, Han-Jou; Mitchell, Jacqueline C; Novoselov, Sergey; Miller, Jack; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline A; Cheetham, Michael E; Shaw, Christopher E

    2016-05-01

    Detergent-resistant, ubiquitinated and hyperphosphorylated Tar DNA binding protein 43 (TDP-43, encoded by TARDBP) neuronal cytoplasmic inclusions are the pathological hallmark in ∼95% of amyotrophic lateral sclerosis and ∼60% of frontotemporal lobar degeneration cases. We sought to explore the role for the heat shock response in the clearance of insoluble TDP-43 in a cellular model of disease and to validate our findings in transgenic mice and human amyotrophic lateral sclerosis tissues. The heat shock response is a stress-responsive protective mechanism regulated by the transcription factor heat shock factor 1 (HSF1), which increases the expression of chaperones that refold damaged misfolded proteins or facilitate their degradation. Here we show that manipulation of the heat shock response by expression of dominant active HSF1 results in a dramatic reduction of insoluble and hyperphosphorylated TDP-43 that enhances cell survival, whereas expression of dominant negative HSF1 leads to enhanced TDP-43 aggregation and hyperphosphorylation. To determine which chaperones were mediating TDP-43 clearance we over-expressed a range of heat shock proteins (HSPs) and identified DNAJB2a (encoded by DNAJB2, and also known as HSJ1a) as a potent anti-aggregation chaperone for TDP-43. DNAJB2a has a J domain, allowing it to interact with HSP70, and ubiquitin interacting motifs, which enable it to engage the degradation of its client proteins. Using functionally deleted DNAJB2a constructs we demonstrated that TDP-43 clearance was J domain-dependent and was not affected by ubiquitin interacting motif deletion or proteasome inhibition. This indicates that TDP-43 is maintained in a soluble state by DNAJB2a, leaving the total levels of TDP-43 unchanged. Additionally, we have demonstrated that the levels of HSF1 and heat shock proteins are significantly reduced in affected neuronal tissues from a TDP-43 transgenic mouse model of amyotrophic lateral sclerosis and patients with

  4. Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model.

    PubMed

    Lee, Won Jai; Lee, Ju Hee; Ahn, Hyo Min; Song, Seung Yong; Kim, Yong Oock; Lew, Dae Hyun; Yun, Chae-Ok

    2015-09-01

    The 90-kDa heat-shock protein (heat-shock protein 90) is an abundant cytosolic chaperone, and inhibition of heat-shock protein 90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) compromises transforming growth factor (TGF)-β-mediated transcriptional responses by enhancing TGF-β receptor I and II degradation, thus preventing Smad2/3 activation. In this study, the authors evaluated whether heat-shock protein 90 regulates TGF-β signaling in the pathogenesis and treatment of keloids. Keloid fibroblasts were treated with 17-AAG (10 μM), and mRNA levels of collagen types I and III were determined by real-time reverse- transcriptase polymerase chain reaction. Also, secreted TGF-β1 was assessed by enzyme-linked immunosorbent assay. The effect of 17-AAG on protein levels of Smad2/3 complex was determined by Western blot analysis. In addition, in 17-AAG-treated keloid spheroids, the collagen deposition and expression of major extracellular matrix proteins were investigated by means of Masson trichrome staining and immunohistochemistry. The authors found that heat-shock protein 90 is overexpressed in human keloid tissue compared with adjacent normal tissue, and 17-AAG decreased mRNA levels of type I collagen, secreted TGF-ß1, and Smad2/3 complex protein expression in keloid fibroblasts. Masson trichrome staining revealed that collagen deposition was decreased in 17-AAG-treated keloid spheroids, and immunohistochemical analysis showed that expression of collagen types I and III, elastin, and fibronectin was markedly decreased in 17-AAG-treated keloid spheroids. These results suggest that the antifibrotic action of heat-shock protein 90 inhibitors such as 17-AAG may have therapeutic effects on keloids.

  5. Experimental Investigation of Shock-Shock Interactions Over a 2-D Wedge at M=6

    NASA Technical Reports Server (NTRS)

    Jones, Michelle L.

    2013-01-01

    The effects of fin-leading-edge radius and sweep angle on peak heating rates due to shock-shock interactions were investigated in the NASA Langley Research Center 20-inch Mach 6 Air Tunnel. The fin model leading edges, which represent cylindrical leading edges or struts on hypersonic vehicles, were varied from 0.25 inches to 0.75 inches in radius. A 9deg wedge generated a planar oblique shock at 16.7deg to the flow that intersected the fin bow shock, producing a shock-shock interaction that impinged on the fin leading edge. The fin angle of attack was varied from 0deg (normal to the free-stream) to 15deg and 25deg swept forward. Global temperature data was obtained from the surface of the fused silica fins through phosphor thermography. Metal oil flow models with the same geometries as the fused silica models were used to visualize the streamline patterns for each angle of attack. High-speed zoom-schlieren videos were recorded to show the features and temporal unsteadiness of the shock-shock interactions. The temperature data were analyzed using one-dimensional semi-infinite as well as one- and two-dimensional finite-volume methods to determine the proper heat transfer analysis approach to minimize errors from lateral heat conduction due to the presence of strong surface temperature gradients induced by the shock interactions. The general trends in the leading-edge heat transfer behavior were similar for the three shock-shock interactions, respectively, between the test articles with varying leading-edge radius. The dimensional peak heat transfer coefficient augmentation increased with decreasing leading-edge radius. The dimensional peak heat transfer output from the two-dimensional code was about 20% higher than the value from a standard, semi-infinite one-dimensional method.

  6. Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.

    PubMed

    Soncin, Fabrice; Zhang, Xinfeng; Chu, Boyang; Wang, Xiaozhe; Asea, Alexzander; Ann Stevenson, Mary; Sacks, David B; Calderwood, Stuart K

    2003-04-04

    Heat shock factor-1 (HSF-1) is the regulator of hsp molecular chaperone transcription, although the intracellular mechanisms involved in HSF-1 activation have not been fully elucidated. As HSF1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase CK2, we have investigated the role of CK2 in HSF1 activation. We demonstrate that HSF-1 is phosphorylated by CK2 on both serine and threonine residues and has characterized a phosphorylation site at threonine 142. Mutation of Thr-142 to alanine (T142A) inhibits trans-activation of the HSP70 gene by HSF1 and in addition inhibits the accumulation of HSF-1 competent to bind heat shock elements in the nucleus. HSF1 activation by heat is correlated with the thermal activation of nuclear CK2 and overexpression of CK2 activates HSF1. Phosphorylation by CK2 on threonine 142 may therefore be an essential step in the thermal activation of latent HSF1 by stresses.

  7. Shock wave as a probe of flux-dimited thermal transport in laser-heated solids

    NASA Astrophysics Data System (ADS)

    Smith, K.; Forsman, A.; Chiu, G.

    1996-11-01

    Laser-generated shock waves in solids result from the ablation of the target material. Where radiation transport is negligible, the ablation process is dominated by electron thermal conduction. This offers an opportunity to probe the degree of transport inhibition (compared with classical heat flow) for steep temperature gradients in a dense plasma. Using a 1-dimensional hydrodynamic code, we have examined the effect of flux-limited thermal conduction on the amplitude of the resulting shock wave.

  8. The expression and function of hsp30-like small heat shock protein genes in amphibians, birds, fish, and reptiles.

    PubMed

    Heikkila, John J

    2017-01-01

    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.

  9. Heat Shock Proteins Are Important Mediators of Skeletal Muscle Insulin Sensitivity

    PubMed Central

    Geiger, Paige C.; Gupte, Anisha A.

    2013-01-01

    Endogenous heat shock proteins (HSP) are decreased in disease states associated with insulin resistance and aging. Induction of HSPs has been shown to decrease oxidative stress, inhibit inflammatory pathways, and enhance metabolic characteristics in skeletal muscle. As such, HSPs have the potential to function as an important defense system against the development of insulin resistance and type 2 diabetes. PMID:21088604

  10. Prostaglandin E synthase interacts with inducible heat shock protein 70 after heat stress in bovine primary dermal fibroblast cells.

    PubMed

    Richter, Constanze; Viergutz, Torsten; Schwerin, Manfred; Weitzel, Joachim M

    2015-01-01

    Exposure to heat stress in dairy cows leads to undesired side effects that are reflected by complex alterations in endocrine parameters, such as reduced progesterone, estradiol, and thyroid hormone concentrations. These endocrine maladaptation leads to failure to resume cyclicity, a poor uterine environment and inappropriate immune responses in postpartum dairy cows. Prostaglandins (PG's) are lipid mediators, which serve as signal molecules in response to various external stimuli as well as to cell-specific internal signal molecules. A central role in PG synthesis plays prostaglandin E synthase (PGES) that catalyzes the isomerization of PGH2 to PGE2 .The present study was conducted to investigate heat stress associated PGES expression. Expression of PGES and inducible heat shock protein 70 (HSP70), as a putative chaperonic protein, was studied in bovine primary fibroblasts under different heat shock conditions. Bovine primary fibroblasts produce PGE2 at homoiothermical norm temperature (38.5°C in bovine), but reduce PGE2 production rates under extreme heat stress (at 45°C for 6 h). By contrast, PGE2 production rates are maintained after a milder heat stress (at 41.5°C for 6 h). PGE2 synthesis is abolished by application of cyclooxygenase inhibitor indomethacin, indicating de novo synthesis. Heat stress increases HSP70 but not PGES protein concentrations. HSP70 physically interacts with PGES and the PGES-HSP70 complex did not dissociate upon heat stress at 45°C even after returning the cells to 37°C. The PGE2 production negatively correlates with the portion of PGES-HSP70 complex. These results suggest a protein interaction between HSP70 and PGES in dermal fibroblast cells. Blockage of PGES protein by HSP70 seems to interfere with the regulatory processes essential for cellular adaptive protection. © 2014 International Society for Advancement of Cytometry. © 2014 International Society for Advancement of Cytometry.

  11. Development of a simultaneous Hugoniot and temperature measurement for preheated-metal shock experiments: melting temperatures of Ta at pressures of 100 GPa.

