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Sample records for apoptotic enzymes escape

  1. Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1

    Directory of Open Access Journals (Sweden)

    Dong L

    2015-12-01

    Full Text Available Liwei Dong,1 Hongge Wang,1 Jiajing Niu,1 Mingwei Zou,2 Nuoting Wu,1 Debin Yu,1 Ye Wang,1 Zhihua Zou11Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Psychology, College of Liberal Arts and Social Sciences, University of Houston, Houston, TX, USA Abstract: Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymatic reaction as a high-throughput in vitro screening assay to search for natural compounds capable of inhibiting MTH1. Echinacoside, a compound derived from the medicinal plants Cistanche and Echinacea, effectively inhibited the catalytic activity of MTH1 in an in vitro assay. Treatment of various human cancer cell lines with Echinacoside resulted in a significant increase in the cellular level of oxidized guanine (8-oxoguanine, while cellular reactive oxygen species level remained unchanged, indicating that Echinacoside also inhibited the activity of cellular MTH1. Consequently, Echinacoside treatment induced an immediate and dramatic increase in DNA damage markers and upregulation of the G1/S-CDK inhibitor p21, which were followed by marked apoptotic cell death and cell cycle arrest in cancer but not in noncancer cells. Taken together, these studies identified a natural compound as an MTH1 inhibitor and suggest that natural products can be an important source of anticancer agents. Keywords: Echinacoside, MTH1, 8-oxoG, DNA damage, apoptosis, cell cycle arrest

  2. Thymosin beta 4 protects cardiomyocytes from oxidative stress by targeting anti-oxidative enzymes and anti-apoptotic genes.

    Directory of Open Access Journals (Sweden)

    Chuanyu Wei

    Full Text Available Thymosin beta-4 (Tβ4 is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. The mechanism by which Tβ4 modulates cardiac protection under oxidative stress is not known. The purpose of this study is to dissect the cardioprotective mechanism of Tβ4 on H(2O(2 induced cardiac damage.Rat neonatal cardiomyocytes with or without Tβ4 pretreatment were exposed to H(2O(2 and expression of antioxidant, apoptotic, and anti-inflammatory genes was evaluated by quantitative real-time PCR and western blotting. ROS levels were estimated by DCF-DA using fluorescent microscopy and fluorimetry. Selected antioxidant, anti-inflammatory and antiapoptotic genes were silenced by siRNA transfections in neonatal cardiomyocytes and effect of Tβ4 on H(2O(2-induced cardiac damage was evaluated.Pre-treatment of Tβ4 resulted in reduction of the intracellular ROS levels induced by H(2O(2 in cardiomyocytes. Tβ4 pretreatment also resulted in an increase in the expression of antiapoptotic proteins and reduction of Bax/BCl(2 ratio in the cardiomyocytes. Pretreatment with Tβ4 resulted in stimulating the expression of antioxidant enzymes copper/zinc SOD and catalase in cardiomyocytes at both transcription and translation levels. Tβ4 treatment resulted in the increased expression of anti-apoptotic and anti-inflammatory genes. Silencing of Cu/Zn SOD and catalase gene resulted in apoptotic cell death in the cardiomyocytes which was prevented by treatment with Tβ4.This is the first report that demonstrates the effect of Tβ4 on cardiomyocytes and its capability to selectively upregulate anti-oxidative enzymes, anti-inflammatory genes, and antiapoptotic enzymes in the neonatal cardiomyocytes thus preventing cell death thereby protecting the myocardium. Tβ4 treatment resulted in decreased oxidative stress and inflammation in the myocardium under oxidative stress.

  3. Enzyme

    Science.gov (United States)

    Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

  4. Titan's hydrodynamically escaping atmosphere

    Science.gov (United States)

    Strobel, Darrell F.

    2008-02-01

    The upper atmosphere of Titan is currently losing mass at a rate ˜(4-5)×10 amus, by hydrodynamic escape as a high density, slow outward expansion driven principally by solar UV heating by CH 4 absorption. The hydrodynamic mass loss is essentially CH 4 and H 2 escape. Their combined escape rates are restricted by power limitations from attaining their limiting rates (and limiting fluxes). Hence they must exhibit gravitational diffusive separation in the upper atmosphere with increasing mixing ratios to eventually become major constituents in the exosphere. A theoretical model with solar EUV heating by N 2 absorption balanced by HCN rotational line cooling in the upper thermosphere yields densities and temperatures consistent with the Huygens Atmospheric Science Investigation (HASI) data [Fulchignoni, M., and 42 colleagues, 2005. Nature 438, 785-791], with a peak temperature of ˜185-190 K between 3500-3550 km. This model implies hydrodynamic escape rates of ˜2×10 CHs and 5×10 Hs, or some other combination with a higher H 2 escape flux, much closer to its limiting value, at the expense of a slightly lower CH 4 escape rate. Nonthermal escape processes are not required to account for the loss rates of CH 4 and H 2, inferred by the Cassini Ion Neutral Mass Spectrometer (INMS) measurements [Yelle, R.V., Borggren, N., de la Haye, V., Kasprzak, W.T., Niemann, H.B., Müller-Wodarg, I., Waite Jr., J.H., 2006. Icarus 182, 567-576].

  5. Restricting wolves risks escape

    Science.gov (United States)

    Mech, L. David; Ballard, Warren; Bangs, Ed; Ream, Bob

    2010-01-01

    Implementing the proposal set forth by Licht and colleagues (BioScience 60: 147–153) requires restricting wolves to tiny "islands," areas that are magnitudes smaller than the ranges of most wolf populations. Wolves naturally have large ranges; restricting their spatial needs increases the risk of wolves escaping, exacerbating public relations and political and legal problems.

  6. Escape from the Alternative

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2006-12-01

    Full Text Available This paper sets out to elaborate on Romania’s specific agenda regarding the approach to the integration process in the EU as a project of modernization. The focus is on the functional aspects, the type of strategic solutions destined to consolidate the specific transformations belonging to post-communist transition seen as an internal transition, on the one hand and on the other hand to push convergence as the essence of integration, marked by the vision of EU integration as a continuation of change, which is the stage of external transition. Identifying the prominent factors and the pragmatic priorities of the escape from the peripheries of development by engaging in evolution by way of the second modernization constitutes as well a target for analysis. One particularity of the method of analysis is the review if the value-set of the bobsled effect of path dependency – the path of the peripheries – as well as of the set of values of the escape from the peripheries.

  7. THERMALLY DRIVEN ATMOSPHERIC ESCAPE: TRANSITION FROM HYDRODYNAMIC TO JEANS ESCAPE

    International Nuclear Information System (INIS)

    Volkov, Alexey N.; Johnson, Robert E.; Tucker, Orenthal J.; Erwin, Justin T.

    2011-01-01

    Thermally driven escape from planetary atmospheres changes in nature from an organized outflow (hydrodynamic escape) to escape on a molecule-by-molecule basis (Jeans escape) with increasing Jeans parameter, λ, the ratio of the gravitational to thermal energy of the atmospheric molecules. This change is described here for the first time using the direct simulation Monte Carlo method. When heating is predominantly below the lower boundary of the simulation region, R 0 , and well below the exobase of a single-component atmosphere, the nature of the escape process changes over a surprisingly narrow range of Jeans parameters, λ 0 , evaluated at R 0 . For an atomic gas, the transition occurs over λ 0 ∼ 2-3, where the lower bound, λ 0 ∼ 2.1, corresponds to the upper limit for isentropic, supersonic outflow. For λ 0 > 3 escape occurs on a molecule-by-molecule basis and we show that, contrary to earlier suggestions, for λ 0 > ∼6 the escape rate does not deviate significantly from the familiar Jeans rate. In a gas composed of diatomic molecules, the transition shifts to λ 0 ∼ 2.4-3.6 and at λ 0 > ∼4 the escape rate increases a few tens of percent over that for the monatomic gas. Scaling by the Jeans parameter and the Knudsen number, these results can be applied to thermally induced escape of the major species from solar and extrasolar planets.

  8. Hydrodynamic escape from planetary atmospheres

    Science.gov (United States)

    Tian, Feng

    Hydrodynamic escape is an important process in the formation and evolution of planetary atmospheres. Due to the existence of a singularity point near the transonic point, it is difficult to find transonic steady state solutions by solving the time-independent hydrodynamic equations. In addition to that, most previous works assume that all energy driving the escape flow is deposited in one narrow layer. This assumption not only results in less accurate solutions to the hydrodynamic escape problem, but also makes it difficult to include other chemical and physical processes in the hydrodynamic escape models. In this work, a numerical model describing the transonic hydrodynamic escape from planetary atmospheres is developed. A robust solution technique is used to solve the time dependent hydrodynamic equations. The method has been validated in an isothermal atmosphere where an analytical solution is available. The hydrodynamic model is applied to 3 cases: hydrogen escape from small orbit extrasolar planets, hydrogen escape from a hydrogen rich early Earth's atmosphere, and nitrogen/methane escape from Pluto's atmosphere. Results of simulations on extrasolar planets are in good agreement with the observations of the transiting extrasolar planet HD209458b. Hydrodynamic escape of hydrogen from other hypothetical close-in extrasolar planets are simulated and the influence of hydrogen escape on the long-term evolution of these extrasolar planets are discussed. Simulations on early Earth suggest that hydrodynamic escape of hydrogen from a hydrogen rich early Earth's atmosphere is about two orders magnitude slower than the diffusion limited escape rate. A hydrogen rich early Earth's atmosphere could have been maintained by the balance between the hydrogen escape and the supply of hydrogen into the atmosphere by volcanic outgassing. Origin of life may have occurred in the organic soup ocean created by the efficient formation of prebiotic molecules in the hydrogen rich early

  9. Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology.

    Science.gov (United States)

    Bidmon, H J; Emde, B; Kowalski, T; Schmitt, M; Mayer, B; Kato, K; Asayama, K; Witte, O W; Zilles, K

    2001-09-01

    Neuronal nitric oxide-I is constitutively expressed in approximately 2% of cortical interneurons and is co-localized with gamma-amino butric acid, somatostatin or neuropeptide Y. These interneurons additionally express high amounts of glutamate receptors which mediate the glutamate-induced hyperexcitation following cerebral injury, under these conditions nitric oxide production increases contributing to a potentiation of oxidative stress. However, perilesional nitric oxide synthase-I containing neurons are known to be resistant to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in neuroprotection. The question remains of how these cells are protected against their own high intracellular nitric oxide production after activation. In this study, we investigated immunocytochemically nitric oxide synthase-I containing cortical neurons in rats after unilateral, cortical photothrombosis. In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase. This enhanced antioxidant expression was accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein. No colocalization was detectable with upregulated heme oxygenase-1 in glia and the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons. These results suggest that nitric oxide synthase-I containing interneurons are protected against intracellular oxidative damage and apoptosis by Bcl-2 and several potent antioxidative enzymes. Since nitric oxide synthase-I positive neurons do not express superoxide-producing enzymes such as cyclooxygenase-1, xanthine oxidase and cyclooxygenase-2 in response to injury, this may additionally contribute to their resistance by reducing their internal

  10. Induction of apoptotic cell death by putrescine

    DEFF Research Database (Denmark)

    Takao, Koichi; Rickhag, Karl Mattias; Hegardt, Cecilia

    2006-01-01

    that overexpression of a metabolically stable ODC in CHO cells induced a massive cell death unless the cells were grown in the presence of the ODC inhibitor alpha-difluoromethylornithine (DFMO). Cells overexpressing wild-type (unstable) ODC, on the other hand, were not dependent on the presence of DFMO...... for their growth. The induction of cell death was correlated with a dramatic increase in cellular putrescine levels. Analysis using flow cytometry revealed perturbed cell cycle kinetics, with a large accumulation of cells with sub-G1 amounts of DNA, which is a typical sign of apoptosis. Another strong indication...... of apoptosis was the finding that one of the key enzymes in the apoptotic process, caspase-3, was induced when DFMO was omitted from the growth medium. Furthermore, inhibition of the caspase activity significantly reduced the recruitment of cells to the sub-G1 fraction. In conclusion, deregulation of polyamine...

  11. Immunosuppressive effects of apoptotic cells

    Science.gov (United States)

    Voll, Reinhard E.; Herrmann, Martin; Roth, Edith A.; Stach, Christian; Kalden, Joachim R.; Girkontaite, Irute

    1997-11-01

    Apoptotic cell death is important in the development and homeostasis of multicellular organisms and is a highly controlled means of eliminating dangerous, damaged or unnecessary cells without causing an inflammatory response or tissue damage,. We now show that the presence of apoptotic cells during monocyte activation increases their secretion of the anti-inflammatory and immunoregulatory cytokine interleukin 10 (IL-10) and decreases secretion of the proinflammatory cytokines tumour necrosis factor-α (TNF-α), IL-1 and IL-12. This may inhibit inflammation and contribute to impaired cell-mediated immunity in conditions associated with increased apoptosis, such as viral infections, pregnancy, cancer and exposure to radiation.

  12. Creating Engaging Escape Rooms for the Classroom

    Science.gov (United States)

    Nicholson, Scott

    2018-01-01

    Escape rooms are "live-action team-based games where players discover clues, solve puzzles, and accomplish tasks in one or more rooms in order to accomplish a specific goal (usually escaping from the room) in a limited amount of time." Escape Rooms are one type of Escape Game, which are narrative-based challenges that use puzzles, tasks,…

  13. Prosthetic Mitral Valve Leaflet Escape

    Science.gov (United States)

    Kim, Darae; Hun, Sin Sang; Cho, In-Jeong; Shim, Chi-Young; Ha, Jong-Won; Chung, Namsik; Ju, Hyun Chul; Sohn, Jang Won

    2013-01-01

    Leaflet escape of prosthetic valve is rare but potentially life threatening. It is essential to make timely diagnosis in order to avoid mortality. Transesophageal echocardiography and cinefluoroscopy is usually diagnostic and the location of the missing leaflet can be identified by computed tomography (CT). Emergent surgical correction is mandatory. We report a case of fractured escape of Edward-Duromedics mitral valve 27 years after the surgery. The patient presented with symptoms of acute decompensated heart failure and cardiogenic shock. She was instantly intubated and mechanically ventilated. After prompt evaluation including transthoracic echocardiography and CT, the escape of the leaflet was confirmed. The patient underwent emergent surgery for replacement of the damaged prosthetic valves immediately. Eleven days after the surgery, the dislodged leaflet in iliac artery was removed safely and the patient recovered well. PMID:23837121

  14. Automated Escape Guidance Algorithms for An Escape Vehicle

    Science.gov (United States)

    Flanary, Ronald; Hammen, David; Ito, Daigoro; Rabalais, Bruce; Rishikof, Brian; Siebold, Karl

    2002-01-01

    An escape vehicle was designed to provide an emergency evacuation for crew members living on a space station. For maximum escape capability, the escape vehicle needs to have the ability to safely evacuate a station in a contingency scenario such as an uncontrolled (e.g., tumbling) station. This emergency escape sequence will typically be divided into three events: The fust separation event (SEP1), the navigation reconstruction event, and the second separation event (SEP2). SEP1 is responsible for taking the spacecraft from its docking port to a distance greater than the maximum radius of the rotating station. The navigation reconstruction event takes place prior to the SEP2 event and establishes the orbital state to within the tolerance limits necessary for SEP2. The SEP2 event calculates and performs an avoidance burn to prevent station recontact during the next several orbits. This paper presents the tools and results for the whole separation sequence with an emphasis on the two separation events. The fust challenge includes collision avoidance during the escape sequence while the station is in an uncontrolled rotational state, with rotation rates of up to 2 degrees per second. The task of avoiding a collision may require the use of the Vehicle's de-orbit propulsion system for maximum thrust and minimum dwell time within the vicinity of the station vicinity. The thrust of the propulsion system is in a single direction, and can be controlled only by the attitude of the spacecraft. Escape algorithms based on a look-up table or analytical guidance can be implemented since the rotation rate and the angular momentum vector can be sensed onboard and a-priori knowledge of the position and relative orientation are available. In addition, crew intervention has been provided for in the event of unforeseen obstacles in the escape path. The purpose of the SEP2 burn is to avoid re-contact with the station over an extended period of time. Performing this maneuver properly

  15. Cnidoscolus (Euphorbiaceae) escaped in Malesia?

    NARCIS (Netherlands)

    Welzen, van P.C.; Fernández-Casas, F.J.

    2017-01-01

    The genus Cnidoscolus, a species rich genus in the Americas, has been introduced in the Philippines. A cultivar of Cnidoscolus aconitifolius is used as vegetable and has been collected from gardens in Manila and Pasay City and two times near Cebu City. It cannot be excluded that it has escaped

  16. Apoptotic markers in protozoan parasites

    Directory of Open Access Journals (Sweden)

    Fasel Nicolas

    2010-11-01

    Full Text Available Abstract The execution of the apoptotic death program in metazoans is characterized by a sequence of morphological and biochemical changes that include cell shrinkage, presentation of phosphatidylserine at the cell surface, mitochondrial alterations, chromatin condensation, nuclear fragmentation, membrane blebbing and the formation of apoptotic bodies. Methodologies for measuring apoptosis are based on these markers. Except for membrane blebbing and formation of apoptotic bodies, all other events have been observed in most protozoan parasites undergoing cell death. However, while techniques exist to detect these markers, they are often optimised for metazoan cells and therefore may not pick up subtle differences between the events occurring in unicellular organisms and multi-cellular organisms. In this review we discuss the markers most frequently used to analyze cell death in protozoan parasites, paying special attention to changes in cell morphology, mitochondrial activity, chromatin structure and plasma membrane structure/permeability. Regarding classical regulators/executors of apoptosis, we have reviewed the present knowledge of caspase-like and nuclease activities.