    PubMed

    Li, Jun; Zhou, Xianming; Li, Jiabo; Wu, Qiang; Cai, Lingcang; Dai, Chengda

    2012-05-01

    Equations of state of metals are important issues in earth science and planetary science. A major limitation of them is the lack of experimental data for determining pressure-volume and temperature of shocked metal simultaneously. By measuring them in a single experiment, a major source of systematic error is eliminated in determining from which shock pressure release pressure originates. Hence, a non-contact fast optical method was developed and demonstrated to simultaneously measure a Hugoniot pressure-volume (P(H)-V(H)) point and interfacial temperature T(R) on the release of Hugoniot pressure (P(R)) for preheated metals up to 1000 K. Experimental details in our investigation are (i) a Ni-Cr resistance coil field placed around the metal specimen to generate a controllable and stable heating source, (ii) a fiber-optic probe with an optical lens coupling system and optical pyrometer with ns time resolution to carry out non-contact fast optical measurements for determining P(H)-V(H) and T(R). The shock response of preheated tantalum (Ta) at 773 K was investigated in our work. Measured data for shock velocity versus particle velocity at an initial state of room temperature was in agreement with previous shock compression results, while the measured shock data between 248 and 307 GPa initially heated to 773 K were below the Hugoniot evaluation from its off-Hugoniot states. Obtained interfacial temperatures on release of Hugoniot pressures (100-170 GPa) were in agreement with shock-melting points at initial ambient condition and ab initio calculations of melting curve. It indicates a good consistency for shock melting data of Ta at different initial temperatures. Our combined diagnostics for Hugoniot and temperature provides an important approach for studying EOS and the temperature effect of shocked metals. In particular, our measured melting temperatures of Ta address the current controversy about the difference by more than a factor of 2 between the melting

  12. An effective trigger for energy release of vinylheptafulvene-based solar heat batteries.

    PubMed

    Cacciarini, Martina; Vlasceanu, Alexandru; Jevric, Martyn; Nielsen, Mogens Brøndsted

    2017-05-30

    Stoichiometric copper(i) tetrakis(acetonitrile) is found to activate the thermal ring-closure reaction of a series of high-energy vinylheptafulvene isomers to the corresponding low-energy and photoactive dihydroazulenes, allowing the release of energy upon request.

  13. Triggering Receptor Expressed on Myeloid Cells-1 Signaling: Protective and Pathogenic Roles on Streptococcal Toxic-Shock-Like Syndrome Caused by Streptococcus suis.

    PubMed

    Han, Li; Fu, Lei; Peng, Yongbo; Zhang, Anding

    2018-01-01

    Streptococcus suis infections can cause septic shock, which is referred to as streptococcal toxic-shock-like syndrome (STSLS). The disease is characterized by a severe inflammatory response, multiple organ failure, and high mortality. However, no superantigen that is responsible for toxic shock syndrome was detected in S. suis , indicating that the mechanism underlying STSLS is different and remains to be elucidated. Triggering receptor expressed on myeloid cells-1 (TREM-1), belonging to the Ig superfamily, is an activating receptor expressed on myeloid cells, and has been recognized as a critical immunomodulator in several inflammatory diseases of both infectious and non-infectious etiologies. In this review, we discuss the current understanding of the immunoregulatory functions of TREM-1 on acute infectious diseases and then highlight the crucial roles of TREM-1 on the development of STSLS.

  14. Shock initiated thermal and chemical responses of HMX crystal from ReaxFF molecular dynamics simulation.

    PubMed

    Zhou, Tingting; Song, Huajie; Liu, Yi; Huang, Fenglei

    2014-07-21

    To gain an atomistic-level understanding of the thermal and chemical responses of condensed energetic materials under thermal shock, we developed a thermal shock reactive dynamics (TS-RD) computational protocol using molecular dynamics simulation coupled with ReaxFF force field. β-Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) was selected as a a target explosive due to its wide usage in the military and industry. The results show that a thermal shock initiated by a large temperature gradient between the "hot" region and the "cold" region results in thermal expansion of the particles and induces a thermal-mechanical wave propagating back and forth in the system with an averaged velocity of 3.32 km s(-1). Heat propagating along the direction of thermal shock leads to a temperature increment of the system and thus chemical reaction initiation. Applying a continuum reactive heat conduction model combined with the temperature distribution obtained from the RD simulation, a heat conduction coefficient is derived as 0.80 W m(-1) K(-1). The chemical reaction mechanisms during thermal shock were analyzed, showing that the reaction is triggered by N-NO2 bond breaking followed by HONO elimination and ring fission. The propagation rates of the reaction front and reaction center are obtained to be 0.069 and 0.038 km s(-1), based on the time and spatial distribution of NO2. The pressure effect on the thermal shock was also investigated by employing uniaxial compression before the thermal shock. We find that compression significantly accelerates thermal-mechanical wave propagation and heat conduction, resulting in higher temperature and more excited molecules and thus earlier initiation and faster propagation of chemical reactions.

  15. Shock and Release Behaviour of Silica Based Granular Materials

    NASA Astrophysics Data System (ADS)

    Braithwaite, Chris; Perry, James; Taylor, Nicholas

    2017-06-01

    A large number of experiments have been conducted using the Cavendish single stage gas gun to investigate the dynamic properties of sand. The results included successful measurements of release in dry materials, demonstrating that this is markedly different to the loading path. The effect of moisture was examined and shown to be strongest where the material was close to saturation, at which point the microstructure of the exact sample configuration plays a significant role in the response. Finally, the effect of sample morphology was probed, and whilst it was found to be significant at low rates, in the shock regime impedance appears to be more strongly influenced by the presence of moisture or a fraction of small particle size debris.

  16. Unraveling Regulation of the Small Heat Shock Proteins by the Heat Shock Factor HvHsfB2c in Barley: Its Implications in Drought Stress Response and Seed Development

    PubMed Central

    Reddy, Palakolanu Sudhakar; Kavi Kishor, Polavarapu B.; Seiler, Christiane; Kuhlmann, Markus; Eschen-Lippold, Lennart; Lee, Justin; Reddy, Malireddy K.; Sreenivasulu, Nese

    2014-01-01

    The rapid increase in heat shock proteins upon exposure to damaging stresses and during plant development related to desiccation events reveal their dual importance in plant development and stress tolerance. Genome-wide sequence survey identified 20 non-redundant small heat shock proteins (sHsp) and 22 heat shock factor (Hsf) genes in barley. While all three major classes (A, B, C) of Hsfs are localized in nucleus, the 20 sHsp gene family members are localized in different cell organelles like cytoplasm, mitochondria, plastid and peroxisomes. Hsf and sHsp members are differentially regulated during drought and at different seed developmental stages suggesting the importance of chaperone role under drought as well as seed development. In silico cis-regulatory motif analysis of Hsf promoters showed an enrichment with abscisic acid responsive cis-elements (ABRE), implying regulatory role of ABA in mediating transcriptional response of HvsHsf genes. Gene regulatory network analysis identified HvHsfB2c as potential central regulator of the seed-specific expression of several HvsHsps including 17.5CI sHsp. These results indicate that HvHsfB2c is co-expressed in the central hub of small Hsps and therefore it may be regulating the expression of several HvsHsp subclasses HvHsp16.88-CI, HvHsp17.5-CI and HvHsp17.7-CI. The in vivo relevance of binding specificity of HvHsfB2C transcription factor to HSE-element present in the promoter of HvSHP17.5-CI under heat stress exposure is confirmed by gel shift and LUC-reporter assays. Further, we isolated 477 bp cDNA from barley encoding a 17.5 sHsp polypeptide, which was predominantly upregulated under drought stress treatments and also preferentially expressed in developing seeds. Recombinant HvsHsp17.5-CI protein was expressed in E. coli and purified to homogeneity, which displayed in vitro chaperone activity. The predicted structural model of HvsHsp-17.5-CI protein suggests that the α-crystallin domain is evolutionarily highly

  17. Unraveling regulation of the small heat shock proteins by the heat shock factor HvHsfB2c in barley: its implications in drought stress response and seed development.

    PubMed

    Reddy, Palakolanu Sudhakar; Kavi Kishor, Polavarapu B; Seiler, Christiane; Kuhlmann, Markus; Eschen-Lippold, Lennart; Lee, Justin; Reddy, Malireddy K; Sreenivasulu, Nese

    2014-01-01

    The rapid increase in heat shock proteins upon exposure to damaging stresses and during plant development related to desiccation events reveal their dual importance in plant development and stress tolerance. Genome-wide sequence survey identified 20 non-redundant small heat shock proteins (sHsp) and 22 heat shock factor (Hsf) genes in barley. While all three major classes (A, B, C) of Hsfs are localized in nucleus, the 20 sHsp gene family members are localized in different cell organelles like cytoplasm, mitochondria, plastid and peroxisomes. Hsf and sHsp members are differentially regulated during drought and at different seed developmental stages suggesting the importance of chaperone role under drought as well as seed development. In silico cis-regulatory motif analysis of Hsf promoters showed an enrichment with abscisic acid responsive cis-elements (ABRE), implying regulatory role of ABA in mediating transcriptional response of HvsHsf genes. Gene regulatory network analysis identified HvHsfB2c as potential central regulator of the seed-specific expression of several HvsHsps including 17.5CI sHsp. These results indicate that HvHsfB2c is co-expressed in the central hub of small Hsps and therefore it may be regulating the expression of several HvsHsp subclasses HvHsp16.88-CI, HvHsp17.5-CI and HvHsp17.7-CI. The in vivo relevance of binding specificity of HvHsfB2C transcription factor to HSE-element present in the promoter of HvSHP17.5-CI under heat stress exposure is confirmed by gel shift and LUC-reporter assays. Further, we isolated 477 bp cDNA from barley encoding a 17.5 sHsp polypeptide, which was predominantly upregulated under drought stress treatments and also preferentially expressed in developing seeds. Recombinant HvsHsp17.5-CI protein was expressed in E. coli and purified to homogeneity, which displayed in vitro chaperone activity. The predicted structural model of HvsHsp-17.5-CI protein suggests that the α-crystallin domain is evolutionarily highly

  18. The differential effects of heat-shocking on the viability of spores from Bacillus anthracis, Bacillus subtilis, and Clostridium sporogenes after treatment with peracetic acid- and glutaraldehyde-based disinfectants.

    PubMed

    March, Jordon K; Pratt, Michael D; Lowe, Chinn-Woan; Cohen, Marissa N; Satterfield, Benjamin A; Schaalje, Bruce; O'Neill, Kim L; Robison, Richard A

    2015-10-01

    This study investigated (1) the susceptibility of Bacillus anthracis (Ames strain), Bacillus subtilis (ATCC 19659), and Clostridium sporogenes (ATCC 3584) spores to commercially available peracetic acid (PAA)- and glutaraldehyde (GA)-based disinfectants, (2) the effects that heat-shocking spores after treatment with these disinfectants has on spore recovery, and (3) the timing of heat-shocking after disinfectant treatment that promotes the optimal recovery of spores deposited on carriers. Suspension tests were used to obtain inactivation kinetics for the disinfectants against three spore types. The effects of heat-shocking spores after disinfectant treatment were also determined. Generalized linear mixed models were used to estimate 6-log reduction times for each spore type, disinfectant, and heat treatment combination. Reduction times were compared statistically using the delta method. Carrier tests were performed according to AOAC Official Method 966.04 and a modified version that employed immediate heat-shocking after disinfectant treatment. Carrier test results were analyzed using Fisher's exact test. PAA-based disinfectants had significantly shorter 6-log reduction times than the GA-based disinfectant. Heat-shocking B. anthracis spores after PAA treatment resulted in significantly shorter 6-log reduction times. Conversely, heat-shocking B. subtilis spores after PAA treatment resulted in significantly longer 6-log reduction times. Significant interactions were also observed between spore type, disinfectant, and heat treatment combinations. Immediately heat-shocking spore carriers after disinfectant treatment produced greater spore recovery. Sporicidal activities of disinfectants were not consistent across spore species. The effects of heat-shocking spores after disinfectant treatment were dependent on both disinfectant and spore species. Caution must be used when extrapolating sporicidal data of disinfectants from one spore species to another. Heat-shocking

  19. The Response to Heat Shock and Oxidative Stress in Saccharomyces cerevisiae

    PubMed Central

    Morano, Kevin A.; Grant, Chris M.; Moye-Rowley, W. Scott

    2012-01-01

    A common need for microbial cells is the ability to respond to potentially toxic environmental insults. Here we review the progress in understanding the response of the yeast Saccharomyces cerevisiae to two important environmental stresses: heat shock and oxidative stress. Both of these stresses are fundamental challenges that microbes of all types will experience. The study of these environmental stress responses in S. cerevisiae has illuminated many of the features now viewed as central to our understanding of eukaryotic cell biology. Transcriptional activation plays an important role in driving the multifaceted reaction to elevated temperature and levels of reactive oxygen species. Advances provided by the development of whole genome analyses have led to an appreciation of the global reorganization of gene expression and its integration between different stress regimens. While the precise nature of the signal eliciting the heat shock response remains elusive, recent progress in the understanding of induction of the oxidative stress response is summarized here. Although these stress conditions represent ancient challenges to S. cerevisiae and other microbes, much remains to be learned about the mechanisms dedicated to dealing with these environmental parameters. PMID:22209905

  20. Study of the heat-transfer crisis on heat-release surfaces of annular channels with swirl and transit flows

    NASA Astrophysics Data System (ADS)

    Boltenko, E. A.

    2016-10-01

    The results of the experimental study of the heat-transfer crisis on heat-release surfaces of annular channels with swirl and transit flow are presented. The experiments were carried out using electric heated annular channels with one and (or) two heat-release surfaces. For the organization of transit flow on a convex heat-release surface, four longitudinal ribs were installed uniformly at its perimeter. Swirl flow was realized using a capillary wound tightly (without gaps) on the ribs. The ratio between swirl and transit flows in the annular gap was varied by applying longitudinal ribs of different height. The experiments were carried out using a closed-type circulatory system. The experimental data were obtained in a wide range of regime parameters. Both water heated to the temperature less than the saturation temperature and water-steam mixture were fed at the inlet of the channels. For the measurement of the temperature of the heat-release surfaces, chromel-copel thermocouples were used. It was shown that the presence of swirl flow on a convex heatrelease surface led to a significant decrease in critical heat flows (CHF) compared to a smooth surface. To increase CHF, it was proposed to use the interaction of swirl flows of the heat carrier. The second swirl flow was transit flow, i.e., swirl flow with the step equal to infinity. It was shown that CHF values for a channel with swirl and transit flow in all the studied range of regime parameters was higher than CHF values for both a smooth annular channel and a channel with swirl. The empirical ratios describing the dependence of CHF on convex and concave heat-release surfaces of annular channels with swirl and transit flow on the geometrical characteristics of channels and the regime parameters were obtained. The experiments were carried out at the pressure p = 3.0-16.0 MPa and the mass velocity ρw = 250-3000 kg/(m2s).

  1. Adsorption and release of ofloxacin from acid- and heat-treated halloysite.

    PubMed

    Wang, Qin; Zhang, Junping; Zheng, Yue; Wang, Aiqin

    2014-01-01

    Halloysite nanotube is an ideal vehicle of the controlled release of drugs. In this study, we systematically investigated the effects of acid- and heat-treatments on the physicochemical properties, structure and morphology of halloysite by XRD, FTIR, SEM and TEM. Afterwards, the adsorption and in vitro release properties of halloysite for cationic ofloxacin (OFL) were evaluated. The results indicate that HCl treatment has no influence on the crystal structure of halloysite, whereas it becomes amorphous after calcined at temperature higher than 500 °C. Both acid- and heat-treatments have no evident influence on the tubular structure of halloysite. OFL was adsorbed onto halloysite via electrostatic interaction between protonated OFL and negative halloysite surface, cation exchange as well as electrostatic interaction between the OFL-Al(3+) complexes and the negative halloysite surface. Acid-treatment facilitates the release of the adsorbed OFL compared with the natural halloysite in spite of a slight decrease of adsorption capacity. However, heat-treatment results in a sharp decrease of adsorption capacity for OFL owning to the OFL-promoted dissolution of aluminum and the disappearance of the porous structure. Although heat-treatment also facilitates release of the adsorbed OFL, the amount of OFL released is in fact less than the natural halloysite owing to the very low adsorption capacity. Thus, acid-activation is an effective protocol to improve the adsorption and release of halloysite for cationic drug molecules. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Heritable variation in heat shock gene expression: a potential mechanism for adaptation to thermal stress in embryos of sea turtles

    PubMed Central

    Kennington, W. J.; Tomkins, J. L.; Berry, O.; Whiting, S.; Meekan, M. G.; Mitchell, N. J.

    2016-01-01

    The capacity of species to respond adaptively to warming temperatures will be key to their survival in the Anthropocene. The embryos of egg-laying species such as sea turtles have limited behavioural means for avoiding high nest temperatures, and responses at the physiological level may be critical to coping with predicted global temperature increases. Using the loggerhead sea turtle (Caretta caretta) as a model, we used quantitative PCR to characterise variation in the expression response of heat-shock genes (hsp60, hsp70 and hsp90; molecular chaperones involved in cellular stress response) to an acute non-lethal heat shock. We show significant variation in gene expression at the clutch and population levels for some, but not all hsp genes. Using pedigree information, we estimated heritabilities of the expression response of hsp genes to heat shock and demonstrated both maternal and additive genetic effects. This is the first evidence that the heat-shock response is heritable in sea turtles and operates at the embryonic stage in any reptile. The presence of heritable variation in the expression of key thermotolerance genes is necessary for sea turtles to adapt at a molecular level to warming incubation environments. PMID:26763709

  3. Biology of the Heat Shock Response and Protein Chaperones: Budding Yeast (Saccharomyces cerevisiae) as a Model System

    PubMed Central

    Verghese, Jacob; Abrams, Jennifer; Wang, Yanyu

    2012-01-01

    Summary: The eukaryotic heat shock response is an ancient and highly conserved transcriptional program that results in the immediate synthesis of a battery of cytoprotective genes in the presence of thermal and other environmental stresses. Many of these genes encode molecular chaperones, powerful protein remodelers with the capacity to shield, fold, or unfold substrates in a context-dependent manner. The budding yeast Saccharomyces cerevisiae continues to be an invaluable model for driving the discovery of regulatory features of this fundamental stress response. In addition, budding yeast has been an outstanding model system to elucidate the cell biology of protein chaperones and their organization into functional networks. In this review, we evaluate our understanding of the multifaceted response to heat shock. In addition, the chaperone complement of the cytosol is compared to those of mitochondria and the endoplasmic reticulum, organelles with their own unique protein homeostasis milieus. Finally, we examine recent advances in the understanding of the roles of protein chaperones and the heat shock response in pathogenic fungi, which is being accelerated by the wealth of information gained for budding yeast. PMID:22688810

  4. Dynamics of heat shock protein 60 in endothelial cells exposed to cigarette smoke extract

    PubMed Central

    Kreutmayer, Simone Barbara; Messner, Barbara; Knoflach, Michael; Henderson, Blair; Niederegger, Harald; Böck, Günther; Van der Zee, Ruurd; Wick, Georg; Bernhard, David

    2011-01-01

    Heat shock protein 60 (HSP60), expressed on the surface of endothelial cells (ECs) stressed by e.g. oxidized LDL or mechanical shear, was shown to function as an auto-antigen and thus as a pro-atherosclerotic molecule. The aim of this study was to determine whether cigarette smoke chemicals can lead to the activation of the “HSP60 pathway.” It was also our aim to elucidate the dynamics of HSP60 from gene expression to endothelial surface expression and secretion. Here we show for the first time that the exposure of human umbilical vein endothelial cells (HUVECs) to cigarette smoke extract (CSE) results in an up-regulation of HSP60 mRNA. Live cell imaging analysis of a HSP60-EYFP fusion protein construct transfected into ECs revealed that mitochondrial structures collapse in response to CSE exposure. As a result, HSP60 is released from the mitochondria, transported to the cell surface, and released into the cell culture supernatant. Analysis of HSP60 in the sera of healthy young individuals exposed to secondhand smoke revealed significantly elevated levels of HSP60. Cigarette smoking is one of the most relevant risk factors for atherosclerosis. Herein, we provide evidence that cigarette smoke may initiate atherosclerosis in the sense of the “auto-immune hypothesis of atherosclerosis.” PMID:21798264