  17. Escaping carbon lock-in

    International Nuclear Information System (INIS)

    Unruh, G.C.

    2002-01-01

    This article explores the climate policy implications of the arguments made in ''Understanding carbon lock-in'' (Unruh, 2000), which posited that industrial countries have become locked-into fossil fuel-based energy systems through path dependent processes driven by increasing returns to scale. Carbon lock-in arises through technological, organizational, social and institutional co-evolution, ''culminating'' in what was termed as techno-institutional complex (TIC). In order to resolve the climate problem, an escape from the lock-in condition is required. However, due to the self-referential nature of TIC, escape conditions are unlikely to be generated internally and it is argued here that erogenous forces are probably required. (author)

  18. EscapED: A Framework for Creating Educational Escape Rooms and Interactive Games to For Higher/Further Education.

    Directory of Open Access Journals (Sweden)

    Samantha Jane Clarke

    2017-09-01

    Full Text Available Game-based learning (GBL is often found to be technologically driven and more often than not, serious games for instance, are conceptualised and designed solely for digital platforms and state of the art technologies. To encourage a greater discussion on the potential benefits and challenges of a more holistic approach to developing GBL that promote human centered interactions and play for learning, the authors present the escapED programme. The escapED programme was conceived following the recent entertainment trend of escape rooms and is used for developing non-digital GBL approaches within education. escapED aids the design and creation of educational Escape Rooms and Interactive Gaming Experiences for staff and students in further/higher education settings. The paper first presents a pilot study that was used to assess the feasibility and acceptance of University teaching staff of embedding interactive GBL into a higher education environment. The authors then present the escapED theoretical framework that was used to create the prototype game for the pilot study as a tool to aid future design and development of on-site interactive experiences. The paper also presents an external developer report of using the escapED framework to develop a prototype game for teaching research methods to Southampton University students. Finally, the authors present a discussion on the use of the escapED framework so far and plans for future work and evaluation in order to provide engaging alternatives for learning and soft skills development amongst higher education staff andstudents.

  19. Malaria parasites: the great escape

    Directory of Open Access Journals (Sweden)

    Laurent Rénia

    2016-11-01

    Full Text Available Parasites of the genus Plasmodium have a complex life cycle. They alternate between their final mosquito host and their intermediate hosts. The parasite can be either extra- or intracellular, depending on the stage of development. By modifying their shape, motility, and metabolic requirements, the parasite adapts to the different environments in their different hosts. The parasite has evolved to escape the multiple immune mechanisms in the host that try to block parasite development at the different stages of their development. In this article, we describe the mechanisms reported thus far that allow the Plasmodium parasite to evade innate and adaptive immune responses.

  20. Apoptotic engulfment pathway and schizophrenia.

    LENUS (Irish Health Repository)

    Chen, Xiangning

    2009-01-01

    BACKGROUND: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease. METHODOLOGY\\/PRINCIPAL FINDINGS: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples. CONCLUSIONS\\/SIGNIFICANCE: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.

  1. Studying apoptotic cell death by flow cytometry

    International Nuclear Information System (INIS)

    Ormerod, Michael G.

    1998-01-01

    Full text: Programmed cell death (PCD) is of fundamental importance in the normal development of an animal and also in tumour biology and radiation biology. During PCD a sequence of changes occurs in cells giving rise to an apoptotic cascade of events. The main elements of this cascade are rapidly being elucidated. Flow cytometry has been used to follow many of these changes. It also has been used to quantify the number of apoptotic cells in a culture and, more recently, in clinical samples. In this review, the properties of apoptotic cells and the main feature of apoptotic cascade will be described. How flow cytometry can be used to follow changes during the apoptotic cascade will be discussed

  2. Two examples of escaping harmonic maps

    International Nuclear Information System (INIS)

    Pereira do Valle, A.; Verjovsky, A.

    1988-12-01

    This paper is part of a study on the existence of special harmonic maps on complete non-compact Riemannian manifolds. We generalize the notion of escaping geodesic and prove some results on the existence of escaping harmonic maps. 11 refs, 6 figs

  3. Mitotic and apoptotic activity in colorectal neoplasia.

    Science.gov (United States)

    Kohoutova, Darina; Pejchal, Jaroslav; Bures, Jan

    2018-05-18

    Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia. A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3. In controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity. Significant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.

  4. Physics escape room as an educational tool

    Science.gov (United States)

    Vörös, Alpár István Vita; Sárközi, Zsuzsa

    2017-12-01

    Escape rooms have flourished in the last decade. These are adventure games in which players work together to solve puzzles using hints, clues and a strategy to escape from a locked room. In many cases they use different phenomena related to physics. Hence the idea of using escape rooms in science centers or even in classroom activities. Escape rooms are designed for one single team of players, the method is more suitable for activities in a science centre. In our paper, we show that escape rooms' puzzle solving methods could be used in physics classroom activities as well, taking into account that several teams have to work together in the same room/place. We have developed an educational escape game for physics of fluids, as this topic is left out from the Romanian high-school curriculum. We have tried out our game during the project week called "Şcoala altfel" ("school in a different way") and in a physics camp for gifted students. We present the designed physics escape game and the results.

  5. A Model for SEP Escape

    Science.gov (United States)

    Antiochos, S. K.; Masson, S.; DeVore, C. R.

    2012-01-01

    Magnetic reconnection in the solar atmosphere is believed to be the driver of most solar explosive phenomena. Therefore, the topology of the coronal magnetic field is central to understanding the solar drivers of space weather. Of particular importance to space weather are the impulsive Solar Energetic particles that are associated with some CME/eruptive flare events. Observationally, the magnetic configuration of active regions where solar eruptions originate appears to agree with the standard eruptive flare model. According to this model, particles accelerated at the flare reconnection site should remain trapped in the corona and the ejected plasmoid. However, flare-accelerated particles frequently reach the Earth long before the CME does. We present a model that may account for the injection of energetic particles onto open magnetic flux tubes connecting to the Earth. Our model is based on the well-known 2.5D breakout topology, which has a coronal null point (null line) and a four-flux system. A key new addition, however, is that we include an isothermal solar wind with open-flux regions. Depending on the location of the open flux with respect to the null point, we find that the flare reconnection can consist of two distinct phases. At first, the flare reconnection involves only closed field, but if the eruption occurs close to the open field, we find a second phase involving interchange reconnection between open and closed. We argue that this second reconnection episode is responsible for the injection of flare-accelerated particles into the interplanetary medium. We will report on our recent work toward understanding how flare particles escape to the heliosphere. This work uses high-resolution 2.5D MHD numerical simulations performed with the Adaptively Refined MHD Solver (ARMS).

  6. Narrow Escape of Interacting Diffusing Particles

    Science.gov (United States)

    Agranov, Tal; Meerson, Baruch

    2018-03-01

    The narrow escape problem deals with the calculation of the mean escape time (MET) of a Brownian particle from a bounded domain through a small hole on the domain's boundary. Here we develop a formalism which allows us to evaluate the nonescape probability of a gas of diffusing particles that may interact with each other. In some cases the nonescape probability allows us to evaluate the MET of the first particle. The formalism is based on the fluctuating hydrodynamics and the recently developed macroscopic fluctuation theory. We also uncover an unexpected connection between the narrow escape of interacting particles and thermal runaway in chemical reactors.

  7. Dynamic Escape Routes for Naval Ships

    National Research Council Canada - National Science Library

    Villalonga, Francisco J

    2005-01-01

    This thesis addresses the problem of optimal evacuation of a naval ship. We propose the use of a dynamic escape-route system which employs a signaling system to adapt the emergency egress process to the instigating contingency...

  8. St.Petersburg Escape Experience Tour

    OpenAIRE

    Palagina, Mariia; Zhak, Svetlana

    2017-01-01

    The growing popularity of Russia as a tourist destination and the high interest towards escape rooms and quests opens new business opportunities and market niches. The aim of this thesis is to develop a tourist product based on the new escape room tourism concept combining the historical, cultural and game experiences. The choice of the theme and destination was determined by the authors’ personal backgrounds and the destination proximity to Finland. The theoretical research was implement...

  9. Pancreatic Enzymes

    Science.gov (United States)

    ... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  10. Comparative Antioxidant, Antiproliferative and Apoptotic Effects of ...

    African Journals Online (AJOL)

    Purpose: To determine and compare the antioxidant, antiproliferative and apoptotic effects of leaf infusions of Ilex laurina ... Both plant infusions inhibited viability and cell growth of SW480 and SW620 cells. .... 100 g of dry extract, from a gallic acid calibration curve [9]. ..... antioxidant capacity and in vitro inhibition of colon.

  11. Comparative Antioxidant, Antiproliferative and Apoptotic Effects of ...

    African Journals Online (AJOL)

    Purpose: To determine and compare the antioxidant, antiproliferative and apoptotic effects of leaf infusions of Ilex laurina and Ilex paraguariensis in colon cancer cells. Methods: Antioxidant activity was determined by ORAC (Oxygen Radical Absorbance Capacity) and FRAP (Ferric Reducing Antioxidant Power). Cytotoxic ...

  12. Detection of apoptotic cells using immunohistochemistry

    NARCIS (Netherlands)

    Newbold, Andrea; Martin, Ben P.; Cullinane, Carleen; Bots, Michael

    2014-01-01

    Immunohistochemistry is commonly used to show the presence of apoptotic cells in situ. In this protocol, B-cell lymphoma cells are injected into recipient mice and, on tumor formation, the mice are treated with the apoptosis inducer vorinostat (a histone deacetylase inhibitor). Tumor samples are

  13. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    Science.gov (United States)

    Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

    2015-06-01

    CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.

  14. Escape of magnetic toroids from the Sun

    International Nuclear Information System (INIS)

    Bieber, John W.; Rust, David M.

    1996-01-01

    Analysis of heliospheric magnetic fields at 1 AU shows that 10 24 Mx of net toroidal flux escapes from the Sun per solar cycle. This rate is compared with the apparent rate of flux emergence at the solar surface, and it is concluded that escaping toroids will remove at least 20% of the emerging flux, and may remove as much as 100% of emerging flux if multiple eruptions occur on the toroids. The data imply that flux escapes the Sun with an efficiency far exceeding Parker's upper limit estimate of 3%. Toroidal flux escape is almost certainly the source of the observed overwinding of the interplanetary magnetic field spiral. Two mechanisms to facilitate net flux escape are discussed: helicity charging to push open the fields and flux transport with reconnection to close them off. We estimate the Sun will shed ∼2x10 45 Mx 2 of magnetic helicity per solar cycle, leading to a mean helicity density of 100 Mx 2 cm -3 at 1 AU, which agrees well with observations

  15. Thermal escape from extrasolar giant planets.

    Science.gov (United States)

    Koskinen, Tommi T; Lavvas, Panayotis; Harris, Matthew J; Yelle, Roger V

    2014-04-28

    The detection of hot atomic hydrogen and heavy atoms and ions at high altitudes around close-in extrasolar giant planets (EGPs) such as HD209458b implies that these planets have hot and rapidly escaping atmospheres that extend to several planetary radii. These characteristics, however, cannot be generalized to all close-in EGPs. The thermal escape mechanism and mass loss rate from EGPs depend on a complex interplay between photochemistry and radiative transfer driven by the stellar UV radiation. In this study, we explore how these processes change under different levels of irradiation on giant planets with different characteristics. We confirm that there are two distinct regimes of thermal escape from EGPs, and that the transition between these regimes is relatively sharp. Our results have implications for thermal mass loss rates from different EGPs that we discuss in the context of currently known planets and the detectability of their upper atmospheres.

  16. Black holes escaping from domain walls

    International Nuclear Information System (INIS)

    Flachi, Antonino; Sasaki, Misao; Pujolas, Oriol; Tanaka, Takahiro

    2006-01-01

    Previous studies concerning the interaction of branes and black holes suggested that a small black hole intersecting a brane may escape via a mechanism of reconnection. Here we consider this problem by studying the interaction of a small black hole and a domain wall composed of a scalar field and simulate the evolution of this system when the black hole acquires an initial recoil velocity. We test and confirm previous results, however, unlike the cases previously studied, in the more general set-up considered here, we are able to follow the evolution of the system also during the separation, and completely illustrate how the escape of the black hole takes place

  17. Martian Atmospheric and Ionospheric plasma Escape

    Science.gov (United States)

    Lundin, Rickard

    2016-04-01

    Solar forcing is responsible for the heating, ionization, photochemistry, and erosion processes in the upper atmosphere throughout the lifetime of the terrestrial planets. Of the four terrestrial planets, the Earth is the only one with a fully developed biosphere, while our kin Venus and Mars have evolved into arid inhabitable planets. As for Mars, there are ample evidences for an early Noachian, water rich period on Mars. The question is, what made Mars evolve so differently compared to the Earth? Various hydrosphere and atmospheric evolution scenarios for Mars have been forwarded based on surface morphology, chemical composition, simulations, semi-empiric (in-situ data) models, and the long-term evolution of the Sun. Progress has been made, but the case is still open regarding the changes that led to the present arid surface and tenuous atmosphere at Mars. This presentation addresses the long-term variability of the Sun, the solar forcing impact on the Martian atmosphere, and its interaction with the space environment - an electromagnetic wave and particle interaction with the upper atmosphere that has implications for its photochemistry, composition, and energization that governs thermal and non-thermal escape. Non-thermal escape implies an electromagnetic upward energization of planetary ions and molecules to velocities above escape velocity, a process governed by a combination of solar EUV radiation (ionization), and energy and momentum transfer by the solar wind. The ion escape issue dates back to the early Soviet and US-missions to Mars, but the first more accurate estimates of escape rates came with the Phobos-2 mission in 1989. Better-quality ion composition measurement results of atmospheric/ionospheric ion escape from Mars, obtained from ESA Mars Express (MEX) instruments, have improved our understanding of the ion escape mechanism. With the NASA MAVEN spacecraft orbiting Mars since Sept. 2014, dual in-situ measurement with plasma instruments are now

  18. Do the visual conditions at the point of escape affect European sea bass escape behavior?

    Directory of Open Access Journals (Sweden)

    I.E. PAPADAKIS

    2013-03-01

    Full Text Available European sea bass (Dicentrarchus labrax, an important species for the Mediterranean aquaculture industry, has been reported to escape from sea cage installations. Fish escapes are caused mainly by operational and technical failures that eventually result into a creation of a tear. Escapees may interact with wild stocks through interbreeding, transfer of pathogens and competition for food. The aim of this study was to examine at which extent the presence of a visible obstacle close to a tear on the net have an influence on sea bass propensity to escape. Fish were initially confined into small sea cages, with a tear at one side. The escape behavior was tested under experimental conditions. It is clearly demonstrated that sea bass was able to locate a tear on the net pen, immediately after its appearance. Crossings occurred in all cages, in singles or in a series of up to seven individuals. The presence of an obstacle close to the net tear altered the escape behavior of D. labrax resulting in a delay that eventually reduced the escape rate. Concluding, it is highly recommended that sea bass cages should be kept internally the culture array. Furthermore, the placement of artificial obstacles close to the sea cages could be an efficient practice that mitigates the escape risk after severe environmental conditions.

  19. Stabilization Of Apoptotic Cells: Generation Of Zombie Cells

    Directory of Open Access Journals (Sweden)

    José A. Sánchez Alcázar

    2015-08-01

    Stabilization of apoptotic cells can be used for reliable detection and quantification of apoptosis in cultured cells and may allow a safer administration of apoptotic cells in clinical applications. Furthermore, it opens new avenues in the functional reconstruction of apoptotic cells for longer preservation.

  20. SYTO probes: markers of apoptotic cell demise.

    Science.gov (United States)

    Wlodkowic, Donald; Skommer, Joanna

    2007-10-01

    As mechanistic studies on tumor cell death advance towards their ultimate translational goal, there is a need for specific, rapid, and high-throughput analytical tools to detect diverse cell demise modes. Patented DNA-binding SYTO probes, for example, are gaining increasing interest as easy-to-use markers of caspase-dependent apoptotic cell death. They are proving convenient for tracking apoptosis in diverse hematopoietic cell lines and primary tumor samples, and, due to their spectral characteristics, appear to be useful for the development of multiparameter flow cytometry assays. Herein, several protocols for multiparametric assessment of apoptotic events using SYTO probes are provided. There are protocols describing the use of green fluorescent SYTO 16 and red fluorescent SYTO 17 dyes in combination with plasma membrane permeability markers. Another protocol highlights the multiparametric use of SYTO 16 dye in conjunction with the mitochondrial membrane potential sensitive probe, tetramethylrhodamine methyl ester (TMRM), and the plasma membrane permeability marker, 7-aminoactinomycin D (7-AAD).

  1. Learning from escaped prescribed fire reviews

    Science.gov (United States)

    Anne E. Black; Dave Thomas; James Saveland; Jennifer D. Ziegler

    2011-01-01

    The U.S. wildland fire community has developed a number of innovative methods for conducting a review following escape of a prescribed fire (expanding on the typical regional or local reviews, to include more of a learning focus - expanded After Action Reviews, reviews that incorporate High Reliability Organizing, Facilitated Learning Analyses, etc). The stated purpose...

  2. Genomics of Stress Escape in Arabidopsis Thaliana

    NARCIS (Netherlands)

    Das, D.

    2016-01-01

    In nature, two highly diverse environmental signals, flooding and shade, sensed through their own unique receptor systems, share physiological and molecular similarities in the context of accelerated shoot elongation in plants (a conserved stress-escape strategy), suggesting a possible cross-talk

  3. Centrifugally Stimulated Exospheric Ion Escape at Mercury

    Science.gov (United States)

    Delcourt, Dominique; Seki, K.; Terada, N.; Moore, Thomas E.