  5. Dynamics of heat shock protein 60 in endothelial cells exposed to cigarette smoke extract.

    PubMed

    Kreutmayer, Simone Barbara; Messner, Barbara; Knoflach, Michael; Henderson, Blair; Niederegger, Harald; Böck, Günther; Van der Zee, Ruurd; Wick, Georg; Bernhard, David

    2011-11-01

    Heat shock protein 60 (HSP60), expressed on the surface of endothelial cells (ECs) stressed by e.g. oxidized LDL or mechanical shear, was shown to function as an auto-antigen and thus as a pro-atherosclerotic molecule. The aim of this study was to determine whether cigarette smoke chemicals can lead to the activation of the "HSP60 pathway." It was also our aim to elucidate the dynamics of HSP60 from gene expression to endothelial surface expression and secretion. Here we show for the first time that the exposure of human umbilical vein endothelial cells (HUVECs) to cigarette smoke extract (CSE) results in an up-regulation of HSP60 mRNA. Live cell imaging analysis of a HSP60-EYFP fusion protein construct transfected into ECs revealed that mitochondrial structures collapse in response to CSE exposure. As a result, HSP60 is released from the mitochondria, transported to the cell surface, and released into the cell culture supernatant. Analysis of HSP60 in the sera of healthy young individuals exposed to secondhand smoke revealed significantly elevated levels of HSP60. Cigarette smoking is one of the most relevant risk factors for atherosclerosis. Herein, we provide evidence that cigarette smoke may initiate atherosclerosis in the sense of the "auto-immune hypothesis of atherosclerosis." Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Characterizing HSF1 Binding and Post-Translational Modifications of hsp70 Promoter in Cultured Cortical Neurons: Implications in the Heat-Shock Response

    PubMed Central

    Gómez, Andrea V.; Córdova, Gonzalo; Munita, Roberto; Parada, Guillermo E.; Barrios, Álvaro P.; Cancino, Gonzalo I.; Álvarez, Alejandra R.; Andrés, María E.

    2015-01-01

    Causes of lower induction of Hsp70 in neurons during heat shock are still a matter of debate. To further inquire into the mechanisms regulating Hsp70 expression in neurons, we studied the activity of Heat Shock Factor 1 (HSF1) and histone posttranslational modifications (PTMs) at the hsp70 promoter in rat cortical neurons. Heat shock induced a transient and efficient translocation of HSF1 to neuronal nuclei. However, no binding of HSF1 at the hsp70 promoter was detected while it bound to the hsp25 promoter in cortical neurons during heat shock. Histone PTMs analysis showed that the hsp70 promoter harbors lower levels of histone H3 and H4 acetylation in cortical neurons compared to PC12 cells under basal conditions. Transcriptomic profiling data analysis showed a predominant usage of cryptic transcriptional start sites at hsp70 gene in the rat cerebral cortex, compared with the whole brain. These data support a weaker activation of hsp70 canonical promoter. Heat shock increased H3Ac at the hsp70 promoter in PC12 cells, which correlated with increased Hsp70 expression while no modifications occurred at the hsp70 promoter in cortical neurons. Increased histone H3 acetylation by Trichostatin A led to hsp70 mRNA and protein induction in cortical neurons. In conclusion, we found that two independent mechanisms maintain a lower induction of Hsp70 in cortical neurons. First, HSF1 fails to bind specifically to the hsp70 promoter in cortical neurons during heat shock and, second, the hsp70 promoter is less accessible in neurons compared to non-neuronal cells due to histone deacetylases repression. PMID:26053851

  7. Triggered release of model drug from AuNP-doped BSA nanocarriers in hair follicles using IRA radiation.

    PubMed

    Lademann, J; Richter, H; Knorr, F; Patzelt, A; Darvin, M E; Rühl, E; Cheung, K Y; Lai, K K; Renneberg, R; Mak, W C

    2016-01-01

    Recent advances in the field of dermatotherapy have resulted in research efforts focusing on the use of particle-based drug delivery systems for the stimuli-responsive release of drugs in the skin and skin appendages, i.e. hair follicles and sebaceous glands. However, effective and innocuous trigger mechanisms which result in the release of the drugs from the nanocarriers upon reaching the target structures are still lacking. For the first time, the present study demonstrated the photo-activated release of the model drug fluorescein isothiocyanate (FITC) from topically applied gold nanoparticle-doped bovine serum albumin (AuNPs-doped BSA) particles (approx. 545nm) using water-filtered infrared A (IRA) radiation in the hair follicles of an ex vivo porcine skin model. The IRA radiation-induced plasmonic heating of the AuNPs results in the partial decomposition or opening of the albumin particles and release the model drug, while control particles without AuNPs show insignificant release. The results demonstrate the feasibility of using IRA radiation to induce release of encapsulated drugs from plasmonic nanocarriers for the targeting of follicular structures. However, the risk of radiation-induced skin damage subsequent to repeated applications of high infrared dosages may be significant. Future studies should aim at determining the suitability of lower infrared A dosages, such as for medical treatment regimens which may necessitate repeated exposure to therapeutics. Follicular targeting using nanocarriers is of increasing importance in the prophylaxis and treatment of dermatological or other diseases. For the first time, the present study demonstrated the photo-activated release of the model drug fluorescein isothiocyanate (FITC) from topically applied gold nanoparticle-doped bovine serum albumin (AuNPs-doped BSA) particles using water-filtered infrared A (IRA) radiation in the hair follicles of an ex vivo porcine skin model. The results demonstrate the feasibility

  8. The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis.

    PubMed

    Dai, Chengkai

    2018-01-19

    The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is characterized by induction of heat-shock proteins (HSPs). As molecular chaperones, HSPs facilitate the folding, assembly, transportation and degradation of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR is essential to proteome homeostasis, or proteostasis, thereby resisting stress and antagonizing protein misfolding diseases and ageing. Contrasting with these benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas HSF1 remains latent in primary cells without stress, it becomes constitutively activated within malignant cells, rendering them addicted to HSF1 for their growth and survival. Highlighting the HSR/HPSR as an integral component of the oncogenic network, several key pathways governing HSF1 activation by environmental stressors are causally implicated in malignancy. Importantly, HSF1 impacts the cancer proteome systemically. By suppressing tumour-suppressive amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant state, both providing insight into how HSF1 enables tumorigenesis and suggesting disruption of cancer proteostasis as a therapeutic strategy. This review provides an overview of the role of HSF1 in oncogenesis, mechanisms underlying its constitutive activation within cancer cells and its pro-oncogenic action, as well as potential HSF1-targeting strategies.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'. © 2017 The Author(s).

  9. Detection of 70 kDa heat shock protein in the saliva of dairy cows.

    PubMed

    Lamy, Elsa; Jurkovich, Viktor; Rodrigues, Lénia; Geraldo, Ana; Cachucho, Liliana; Silva, Flávio; Matos, Catarina; Capela E Silva, Fernando; Pinheiro, Cristina; Könyves, László; Bakony, Mikolt; Pereira, Alfredo

    2017-08-01

    This Research Communication describes, for the first time, the detection of HSP70 in saliva of dairy cows. Thermal stress is a major environmental stress that limits animal growth, metabolism, and productivity. The cellular response to heat stress involves the synthesis of heat shock proteins (HSPs), presumably to protect the functional stability of cells at increasing temperatures. HSP70 has been found to be present in cattle blood serum and may also be present in other secretory fluids, such as saliva, as already observed in humans. The aim of this study was to detect heat shock protein HSP70 in bovine saliva. Saliva samples were taken from higher- (n = 5) and lower milk producing (n = 5) Holstein-Friesian cows in summer and in winter for the detection of HSP70. HSP70 concentrations were assayed using the ELISA technique. Salivary HSP70 concentrations ranged from 0·524 to 12·174 ng/ml in cows. Higher salivary HSP70 concentrations were significantly associated with higher milk production and higher environmental temperature, but not with rectal temperature.

  10. Effect of Latent Heat Released by Freezing Droplets during Frost Wave Propagation.

    PubMed

    Chavan, Shreyas; Park, Deokgeun; Singla, Nitish; Sokalski, Peter; Boyina, Kalyan; Miljkovic, Nenad

    2018-05-21

    Frost spreads on nonwetting surfaces during condensation frosting via an interdroplet frost wave. When a supercooled condensate water droplet freezes on a hydrophobic or superhydrophobic surface, neighboring droplets still in the liquid phase begin to evaporate. Two possible mechanisms govern the evaporation of neighboring water droplets: (1) The difference in saturation pressure of the water vapor surrounding the liquid and frozen droplets induces a vapor pressure gradient, and (2) the latent heat released by freezing droplets locally heats the substrate, leading to evaporation of nearby droplets. The relative significance of these two mechanisms is still not understood. Here, we study the significance of the latent heat released into the substrate by freezing droplets, and its effect on adjacent droplet evaporation, by studying the dynamics of individual water droplet freezing on aluminum-, copper-, and glass-based hydrophobic and superhydrophobic surfaces. The latent heat flux released into the substrate was calculated from the measured droplet sizes and the respective freezing times ( t f ), defined as the time from initial ice nucleation within the droplet to complete droplet freezing. To probe the effect of latent heat release, we performed three-dimensional transient finite element simulations showing that the transfer of latent heat to neighboring droplets is insignificant and accounts for a negligible fraction of evaporation during microscale frost wave propagation. Furthermore, we studied the effect of substrate thermal conductivity on the transfer of latent heat transfer to neighboring droplets by investigating the velocity of ice bridge formation. The velocity of the ice bridge was independent of the substrate thermal conductivity, indicating that adjacent droplet evaporation during condensation frosting is governed solely by vapor pressure gradients. This study not only provides key insights into the individual droplet freezing process but also