    2012-01-01

    We investigate the transport of ions in the low-altitude magnetosphere magnetosphere of Mercury. We show that, because of small spatial scales, the centrifugal effect due to curvature of the E B drift paths can lead to significant particle energization in the parallel direction. We demonstrate that because of this effect, ions with initial speed smaller than the escape speed such as those produced via thermal desorption can overcome gravity and escape into the magnetosphere. The escape route of this low-energy exosphere originating material is largely controlled by the magnetospheric convection rate. This escape route spreads over a narrower range of altitudes when the convection rate increases. Bulk transport of low-energy planetary material thus occurs within a limited region of space once moderate magnetospheric convection is established. These results suggest that, via release of material otherwise gravitationally trapped, the E B related centrifugal acceleration is an important mechanism for the net supply of plasma to the magnetosphere of Mercury.

  4. Pade approximant calculations for neutron escape probability

    International Nuclear Information System (INIS)

    El Wakil, S.A.; Saad, E.A.; Hendi, A.A.

    1984-07-01

    The neutron escape probability from a non-multiplying slab containing internal source is defined in terms of a functional relation for the scattering function for the diffuse reflection problem. The Pade approximant technique is used to get numerical results which compare with exact results. (author)

  5. Net escapement of Antartic krill in trawls

    DEFF Research Database (Denmark)

    Krafft, B.A.; Krag, Ludvig Ahm; Herrmann, Bent

    This document describes the aims and methodology of a three year project (commenced in 2012) entitled Net Escapement of Antarctic krill in Trawls (NEAT). The study will include a morphology based mathematical modeling (FISHSELECT) of different sex and maturity groups of Antarctic krill (Euphausia...

  6. Life events and escape in conversion disorder.

    Science.gov (United States)

    Nicholson, T R; Aybek, S; Craig, T; Harris, T; Wojcik, W; David, A S; Kanaan, R A

    2016-09-01

    Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged. Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel 'escape' rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of 'secondary gain'. CD patients had significantly more severe life events and 'escape' events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients - significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56-13.70] and healthy controls (OR 5.81, 95% CI 1.86-18.2). In the same time period 53% of CD patients had at least one 'high escape' event - again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05-23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events. Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation.

  7. The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity

    Science.gov (United States)

    Wang, Xiaowan; Li, Hailong; Ding, Shinghua

    2014-01-01

    NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. PMID:25387075

  8. Rumen escape protein in grass and grass silage deterimened with a nylon bag and an enzymatic technique

    NARCIS (Netherlands)

    Cone, J.W.; Gelder, van A.H.; Mathijssen-Kamman, A.A.; Hindle, V.A.

    2004-01-01

    Rumen escape protein (REP) was determined for six grasses and 16 grass silages using a nylon bag technique and an in vitro technique using a proteolytic enzyme preparation of Streptomyces griseus. In vitro, the samples were incubated for 0, 1, 6 and 24 h. The highest correlation observed between

  9. Launch Pad Escape System Design (Human Spaceflight)

    Science.gov (United States)

    Maloney, Kelli

    2011-01-01

    A launch pad escape system for human spaceflight is one of those things that everyone hopes they will never need but is critical for every manned space program. Since men were first put into space in the early 1960s, the need for such an Emergency Escape System (EES) has become apparent. The National Aeronautics and Space Administration (NASA) has made use of various types of these EESs over the past 50 years. Early programs, like Mercury and Gemini, did not have an official launch pad escape system. Rather, they relied on a Launch Escape System (LES) of a separate solid rocket motor attached to the manned capsule that could pull the astronauts to safety in the event of an emergency. This could only occur after hatch closure at the launch pad or during the first stage of flight. A version of a LES, now called a Launch Abort System (LAS) is still used today for all manned capsule type launch vehicles. However, this system is very limited in that it can only be used after hatch closure and it is for flight crew only. In addition, the forces necessary for the LES/LAS to get the capsule away from a rocket during the first stage of flight are quite high and can cause injury to the crew. These shortcomings led to the development of a ground based EES for the flight crew and ground support personnel as well. This way, a much less dangerous mode of egress is available for any flight or ground personnel up to a few seconds before launch. The early EESs were fairly simple, gravity-powered systems to use when thing's go bad. And things can go bad very quickly and catastrophically when dealing with a flight vehicle fueled with millions of pounds of hazardous propellant. With this in mind, early EES designers saw such a passive/unpowered system as a must for last minute escapes. This and other design requirements had to be derived for an EES, and this section will take a look at the safety design requirements had to be derived for an EES, and this section will take a look at

  10. Escape of atmospheres and loss of water

    International Nuclear Information System (INIS)

    Hunten, D.M.; Donahue, T.M.; Walker, J.C.G.; Kasting, J.F.

    1989-01-01

    The properties and limitations of several loss processes for atmospheric gases are presented and discussed. They include thermal loss (Jeans and hydrodynamic); nonthermal loss (all processes involve charged particles); and impact erosion, including thermal escape from a molten body heated by rapid accretion. Hydrodynamic escape, or blowoff, is of particular interest because it offers the prospect of processing large quantities of gas and enriching the remainder in heavy elements and isotopes. In a second part, the water budgets and likely evolutionary histories of Venus, Earth and Mars are assessed. Although it is tempting to associate the great D/H enrichment on Venus with loss of a large initial endowment, a steady state with juvenile water (perhaps from comets) is equally probable

  11. Biomechanics of Tetrahymena escaping from dead ends

    Science.gov (United States)

    Ishikawa, Takuji; Kikuchi, Kenji

    2017-11-01

    Behaviors of swimming microorganisms in complex environments are important in understanding cells' distribution in nature and in industries. Although cell's swimming and spreading in an infinite fluid has been intensively investigated, that in a narrow region bounded by walls is still unclear. Thus, in this study, we used Tetrahymena thermophila as a model microorganism, and experimentally investigated its behavior between flat plates with an angle. The results showed that the cells tended to escape from the narrow region, and the swimming velocity and the radius of curvature of the trajectories decreased as they swam narrower region. We then developed a computational model of swimming Tetrahymena. The results showed that the escaping behavior could be well explained by fluid mechanics. The obtained knowledge is useful in understanding cells' behaviors in complex environments, such as in porous media and in a granular matter. This research was supported by JSPS KAKENHI Grants, numbers 25000008 and 17H00853.

  12. Constraining Lyman continuum escape using Machine Learning

    Science.gov (United States)

    Giri, Sambit K.; Zackrisson, Erik; Binggeli, Christian; Pelckmans, Kristiaan; Cubo, Rubén; Mellema, Garrelt

    2018-05-01

    The James Webb Space Telescope (JWST) will observe the rest-frame ultraviolet/optical spectra of galaxies from the epoch of reionization (EoR) in unprecedented detail. While escaping into the intergalactic medium, hydrogen-ionizing (Lyman continuum; LyC) photons from the galaxies will contribute to the bluer end of the UV slope and make nebular emission lines less prominent. We present a method to constrain leakage of the LyC photons using the spectra of high redshift (z >~ 6) galaxies. We simulate JWST/NIRSpec observations of galaxies at z =6-9 by matching the fluxes of galaxies observed in the Frontier Fields observations of galaxy cluster MACS-J0416. Our method predicts the escape fraction fesc with a mean absolute error Δfesc ~ 0.14. The method also predicts the redshifts of the galaxies with an error .

  13. Measurement of the resonance escape probability

    International Nuclear Information System (INIS)

    Anthony, J.P.; Bacher, P.; Lheureux, L.; Moreau, J.; Schmitt, A.P.

    1957-01-01

    The average cadmium ratio in natural uranium rods has been measured, using equal diameter natural uranium disks. These values correlated with independent measurements of the lattice buckling, enabled us to calculate values of the resonance escape probability for the G1 reactor with one or the other of two definitions. Measurements were performed on 26 mm and 32 mm rods, giving the following values for the resonance escape probability p: 0.8976 ± 0.005 and 0.912 ± 0.006 (d. 26 mm), 0.8627 ± 0.009 and 0.884 ± 0.01 (d. 32 mm). The influence of either definition on the lattice parameters is discussed, leading to values of the effective integral. Similar experiments have been performed with thorium rods. (author) [fr

  14. Asymmetric Effects on Escape Rates of Bistable System

    International Nuclear Information System (INIS)

    Wang Canjun; Mei Dongcheng; Dai Zucheng

    2011-01-01

    The asymmetric effects on the escape rates from the stable states x ± in the bistable system are analyzed. The results indicate that the multiplicative noise and the additive noise always enhance the particle escape from stable states x ± of bistable. However, the asymmetric parameter r enhances the particle escape from stable state x + , and holds back the particle escape from stable state x - . (general)

  15. Escape and transmission probabilities in cylindrical geometry

    International Nuclear Information System (INIS)

    Bjerke, M.A.

    1980-01-01

    An improved technique for the generation of escape and transmission probabilities in cylindrical geometry was applied to the existing resonance cross section processing code ROLAIDS. The algorithm of Hwang and Toppel, [ANL-FRA-TM-118] (with modifications) was employed. The probabilities generated were found to be as accurate as those given by the method previously applied in ROLAIDS, while requiring much less computer core storage and CPU time

  16. Xenon Fractionation and Archean Hydrogen Escape

    Science.gov (United States)

    Zahnle, K. J.

    2015-01-01

    Xenon is the heaviest gas found in significant quantities in natural planetary atmospheres. It would seem the least likely to escape. Yet there is more evidence for xenon escape from Earth than for any element other than helium and perhaps neon. The most straightforward evidence is that most of the radiogenic Xe from the decay of (129)I (half-life 15.7 Myr) and (244)Pu (half-life 81 Myr) that is Earth's birthright is missing. The missing xenon is often attributed to the impact erosion of early atmospheres of Earth and its ancestors. It is obvious that if most of the radiogenic xenon were driven off by impacts, most of the rest of the atmophiles fared the same fate. The other line of evidence is in the nonradiogenic isotopes of xenon and its silent partner, krypton. Atmospheric xenon is strongly mass fractionated (at about 4% per amu) compared to any known solar system source (Figure 1). This is in stark contrast to krypton, which may not be fractionated at all: atmospheric Kr is slightly heavier than solar Kr (at about 0.5% per amu), but it is the same as in carbonaceous chondrites. Nonradiogenic xenon is also under abundant relative to krypton (the so-called "missing xenon" problem). Together these observations imply that xenon has been subject to fractionating escape and krypton not.

  17. Escape probabilities for fluorescent x-rays

    International Nuclear Information System (INIS)

    Dance, D.R.; Day, G.J.

    1985-01-01

    Computation of the energy absorption efficiency of an x-ray photon detector involves consideration of the histories of the secondary particles produced in any initial or secondary interaction which may occur within the detector. In particular, the K or higher shell fluorescent x-rays which may be emitted following a photoelectric interaction can carry away a large fraction of the energy of the incident photon, especially if this energy is just above an absorption edge. The effects of such photons cannot be ignored and a correction term, depending upon the probability that the fluorescent x-rays will escape from the detector, must be applied to the energy absorption efficiency. For detectors such as x-ray intensifying screens, it has been usual to calculate this probability by numerical integration. In this note analytic expressions are derived for the escape probability of fluorescent photons from planar detectors in terms of exponential integral functions. Rational approximations for these functions are readily available and these analytic expressions therefore facilitate the computation of photon absorption efficiencies. A table is presented which should obviate the need for calculating the escape probability for most cases of interest. (author)

  18. Apoptotic pathways as regulators of recombination

    International Nuclear Information System (INIS)

    Gauny, S.S.; Kronenberg, A.; Liu, W.-C.

    2003-01-01

    Apoptosis, or programmed cell death (PCD), is a fundamental process that protects organismal integrity. In earlier work, we demonstrated that over-expression of either of two anti-apoptotic members of the BCL-2 family (BCL-2 or BCL-X L could elevate the frequency of radiation-induced mutations at the autosomal TK1 locus in human TK6 lymphoblasts that express wild-type TP53. Ectopic expression of BCL-X L also elevated the frequencies of double-strand break-induced gene conversion. The purpose of this study is to determine if BCL-2 family proteins promote radiation mutagenesis indirectly through their suppression of PCD, or whether the 'pro-mutagenic' function of these proteins can be separated from their anti-apoptotic function. We developed stable transfectants of TK6 cells that express a mutated form of BCL-X L with a single amino acid substitution in the BH1 domain that is known to interfere with the ability to suppress PCD (BCL-X L gly159ala). We also developed stable transfectants of TK6 cells that express a dominant negative caspase-9 that suppresses PCD. The results to date indicate that the mutated form of BCL-X L (gly159ala) does not suppress x-ray-induced PCD in TK6 cells, but it elevates radiation-induced TK1 mutant frequencies to the same extent as high level expression of wild-type BCL-X L . These data suggest that the anti-apoptotic function of BCL-2 family proteins is not required to elevate radiation mutagenesis. Separate experiments using TK6 cells that express a dominant negative caspase-9 indicate that this protein inhibits x-ray-induced PCD but TK1 mutant frequencies are not elevated. Taken together, the results suggest there is a separate function of BCL-2 family proteins that elevates radiation-induced mutagenesis independent of the well-known anti-apoptotic effect of these proteins of importance in human carcinogenesis

  19. Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.

    Directory of Open Access Journals (Sweden)

    Emanuele Bernardinelli

    Full Text Available Lipoyl(Octanoyl Transferase 2 (LIPT2 is a protein involved in the post-translational modification of key energy metabolism enzymes in humans. Defects of lipoic acid synthesis and transfer start to emerge as causes of fatal or severe early-onset disease. We show that the first 31 amino acids of the N-terminus of LIPT2 represent a mitochondrial targeting sequence and inhibition of the transit of LIPT2 to the mitochondrion results in apoptotic cell death associated with activation of the apoptotic volume decrease (AVD current in normotonic conditions, as well as over-activation of the swelling-activated chloride current (IClswell, mitochondrial membrane potential collapse, caspase-3 cleavage and nuclear DNA fragmentation. The findings presented here may help elucidate the molecular mechanisms underlying derangements of lipoic acid biosynthesis.

  20. Enzyme Informatics

    Science.gov (United States)

    Alderson, Rosanna G.; Ferrari, Luna De; Mavridis, Lazaros; McDonagh, James L.; Mitchell, John B. O.; Nath, Neetika

    2012-01-01

    Over the last 50 years, sequencing, structural biology and bioinformatics have completely revolutionised biomolecular science, with millions of sequences and tens of thousands of three dimensional structures becoming available. The bioinformatics of enzymes is well served by, mostly free, online databases. BRENDA describes the chemistry, substrate specificity, kinetics, preparation and biological sources of enzymes, while KEGG is valuable for understanding enzymes and metabolic pathways. EzCatDB, SFLD and MACiE are key repositories for data on the chemical mechanisms by which enzymes operate. At the current rate of genome sequencing and manual annotation, human curation will never finish the functional annotation of the ever-expanding list of known enzymes. Hence there is an increasing need for automated annotation, though it is not yet widespread for enzyme data. In contrast, functional ontologies such as the Gene Ontology already profit from automation. Despite our growing understanding of enzyme structure and dynamics, we are only beginning to be able to design novel enzymes. One can now begin to trace the functional evolution of enzymes using phylogenetics. The ability of enzymes to perform secondary functions, albeit relatively inefficiently, gives clues as to how enzyme function evolves. Substrate promiscuity in enzymes is one example of imperfect specificity in protein-ligand interactions. Similarly, most drugs bind to more than one protein target. This may sometimes result in helpful polypharmacology as a drug modulates plural targets, but also often leads to adverse side-effects. Many cheminformatics approaches can be used to model the interactions between druglike molecules and proteins in silico. We can even use quantum chemical techniques like DFT and QM/MM to compute the structural and energetic course of enzyme catalysed chemical reaction mechanisms, including a full description of bond making and breaking. PMID:23116471

  1. Risks incurred by hydrogen escaping from containers and conduits

    Energy Technology Data Exchange (ETDEWEB)

    Swain, M.R.; Grilliot, E.S. [Univ. of Miami, Coral Gables, FL (United States); Swain, M.N. [Analytical Technologies, Inc., Miami, FL (United States)

    1998-08-01

    This paper is a discussion of a method for hydrogen leak classification. Leaks are classified as; gas escapes into enclosed spaces, gas escapes into partially enclosed spaces (vented), and gas escapes into unenclosed spaces. Each of the three enclosure classifications is further divided into two subclasses; total volume of hydrogen escaped and flow rate of escaping hydrogen. A method to aid in risk assessment determination in partially enclosed spaces is proposed and verified for several enclosure geometries. Examples are discussed for additional enclosure geometries.

  2. The cost of the sword: escape performance in male swordtails.

    Directory of Open Access Journals (Sweden)

    Alex Baumgartner

    2011-01-01

    Full Text Available The handicap theory of sexual selection posits that male display traits that are favored in mate choice come at a significant cost to performance. We tested one facet of this hypothesis in the green swordtail (Xiphophorus helleri. In this species, the lower ray of male caudal fin is extended into a 'sword', which serves to attract potential mates. However, bearing a long sword may increase drag and thus compromise a male's ability to swim effectively. We tested escape performance in this species by eliciting C-start escape responses, an instinctive escape behavior, in males with various sword lengths. We then removed males' swords and retested escape performance. We found no relationship between escape performance and sword length and no effect of sword removal on escape performance. While having a large sword may attract a predator's attention, our results suggest that sword size does not compromise a male's escape performance.