  11. MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1β Independently of Gasdermin-D.

    PubMed

    Gutierrez, Kimberley D; Davis, Michael A; Daniels, Brian P; Olsen, Tayla M; Ralli-Jain, Pooja; Tait, Stephen W G; Gale, Michael; Oberst, Andrew

    2017-03-01

    Necroptosis is a form of programmed cell death defined by activation of the kinase receptor interacting protein kinase 3 and its downstream effector, the pseudokinase mixed lineage kinase domain-like (MLKL). Activated MLKL translocates to the cell membrane and disrupts it, leading to loss of cellular ion homeostasis. In this study, we use a system in which this event can be specifically triggered by a small-molecule ligand to show that MLKL activation is sufficient to induce the processing and release of bioactive IL-1β. MLKL activation triggers potassium efflux and assembly of the NLRP3 inflammasome, which is required for the processing and activity of IL-1β released during necroptosis. Notably, MLKL activation also causes cell membrane disruption, which allows efficient release of IL-1β independently of the recently described pyroptotic effector gasdermin-D. Taken together, our findings indicate that MLKL is an endogenous activator of the NLRP3 inflammasome, and that MLKL activation provides a mechanism for concurrent processing and release of IL-1β independently of gasdermin-D. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. ELEVATED LEVELS OF INDUCIBLE HEAT SHOCK PROTEIN (HSP70-1) PROTECT MCF-7 CELLS FROM ARSENITE TOXICITY

    EPA Science Inventory

    Heat shock proteins (HSPs) belong to the highly conserved family of stress proteins and are induced following exposure to arsenic. Elevated HSPs protect against cellular damage from heat but it is unclear whether HSP induction alters the damaging effects of environmental chemical...

  13. Differential expression pattern of heat shock protein 70 gene in tissues and heat stress phenotypes in goats during peak heat stress period.

    PubMed

    Rout, P K; Kaushik, R; Ramachandran, N

    2016-07-01

    It has been established that the synthesis of heat shock protein 70 (Hsp70) is temperature-dependent. The Hsp70 response is considered as a cellular thermometer in response to heat stress and other stimuli. The variation in Hsp70 gene expression has been positively correlated with thermotolerance in Drosophila melanogaster, Caenorhabditis elegans, rodents and human. Goats have a wide range of ecological adaptability due to their anatomical and physiological characteristics; however, the productivity of the individual declines during thermal stress. The present study was carried out to analyze the expression of heat shock proteins in different tissues and to contrast heat stress phenotypes in response to chronic heat stress. The investigation has been carried out in Jamunapari, Barbari, Jakhrana and Sirohi goats. These breeds differ in size, coat colour and production performance. The heat stress assessment in goats was carried out at a temperature humidity index (THI) ranging from 85.36-89.80 over the period. Phenotyping for heat stress susceptibility was carried out by combining respiration rate (RR) and heart rate (HR). Based on the distribution of RR and HR over the breeds in the population, individual animals were recognized as heat stress-susceptible (HSS) and heat stress-tolerant (HST). Based on their physiological responses, the selected animals were slaughtered for tissue collection during peak heat stress periods. The tissue samples from different organs such as liver, spleen, heart, testis, brain and lungs were collected and stored at -70 °C for future use. Hsp70 concentrations were analyzed from tissue extract with ELISA. mRNA expression levels were evaluated using the SYBR green method. Kidney, liver and heart had 1.5-2.0-fold higher Hsp70 concentrations as compared to other organs in the tissue extracts. Similarly, the gene expression pattern of Hsp70 in different organs indicated that the liver, spleen, brain and kidney exhibited 5.94, 4.96, 5

  14. Engagement of Components of DNA-Break Repair Complex and NFκB in Hsp70A1A Transcription Upregulation by Heat Shock.

    PubMed

    Hazra, Joyita; Mukherjee, Pooja; Ali, Asif; Poddar, Soumita; Pal, Mahadeb

    2017-01-01

    An involvement of components of DNA-break repair (DBR) complex including DNA-dependent protein kinase (DNA-PK) and poly-ADP-ribose polymerase 1 (PARP-1) in transcription regulation in response to distinct cellular signalling has been revealed by different laboratories. Here, we explored the involvement of DNA-PK and PARP-1 in the heat shock induced transcription of Hsp70A1A. We find that inhibition of both the catalytic subunit of DNA-PK (DNA-PKc), and Ku70, a regulatory subunit of DNA-PK holo-enzyme compromises transcription of Hsp70A1A under heat shock treatment. In immunoprecipitation based experiments we find that Ku70 or DNA-PK holoenzyme associates with NFκB. This NFκB associated complex also carries PARP-1. Downregulation of both NFκB and PARP-1 compromises Hsp70A1A transcription induced by heat shock treatment. Alteration of three bases by site directed mutagenesis within the consensus κB sequence motif identified on the promoter affected inducibility of Hsp70A1A transcription by heat shock treatment. These results suggest that NFκB engaged with the κB motif on the promoter cooperates in Hsp70A1A activation under heat shock in human cells as part of a DBR complex including DNA-PK and PARP-1.

  15. Ploidy Manipulation of Zebrafish Embryos with Heat Shock 2 Treatment

    PubMed Central

    Baars, Destiny L.; Pelegri, Francisco

    2016-01-01

    Manipulation of ploidy allows for useful transformations, such as diploids to tetraploids, or haploids to diploids. In the zebrafish Danio rerio, specifically the generation of homozygous gynogenetic diploids is useful in genetic analysis because it allows the direct production of homozygotes from a single heterozygous mother. This article describes a modified protocol for ploidy duplication based on a heat pulse during the first cell cycle, Heat Shock 2 (HS2). Through inhibition of centriole duplication, this method results in a precise cell division stall during the second cell cycle. The precise one-cycle division stall, coupled to unaffected DNA duplication, results in whole genome duplication. Protocols associated with this method include egg and sperm collection, UV treatment of sperm, in vitro fertilization and heat pulse to cause a one-cell cycle division delay and ploidy duplication. A modified version of this protocol could be applied to induce ploidy changes in other animal species. PMID:28060351

  16. Hsp60 expression profiles in the reef-building coral Seriatopora caliendrum subjected to heat and cold shock regimes.

    PubMed

    Seveso, Davide; Montano, Simone; Strona, Giovanni; Orlandi, Ivan; Galli, Paolo; Vai, Marina

    2016-08-01

    Climate changes have increased the intensity/frequency of extreme thermal events, which represent serious threats to the health of reef-building corals. Since the vulnerability of corals exposed to thermal stresses are related to their ability to regulate Heat shock proteins (Hsps), we have analyzed together the time related expression profiles of the mitochondrial Hsp60 and the associated changes in tissue pigmentation in Seriatopora caliendrum subjected to 48 h of heat and cold treatments characterized by moderate (±2 °C) and severe (±6 °C) shocks. For the first time, an Hsp60 response was observed in a scleractinian coral exposed to cold stresses. Furthermore, the Hsp60 modulations and the changes in the tissue coloration were found to be specific for each treatment. A strong down-regulation at the end of the treatments was observed following both the severe shocks, but only the severe heat stress led to bleaching in concert with the lowest levels of Hsp60, suggesting that a severe heat shock can be more deleterious than an exposure to a severe cold temperature. On the contrary, a moderate cold stress seems to be more harmful than a moderate temperature increase, which could allow coral acclimation. Our results can provide a potential framework for understanding the physiological tolerance of corals under possible future climate changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Photo-triggered release from liposomes without membrane solubilization, based on binding to poly(vinyl alcohol) carrying a malachite green moiety.

    PubMed

    Uda, Ryoko M; Kato, Yutaka; Takei, Michiko

    2016-10-01

    When working with liposomes analogous to cell membranes, it is important to develop substrates that can regulate interactions with the liposome surface in response to light. We achieved a photo-triggered release from liposomes by using a copolymer of poly(vinyl alcohol) carrying a malachite green moiety (PVAMG). Although PVAMG is a neutral polymer under dark conditions, it is photoionized upon exposure to UV light, resulting in the formation of a cationic site for binding to liposomes with a negatively charged surface. Under UV irradiation, PVAMG showed effective interaction with liposomes, releasing the encapsulated compound; however, this release was negligible under dark conditions. The poly(vinyl alcohol) moiety of PVAMG played an important role in the photo-triggered release. This release was caused by membrane destabilization without lipid solubilization. We also investigated different aspects of liposome/PVAMG interactions, including PVAMG-induced fusion between the liposomes and the change in the liposome morphologies. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Butyric acid released during milk lipolysis triggers biofilm formation of Bacillus species.