  3. Transglutaminase 2 is needed for the formation of an efficient phagocyte portal in macrophages engulfing apoptotic cells.

    Science.gov (United States)

    Tóth, Beáta; Garabuczi, Eva; Sarang, Zsolt; Vereb, György; Vámosi, György; Aeschlimann, Daniel; Blaskó, Bernadett; Bécsi, Bálint; Erdõdi, Ferenc; Lacy-Hulbert, Adam; Zhang, Ailiang; Falasca, Laura; Birge, Raymond B; Balajthy, Zoltán; Melino, Gerry; Fésüs, László; Szondy, Zsuzsa

    2009-02-15

    Transglutaminase 2 (TG2), a protein cross-linking enzyme with many additional biological functions, acts as coreceptor for integrin beta(3). We have previously shown that TG2(-/-) mice develop an age-dependent autoimmunity due to defective in vivo clearance of apoptotic cells. Here we report that TG2 on the cell surface and in guanine nucleotide-bound form promotes phagocytosis. Besides being a binding partner for integrin beta(3), a receptor known to mediate the uptake of apoptotic cells via activating Rac1, we also show that TG2 binds MFG-E8 (milk fat globulin EGF factor 8), a protein known to bridge integrin beta(3) to apoptotic cells. Finally, we report that in wild-type macrophages one or two engulfing portals are formed during phagocytosis of apoptotic cells that are characterized by accumulation of integrin beta(3) and Rac1. In the absence of TG2, integrin beta(3) cannot properly recognize the apoptotic cells, is not accumulated in the phagocytic cup, and its signaling is impaired. As a result, the formation of the engulfing portals, as well as the portals formed, is much less efficient. We propose that TG2 has a novel function to stabilize efficient phagocytic portals.

  4. Strange culinary encounters::stranger fetichism in "Jamie's Italian escape" and "Gordon's great escape"

    OpenAIRE

    Leer, Jonatan; Kjær, Katrine Meldgaard

    2015-01-01

    In this article, we examine the ways in which the encountering of 'other' food cultures is played out in the two travelogue cooking shows Gordon's Great Escape and Jamie's Italian Escape. We investigate how the two protagonist chefs Jamie Oliver and Gordon Ramsay imagine, meet and evaluate the ‘other’ food cultures in these programs, paying special attention to how the encounter with the local Indian and Italian is imagined to be a gateway to an authentic and/or primitive experience. Our main...

  5. Room escape at class: Escape games activities to facilitate the motivation and learning in computer science

    Directory of Open Access Journals (Sweden)

    Carlos Borrego

    2017-06-01

    Full Text Available Real-life room-escape games are ludic activities in which participants enter a room in order to get out of it only after solving some riddles. In this paper, we explain a Room Escape teaching experience developed in the Engineering School at Universitat Autònoma de Barcelona. The goal of this activity is to increase student’s motivation and to improve their learning on two courses of the second year in the Computer Engineering degree: Computer Networksand Information and Security.

  6. Room escape at class: escape games activities to facilitate the motivation and learning in computer science

    OpenAIRE

    Borrego, Carlos; Fernández, Cristina; Blanes, Ian; Robles, Sergi

    2017-01-01

    Real-life room-escape games are ludic activities in which participants enter a room in order to get out of it only after solving some riddles. In this paper, we explain a Room Escape teaching experience developed in the Engineering School at Universitat Autònoma de Barcelona. The goal of this activity is to increase student’s motivation and to improve their learning on two courses of the second year in the Computer Engineering degree: Computer Networksand Information and Security Peer Revi...

  7. Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis

    Directory of Open Access Journals (Sweden)

    Nakamura Shinichiro

    2011-01-01

    Full Text Available Abstract Background Runt-related transcription factor 3 (RUNX3 is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC. Methods RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results RUNX3 protein expression was frequently inactivated in the HCC cell lines (91% and tissues (90%. RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.

  8. Arduino adventures escape from Gemini station

    CERN Document Server

    Kelly, James Floyd

    2013-01-01

    Arduino Adventures: Escape from Gemini Station provides a fun introduction to the Arduino microcontroller by putting you (the reader) into the action of a science fiction adventure story.  You'll find yourself following along as Cade and Elle explore Gemini Station-an orbiting museum dedicated to preserving and sharing technology throughout the centuries. Trouble ensues. The station is evacuated, including Cade and Elle's class that was visiting the station on a field trip. Cade and Elle don't make it aboard their shuttle and are trapped on the station along with a friendly artificial intellig

  9. Effects of dietary supplementation of multi-enzyme complex on the ...

    African Journals Online (AJOL)

    Jane

    2011-07-25

    Jul 25, 2011 ... and protein escape digestion, reach the midgut and undergo fermentation ... soybean broiler starter diet with an enzyme preparation containing a mixture .... due to the rapid food rate and the deficiency of the necessary innate ...

  10. The regulation of apoptotic cell death

    Directory of Open Access Journals (Sweden)

    Amarante-Mendes G.P.

    1999-01-01

    Full Text Available Apoptosis is a fundamental biological phenomenon in which the death of a cell is genetically and biochemically regulated. Different molecules are involved in the regulation of the apoptotic process. Death receptors, coupled to distinct members of the caspases as well as other adapter molecules, are involved in the initiation of the stress signals (The Indictment. Members of the Bcl-2 family control at the mitochondrial level the decision between life and death (The Judgement. The effector caspases are responsible for all morphological and biochemical changes related to apoptosis including the "eat-me" signals perceived by phagocytes and neighboring cells (The Execution. Finally, apoptosis would have little biological significance without the recognition and removal of the dying cells (The Burial.

  11. Mars atmospheric escape and evolution; interaction with the solar wind

    Science.gov (United States)

    Chassefière, Eric; Leblanc, François

    2004-09-01

    This tutorial deals with the question of atmospheric escape on Mars. After a brief introduction describing the general context of Mars escape studies, we will present in Section 2 a simplified theory of thermal escape, of both Jeans and hydrodynamic types. The phenomenon of hydrodynamic escape, still hypothetical and not proved to have ever existed on terrestrial planets, will be treated with the help of two well known examples: (i) the isotopic fractionation of xenon in Mars and Earth atmospheres, (ii) the paradox of missing oxygen in Venus atmosphere. In Section 3, a simplified approach of non-thermal escape will be developed, treating in a specific way the different kinds of escape (photochemical escape, ion sputtering, ion escape and ionospheric outflow). As a matter of illustration, some calculations of the relative contributions of these mechanisms, and of their time evolutions, will be given, and the magnitude of the total amount of atmosphere lost by non-thermal escape will be estimated. Section 4 will present the state of knowledge concerning the constraints derived from Mars isotopic geochemistry in terms of past escape and evolution. Finally, a few conclusions, which are more interrogations, will be proposed.

  12. Molecular Dications in Planetary Atmospheric Escape

    Directory of Open Access Journals (Sweden)

    Stefano Falcinelli

    2016-08-01

    Full Text Available Fundamental properties of multiply charged molecular ions, such as energetics, structure, stability, lifetime and fragmentation dynamics, are relevant to understand and model the behavior of gaseous plasmas as well as ionosphere and astrophysical environments. Experimental determinations of the Kinetic Energy Released (KER for ions originating from dissociations reactions, induced by Coulomb explosion of doubly charged molecular ions (molecular dications produced by double photoionization of CO2, N2O and C2H2 molecules of interest in planetary atmospheres, are reported. The KER measurement as a function of the ultraviolet (UV photon energy in the range of 28–65 eV was extracted from the electron-ion-ion coincidence spectra obtained by using tunable synchrotron radiation coupled with ion imaging techniques at the ELETTRA Synchrotron Light Laboratory Trieste, Italy. These experiments, coupled with a computational analysis based on a Monte Carlo trajectory simulation, allow assessing the probability of escape for simple ionic species in the upper atmosphere of Mars, Venus and Titan. The measured KER in the case of H+, C+, CH+, CH2+, N+, O+, CO+, N2+ and NO+ fragment ions range between 1.0 and 5.5 eV, being large enough to allow these ionic species to participate in the atmospheric escape from such planets into space. In the case of Mars, we suggest a possible explanation for the observed behavior of the O+ and CO22+ ion density profiles.

  13. Escape from viscosity : the kinematics and hydrodynamics of copepod foraging and escape swimming

    NARCIS (Netherlands)

    van Duren, LA; Videler, JJ

    Feeding and escape swimming in adult females of the calanoid copepod. Temora lopgicornis Muller were investigated and compared. Swimming velocities were calculated using a 3-D filming setup., Foraging velocities ranged between 2 and 6 min s(-1), while maximum velocities of up to 80 mm s(-1) were

  14. Titan's hydrodynamically escaping atmosphere: Escape rates and the structure of the exobase region

    Science.gov (United States)

    Strobel, Darrell F.

    2009-08-01

    In Strobel [Strobel, D.F., 2008. Icarus, 193, 588-594] a mass loss rate from Titan's upper atmosphere, ˜4.5×10 amus, was calculated for a single constituent, N 2 atmosphere by hydrodynamic escape as a high density, slow outward expansion driven principally by solar UV heating due to CH 4 absorption. It was estimated, but not proven, that the hydrodynamic mass loss is essentially CH 4 and H 2 escape. Here the individual conservation of momentum equations for the three major components of the upper atmosphere (N 2, CH 4, H 2) are solved in the low Mach number limit and compared with Cassini Ion Neutral Mass Spectrometer (INMS) measurements to demonstrate that light gases (CH 4, H 2) preferentially escape over the heavy gas (N 2). The lightest gas (H 2) escapes with a flux 99% of its limiting flux, whereas CH 4 is restricted to ⩾75% of its limiting flux because there is insufficient solar power to support escape at the limiting rate. The respective calculated H 2 and CH 4 escape rates are 9.2×10 and 1.7×10 s, for a total of ˜4.6×10 amus. From the calculated densities, mean free paths of N 2, CH 4, H 2, and macroscopic length scales, an extended region above the classic exobase is inferred where frequent collisions are still occurring and thermal heat conduction can deliver power to lift the escaping gas out of the gravitational potential well. In this region rapid acceleration of CH 4 outflow occurs. With the thermal structure of Titan's thermosphere inferred from INMS data by Müller-Wodarg et al. [Müller-Wodarg, I.C.F., Yelle, R.V., Cui, J., Waite Jr., J.H., 2008. J. Geophys. Res. 113, doi:10.1029/2007JE003033. E10005], in combination with calculated temperature profiles that include sputter induced plasma heating at the exobase, it is concluded that on average that the integrated, globally average, orbit-averaged, plasma heating rate during the Cassini epoch does not exceed ˜5×10 eVcms ( ˜0.0008 ergcms).

  15. Some Possible Cases of Escape Mimicry in Neotropical Butterflies.

    Science.gov (United States)

    Pinheiro, C E G; Freitas, A V L

    2014-10-01

    The possibility that escape or evasive mimicry evolved in butterflies and other prey insects in a similar fashion to classical Batesian and Müllerian mimicry has long been advanced in the literature. However, there is a general disagreement among lepidopterists and evolutionary biologists on whether or not escape mimicry exists, as well as in which mimicry rings this form of mimicry has evolved. Here, we review some purported cases of escape mimicry in Neotropical butterflies and suggest new mimicry rings involving several species of Archaeoprepona, Prepona, and Doxocopa (the "bright blue bands" ring) and species of Colobura and Hypna (the "creamy bands" ring) where the palatability of butterflies, their ability to escape predator attacks, geographic distribution, relative abundance, and co-occurrence in the same habitats strongly suggest that escape mimicry is involved. In addition, we also indicate other butterfly taxa whose similarities of coloration patterns could be due to escape mimicry and would constitute important case studies for future investigation.

  16. Multicolor fluorescence technique to detect apoptotic cells in advanced coronary atherosclerotic plaques

    Directory of Open Access Journals (Sweden)

    C Soldani

    2009-06-01

    . Their death may decrease the cell number in the lipid core and generate a possibly defective apoptotic clearance: the resulting release of matrix-degrading enzymes could contribute to weakening the fibrous cap and promote the plaque rupture with the risk of acute ischemic events, while increasing the thrombogenic pultaceous pool of the plaque core.

  17. The atmospheric escape at Mars: complementing the scenario

    Science.gov (United States)

    Lilensten, Jean; Simon, Cyril; Barthélémy, Mathieu; Thissen, Roland; Ehrenreich, David; Gronoff, Guillaume; Witasse, Olivier

    2013-04-01

    In the recent years, the presence of dications in the atmospheres of Mars, Venus, Earth and Titan has been modeled and assessed. These studies also suggested that these ions could participate to the escape of the planetary atmospheres because a large fraction of them is unstable and highly ener- getic. When they dissociate, their internal energy is transformed into kinetic energy which may be larger than the escape energy. This study assesses the impact of the doubly-charged ions in the escape of CO2-dominated planetary atmospheres and to compare it to the escape of thermal photo-ions.We solve a Boltzmann transport equation at daytime taking into account the dissociative states of CO++ for a simplified single constituent atmosphere of a 2 case-study planet. We compute the escape of fast ions using a Beer-Lambert approach. We study three test-cases. On a Mars-analog planet in today's conditions, we retrieve the measured electron escape flux. When comparing the two mechanisms (i.e. excluding solar wind effects, sputtering ...), the escape due to the fast ions issuing from the dissociation of dications may account for up to 6% of the total and the escape of thermal ions for the remaining. We show that these two mechanisms cannot explain the escape of the atmosphere since the magnetic field vanished but complement the other processes and allow writing the scenario of the Mars escape. We show that the atmosphere of a Mars analog planet would empty in another giga years and a half. At Venus orbit, the contribution of the dications in the escape rate is negligible.When simulating the hot Jupiter HD209458b, the two processes cannot explain the measured escape flux of C+.

  18. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells

    Science.gov (United States)

    Rivera, Mariela; Ramos, Yanilda; Rodríguez-Valentín, Madeline; López-Acevedo, Sheila; Cubano, Luis A.; Zou, Jin; Zhang, Qiang; Wang, Guangdi

    2017-01-01

    Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12) and Poly (ADP-ribose) polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses. PMID:28628644

  19. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Mariela Rivera

    Full Text Available Curcumin, an extract from the turmeric rhizome (Curcuma longa, is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12 and Poly (ADP-ribose polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses.

  20. Non-thermal escape of molecular hydrogen from Mars

    Science.gov (United States)

    Gacesa, M.; Zhang, P.; Kharchenko, V.

    2012-05-01

    We present a detailed theoretical analysis of non-thermal escape of molecular hydrogen from Mars induced by collisions with hot atomic oxygen from the Martian corona. To accurately describe the energy transfer in O + H2(v, j) collisions, we performed extensive quantum-mechanical calculations of state-to-state elastic, inelastic, and reactive cross sections. The escape flux of H2 molecules was evaluated using a simplified 1D column model of the Martian atmosphere with realistic densities of atmospheric gases and hot oxygen production rates for low solar activity conditions. An average intensity of the non-thermal escape flux of H2 of 1.9 × 105 cm-2s-1 was obtained considering energetic O atoms produced in dissociative recombinations of O2+ ions. Predicted ro-vibrational distribution of the escaping H2 was found to contain a significant fraction of higher rotational states. While the non-thermal escape rate was found to be lower than Jeans rate for H2 molecules, the non-thermal escape rates of HD and D2 are significantly higher than their respective Jeans rates. The accurate evaluation of the collisional escape flux of H2 and its isotopes is important for understanding non-thermal escape of molecules from Mars, as well as for the formation of hot H2 Martian corona. The described molecular ejection mechanism is general and expected to contribute to atmospheric escape of H2 and other light molecules from planets, satellites, and exoplanetary bodies.

  1. Significance of apoptotic cell death after γ-irradiation

    International Nuclear Information System (INIS)

    Wu, H.G.; Kim, I.H.; Ha, S.W.; Park, C.I.

    2003-01-01

    Full text: The objectives of this study are to investigate the significance of apoptotic death compared to total cell death after γ-ray irradiation in human Hand N cancer cell lines and to find out correlation between apoptosis and radiation sensitivity. Materials and Method: Head and neck cancer cell lines (PCI-1, PCI-13, and SNU-1066), leukemia cell line (CCRF-CEM), and fibroblast cell line (LM217) as a normal control were used for this study. Cells were irradiated using Cs-137 animal experiment irradiator. Total cell death was measured by clonogenic assay. Annexin-V staining was used to detect the fraction of apoptotic death. The resulting data was analyzed with two parameters, apoptotic index (AI) and apoptotic fraction(AF). AI is ratio of apoptotic cells to total cells, and AF is ration of apoptotic cell death to mutant frequencytion ex(Number of apoptotic cells) / (Number of total cells counted) AF = {(AI) / (1-survival fraction)} x 100 (%) Results. Surviving fraction at 2 Gy (SF2) were 0.741, 0.544, 0.313, 0.302, and 0.100 for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217 cell lines, respectively. Apoptosis was detected in all cell lines. Apoptotic index reached peak value at 72 hours after irradiation in head and neck cancer cell lines, and that was at 24 hours in CCRF-CEM and LM217. Total cell death increased exponentially with increasing radiation dose from 0 Gy to 8 Gy, but the change was minimal in apoptotic index (Fig. 1.). Apoptotic fractions at 2 Gy were 46%, 48%, 46%, 24%, and 19% and at 6 Gy were 20%, 33%, 35%, 17%, and 20% for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217, respectively. The radioresistant cell lines showed more higher apoptotic fraction at 2 Gy (Table 1.), but there was not such correlation at 6 Gy. Conclusion: All cell lines used in this study showed apoptosis after irradiation, but time course of apoptosis was different from that of leukemia cell line and normal fibroblast cell line. Reproductive cell death was more important

  2. Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes.

    Directory of Open Access Journals (Sweden)

    Kristy Zera

    Full Text Available Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism and energy production in the brain. In developed countries, thiamine deficiency (TD is most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation and excitotoxicity. These biochemical lesions result in apoptotic cell death in both neurons and astrocytes. Comparable histological injuries in patients with hypoxia/ischemia and TD have been described in the thalamus and mammillary bodies, suggesting a congruency between the cellular responses to these stresses. Consistent with hypoxia/ischemia, TD stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α under physiological oxygen levels. However, the role of TD-induced HIF-1α in neurological injury is currently unknown. Using Western blot analysis and RT-PCR, we have demonstrated that TD induces HIF-1α expression and activity in primary mouse astrocytes. We observed a time-dependent increase in mRNA and protein expression of the pro-apoptotic and pro-inflammatory HIF-1α target genes MCP1, BNIP3, Nix and Noxa during TD. We also observed apoptotic cell death in TD as demonstrated by PI/Annexin V staining, TUNEL assay, and Cell Death ELISA. Pharmacological inhibition of HIF-1α activity using YC1 and thiamine repletion both reduced expression of pro-apoptotic HIF-1α target genes and apoptotic cell death in TD. These results demonstrate that induction of HIF-1α mediated transcriptional up-regulation of pro-apoptotic/inflammatory signaling contributes to astrocyte cell death during thiamine deficiency.

  3. Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

    Science.gov (United States)

    Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

    2018-03-01

    Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

  4. TAM receptors in apoptotic cell clearance, autoimmunity, and cancer.

    Science.gov (United States)

    Nguyen, Khanh-Quynh; Tsou, Wen-I; Kotenko, Sergei; Birge, Raymond B

    2013-08-01

    Receptor tyrosine kinases, Tyro-3, Axl and Mer, collectively designated as TAM, are involved in the clearance of apoptotic cells. TAM ligands, Gas6 and Protein S, bind to the surfaces of apoptotic cells, and at the same time, interact directly with TAM expressed on phagocytes, impacting the engulfment and clearance of apoptotic cells and debris. The well-tuned and balanced actions of TAM may affect a variety of human pathologies including autoimmunity, retinal degeneration, and cancer. This article emphasizes some of the emerging findings and mechanistic insights into TAM functions that are clinically relevant and possibly therapeutically targeted.

  5. 30 CFR 75.382 - Mechanical escape facilities.

    Science.gov (United States)

    2010-07-01

    ... with brakes that can stop the fully loaded platform, cage, or other device. (c) Mechanical escape facilities, including automatic elevators, shall be examined weekly. The weekly examination of this equipment... cages, platforms, or elevators. (e) Mechanical escape facilities shall have rated capacities consistent...

  6. Buying to blunt negative feelings : Materialistic escape from the self

    NARCIS (Netherlands)

    Donnelly, Grant E.; Ksendzova, Masha; Howell, Ryan T.; Vohs, Kathleen D.; Baumeister, Roy F.

    2016-01-01

    We propose that escape theory, which describes how individuals seek to free themselves from aversive states of self-awareness, helps explain key patterns of materialistic people's behavior. As predicted by escape theory, materialistic individuals may feel dissatisfied with their standard of living,

  7. Teachers Offering Healthy Escape Options for Teenagers in Pain

    Science.gov (United States)

    Kaywell, Joan F.

    2005-01-01

    "[T]wenty-five percent of today's teenagers have inordinate emotional baggage beyond the normal angst of adolescence." This burden can lead to unhealthy escapes, including substance abuse, sexual activity, violence, eating disorders, and suicide. One healthy escape, however, lies in books, where students can read about teenagers living in painful…

  8. Escape of protists in predator-generated feeding currents

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2002-01-01

    The ciliate Strobilidium sp. and 2 flagellates, Chrysochromulina simplex and Gymnodinium sp., were exposed to predator-generated feeding currents, and their escape responses were quantified using 2- and 3-dimensional video techniques. All 3 studied organisms responded by escaping at a defined dis...

  9. faloabi@uniben.edu Antiproliferative and Pro-apoptotic activities

    African Journals Online (AJOL)

    MICHAEL HORSFALL

    Keyword: Persea americana, antiproliferative activity, apoptotic effect, flow ... of the stem bark of Persea americana in MCF-7 cell line by flow cytometer. .... of an electric milling machine. ... Flow Cytometric Measurement Of Cell Proliferation:.

  10. Immune escape strategies of malaria parasites

    Directory of Open Access Journals (Sweden)

    Pollyanna Stephanie Gomes

    2016-10-01

    Full Text Available Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

  11. Nonthermal atmospheric escape from Mars and Titan

    International Nuclear Information System (INIS)

    Lammer, H.; Bauer, S.J.

    1991-01-01

    Energy flux spectra and particle concentrations of the hot O and N coronae from Mars and Titan, respectively, resulting primarily from dissociative recombination of molecular ions, have been calculated by means of a Monte Carlo method. The calculated energy flux spectra lead to an escape flux null esc ∼ 6 x 10 6 cm -2 s -1 for Mars and null esc ∼ 2 x 10 6 cm -2 s -1 for Titan, corresponding to a mass loss of about 0.14 kg/s for Mars and about 0.3 kg/s for Titan. (The contribution of electron impact ionization on N 2 amounts to only about 25% of Titan's mass loss.) Mass loss via solar and magnetospheric wind is also estimated using newly calculated mass loading limits. The mass loss via ion pickup from the extended hot atom corona for Mars amounts to about 0.25 kg/s (O + ) and for Titan to about 50 g/s (N 2 + or H 2 CN + ). Thus, the total mass loss rate from Mars and Titan is about the same, i.e., 0.4 kg/s

  12. Leishmania Hijacks Myeloid Cells for Immune Escape

    Directory of Open Access Journals (Sweden)

    María Martínez-López

    2018-05-01

    Full Text Available Protozoan parasites of the Leishmania genus are the causative agents of leishmaniasis, a group of neglected tropical diseases whose clinical manifestations vary depending on the infectious Leishmania species but also on host factors. Recognition of the parasite by host myeloid immune cells is a key to trigger an effective Leishmania-specific immunity. However, the parasite is able to persist in host myeloid cells by evading, delaying and manipulating host immunity in order to escape host resistance and ensure its transmission. Neutrophils are first in infiltrating infection sites and could act either favoring or protecting against infection, depending on factors such as the genetic background of the host or the parasite species. Macrophages are the main host cells where the parasites grow and divide. However, macrophages are also the main effector population involved in parasite clearance. Parasite elimination by macrophages requires the priming and development of an effector Th1 adaptive immunity driven by specific subtypes of dendritic cells. Herein, we will provide a comprehensive outline of how myeloid cells regulate innate and adaptive immunity against Leishmania, and the mechanisms used by the parasites to promote their evasion and sabotage. Understanding the interactions between Leishmania and the host myeloid cells may lead to the development of new therapeutic approaches and improved vaccination to leishmaniases, an important worldwide health problem in which current therapeutic or preventive approaches are limited.

  13. Escape route simulator utilizing augmented reality

    Energy Technology Data Exchange (ETDEWEB)

    Mattos, Karen Salazar Ribeiro de; Mó, Antônio Carlos de A.; Santo, André Cotelli do E.; Silva, Marcio Henrique, E-mail: karensalazar.1190@gmail.com [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Centro Universitário Carioca (UniCarioca), Rio de Janeiro, RJ (Brazil)

    2017-07-01

    Due to increasing demand and interest in the interaction of technology platforms and integration of different types of systems and technologies, some tools are already providing practical ways to develop integrated applications. The tools explored by this article are Unity, a platform for game development, and Vuforia, an SDK, software development kit, for augmented reality creation. The coalition proposal of these resources is to create an intuitive escape route that can be used for the evacuation of buildings or open spaces in view of imminent danger, such as radiation leakage, and that can be accessed from a target available at the institution. It has also the intention of simulating situations that involve training of personnel in order to obtain methods that allow to save financial resources, and even to avoid that those who are involved are exposed to risks unnecessarily. The simulator is expected to help design, test, and improve ways to maintain the physical integrity of the facility and provide end users with a better sense of immersion and attractiveness. (author)

  14. Escape route simulator utilizing augmented reality

    International Nuclear Information System (INIS)

    Mattos, Karen Salazar Ribeiro de; Mó, Antônio Carlos de A.; Santo, André Cotelli do E.; Silva, Marcio Henrique

    2017-01-01

    Due to increasing demand and interest in the interaction of technology platforms and integration of different types of systems and technologies, some tools are already providing practical ways to develop integrated applications. The tools explored by this article are Unity, a platform for game development, and Vuforia, an SDK, software development kit, for augmented reality creation. The coalition proposal of these resources is to create an intuitive escape route that can be used for the evacuation of buildings or open spaces in view of imminent danger, such as radiation leakage, and that can be accessed from a target available at the institution. It has also the intention of simulating situations that involve training of personnel in order to obtain methods that allow to save financial resources, and even to avoid that those who are involved are exposed to risks unnecessarily. The simulator is expected to help design, test, and improve ways to maintain the physical integrity of the facility and provide end users with a better sense of immersion and attractiveness. (author)

  15. Dications and thermal ions in planetary atmospheric escape

    Science.gov (United States)

    Lilensten, J.; Simon Wedlund, C.; Barthélémy, M.; Thissen, R.; Ehrenreich, D.; Gronoff, G.; Witasse, O.

    2013-01-01

    In the recent years, the presence of dications in the atmospheres of Mars, Venus, Earth and Titan has been modeled and assessed. These studies also suggested that these ions could participate to the escape of the planetary atmospheres because a large fraction of them is unstable and highly energetic. When they dissociate, their internal energy is transformed into kinetic energy which may be larger than the escape energy. The goal of this study is to assess the impact of the doubly-charged ions in the escape of CO2-dominated planetary atmospheres and to compare it to the escape of thermal photo-ions. We solve a Boltzmann transport equation at daytime taking into account the dissociative states of CO2++ for a simplified single constituent atmosphere of a case-study planet. We compute the escape of fast ions using a Beer-Lambert approach. We study three test-cases. On a Mars-analog planet in today's conditions, we retrieve the measured electron escape flux. When comparing the two mechanisms (i.e. excluding solar wind effects, sputtering, etc.), the escape due to the fast ions issuing from the dissociation of dications may account for up to 6% of the total and the escape of thermal ions for the remaining. We show that these two mechanisms cannot explain the escape of the atmosphere since the magnetic field vanished and even contribute only marginally to this loss. We show that with these two mechanisms, the atmosphere of a Mars analog planet would empty in another giga years and a half. At Venus orbit, the contribution of the dications in the escape rate is negligible. When simulating the hot Jupiter HD 209458 b, the two processes cannot explain the measured escape flux of C+. This study shows that the dications may constitute a source of the escape of planetary atmospheres which had not been taken into account until now. This source, although marginal, is not negligible. The influence of the photoionization is of course large, but cannot explain alone the loss of Mars

  16. Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis

    Directory of Open Access Journals (Sweden)

    Philippe Saas

    2017-10-01

    Full Text Available Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft-versus-host disease. However, whether early-stage apoptotic cell infusion can be used to treat ongoing inflammatory disorders has not been reported extensively. Recently, we have provided evidence that early-stage apoptotic cell infusion is able to control, at least transiently, ongoing collagen-induced arthritis. This beneficial therapeutic effect is associated with the modulation of antigen-presenting cell functions mainly of macrophages and plasmacytoid dendritic cells, as well as the induction of collagen-specific regulatory CD4+ T cells (Treg. Furthermore, the efficacy of this approach is not altered by the association with two standard treatments of rheumatoid arthritis (RA, methotrexate and tumor necrosis factor (TNF inhibition. Here, in the light of these observations and recent data of the literature, we discuss the mechanisms of early-stage apoptotic cell infusion and how this therapeutic approach can be transposed to patients with RA.

  17. A New Paradigm for Evaluating Avoidance/Escape Motivation.

    Science.gov (United States)

    Tsutsui-Kimura, Iku; Bouchekioua, Youcef; Mimura, Masaru; Tanaka, Kenji F

    2017-07-01

    Organisms have evolved to approach pleasurable opportunities and to avoid or escape from aversive experiences. These 2 distinct motivations are referred to as approach and avoidance/escape motivations and are both considered vital for survival. Despite several recent advances in understanding the neurobiology of motivation, most studies addressed approach but not avoidance/escape motivation. Here we develop a new experimental paradigm to quantify avoidance/escape motivation and examine the pharmacological validity. We set up an avoidance variable ratio 5 task in which mice were required to press a lever for variable times to avoid an upcoming aversive stimulus (foot shock) or to escape the ongoing aversive event if they failed to avoid it. We i.p. injected ketamine (0, 1, or 5 mg/kg) or buspirone (0, 5, or 10 mg/kg) 20 or 30 minutes before the behavioral task to see if ketamine enhanced avoidance/escape behavior and buspirone diminished it as previously reported. We found that the performance on the avoidance variable ratio 5 task was sensitive to the intensity of the aversive stimulus. Treatment with ketamine increased while that with buspirone decreased the probability of avoidance from an aversive stimulus in the variable ratio 5 task, being consistent with previous reports. Our new paradigm will prove useful for quantifying avoidance/escape motivation and will contribute to a more comprehensive understanding of motivation. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  18. MAVEN Pickup Ion Constraints on Mars Neutral Escape

    Science.gov (United States)

    Rahmati, A.; Larson, D. E.; Cravens, T.; Lillis, R. J.; Dunn, P.; Halekas, J. S.; McFadden, J. P.; Mitchell, D. L.; Thiemann, E.; Connerney, J. E. P.; DiBraccio, G. A.; Espley, J. R.; Eparvier, F. G.

    2017-12-01

    Mars is currently losing its atmosphere mainly due to the escape of neutral hydrogen and oxygen. Directly measuring the rate of escaping neutrals is difficult, because the neutral density in the Mars exosphere is dominated, up to several Martian radii, by atoms that are gravitationally bound to the planet. Neutral atoms in the Martian exosphere, however, can get ionized, picked up, and accelerated by the solar wind motional electric field and energized to energies high enough for particle detectors to measure them. The MAVEN SEP instrument detects O+ pickup ions that are created at altitudes where the escaping part of the exosphere is dominant. Fluxes of these ions reflect neutral densities in the distant exosphere of Mars, allowing us to constrain neutral oxygen escape rates. The MAVEN SWIA and STATIC instruments measure pickup H+ and O+ created closer to Mars; comparisons of these data with models can be used to constrain exospheric hot O and thermal H densities and escape rates. In this work, pickup ion measurements from SEP, SWIA, and STATIC, taken during the first 3 Earth years of the MAVEN mission, are compared to the outputs of a pickup ion model to constrain the variability of neutral escape at Mars. The model is based on data from six MAVEN instruments, namely, MAG providing magnetic field used in calculating pickup ion trajectories, SWIA providing solar wind velocity as well as 3D pickup H+ and O+ spectra, SWEA providing solar wind electron spectrum used in electron impact ionization rate calculations, SEP providing pickup O+ spectra, STATIC providing mass resolved 3D pickup H+ and O+ spectra, and EUVM providing solar EUV spectra used in photoionization rate calculations. A variability of less than a factor of two is observed in hot oxygen escape rates, whereas thermal escape of hydrogen varies by an order of magnitude with Mars season. This hydrogen escape variability challenges our understanding of the H cycle at Mars, but is consistent with other

  19. Surface code—biophysical signals for apoptotic cell clearance

    International Nuclear Information System (INIS)

    Biermann, Mona; Maueröder, Christian; Brauner, Jan M; Chaurio, Ricardo; Herrmann, Martin; Muñoz, Luis E; Janko, Christina

    2013-01-01

    Apoptotic cell death and the clearance of dying cells play an important and physiological role in embryonic development and normal tissue turnover. In contrast to necrosis, apoptosis proceeds in an anti-inflammatory manner. It is orchestrated by the timed release and/or exposure of so-called ‘find-me’, ‘eat me’ and ‘tolerate me’ signals. Mononuclear phagocytes are attracted by various ‘find-me’ signals, including proteins, nucleotides, and phospholipids released by the dying cell, whereas the involvement of granulocytes is prevented via ‘stay away’ signals. The exposure of anionic phospholipids like phosphatidylserine (PS) by apoptotic cells on the outer leaflet of the plasma membrane is one of the main ‘eat me’ signals. PS is recognized by a number of innate receptors as well as by soluble bridging molecules on the surface of phagocytes. Importantly, phagocytes are able to discriminate between viable and apoptotic cells both exposing PS. Due to cytoskeleton remodeling PS has a higher lateral mobility on the surfaces of apoptotic cells thereby promoting receptor clustering on the phagocyte. PS not only plays an important role in the engulfment process, but also acts as ‘tolerate me’ signal inducing the release of anti-inflammatory cytokines by phagocytes. An efficient and fast clearance of apoptotic cells is required to prevent secondary necrosis and leakage of intracellular danger signals into the surrounding tissue. Failure or prolongation of the clearance process leads to the release of intracellular antigens into the periphery provoking inflammation and development of systemic inflammatory autoimmune disease like systemic lupus erythematosus. Here we review the current findings concerning apoptosis-inducing pathways, important players of apoptotic cell recognition and clearance as well as the role of membrane remodeling in the engulfment of apoptotic cells by phagocytes. (paper)

  20. Curcumin induces differential expression of cytoprotective enzymes but similar apoptotic responses in fibroblasts and myofibroblasts

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Pennings, S.W.C.; Brouwer, K.M.; Mtaya-Mlangwa, M.; Mugonzibwa, E.A.; Kuijpers-Jagtman, A.M.; Hoff, J.W. Von den; Wagener, F.A.D.T.G.