    PubMed

    Pasvolsky, Ronit; Zakin, Varda; Ostrova, Ievgeniia; Shemesh, Moshe

    2014-07-02

    Bacillus species form biofilms within milking pipelines and on surfaces of equipment in the dairy industry which represent a continuous hygiene problem and can lead to serious economic losses due to food spoilage and equipment impairment. Although much is known about the mechanism by which the model organism Bacillus subtilis forms biofilms in laboratory mediums in vitro, little is known of how these biofilms are formed in natural environments such as milk. Besides, little is known of the signaling pathways leading to biofilm formation in other Bacillus species, such as Bacillus cereus and Bacillus licheniformis, both of which are known to contaminate milk. In this study, we report that milk triggers the formation of biofilm-related structures, termed bundles. We show this to be a conserved phenomenon among all Bacillus members tested. Moreover, we demonstrate that the tasA gene, which encodes a major portion of the matrix which holds the biofilm together, is vital for this process. Furthermore, we show that the free fatty acid (FFA) - butyric acid (BA), which is released during lipolysis of milk fat and demonstrates antimicrobial activity, is the potent trigger for biofilm bundle formation. We finally show that BA-triggered biofilm bundle formation is mediated by the histidine kinase, KinD. Taken together, these observations indicate that BA, which is a major FFA within milk triggers biofilm formation in a conserved mechanism among members of the Bacillus genus. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Insights into the role of heat shock protein 72 to whole-body heat acclimation in humans

    PubMed Central

    Amorim, Fabiano Trigueiro; Fonseca, Ivana T; Machado-Moreira, Christiano A; Magalhães, Flávio de Castro

    2015-01-01

    Abstract Heat acclimation results in systemic and cellular adaptions that reduce the negative effect of heat and, consequently, the risk of heat illness. Although the classical changes observed with heat acclimation lead to increased tolerance to exercise in the heat by reducing heat storage (reflected in reduced core and skin temperatures) and increasing whole-body capacity for heat dissipation (greater plasma volume, sweat output, and skin blood flow), it appears that heat acclimation also induces changes at the cellular level that might increase tolerance of the whole organism to a higher core temperature for the development of fatigue. Thermotolerance is a process that involves increased resilience to an otherwise lethal heat stress that follows a sublethal exposure to heat. Thermotolerance is believed to be the result of increased content of heat shock proteins (Hsp), specially a member of the 70 kDa family, Hsp72 kDa. In humans, we and others have reported that heat acclimation increases intracellular Hsp72 levels. This increase in intracellular Hsp72 could improve whole-body organism thermotolerance by maintaining intestinal epithelial tight junction barriers, by increasing resistance to gut-associated endotoxin translocation, or by reducing the inflammatory response. In this review, we will initially provide an overview of the physiological adaptations induced by heat acclimation and emphasize the main cellular changes that occur with heat acclimation associated with intracellular accumulation of Hsp72. Finally, we will present an argument for a role of whole-body heat acclimation in augmenting cellular thermotolerance, which may protect vital organs from deleterious effects of heat stress in humans. PMID:27227070

  20. Responses of bovine lymphocytes to heat shock as modified by breed and antioxidant status.

    PubMed

    Kamwanja, L A; Chase, C C; Gutierrez, J A; Guerriero, V; Olson, T A; Hammond, A C; Hansen, P J

    1994-02-01

    We tested whether resistance of lymphocytes to heat stress is modified by breed, intracellular glutathione content, and extracellular antioxidants. In the first experiment, lymphocytes from Angus (Bos taurus, non-heat-tolerant), Brahman (B. indicus, heat-tolerant), and Senepol (B. taurus, heat-tolerant) heifers (12 heifers per breed) were cultured at 45 degrees C for 3 h to evaluate thermal killing, at 42 degrees C for 12 h in a 60-h phytohemagglutinin-induced proliferation test, and at 42 degrees C for 1 h to measure induction of heat shock protein 70 (HSP70). Killing at 45 degrees C was affected by breed x temperature (P < .01); the decrease in viability caused by a temperature of 45 degrees C was greater for Angus than for Brahman or Senepol. For phytohemagglutinin-stimulated lymphocytes, heating to 42 degrees C reduced [3H]thymidine incorporation equally for all breeds. Viability at the end of culture was affected (P < .001) by a breed x temperature interaction because the decrease in viability caused by culture at 42 degrees C was greatest for lymphocytes from Angus heifers. Heat shock for 1 h at 42 degrees C caused a two- to threefold increase in intracellular concentrations of HSP70, but there was no interaction of temperature with breed. In another experiment (with lymphocytes harvested from three Holstein cows), buthionine sulfoximine, a glutathione synthesis inhibitor, inhibited (P < .01) proliferation of phytohemagglutinin-stimulated lymphocytes at 38.5 and 42 degrees C. Addition of the antioxidants glutathione or thioredoxin to culture did not reduce the effects of heating to 42 degrees C on proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Acquired thermotolerance and heat shock in the extremely thermophilic archaebacterium Sulfolobus sp. strain B12

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

    Trent, J.D.; Osipiuk, J.; Pinkau, T.

    1990-03-01

    The extreme thermophile Sulfolobus sp. strain B12 exhibits an acquired thermotolerance response. Thus, survival of cells from a 70{degrees}C culture at the lethal temperature of 92{degrees}C was enhanced by as much as 6 orders of magnitude over a 2-h period if the culture was preheated to 88{degrees}C for 60 min or longer before being exposed to the lethal temperature. In eubacteria and eucaryotes, acquired thermotolerance correlates with the induced synthesis of a dozen or so proteins known as heat shock proteins. In this Sulfolobus species, it correlates with the preferential synthesis of primarily one major protein (55 kilodaltons) and, tomore » a much lesser extent, two minor proteins (28 and 35 kilodaltons). Since the synthesis of all other proteins was radically reduced and these proteins were apparently not degraded or exported, their relative abundance within the cell increased during the time the cells were becoming thermotolerant. They could not yet be related to known heat shock proteins. In immunoassays, they were not cross-reactive with antibodies against heat shock proteins from Escherichia coli (DnaK and GroE), which are highly conserved between eubacteria and eucaryotes. However, it appears that if acquired thermotolerance depends on the synthesis of protective proteins, then in this extremely thermophilic archaebacterium it depends primarily on one protein.« less

  2. Acquired thermotolerance and heat shock in the extremely thermophilic archaebacterium Sulfolobus sp. strain B12.

    PubMed

    Trent, J D; Osipiuk, J; Pinkau, T

    1990-03-01

    The extreme thermophile Sulfolobus sp. strain B12 exhibits an acquired thermotolerance response. Thus, survival of cells from a 70 degrees C culture at the lethal temperature of 92 degrees C was enhanced by as much as 6 orders of magnitude over a 2-h period if the culture was preheated to 88 degrees C for 60 min or longer before being exposed to the lethal temperature. In eubacteria and eucaryotes, acquired thermotolerance correlates with the induced synthesis of a dozen or so proteins known as heat shock proteins. In this Sulfolobus species, it correlates with the preferential synthesis of primarily one major protein (55 kilodaltons) and, to a much lesser extent, two minor proteins (28 and 35 kilodaltons). Since the synthesis of all other proteins was radically reduced and these proteins were apparently not degraded or exported, their relative abundance within the cell increased during the time the cells were becoming thermotolerant. They could not yet be related to known heat shock proteins. In immunoassays, they were not cross-reactive with antibodies against heat shock proteins from Escherichia coli (DnaK and GroE), which are highly conserved between eubacteria and eucaryotes. However, it appears that if acquired thermotolerance depends on the synthesis of protective proteins, then in this extremely thermophilic archaebacterium it depends primarily on one protein.

  3. CHEMOSENSITIZATION BY A NON-APOPTOGENIC HEAT SHOCK PROTEIN 70-BINDING APOPTOSIS INDUCING FACTOR MUTANT

    EPA Science Inventory

    Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis inducing factor mutant

    Abstract
    HSP70 inhibits apoptosis by neutralizing the caspase activator Apaf-1 and by interacting with apoptosis inducing factor (AIF), a mitochondrial flavoprotein wh...

  4. Shock Reactivity of Non-Porous Mixtures of Manganese and Sulfur

    NASA Astrophysics Data System (ADS)

    Jetté, F. X.; Goroshin, S.; Higgins, A. J.

    2007-12-01

    Equimolar mixtures of manganese powder and sulfur were melt-cast into solid pellets in order to study the mechanism of shock-enhanced reactivity in non-porous heterogeneous mixtures. This mixture was selected due to the large exothermic heat release of the manganese-sulfur reaction (214 kJ/mol), which causes the reaction to be self-sustaining once initiated. The test samples were placed in planar recovery ampoules and a strong shock was delivered via the detonation of a charge of amine-sensitized nitromethane. Various shock strengths were achieved by placing different thicknesses of PMMA attenuator discs between the explosive charge and the ampoule. The results confirmed that shock-induced reactions can be produced in highly non-porous mixtures. Indeed, the critical shock pressure that caused ignition of the mixture in the ampoule was found to be in the range 2.2-3.0 GPa (pressures were estimated using LS-DYNA simulations of samples with 100% TMD).

  5. Magnetic Heating of Iron Oxide Nanoparticles and Magnetic Micelles for Cancer Therapy.

    PubMed

    Glover, Amanda L; Bennett, James B; Pritchett, Jeremy S; Nikles, Sarah M; Nikles, David E; Nikles, Jacqueline A; Brazel, Christopher S

    2013-01-01

    The inclusion of magnetic nanoparticles into block copolymer micelles was studied towards the development of a targeted, magnetically triggered drug delivery system for cancer therapy. Herein, we report the synthesis of magnetic nanoparticles and poly(ethylene glycol-b-caprolactone) block copolymers, and experimental verification of magnetic heating of the nanoparticles, self-assembly of the block copolymers to form magnetic micelles, and thermally-enhanced drug release. The semicrystalline core of the micelles melted at temperatures just above physiological conditions, indicating that they could be used to release a chemotherapy agent from a thermo-responsive polymer system. The magnetic nanoparticles were shown to heat effectively in high frequency magnetic fields ranging from 30-70 kA/m. Magnetic micelles also showed heating properties, that when combined with a chemotherapeutic agent and a targeting ligand could be developed for localized, triggered drug delivery. During the magnetic heating experiments, a time lag was observed in the temperature profile for magnetic micelles, likely due to the heat of fusion of melting of polycaprolactone micelle cores before bulk solution temperatures increased. Doxorubicin, incorporated into the micelles, released faster when the micelles were heated above the core melting point.

  6. Modification of tooth development by heat shock protein 60

    PubMed Central

    Papp, Tamas; Polyak, Angela; Papp, Krisztina; Meszar, Zoltan; Zakany, Roza; Meszar-Katona, Eva; Tünde, Palne Terdik; Ham, Chang Hwa; Felszeghy, Szabolcs

    2016-01-01

    Although several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 (Hsp 60). To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot (EK) and stratum intermedium (SI). Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2-deoxyuridine (BrdU) incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes. PMID:27025262

  7. Septic Shock

    PubMed Central

    Lansing, Allan M.