    2015-01-01

    Excessive extracellular matrix (ECM) deposition and tissue contraction after injury can lead to esthetic and functional problems. Fibroblasts and myofibroblasts activated by transforming growth factor (TGF)-beta1 play a key role in these processes. The persistence of (myo)fibroblasts and their

  1. A Novel Non-Apoptotic Role of Procaspase-3 in the Regulation of Mitochondrial Biogenesis Activators.

    Science.gov (United States)

    Kim, Ji-Soo; Ha, Ji-Young; Yang, Sol-Ji; Son, Jin H

    2018-01-01

    The executioner caspase-3 has been proposed as a pharmacological intervention target to preserve degenerating dopaminergic (DA) neurons because apoptotic mechanisms involving caspase-3 contribute, at least in part, to the loss of DA neurons in patients and experimental models of Parkinson's disease (PD). Here, we determined that genetic intervention of caspase-3 was sufficient to prevent cell death against oxidative stress (OS), accompanied by unexpected severe mitochondrial dysfunction. Specifically, as we expected, caspase-3-deficient DA neuronal cells were very significantly resistant to OS-induced cell death, while the activation of the initiator caspase-9 by OS was preserved. Moreover, detailed phenotypic characterization of caspase-3-deficient DA cells revealed severe mitochondrial dysfunction, including an accumulation of damaged mitochondria with a characteristic swollen structure and broken cristae, reduced membrane potential, increased levels of reactive oxygen species (ROS), and deficits in mitochondrial oxidative phosphorylation (OXPHOS) enzymes. Of great interest, we found that mitochondrial biogenesis was dramatically decreased in caspase-3-deficient DA cells, whereas their capability of mitophagy was normal. In accordance with this observation, caspase-3 gene knock down (KD) resulted in dramatically decreased expression of the key transcriptional activators of mitochondrial biogenesis, such as Tfam and Nrf-1, implicating a non-apoptotic role of procaspase-3 in mitochondrial biogenesis. Therefore, a prolonged anti-apoptotic intervention targeting caspase-3 should be considered with caution due to the potential adverse effects in mitochondria dynamics resulting from a novel potential functional role of procaspase-3 in mitochondrial biogenesis via regulating the expression of mitochondrial biogenesis activators. J. Cell. Biochem. 119: 347-357, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes.

    Science.gov (United States)

    Kloesch, Burkhard; Becker, Tatjana; Dietersdorfer, Elisabeth; Kiener, Hans; Steiner, Guenter

    2013-02-01

    It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA). MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and -7 was checked with specific antibodies. Curcumin effectively blocked IL-1β and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1β. Furthermore, curcumin inhibited activation of NF-κB and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis. The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Escape/Aggression Incidence in Sexually Abused Juvenile Delinquents.

    Science.gov (United States)

    Reich, John W.; Gutierres, Sara E.

    1979-01-01

    Reports a continuation of prior research testing a theoretical model which predicts that juveniles subjected to abuse will not become aggressive but will engage in escape and social avoidance behaviors. Analysis supported the hypothesis. (Author)

  4. 30 CFR 57.11053 - Escape and evacuation plans.

    Science.gov (United States)

    2010-07-01

    ... of principal air flow, location of escape routes and locations of existing telephones, primary fans... maps or diagrams shall be posted at all shaft stations and in underground shops, lunchrooms, and...

  5. Amplitude modulation control of escape from a potential well

    International Nuclear Information System (INIS)

    Chacón, R.; Martínez García-Hoz, A.; Miralles, J.J.; Martínez, P.J.

    2014-01-01

    We demonstrate the effectiveness of periodic amplitude modulations in controlling (suppressing and enhancing) escape from a potential well through the universal model of a damped Helmholtz oscillator subjected to an external periodic excitation (the escape-inducing excitation) whose amplitude is periodically modulated (the escape-controlling excitation). Analytical and numerical results show that this multiplicative control works reliably for different subharmonic resonances between the two periodic excitations involved, and that its effectiveness is comparable to those of different methods of additive control. Additionally, we demonstrate the robustness of the multiplicative control against the presence of low-intensity Gaussian noise. -- Highlights: •Multiplicative control of escape from a potential well has been demonstrated. •Theoretical predictions are obtained from a Melnikov analysis. •It has been shown the robustness of the multiplicative control against noise.

  6. Escape panels in trawls – a consistent management tool?

    DEFF Research Database (Denmark)

    Krag, Ludvig Ahm; Herrmann, Bent; Feekings, Jordan P.

    2016-01-01

    ), saithe (Pollachius virens), haddock (Melanogrammus aeglefinus), plaice (Pleuronectes platessa) and Norway lobster (Nephrops norvegicus). Thus the modification by fishers of certain gear properties not specified in the legislation can significantly influence the efficiency of an escape panel. We discuss...

  7. GREEN PEA GALAXIES REVEAL SECRETS OF Lyα ESCAPE

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Huan; Wang, Junxian [CAS Key Laboratory for Research in Galaxies and Cosmology, Department of Astronomy, University of Science and Technology of China (China); Malhotra, Sangeeta; Rhoads, James E. [Arizona State University, School of Earth and Space Exploration (United States); Gronke, Max; Dijkstra, Mark [Institute of Theoretical Astrophysics, University of Oslo (Norway); Jaskot, Anne [Smith College, Northampton, MA (United States); Zheng, Zhenya, E-mail: yanghuan@mail.ustc.edu.cn, E-mail: huan.y@asu.edu, E-mail: Sangeeta.Malhotra@asu.edu, E-mail: James.Rhoads@asu.edu [Pontificia Universidad Católica de Chile, Santiago (Chile)

    2016-04-01

    We analyze archival Lyα spectra of 12 “Green Pea” galaxies observed with the Hubble Space Telescope, model their Lyα profiles with radiative transfer models, and explore the dependence of the Lyα escape fraction on various properties. Green Pea galaxies are nearby compact starburst galaxies with [O iii] λ5007 equivalent widths (EWs) of hundreds of Å. All 12 Green Pea galaxies in our sample show Lyα lines in emission, with an Lyα EW distribution similar to high-redshift Lyα emitters. Combining the optical and UV spectra of Green Pea galaxies, we estimate their Lyα escape fractions and find correlations between Lyα escape fraction and kinematic features of Lyα profiles. The escape fraction of Lyα in these galaxies ranges from 1.4% to 67%. We also find that the Lyα escape fraction depends strongly on metallicity and moderately on dust extinction. We compare their high-quality Lyα profiles with single H i shell radiative transfer models and find that the Lyα escape fraction anticorrelates with the derived H i column densities. Single-shell models fit most Lyα profiles well, but not the ones with the highest escape fractions of Lyα. Our results suggest that low H i column density and low metallicity are essential for Lyα escape and make a galaxy an Lyα emitter.

  8. The influence of panic on the efficiency of escape

    Science.gov (United States)

    Shen, Jia-Quan; Wang, Xu-Wen; Jiang, Luo-Luo

    2018-02-01

    Whenever we (such as pedestrians) perceive a high density or imminent danger in a confined space, we tend to be panic, which can lead to severe injuries even in the absence of real dangers. Although it is difficult to measure panics in real conditions, we introduced a simple model to study the collective behaviors in condition of fire with dense smoke. Owing to blocking the sight with dense smoke, pedestrians in this condition have two strategies to escape: random-walking or walking along the wall. When the pedestrians are in moderate panic that mean the two types of behaviors are mixed(random-walking and walking along the wall). Our simulation results show that moderate panic, meaning that two escape strategies are mixed, reduces the escape time. In addition, the results indicate that moderate panic can improve the efficiency of escape, this theory also can be useful in a real escape situation. We hope that our research provides the theoretical understanding of underlying mechanisms of panic escape in the condition of poor sight.

  9. Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation[S

    Science.gov (United States)

    Haka, Abigail S.; Barbosa-Lorenzi, Valéria C.; Lee, Hyuek Jong; Falcone, Domenick J.; Hudis, Clifford A.; Dannenberg, Andrew J.

    2016-01-01

    Many types of apoptotic cells are phagocytosed and digested by macrophages. Adipocytes can be hundreds of times larger than macrophages, so they are too large to be digested by conventional phagocytic processes. The nature of the interaction between macrophages and apoptotic adipocytes has not been studied in detail. We describe a cellular process, termed exophagy, that is important for macrophage clearance of dead adipocytes and adipose tissue homeostasis. Using mouse models of obesity, human tissue, and a cell culture model, we show that macrophages form hydrolytic extracellular compartments at points of contact with dead adipocytes using local actin polymerization. These compartments are acidic and contain lysosomal enzymes delivered by exocytosis. Uptake and complete degradation of adipocyte fragments, which are released by extracellular hydrolysis, leads to macrophage foam cell formation. Exophagy-mediated foam cell formation is a highly efficient means by which macrophages internalize large amounts of lipid, which may ultimately overwhelm the metabolic capacity of the macrophage. This process provides a mechanism for degradation of objects, such as dead adipocytes, that are too large to be phagocytosed by macrophages. PMID:27044658

  10. Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Steffen Nyegaard

    Full Text Available Secretory phospholipase A2 (sPLA2 is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2's do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50-60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2.

  11. Glycine tomentella Hayata inhibits IL-1β and IL-6 production, inhibits MMP-9 activity, and enhances RAW264.7 macrophage clearance of apoptotic cells

    Directory of Open Access Journals (Sweden)

    Sun Yu-Shu

    2010-11-01

    Full Text Available Abstract Background To assess the effects of Glycine tomentella Hayata (GTH, a traditional herbal medicine for treatment of rheumatic diseases on the expression of the proinflammatory cytokines and on the clearance of apoptotic cells by macrophages. Methods RAW264.7 cells were cultured with lipopolysaccharide (LPS in the presence or absence of ethanol extract of GTH. The expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α, and inducible nitric oxide synthase (iNOS and transglutaminase 2 (TG2 were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA. Matrix metalloproteinase (MMP-2 and MMP-9 were assayed by gelatin zymography. For detecting uptake of apoptotic cells, RAW264.7 cells were cultured with carboxyfluorescein diacetate (CFDA-stained apoptotic cells and assayed by flow cytometry. Results The major components of GTH analyzed by high-performance liquid chromatography (HPLC chromatogram were daidzein (42.5%, epicatechin (28.8%, and naringin (9.4%. GTH treatment inhibited the expression of proinflammatory cytokines IL-1β, IL-6 and MMP-9 but did not affect the expression of TNF-α and iNOS. GTH significantly enhanced the expression of TG2 and the clearance of apoptotic cells by RAW264.7 macrophages. Conclusions GTH inhibits proinflammatory cytokine secretion and MMP-9 activity, enhances apoptotic cell uptake and up-regulates TG2 expression. Our data show that GTH might have beneficial effects on rheumatic diseases.

  12. Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles.

    Science.gov (United States)

    Bilyy, Rostyslav O; Shkandina, Tanya; Tomin, Andriy; Muñoz, Luis E; Franz, Sandra; Antonyuk, Volodymyr; Kit, Yuriy Ya; Zirngibl, Matthias; Fürnrohr, Barbara G; Janko, Christina; Lauber, Kirsten; Schiller, Martin; Schett, Georg; Stoika, Rostyslav S; Herrmann, Martin

    2012-01-02

    Inappropriate clearance of apoptotic remnants is considered to be the primary cause of systemic autoimmune diseases, like systemic lupus erythematosus. Here we demonstrate that apoptotic cells release distinct types of subcellular membranous particles (scMP) derived from the endoplasmic reticulum (ER) or the plasma membrane. Both types of scMP exhibit desialylated glycotopes resulting from surface exposure of immature ER-derived glycoproteins or from surface-borne sialidase activity, respectively. Sialidase activity is activated by caspase-dependent mechanisms during apoptosis. Cleavage of sialidase Neu1 by caspase 3 was shown to be directly involved in apoptosis-related increase of surface sialidase activity. ER-derived blebs possess immature mannosidic glycoepitopes and are prioritized by macrophages during clearance. Plasma membrane-derived blebs contain nuclear chromatin (DNA and histones) but not components of the nuclear envelope. Existence of two immunologically distinct types of apoptotic blebs may provide new insights into clearance-related diseases.

  13. Neuroprotective effects of corn silk maysin via inhibition of H2O2-induced apoptotic cell death in SK-N-MC cells.

    Science.gov (United States)

    Choi, Doo Jin; Kim, Sun-Lim; Choi, Ji Won; Park, Yong Il

    2014-07-25

    Neuroprotective effects of maysin, which is a flavone glycoside that was isolated from the corn silk (CS, Zea mays L.) of a Korean hybrid corn Kwangpyeongok, against oxidative stress (H2O2)-induced apoptotic cell death of human neuroblastoma SK-N-MC cells were investigated. Maysin cytotoxicity was determined by measuring cell viability using MTT and lactate dehydrogenase (LDH) assays. Intracellular reactive oxygen species (ROS) were measured using a 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Apoptotic cell death was monitored by annexin V-FITC/PI double staining and by a TUNEL assay. Antioxidant enzyme mRNA levels were determined by real-time PCR. The cleavage of poly (ADP-ribose) polymerase (PARP) was measured by western blotting. Maysin pretreatment reduced the cytotoxic effect of H2O2 on SK-N-MC cells, as shown by the increase in cell viability and by reduced LDH release. Maysin pretreatment also dose-dependently reduced the intracellular ROS level and inhibited PARP cleavage. In addition, DNA damage and H2O2-induced apoptotic cell death were significantly attenuated by maysin pretreatment. Moreover, maysin pretreatment (5-50 μg/ml) for 2h significantly and dose-dependently increased the mRNA levels of antioxidant enzymes (CAT, GPx-1, SOD-1, SOD-2 and HO-1) in H2O2 (200 μM)-insulted cells. These results suggest that CS maysin has neuroprotective effects against oxidative stress (H2O2)-induced apoptotic death of human brain SK-N-MC cells through its antioxidative action. This report is the first regarding neuroprotective health benefits of corn silk maysin by its anti-apoptotic action and by triggering the expression of intracellular antioxidant enzyme systems in SK-N-MC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The apoptotic effect and the plausible mechanism of microwave radiation on rat myocardial cells.

    Science.gov (United States)

    Zhu, Wenhe; Cui, Yan; Feng, Xianmin; Li, Yan; Zhang, Wei; Xu, Junjie; Wang, Huiyan; Lv, Shijie

    2016-08-01

    Microwaves may exert adverse biological effects on the cardiovascular system at the integrated system and cellular levels. However, the mechanism underlying such effects remains poorly understood. Here, we report a previously uncharacterized mechanism through which microwaves damage myocardial cells. Rats were treated with 2450 MHz microwave radiation at 50, 100, 150, or 200 mW/cm(2) for 6 min. Microwave treatment significantly enhanced the levels of various enzymes in serum. In addition, it increased the malondialdehyde content while decreasing the levels of antioxidative stress enzymes, activities of enzyme complexes I-IV, and ATP in myocardial tissues. Notably, irradiated myocardial cells exhibited structural damage and underwent apoptosis. Furthermore, Western blot analysis revealed significant changes in expression levels of proteins involved in oxidative stress regulation and apoptotic signaling pathways, indicating that microwave irradiation could induce myocardial cell apoptosis by interfering with oxidative stress and cardiac energy metabolism. Our findings provide useful insights into the mechanism of microwave-induced damage to the cardiovascular system.

  15. Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism

    Directory of Open Access Journals (Sweden)

    Patrícia E. de Almeida

    2018-03-01

    Full Text Available During Chagas disease, the Trypanosoma cruzi can induce some changes in the host cells in order to escape or manipulate the host immune response. The modulation of the lipid metabolism in the host phagocytes or in the parasite itself is one feature that has been observed. The goal of this mini review is to discuss the mechanisms that regulate intracellular lipid body (LB biogenesis in the course of this parasite infection and their meaning to the pathophysiology of the disease. The interaction host–parasite induces LB (or lipid droplet formation in a Toll-like receptor 2-dependent mechanism in macrophages and is enhanced by apoptotic cell uptake. Simultaneously, there is a lipid accumulation in the parasite due to the incorporation of host fatty acids. The increase in the LB accumulation during infection is correlated with an increase in the synthesis of PGE2 within the host cells and the parasite LBs. Moreover, the treatment with fatty acid synthase inhibitor C75 or non-steroidal anti-inflammatory drugs such as NS-398 and aspirin inhibited the LB biogenesis and also induced the down modulation of the eicosanoid production and the parasite replication. These findings show that LBs are organelles up modulated during the course of infection. Furthermore, the biogenesis of the LB is involved in the lipid mediator generation by both the macrophages and the parasite triggering escape mechanisms.

  16. Ion escape fluxes from the terrestrial high-latitude ionosphere

    International Nuclear Information System (INIS)

    Barakat, A.R.; Schunk, R.W.; Moore, T.E.; Waite, J.H. Jr.

    1987-01-01

    The coupled continuity and momentum equations for H + , O + , and electrons were solved for the terrestrial ionosphere in order to determine the limiting ion escape fluxes at high latitudes. The effects of solar cycle, season, geomagnetic activity, and the altitude of the acceleration region on the ion escape fluxes were studied for average conditions. In addition, a systematic parameter study was conducted to determine the extent to which variations in ionospheric conditions (for example, electron temperature, ion temperature, induced vertical ion drifts, etc.) can affect the results. The main conclusions of the study are as follows: (1) as solar activity increases, the general trend is for an increase in the limiting O + escape flux and a decrease in the limiting H + escape flux; (2) in winter the limiting escape fluxes of both O + and H + are larger than those in summer, particularly for low geomagnetic activity; (3) the O + content of the ion outflow increases with increasing ''demand'' imposed on the ionosphere by a high-altitude acceleration process, with increasing solar activity, with increasing geomagnetic activity, with increasing solar elevation from winter to summer, and with a lowering of the altitude of the acceleration region; (4) when H + is in a near-diffusive equilibrium state and a selective mechanism accelerates O + , the limiting O + escape flux is significantly reduced compared to that obtained when an H + outflow also occurs; and (5) at a given time or location the general trends described above can be significantly modified or even reversed owing to natural variations of the ionospheric ion and electron temperatures, induced vertical ion drifts, etc. The general trends obtained for average conditions appear to mimic the qualitative behavior determined from statistically averaged data for comparable absolute escape flux magnitudes

  17. To run or hide?: escape behaviour in a cryptic African snake | Maritz ...

    African Journals Online (AJOL)

    Optimal escape theory predicts that escape behaviour of an organism is best understood in terms of costs and benefits of escaping relative to risk of predation. However, risk of predation facing an organism is dependent on various biotic and abiotic factors. In order to better understand escape behaviour of an African snake, ...

  18. Improving escape panel selectivity in Nephrops directed fisheries by actively stimulating fish behaviour

    DEFF Research Database (Denmark)

    Krag, Ludvig Ahm; Herrmann, Bent; Feekings, Jordan P.

    2017-01-01

    The efficiency of escape panels inserted in trawls relies on fish actively attempting to escape through them. However, several studies indicate that most fish drift towards the aft end of the trawl, passing the escape panel through which they easily could have escaped, without making contact with...

  19. THE ESCAPE FRACTION OF IONIZING RADIATION FROM GALAXIES

    International Nuclear Information System (INIS)

    Benson, Andrew; Venkatesan, Aparna; Shull, J. Michael

    2013-01-01

    The escape of ionizing radiation from galaxies plays a critical role in the evolution of gas in galaxies, and the heating and ionization history of the intergalactic medium. We present semi-analytic calculations of the escape fraction of ionizing radiation for both hydrogen and helium from galaxies ranging from primordial systems to disk-type galaxies that are not heavily dust-obscured. We consider variations in the galaxy density profile, source type, location, and spectrum, and gas overdensity/distribution factors. For sufficiently hard first-light sources, the helium ionization fronts closely track or advance beyond that of hydrogen. Key new results in this work include calculations of the escape fractions for He I and He II ionizing radiation, and the impact of partial ionization from X-rays from early active galactic nuclei or stellar clusters on the escape fractions from galaxy halos. When factoring in frequency-dependent effects, we find that X-rays play an important role in boosting the escape fractions for both hydrogen and helium, but especially for He II. We briefly discuss the implications of these results for recent observations of the He II reionization epoch at low redshifts, as well as the UV data and emission-line signatures from early galaxies anticipated from future satellite missions.

  20. THE ESCAPE FRACTION OF IONIZING RADIATION FROM GALAXIES

    Energy Technology Data Exchange (ETDEWEB)

    Benson, Andrew [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Venkatesan, Aparna [Department of Physics and Astronomy, University of San Francisco, San Francisco, CA 94117 (United States); Shull, J. Michael, E-mail: abenson@obs.carnegiescience.edu, E-mail: avenkatesan@usfca.edu, E-mail: michael.shull@colorado.edu [CASA, Department of Astrophysical and Planetary Sciences, University of Colorado, Boulder, CO 80309 (United States)

    2013-06-10

    The escape of ionizing radiation from galaxies plays a critical role in the evolution of gas in galaxies, and the heating and ionization history of the intergalactic medium. We present semi-analytic calculations of the escape fraction of ionizing radiation for both hydrogen and helium from galaxies ranging from primordial systems to disk-type galaxies that are not heavily dust-obscured. We consider variations in the galaxy density profile, source type, location, and spectrum, and gas overdensity/distribution factors. For sufficiently hard first-light sources, the helium ionization fronts closely track or advance beyond that of hydrogen. Key new results in this work include calculations of the escape fractions for He I and He II ionizing radiation, and the impact of partial ionization from X-rays from early active galactic nuclei or stellar clusters on the escape fractions from galaxy halos. When factoring in frequency-dependent effects, we find that X-rays play an important role in boosting the escape fractions for both hydrogen and helium, but especially for He II. We briefly discuss the implications of these results for recent observations of the He II reionization epoch at low redshifts, as well as the UV data and emission-line signatures from early galaxies anticipated from future satellite missions.

  1. Cynodon dactylon (L) Pers (Poaceae) root extract induces apoptotic ...

    African Journals Online (AJOL)

    has also been used for the treatment of weak vision, urinary tract infection, .... with an alternating 12 h dark/light cycle in ... detected by Western blot analysis as described previously .... the cyclin signaling pathways, induced apoptotic cell death ...

  2. Detection of apoptotic cells in tumour paraffin sections

    International Nuclear Information System (INIS)

    Pizem, J.; Coer, A.

    2003-01-01

    Apoptosis is a distinct form of cell death characterised by specific morphological features and regulated by complex molecular mechanisms. Its deregulation is fundamental for tumour growth and progression and, moreover, anticancer therapies suppress tumour growth mainly by induction of apoptosis. Since the extent of apoptosis in a tumour may have prognostic as well as therapeutic implications, much effort has been invested in developing specific methods that can be routinely used to detect apoptotic cells in archival formalin- fixed paraffin-embedded tissue. Complex molecular pathways are involved in the regulation of apoptosis. Pro-apoptotic signals trigger activation of caspases that specifically cleave target proteins. Cleavage of proteins (caspase substrates) is responsible for morphological changes of apoptotic cells and DNA fragmentation. In the last decade, detection of apoptotic cells in formalin-fixed tumour tissue sections has been based mainly on morphology and characteristic DNA fragmentation. Recently, specific antibodies to activated caspases and cleaved target proteins (including cytokeratin 18, actin and PARP) have been produced that enable accurate detection of apoptosis in paraffin sections. (author)

  3. Different apoptotic responses to Plasmodium chabaudi malaria in ...

    African Journals Online (AJOL)

    hope&shola

    2010-11-08

    Nov 8, 2010 ... The purpose of this study is to determine whether the apoptotic responses to Plasmodium chabaudi malaria in spleen and liver via mRNA expression of three genes involved in apoptosis (Bax, Bcl-2 and. Caspase-3) are similar or not and to detect if these genes could be a good marker for apoptosis due to.

  4. Growth inhibitory, apoptotic and anti-inflammatory activities ...

    Indian Academy of Sciences (India)

    naturally abundant oleanolic acid, displayed diverse biolog- ical activities ... triterpenoids and natural products. CDDO and its .... ration was determined by treating with anti-BrdU antibody and Texas red ..... apoptotic and necrotic in the tumour tissue. Thus .... Palmer RM, Ashton DS and Moncada S 1988 Vascular endothelial.

  5. Abnormalities in Alternative Splicing of Apoptotic Genes and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Zodwa Dlamini

    2015-11-01

    Full Text Available Apoptosis is required for normal heart development in the embryo, but has also been shown to be an important factor in the occurrence of heart disease. Alternative splicing of apoptotic genes is currently emerging as a diagnostic and therapeutic target for heart disease. This review addresses the involvement of abnormalities in alternative splicing of apoptotic genes in cardiac disorders including cardiomyopathy, myocardial ischemia and heart failure. Many pro-apoptotic members of the Bcl-2 family have alternatively spliced isoforms that lack important active domains. These isoforms can play a negative regulatory role by binding to and inhibiting the pro-apoptotic forms. Alternative splicing is observed to be increased in various cardiovascular diseases with the level of alternate transcripts increasing elevated in diseased hearts compared to healthy subjects. In many cases these isoforms appear to be the underlying cause of the disease, while in others they may be induced in response to cardiovascular pathologies. Regardless of this, the detection of alternate splicing events in the heart can serve as useful diagnostic or prognostic tools, while those splicing events that seem to play a causative role in cardiovascular disease make attractive future drug targets.

  6. Detection of apoptotic cells using propidium iodide staining

    NARCIS (Netherlands)

    Newbold, Andrea; Martin, Ben P.; Cullinane, Carleen; Bots, Michael

    2014-01-01

    Flow cytometry assays are often used to detect apoptotic cells in in vitro cultures. Depending on the experimental model, these assays can also be useful in evaluating apoptosis in vivo. In this protocol, we describe a propidium iodide (PI) flow cytometry assay to evaluate B-cell lymphomas that have

  7. Passive Facebook use, Facebook addiction, and associations with escapism: an experimental vignette study

    OpenAIRE

    Young, LN; Kuss, DJ; Griffiths, MD; Howard, CJ

    2017-01-01

    There is relatively little research considering motivations of passive Facebook use. However, research regarding motivations of general Facebook use indicates that people use Facebook to escape – and that escapism may motivate passive Facebook use. Research also suggests that using Facebook to escape is associated with Facebook addiction. Using an experimental vignette design, the present research investigated whether passive Facebook use is motivated by escapism and whether this escape motiv...

  8. An anticipative escape system for vehicles in water crashes

    Science.gov (United States)

    Shen, Chuanliang; Wang, Jiawei; Yin, Qi; Zhu, Yantao; Yang, Jiawei; Liao, Mengdi; Yang, Liming

    2017-07-01

    In this article, it designs an escape system for vehicles in water crashes. The structure mainly contains sensors, control organs and actuating mechanism for both doors and windows. Sensors judge whether the vehicle falls into water or is in the falling process. The actuating mechanism accepts the signal delivered by the control organs, then open the electronic central lock on doors and meanwhile lower the window. The water escape system is able to anticipate drowning situations for vehicles and controls both doors and windows in such an emergency. Under the premise of doors staying in an undamaged state, it is for sure that people in the vehicle can open the door while drowning in the water and safely escape.

  9. Escaping and Falling into Poverty in India Today.

    Science.gov (United States)

    Thorat, Amit; Vanneman, Reeve; Desai, Sonalde; Dubey, Amaresh

    2017-05-01

    The study examines the dynamic nature of movements into and out of poverty over a period when poverty has fallen substantially in India. The analysis identifies people who escaped poverty and those who fell into it over the period 2005 to 2012. The analysis identifies people who escaped poverty and those who fell into it over the period 2005 to 2012. Using panel data from the India Human Development Survey for 2005 and 2012, we find that the risks of marginalized communities such as Dalits and Adivasis of falling into or remaining in poverty were higher than those for more privileged groups. Some, but not all of these higher risks are explained by educational, financial, and social disadvantages of these groups in 2005. Results from a logistic regression show that some factors that help people escape poverty differ from those that push people into it and that the strength of their effects varies.

  10. Escape response of planktonic protists to fluid mechanical signals

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2001-01-01

    The escape response to fluid mechanical signals was examined in 6 protists, 4 ciliates and 2 dinoflagellates. When exposed to a siphon flow. 3 species of ciliates, Balanion comatum, Strobilidium sp., and Mesodinium pulex, responded with escape jumps. The threshold deformation rates required...... times lower than that of a non-jumping similar sized protist when the predator was Temora longicornis, which captures prey entrained in a feeding current. However, when the predator was the ambush- feeding copepod Acartia tonsa, the predation mortalities of jumping and non-jumping protists were...... of similar magnitude. Escape responses may thus be advantageous in some situations. However, jumping behaviour may also enhance susceptibility to some predators, explaining the different predator avoidance strategies (jumping or not) that have evolved in planktonic protists....

  11. Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers.

    Science.gov (United States)

    García-Cabrerizo, Rubén; García-Fuster, M Julia

    2015-07-01

    While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic FADD, Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of GFAP activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Nickel oxide nanoparticles exert cytotoxicity via oxidative stress and induce apoptotic response in human liver cells (HepG2).

    Science.gov (United States)

    Ahamed, Maqusood; Ali, Daoud; Alhadlaq, Hisham A; Akhtar, Mohd Javed

    2013-11-01

    Increasing use of nickel oxide nanoparticles (NiO NPs) necessitates an improved understanding of their potential impact on human health. Previously, toxic effects of NiO NPs have been investigated, mainly on airway cells. However, information on effect of NiO NPs on human liver cells is largely lacking. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and induction of apoptotic response in human liver cells (HepG2) due to NiO NPs exposure. Prepared NiO NPs were crystalline and spherical shaped with an average diameter of 44 nm. NiO NPs induced cytotoxicity (cell death) and ROS generation in HepG2 cells in dose-dependent manner. Further, ROS scavenger vitamin C reduced cell death drastically caused by NiO NPs exposure indicating that oxidative stress plays an important role in NiO NPs toxicity. Micronuclei induction, chromatin condensation and DNA damage in HepG2 cells treated with NiO NPs suggest that NiO NPs induced cell death via apoptotic pathway. Quantitative real-time PCR analysis showed that following the exposure of HepG2 cells to NiO NPs, the expression level of mRNA of apoptotic genes (bax and caspase-3) were up-regulated whereas the expression level of anti-apoptotic gene bcl-2 was down-regulated. Moreover, activity of caspase-3 enzyme was also higher in NiO NPs treated cells. To the best of our knowledge this is the first report demonstrating that NiO NPs caused cytotoxicity via ROS and induced apoptosis in HepG2 cells, which is likely to be mediated through bax/bcl-2 pathway. This work warrants careful assessment of Ni NPs before their commercial and industrial applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Rapid endosomal escape of prickly nanodiamonds: implications for gene delivery

    Science.gov (United States)

    Chu, Zhiqin; Miu, Kaikei; Lung, Pingsai; Zhang, Silu; Zhao, Saisai; Chang, Huan-Cheng; Lin, Ge; Li, Quan

    2015-06-01

    The prickly nanodiamonds easily entered cells via endocytosis followed by unique intracellular translocation characteristics—quick endosomal escape followed by stable residence in cytoplasm. Endosomal membrane rupturing is identified as the major route of nanodiamonds’ escaping the vesicle confinement and to the cytoplasm. Little cytotoxicity is observed to associate with the nanodiamonds’ cytosolic release. Such features enable its application for gene delivery, which requires both effective cellular uptake and cytosolic release of the gene. Taking green fluorescent protein gene as an example, we demonstrate the successful cytosolic delivery and expression of such a gene using the prickly nanodiamonds as carrier.

  14. Rapid endosomal escape of prickly nanodiamonds: implications for gene delivery

    Science.gov (United States)

    Chu, Zhiqin; Miu, Kaikei; Lung, Pingsai; Zhang, Silu; Zhao, Saisai; Chang, Huan-Cheng; Lin, Ge; Li, Quan

    2015-01-01

    The prickly nanodiamonds easily entered cells via endocytosis followed by unique intracellular translocation characteristics—quick endosomal escape followed by stable residence in cytoplasm. Endosomal membrane rupturing is identified as the major route of nanodiamonds’ escaping the vesicle confinement and to the cytoplasm. Little cytotoxicity is observed to associate with the nanodiamonds’ cytosolic release. Such features enable its application for gene delivery, which requires both effective cellular uptake and cytosolic release of the gene. Taking green fluorescent protein gene as an example, we demonstrate the successful cytosolic delivery and expression of such a gene using the prickly nanodiamonds as carrier. PMID:26123532

  15. Rapid endosomal escape of prickly nanodiamonds: implications for gene delivery.

    Science.gov (United States)

    Chu, Zhiqin; Miu, Kaikei; Lung, Pingsai; Zhang, Silu; Zhao, Saisai; Chang, Huan-Cheng; Lin, Ge; Li, Quan

    2015-06-30

    The prickly nanodiamonds easily entered cells via endocytosis followed by unique intracellular translocation characteristics—quick endosomal escape followed by stable residence in cytoplasm. Endosomal membrane rupturing is identified as the major route of nanodiamonds' escaping the vesicle confinement and to the cytoplasm. Little cytotoxicity is observed to associate with the nanodiamonds' cytosolic release. Such features enable its application for gene delivery, which requires both effective cellular uptake and cytosolic release of the gene. Taking green fluorescent protein gene as an example, we demonstrate the successful cytosolic delivery and expression of such a gene using the prickly nanodiamonds as carrier.

  16. Nosema Tolerant Honeybees (Apis mellifera) Escape Parasitic Manipulation of Apoptosis

    DEFF Research Database (Denmark)

    Kurze, Christoph; Le Conte, Yves; Dussaubat, Claudia

    2015-01-01

    conducted three inoculation experiments to investigate in the apoptotic respond during infection with the intracellular gut pathogen Nosema ceranae, which is considered as potential global threat to the honeybee (Apis mellifera) and other bee pollinators, in sensitive and tolerant honeybees. To explore...

  17. Withaferin A Suppresses Anti-apoptotic BCL2, Bcl-xL, XIAP and ...

    African Journals Online (AJOL)

    apoptotic ... Quantitative real-time polymerase chain reaction (qPCR) was performed using Taq PCR Master ... Keywords: Anti-apoptotic genes, Cervical cancer, Apoptosis, Cell viability, BCL2, .... polyclonal anti-rabbit immunoglobulin HRP-linked.

  18. Enzyme detection by microfluidics

    DEFF Research Database (Denmark)

    2013-01-01

    Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted...... by that enzyme...