    1963-01-01

    Septic shock may be defined as hypotension caused by bacteremia and accompanied by decreased peripheral blood flow, evidenced by oliguria. Clinically, a shaking chill is the warning signal. The immediate cause of hypotension is pooling of blood in the periphery, leading to decreased venous return: later, peripheral resistance falls and cardiac failure may occur. Irreversible shock is comparable to massive reactive hyperemia. Reticuloendothelial failure, histamine release, and toxic hypersensitivity may be factors in the pathogenesis of septic shock. Adrenal failure does not usually occur, but large doses of corticosteroid are employed therapeutically to counteract the effect of histamine release or hypersensitivity to endotoxin. The keys to successful therapy are time, antibiotics, vasopressors, cortisone and correction of acidosis. PMID:14063936

  8. Dhofar 378 Martian shergottite: Evidence of early shock melting

    NASA Astrophysics Data System (ADS)

    Park, Jisun; Bogard, Donald D.; Mikouchi, Takashi; McKay, Gordon A.

    2008-08-01

    Shock heating of the Dhofar 378 (Dho 378) Martian shergottite produced melting, vesiculation, and flow of the plagioclase, which upon cooling recrystallized into complex textures. Heating experiments on the similar Zagami shergottite indicate that Dho 378 was shock heated to 1000-1100°C and was cooled at ~2.5°C/h. An 39Ar-40Ar analysis of Dho 378 plagioclase indicates different Ar diffusion domains and K/Ca ratios. The lower-temperature phase defines an Ar-Ar isochron age of 141 +/- 32 Ma. The higher-temperature phase released more 40Ar but does not define an age. The meteorite's thermal history was examined by constructing a generic model to compare cooling rates for objects of different sizes against fractional diffusion loss of Ar for different cooling times. Using gas diffusion parameter values measured for Dho 378, this model indicates that it is improbable that the major shock heating event occurred at the time that Dho 378 was ejected from Mars ~3 Ma ago. Rather, we suggest that the time of shock heating is probably given by its Ar-Ar age. For Dho 378 to cool sufficiently fast not to lose most of its 40Ar ~3 Ma ago would require it to have been ejected into space as an impossibly small object. Larger and more reasonable Mars ejection sizes indicate that Dho 378 should have lost most of its 40Ar. On the basis of plagioclase texture and Ar data, we suggest that a major impact event ~141 Ma ago melted Dho 378 plagioclase, degassed most of its 40Ar, and deposited it in crater ejecta to cool. A smaller and later impact ejected it into space ~3 Ma ago.

  9. A sequential mechanism for clathrin cage disassembly by 70-kDa heat-shock cognate protein (Hsc70) and auxilin

    PubMed Central

    Rothnie, Alice; Clarke, Anthony R.; Kuzmic, Petr; Cameron, Angus; Smith, Corinne J.

    2011-01-01

    An essential stage in endocytic coated vesicle recycling is the dissociation of clathrin from the vesicle coat by the molecular chaperone, 70-kDa heat-shock cognate protein (Hsc70), and the J-domain-containing protein, auxilin, in an ATP-dependent process. We present a detailed mechanistic analysis of clathrin disassembly catalyzed by Hsc70 and auxilin, using loss of perpendicular light scattering to monitor the process. We report that a single auxilin per clathrin triskelion is required for maximal rate of disassembly, that ATP is hydrolyzed at the same rate that disassembly occurs, and that three ATP molecules are hydrolyzed per clathrin triskelion released. Stopped-flow measurements revealed a lag phase in which the scattering intensity increased owing to association of Hsc70 with clathrin cages followed by serial rounds of ATP hydrolysis prior to triskelion removal. Global fit of stopped-flow data to several physically plausible mechanisms showed the best fit to a model in which sequential hydrolysis of three separate ATP molecules is required for the eventual release of a triskelion from the clathrin–auxilin cage. PMID:21482805

  10. A description of electron heating with an electrostatic potential jump in a parallel, collisionless, fire hose shock

    NASA Technical Reports Server (NTRS)

    Ellison, Donald C.; Jones, Frank C.

    1988-01-01

    The electron heating required if protons scatter elastically in a parallel, collisionless shock is calculated. Near-elastic proton scattering off large amplitude background magnetic field fluctuations might be expected if the waves responsible for the shock dissipation are generated by the fire hose instability. The effects of an electrostatic potential jump in the shock layer are included by assuming that the energy lost by protons in traversing the potential jump is converted into electron thermal pressure. It is found that the electron temperature increase is a strong function of the potential jump. Comparison is made to the parallel shock plasma simulation of Quest (1987).

  11. High efficiency stratification of apple cultivar Ligol seed dormancy by phytohormones, heat shock and pulsed radio frequency.

    PubMed

    Grzesik, Mieczysław; Górnik, Krzysztof; Janas, Regina; Lewandowki, Mariusz; Romanowska-Duda, Zdzislawa; Duijn, Bert van

    2017-12-01

    The aim of the study was to improve the effect of stratification of apple "Ligol" seeds by application of selected compounds, phytohormones, and physical methods For this purpose the seeds were stratified at 3°C in distilled water or in the presence of potassium nitrate (KNO 3 ), ethephon (ET), carbon monoxide (CO), hydrogen peroxide (H 2 O 2 ), a mixture of KNO 3 , ET, CO, H 2 O 2 , gibberellins (GA 3 ), 6-benzylaminopurine (BAP), jasmonic acid (JA), salicylic acid (SA) and a mixture of SA, GA 3 , BAP, JA, nitric oxide (NO), hydrogen chloride (HCL). Arranged protocols included various durations and combinations of selected compounds and phytohormones as well as laser and red light, heat shock - 2h heat shock (45°C) and Pulsed Radio Frequency (PRF) were investigated by germination tests and the activity of selected enzymes, gas exchange and index of chlorophyll in leaves. The obtained results showed the possibility to shorten more effectively the time of the apple 'Ligol' dormancy removal by treatments of the stratified seeds at 3°C with different biological and physical methods Selected compounds and phytohormones acted collectively as a regulatory complex controlling the course of release from dormancy. Physical methods (PRF and heat shock) additionally contributed to dormancy breakage. Duration of phytohormones or compounds impacts during stratification should be prolonged to minimum 7days to assure more balanced conditions of the regulatory complex for the acceleration of dormancy a removal. The most beneficial results were obtained after seed stratification for 7days on filter paper moistened in KNO 3 +Etephon+CO+H 2 O 2 at 3°C, and then on filter paper moistened in phytohormones (GA 3 +BAP+JA) till the end of seed germination (3°C). The application of this protocol could be a very useful tool in a shortening the apple breeding cycle since the period of removing dormancy was reduced by 38days in comparison to stratified in water. PRF has also the additive

  12. Heritable variation in heat shock gene expression: a potential mechanism for adaptation to thermal stress in embryos of sea turtles.

    PubMed

    Tedeschi, J N; Kennington, W J; Tomkins, J L; Berry, O; Whiting, S; Meekan, M G; Mitchell, N J

    2016-01-13

    The capacity of species to respond adaptively to warming temperatures will be key to their survival in the Anthropocene. The embryos of egg-laying species such as sea turtles have limited behavioural means for avoiding high nest temperatures, and responses at the physiological level may be critical to coping with predicted global temperature increases. Using the loggerhead sea turtle (Caretta caretta) as a model, we used quantitative PCR to characterise variation in the expression response of heat-shock genes (hsp60, hsp70 and hsp90; molecular chaperones involved in cellular stress response) to an acute non-lethal heat shock. We show significant variation in gene expression at the clutch and population levels for some, but not all hsp genes. Using pedigree information, we estimated heritabilities of the expression response of hsp genes to heat shock and demonstrated both maternal and additive genetic effects. This is the first evidence that the heat-shock response is heritable in sea turtles and operates at the embryonic stage in any reptile. The presence of heritable variation in the expression of key thermotolerance genes is necessary for sea turtles to adapt at a molecular level to warming incubation environments. © 2016 The Author(s).

  13. Evaluating the Mechanisms of Light-Triggered siRNA Release from Nanoshells for Temporal Control Over Gene Regulation.

    PubMed

    Riley, Rachel S; Dang, Megan N; Billingsley, Margaret M; Abraham, Baxter; Gundlach, Lars; Day, Emily S

    2018-06-13

    The ability to regulate intracellular gene expression with exogenous nucleic acids such as small interfering RNAs (siRNAs) has substantial potential to improve the study and treatment of disease. However, most transfection agents and nanoparticle-based carriers that are used for the intracellular delivery of nucleic acids cannot distinguish between diseased and healthy cells, which may cause them to yield unintended widespread gene regulation. An ideal delivery system would only silence targeted proteins in diseased tissue in response to an external stimulus. To enable spatiotemporal control over gene silencing, researchers have begun to develop nucleic acid-nanoparticle conjugates that keep their nucleic acid cargo inactive until it is released from the nanoparticle on-demand by externally applied near-infrared laser light. This strategy can overcome several limitations of other nucleic acid delivery systems, but the mechanisms by which these platforms operate remain ill understood. Here, we perform a detailed investigation of the mechanisms by which silica core/gold shell nanoshells (NSs) release conjugated siRNA upon excitation with either pulsed or continuous wave (CW) near-infrared (NIR) light, with the goal of providing insight into how these nanoconjugates can enable on-demand gene regulation. We demonstrate that siRNA release from NSs upon pulsed laser irradiation is a temperature-independent process that is substantially more efficient than siRNA release triggered by CW irradiation. Contrary to literature, which suggests that only pulsed irradiation releases siRNA duplexes, we found that both modes of irradiation release a mixture of siRNA duplexes and single-stranded oligonucleotides, but that pulsed irradiation results in a higher percentage of released duplexes. To demonstrate that the siRNA released from NSs upon pulsed irradiation remains functional, we evaluated the use of NSs coated with green fluorescent protein (GFP)-targeted siRNA (siGFP-NS) for

  14. Expression of a non-inactivating K+ channel driven by a rat heat shock promoter increased the resting potential in Aplysia silent neurons.

    PubMed

    Han, J H; Yim, S W; Lim, C S; Park, C W; Kaang, B K

    1999-05-01

    We assessed the role of a non-inactivating K+ channel (aKv5.1) in the resting potential by overexpressing this channel by heat shock in the neurons. A reporter gene lacZ linked to a promoter region spanning from the -285 to the +88 base of the rat HSP70ib gene was induced 62.5-fold when this DNA construct was microinjected into the neurons of the marine mollusk Aplysia and treated with heat shock at 30 degrees C for 3 h. Using this efficient induction system, we induced the expression of aKv5.1 by heat shock in cultured, electrically silent neurons of Aplysia and examined its effect on the resting potential. The channel expression increased the resting potential by approximately 10 mV. This increase was specific to heat shock induction and abolished by treatment with TEA, a specific K+ channel blocker. These results provide the direct evidence that a low voltage-activated, non-inactivating K+ channel can contribute to the resting potential.

  15. Nonequilibrium radiation and dissociation of CO molecules in shock-heated flows

    NASA Astrophysics Data System (ADS)

    Macdonald, R. L.; Munafò, A.; Johnston, C. O.; Panesi, M.

    2016-08-01

    This work addresses the study of the behavior of the excited electronic states of CO molecules in the nonequilibrium relaxation zone behind a normal shock for a CO2-N2 mixture representative of the Mars atmosphere. The hybrid state-to-state (StS) model developed accounts for thermal nonequilibrium between the translational energy mode of the gas and the vibrational energy mode of individual molecules. The electronic states of CO molecules are treated as separate species, allowing for non-Boltzmann distributions of their populations. The StS model is coupled with a nonequilibrium radiation solver, hpc-rad, allowing for the calculation of the radiation signature from the molecular and atomic species in the gas. This study focuses on the radiation from the fourth positive system of CO, which dominates the radiation heating on the forebody for higher speed Mars entry applications. In the rapidly dissociating regime behind strong shock waves, the population of the ground electronic state of CO [ CO(X 1Σ )], departs from Maxwell-Boltzmann distributions, owing to the efficient collisional excitation to the electronically excited CO(A 1Π ) state. In general the assumption of the equilibrium between electronic and vibration fails when the excitation of electronic states is driven by heavy particles. The comparison of the radiation heating predictions obtained using the conventional quasi-steady-state (QSS) approach and the physics-based StS approach revealed differences in radiative heating predictions of up to 50%. These results demonstrate that the choice of nonequilibrium model can have a significant impact on radiative heating simulations, and more importantly, they cast serious doubts on the validity of the QSS assumption for the condition of interest to this work.

  16. Transcription of four Rhopalosiphum padi (L.) heat shock protein genes and their responses to heat stress and insecticide exposure.

    PubMed

    Li, Yuting; Zhao, Qi; Duan, Xinle; Song, Chunman; Chen, Maohua

    2017-03-01

    The bird cherry-oat aphid, Rhopalosiphum padi (L.), a worldwide destructive pest, is more heat tolerant than other wheat aphids, and it has developed resistance to different insecticides. Heat shock proteins (HSPs) play an important role in coping with environmental stresses. To investigate Hsp transcriptional responses to heat and insecticide stress, four full-length Hsp genes from R. padi (RpHsp60, RpHsc70, RpHsp70-1, and RpHsp70-2) were cloned. Four RpHsps were expressed during all R. padi developmental stages, but at varying levels. The mRNA levels of RpHsps were increased under thermal stress and reached maximal induction at a lower temperature (36°C) in the alate morph than in the apterous morph (37°C or 38°C). RpHsp expressions under heat stress suggest that RpHsp70-1 and RpHsp70-2 are inducible in both apterous and alate morphs, RpHsc70 is only heat-inducible in apterous morph, and RpHsp60 exhibits poor sensitivity to heat stress. The pretreatment at 37°C significantly increase both the survival rate and the RpHsps expression level of R. padi at subsequent lethal temperature. Under exposure to two sublethal concentrations (LC 10 and LC 30 ) of beta-cypermethrin, both RpHsp70-1 and RpHsp70-2 expressions were induced and reached a maximum 24h after exposure. In contrast, expression of RpHsp60 was not induced by either sublethal concentration of beta-cypermethrin. Moreover, the responses of RpHsp70-1 and RpHsp70-2 to heat shock were more sensitive than those to beta-cypermethrin. These results suggest that induction of RpHsp expression is related to thermal tolerance, and that RpHsp70-1 and RpHsp70-2 are the primary genes involved in the response to both heat and pesticide stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Immunohistochemical evaluation of the heat shock response to nonablative fractional resurfacing

    NASA Astrophysics Data System (ADS)

    Hantash, Basil M.; Bedi, Vikramaditya P.; Struck, Steven K.; Chan, Kin F.

    2010-11-01

    Despite the emergence of nonablative fractional resurfacing (NFR) as a new therapeutic modality for skin photoaging, little is known about the molecular events that underlie the heat shock response to different treatment parameters. Human subjects are treated with a scanned 1550-nm fractional laser at pulse energies spanning 6 to 40 mJ and a 140-μm spot size. The heat shock response is assessed immunohistochemically immediately through 7 days posttreatment. At the immediately posttreatment time point, we observe subepidermal clefting in most sections. The basal epidermis and dermal zones of sparing are both found to express HSP47, but not HSP72. By day 1, expression of HSP72 is detected throughout the epidermis, while that of HSP47 remains restricted to the basal layer. Both proteins are detected surrounding the dermal portion of the microscopic treatment zone (MTZ). This pattern of expression persists through day 7 post-NFR, although neither protein is found within the MTZ. Immediately posttreatment, the mean collagen denaturation zone width is 50 μm at 6 mJ, increasing to 202 μm at 40 mJ. The zone of cell death exceeds the denaturation zone by 19 to 55% over this pulse energy range. The two zones converge by day 7 posttreatment.

  18. Heat shock protein antagonists in early stage clinical trials for NSCLC.

    PubMed

    Hendriks, Lizza E L; Dingemans, Anne-Marie C

    2017-05-01

    Cancer cells have a higher need of chaperones than normal cells to prevent the toxic effects of intracellular protein misfolding and aggregation. Heat shock proteins (Hsps) belong to these chaperones; they are classified into families according to molecular size. Hsps are upregulated in many cancers and inhibition can inhibit tumor growth by destabilizing proteins necessary for tumor survival. In non-small cell lung cancer (NSCLC), there are three different Hsp antagonist classes that are in (early) clinical trials: Hsp90, Hsp70 and Hsp27 inhibitors. Areas covered: The rationale to use Hsp inhibitors in NSCLC will be summarized and phase I-III trials will be reviewed. Expert opinion: Several Hsp90 inhibitors have been tested in phase I-III trials, until now none was positive in unselected NSCLC; therefore development of AUY922, ganetespib and retaspimycin was halted. Results seem more promising in molecularly selected patients, especially in ALK-rearranged NSCLC. Hsp27 is overexpressed in squamous NSCLC and is a mechanism of chemotherapy resistance. The Hsp27 inhibitor apatorsen is now tested in squamous NSCLC. No phase II/III data are known for Hsp70 inhibitors. Combination of Hsp inhibitors with heat shock transcription factor 1 inhibitors or focal adhesion kinase inhibitors might be of interest for future trials.

  19. Modeling properties of chromospheric evaporation driven by thermal conduction fronts from reconnection shocks

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

    Brannon, Sean; Longcope, Dana

    2014-09-01

    Magnetic reconnection in the corona results in contracting flare loops, releasing energy into plasma heating and shocks. The hydrodynamic shocks produced in this manner drive thermal conduction fronts (TCFs) which transport energy into the chromosphere and drive upflows (evaporation) and downflows (condensation) in the cooler, denser footpoint plasma. Observations have revealed that certain properties of the transition point between evaporation and condensation (the 'flow reversal point' or FRP), such as temperature and velocity-temperature derivative at the FRP, vary between different flares. These properties may provide a diagnostic tool to determine parameters of the coronal energy release mechanism and the loopmore » atmosphere. In this study, we develop a one-dimensional hydrodynamical flare loop model with a simplified three-region atmosphere (chromosphere/transition region/corona), with TCFs initiated by shocks introduced in the corona. We investigate the effect of two different flare loop parameters (post-shock temperature and transition region temperature ratio) on the FRP properties. We find that both of the evaporation characteristics have scaling-law relationships to the varied flare parameters, and we report the scaling exponents for our model. This provides a means of using spectroscopic observations of the chromosphere as quantitative diagnostics of flare energy release in the corona.« less

  20. Ecotypic variation in chloroplast small heat-shock proteins and related thermotolerance in Chenopodium album.

    PubMed

    Shakeel, Samina; Haq, Noor Ul; Heckathorn, Scott A; Hamilton, E William; Luthe, Dawn S

    2011-08-01

    Production of chloroplast-localized small heat-shock proteins (Cp-sHSP) is correlated with increased thermotolerance in plants. Ecotypic variation in function and expression of Cp-sHSPs was analyzed in two Chenopodium album ecotypes from cool vs. warm-temperate USA habitats [New York (NY) and Mississippi (MS) respectively]. P(et) was more heat tolerant in the MS than the NY ecotype, and MS ecotype derived proportionally greater protection of P(et) by Cp-sHSP during high temperatures. Four genes encoding Cp-sHSPs were isolated and characterized: CaHSP25.99n (NY-1) and CaHSP26.23n (NY-2) from NY ecotype, and CaHSP26.04m (MS-1) and CaHSP26.26m (MS-2) from MS ecotype. The genes were nearly identical in predicted amino-acid sequence and hydrophobicity. Gene expression analysis indicated that MS-1 and MS-2 transcripts were constitutively expressed at low levels at 25 °C, while no NY-1 and NY-2 transcripts were detected at this temperature. Maximum accumulation of NY-1 and NY-2 transcripts occurred at 33 °C and 40 °C for MS-1 and MS-2. Immunoblot analysis revealed that (1) protein expression was highest at 37 °C in both ecotypes, but was greater in MS than NY ecotype at 40 °C; and (2) import of Cp-sHSP into chloroplasts was more heat-labile in NY ecotype. The higher expression of one isoform in MS ecotype may contribute to its enhanced thermotolerance. Absence of correlation between protein and transcript levels, suggests the post-transcriptional regulation is occurring. Promoter analysis of these genes revealed significant variations in heat-shock elements (HSE), core motifs required for heat-shock-factor binding. We propose a correlation between unique promoter architecture, Cp-sHSP expression and thermotolerance in both ecotypes. Published by Elsevier Masson SAS.