  19. Escape angles in bulk chi((2)) soliton interactions

    DEFF Research Database (Denmark)

    Johansen, Steffen Kjær; Bang, Ole; Sørensen, Mads Peter

    2002-01-01

    We develop a theory for nonplanar interaction between two identical type I spatial solitons propagating at opposite, but arbitrary transverse angles in quadratic nonlinear (or so-called chi((2))) bulk, media. We predict quantitatively the outwards escape angle, below which the solitons turn around...

  20. Leaflet escape in a new bileaflet mechanical valve: TRI technologies.

    Science.gov (United States)

    Bottio, Tomaso; Casarotto, Dino; Thiene, Gaetano; Caprili, Luca; Angelini, Annalisa; Gerosa, Gino

    2003-05-13

    Leaflet escape is a mode of structural valve failure for mechanical prostheses. This complication previously has been reported for both monoleaflet and bileaflet valve models. We report 2 leaflet escape occurrences observed in 2 patients who underwent valve replacement with a TRI Technologies valve prosthesis. At the University of Padua, between November 2000 and February 2002, 36 TRI Technologies valve prostheses (26 aortic and 10 mitral) were implanted in 34 patients (12 women and 22 men) with a mean age of 59.9+/-10.3 years (range, 30 to 75 years). There were 5 deaths: 3 in hospital, 1 early after discharge, and 1 late. Two patients experienced a catastrophic prosthetic leaflet escape; the first patient was a 52-year-old man who died 10 days after aortic valve and ascending aorta replacement, and the second was a 58-year-old man who underwent a successful emergency reoperation 20 months after mitral valve replacement. Examination of the explanted prostheses showed in both cases a leaflet escape caused by a leaflet's pivoting system fracture. Prophylactic replacement was then successfully accomplished so far in 12 patients, without evidence of structural valve failure in any of them. Among other significant postoperative complications, we observed 3 major thromboembolisms, 1 hemorrhage, and 1 paravalvular leak. These catastrophes prompted us to interrupt the implantation program, and they cast a shadow on the durability of the TRI Technologies valve prosthesis because of its high risk of structural failure.

  1. EscapeScape: Simulating Ecopedagogy for the Tourist

    Science.gov (United States)

    Nakagawa, Yoshifumi

    2018-01-01

    Environmental education as a theory and practice of ecopedagogical simulation positively acknowledges various accidental happenings in the learner's experience. By working with and on the accidents, the learner is encouraged to imagine the real object that escapes his/her experience and thus cannot be and should not be reduced into human…

  2. 46 CFR 169.313 - Means of escape.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Means of escape. 169.313 Section 169.313 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Construction... apart, uniform for the length of the ladder; (3) At least 3 inches from the nearest permanent object in...

  3. Entrapment and Escape: Inventional Metaphors in Ronald Reagan's Economic Rhetoric.

    Science.gov (United States)

    Aden, Roger C.

    1989-01-01

    Examines Ronald Reagan's use of inventional metaphors of entrapment and escape, language meshing with the American public's perception of the economy in the early 1980s. Notes that Reagan's reliance on inventional metaphors produced a rigidity in his approach to new situations, ultimately damaging his ability to lead the nation. (MM)

  4. Escape rate from strange sets as an eigenvalue

    International Nuclear Information System (INIS)

    Tel, T.

    1986-06-01

    A new method is applied for calculating the escape rate from chaotic repellers or semi-attractors, based on the eigenvalue problem of the master equation of discrete dynamical systems. The corresponding eigenfunction is found to be smooth along unstable directions and to be, in general, a fractal measure. Examples of one and two dimensional maps are investigated. (author)

  5. The escape of brownian particle over potential barriers

    International Nuclear Information System (INIS)

    Zhong Yunxiao

    1985-01-01

    A convenient method is introduced to calculate the rate of escape of Brownian particle over potential barriers by exact solution of Smoluchowskian equation. This method is applied to calculate the nuclear fission probabilities. The results for four different cases are compared with the results of other theories

  6. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  7. Ultrastructural apoptotic lesions induced in rat thymocytes after borax ingestion.

    Science.gov (United States)

    Sylvain, I C; Berry, J P; Galle, P

    1998-01-01

    Apoptosis has gained increasing attention in recent years. Several chemical compounds induce apoptotic lesions in the thymus. Male Wistar rats received 2000 ppm of borax (Na2B4O7.10H2O) in their food for 16 days. The rats were sacrificed 2, 5, 9, 12, 19, 21, 26 and 28 days after the beginning of treatment. Thymus samples of all rats were taken. A Philips EM 300 electron microscopy was used to study the ultrastructural morphology. Serious nuclear and cytoplasmic lesions were observed. Moreover, numerous macrophages containing apoptotic cells were present in the thymus. The alterations were observed from the 2nd to the 28th day. The extent of damage was much more important in the rats sacrificed 21, 26 and 28 days after borax ingestion.

  8. Macrophage Clearance of Apoptotic Cells: A Critical Assessment

    Directory of Open Access Journals (Sweden)

    Siamon Gordon

    2018-01-01

    Full Text Available As the body continues to grow and age, it becomes essential to maintain a balance between living and dying cells. Macrophages and dendritic cells play a central role in discriminating among viable, apoptotic, and necrotic cells, as selective and efficient phagocytes, without inducing inappropriate inflammation or immune responses. A great deal has been learnt concerning clearance receptors for modified and non-self-ligands on potential targets, mediating their eventual uptake, disposal, and replacement. In this essay, we assess current understanding of the phagocytic recognition of apoptotic cells within their tissue environment; we conclude that efferocytosis constitutes a more complex process than simply removal of corpses, with regulatory interactions between the target and effector cells, which determine the outcome of this homeostatic process.

  9. Histopathological, Ultrastructural and Apoptotic Changes in Diabetic Rat Placenta

    Directory of Open Access Journals (Sweden)

    Mehmet Gül

    2015-09-01

    Full Text Available Background: The exchange of substances between mother and fetus via the placenta plays a vital role during development. A number of developmental disorders in the fetus and placenta are observed during diabetic pregnancies. Diabetes, together with placental apoptosis, can lead to developmental and functional disorders. Aims: Histological, ultrastructural and apoptotic changes were investigated in the placenta of streptozotocin (STZ induced diabetic rats. Study Design: Animal experimentation. Methods: In this study, a total of 12 female Wistar Albino rats (control (n=6 and diabetic (n=6 were used. Rats in the diabetic group, following the administration of a single dose of STZ, showed blood glucose levels higher than 200 mg/dL after 72 hours. When pregnancy was detected after the rats were bred, two pieces of placenta and the fetuses were collected on the 20th day of pregnancy by cesarean incision under ketamine/xylazine anesthesia from in four rats from the control and diabetic groups. Placenta tissues were processed for light microscopy and transmission electron microscopy (TEM. Hematoxylin-eosin (HE and periodic acid Schiff-diastase (PAS-D staining for light microscopic and caspase-3 staining for immunohistochemical investigations were performed for each placenta. Electron microscopy was performed on thin sections contrasted with uranyl acetate and lead nitrate. Results: Weight gain in the placenta and fetuses of diabetic rats and thinning of the decidual layer, thickening of the hemal membrane, apoptotic bodies, congestion in intervillous spaces, increased PAS-D staining in decidual cells and caspase-3 immunoreactivity were observed in the diabetic group. After the ultrastructural examination, the apoptotic appearance of the nuclei of trophoblastic cells, edema and intracytoplasmic vacuolization, glycogen accumulation, dilation of the endoplasmic reticulum and myelin figures were observed. In addition, capillary basement membrane thickening

  10. Escape manoeuvres in the spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    Domenici, Paolo; Standen, Emily M; Levine, Robert P

    2004-06-01

    The locomotor performance of dogfish during escape responses was observed by means of high-speed video. Dogfish show C-type escape responses that are comparable with those shown previously in teleosts. Dogfish show high variability of turning rates of the anterior part of the body (head to centre of mass), i.e. with peak values from 434 to 1023 deg. s(-1). We suggest that this variability may be due to the presence of two types of escape manoeuvres, i.e. responses with high and low turning rates, as previously found in a teleost species. Fast responses (i.e. with high maximum turning rates, ranging between 766 and 1023 deg. s(-1)) showed significantly higher locomotor performance than slow responses (i.e. with low maximum turning rates, ranging between 434 and 593 deg. s(-1)) in terms of distance covered, speed and acceleration, although no differences were found in the turning radius of the centre of mass during the escape manoeuvres. The existence of two types of escape responses would have implications in terms of both neural control and muscular activation patterns. When compared with literature data for the locomotor performance of bony fishes, dogfish showed relatively low speed and acceleration, comparable turning rates and a turning radius that is in the low part of the range when compared with teleosts, indicating relatively high manoeuvrability. The locomotor performance observed in dogfish is consistent with their morphological characteristics: (1) low locomotor performance associated with low thrust developed by their relatively small posterior depth of section and (2) relatively high manoeuvrability associated with their high flexibility.

  11. Membrane Protected Apoptotic Trophoblast Microparticles Contain Nucleic Acids

    Science.gov (United States)

    Orozco, Aaron F.; Jorgez, Carolina J.; Horne, Cassandra; Marquez-Do, Deborah A.; Chapman, Matthew R.; Rodgers, John R.; Bischoff, Farideh Z.; Lewis, Dorothy E.

    2008-01-01

    Microparticles (MPs) that circulate in blood may be a source of DNA for molecular analyses, including prenatal genetic diagnoses. Because MPs are heterogeneous in nature, however, further characterization is important before use in clinical settings. One key question is whether DNA is either bound to aggregates of blood proteins and lipid micelles or intrinsically associated with MPs from dying cells. To test the latter hypothesis, we asked whether MPs derived in vitro from dying cells were similar to those in maternal plasma. JEG-3 cells model extravillous trophoblasts, which predominate during the first trimester of pregnancy when prenatal diagnosis is most relevant. MPs were derived from apoptosis and increased over 48 hours. Compared with necrotic MPs, DNA in apoptotic MPs was more fragmented and resistant to plasma DNases. Membrane-specific dyes indicated that apoptotic MPs had more membranous material, which protects nucleic acids, including RNA. Flow cytometry showed that MPs derived from dying cells displayed light scatter and DNA staining similar to MPs found in maternal plasma. Quantification of maternal MPs using characteristics defined by MPs generated in vitro revealed a significant increase of DNA+ MPs in the plasma of women with preeclampsia compared with plasma from women with normal pregnancies. Apoptotic MPs are therefore a likely source of stable DNA that could be enriched for both early genetic diagnosis and monitoring of pathological pregnancies. PMID:18974299

  12. Cell shape and organelle modification in apoptotic U937 cells

    Directory of Open Access Journals (Sweden)

    MR Montinari

    2009-12-01

    Full Text Available U937 cells induced to apoptosis, progressively and dramatically modified their cell shape by intense blebbing formation, leading to the production of apoptotic bodies. The blebs evolved with time; milder forms of blebbing involving only a region or just the cortical part of the cytoplasm were observed within the first hour of incubation with puromycin; blebbing involving the whole cell body with very deep constrictions is the most frequent event observed during late times of incubation. The ultrastructural analysis of apoptotic cells revealed characteristic features of nuclear fragmentation (budding and cleavage mode and cytoplasmatic modifications. The cytoplasm of blebs does not contain organelles, such as ribosomes or mitochondria. Scarce presence of endoplasmic reticulum can be observed at the site of bleb detachment. However, blebbing is a dispensable event as evaluated by using inhibitor of actin polymerization. In the present study, the progressive modifications of the nucleus, mitochondria, nuclear fragmentation, cytoplasmic blebs formation and production of apoptotic bodies in U937 monocytic cells induced to apoptosis by puromycin (an inhibitor of protein synthesis were simultaneously analyzed.

  13. Upregulation of intrinsic apoptotic pathway in NSAIDs mediated chemoprevention of experimental lung carcinogenesis.

    Science.gov (United States)

    Setia, Shruti; Sanyal, Sankar N

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) act by inhibition of cyclooxygenase-2 (COX-2), which is overexpressed in cancer. The role of COX-2 and apoptosis were evaluated in 9,10-dimethylbenz(a)anthracene (DMBA)-induced lung cancer in rat and chemoprevention with indomethacin, a traditional NSAID and etoricoxib, a selective COX-2 inhibitor. The animals were divided into Control, DMBA, DMBA+ indomethacin and DMBA+ etoricoxib groups. They received a single intratracheal instillation of DMBA while NSAIDs were given orally daily for 32 weeks. Besides morphology and histology of lungs, RT-PCR, western blots and immunohistochemistry were performed for the expression of apoptotic proteins and COX enzymes. Apoptosis was studied by DNA fragmentation and fluorescent staining. The occurrence of tumors and lesions was noted in the DMBA animals, besides constricted alveolar spaces and hyperplasia. COX-1 was found to be uniformly expressed while COX-2 level was raised significantly in DMBA group. The apoptotic proteins, apaf-1, caspase-9 and caspase-3 were highly diminished in DMBA group but restored to normal level in NSAIDs groups. Also, apoptosis was suppressed in carcinogen group by DNA fragmentation analysis and fluorescent staining of the lung cells while co-administration of NSAIDs along with DMBA led to the restoration of apoptosis. DMBA administration to the rats led to tumorigenesis in the lungs, had no effects on COX-1 expression, while elevating the COX-2 levels and suppressing apoptosis. The treatment with NSAIDs led to the amelioration of these effects. However, etoricoxib which is a COX-2 specific inhibitor, was found to be more effective than the traditional NSAID, indomethacin.

  14. Transmitted/Founder Viruses Rapidly Escape from CD8+ T Cell Responses in Acute Hepatitis C Virus Infection.

    Science.gov (United States)

    Bull, Rowena A; Leung, Preston; Gaudieri, Silvana; Deshpande, Pooja; Cameron, Barbara; Walker, Melanie; Chopra, Abha; Lloyd, Andrew R; Luciani, Fabio

    2015-05-01

    The interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8(+) T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n = 1) or replacement with viral variants leading to establishment of chronic infection (n = 2). CD8(+) T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infection. Higher-magnitude CD8(+) T cell responses were associated with rapid development of immune escape variants at a rate of up to 0.1 per day. Rapid escape from CD8(+) T cell responses has been quantified for the first time in the early phase of primary HCV infection. These rapid escape dynamics were associated with higher-magnitude CD8(+) T cell responses. These findings raise questions regarding optimal selection of immunogens for HCV vaccine development and suggest that detailed analysis of individual epitopes may be required. A major limitation in our detailed understanding of the role of immune response in HCV clearance has been the lack of data on very early primary infection when the transmitted viral variants successfully establish

  15. Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer′s Disease Mice

    Directory of Open Access Journals (Sweden)

    Hui Shen

    2016-01-01

    Conclusions: These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.

  16. Library Lockdown: An escape room by kids for the community

    Directory of Open Access Journals (Sweden)

    Jennifer Thoegersen

    2016-11-01

    Full Text Available In Brief Hoping to bring the unexpected to Nebraska City, the Morton-James Public Library applied for an ALA Association for Library Service to Children Curiosity Creates grant to undertake an ambitious project: build an escape room. In a library storage room. With children. The hope was  by trying something completely different, we could increase interest in the library throughout the community and build a sense of ownership in the participants, while encouraging creativity and having a lot of fun. Library Lockdown was a four-month program that brought several dozen kids together—age 8 to 13—to build a fully-functioning escape room. Their creation, the Lab of Dr. Morton McBrains, is now open for business.

  17. Calculations of condensed moisture escape from a NPP spray pond

    International Nuclear Information System (INIS)

    Bratuta, Eh. G.; Yaroshenko, T.I.

    1988-01-01

    A method for calculating water losses due to condensed moisture escape with a wind away from a spray pond used for cooling steam turbine condensator water and emergency nuclear reactor cooling is developed. The method is based on solving a three-dimensional equation of single drop motion, assuming that during the whole flight only gravity and aerodynamic resistance forces act on a drop. The basic parameter variation ranges are the following: 0-18 m/s wind velocity, 0.04-0.12 MPa pressure drop at the nozzle output, 1-2 m height of sprayers above the pond mirror. The given method permits to determine both the amount of circulation water loss and the local liquid flow rate distribution pattern as well as the area around the pond receiving the escaped moisture that is necessary for estimating the ecological situation near a NPP

  18. Fixation and escape times in stochastic game learning

    International Nuclear Information System (INIS)

    Realpe-Gomez, John; Szczesny, Bartosz; Galla, Tobias; Dall’Asta, Luca

    2012-01-01

    Evolutionary dynamics in finite populations is known to fixate eventually in the absence of mutation. We here show that a similar phenomenon can be found in stochastic game dynamical batch learning, and investigate fixation in learning processes in a simple 2×2 game, for two-player games with cyclic interaction, and in the context of the best-shot network game. The analogues of finite populations in evolution are here finite batches of observations between strategy updates. We study when and how such fixation can occur, and present results on the average time-to-fixation from numerical simulations. Simple cases are also amenable to analytical approaches and we provide estimates of the behaviour of so-called escape times as a function of the batch size. The differences and similarities with escape and fixation in evolutionary dynamics are discussed. (paper)

  19. Quantum and thermal phase escape in extended Josephson systems

    International Nuclear Information System (INIS)

    Kemp, A.

    2006-01-01

    In this work I examine phase escape in long annular Josephson tunnel junctions. The sine-Gordon equation governs the dynamics of the phase variable along the junction. This equation supports topological soliton solutions, which correspond to quanta of magnetic flux trapped in the junction barrier. For such Josephson vortices an effective potential is formed by an external magnetic field, while a bias current acts as a driving force. Both together form a metastable potential well, which the vortex is trapped in. When the driving force exceeds the pinning force of the potential, the vortex escapes and the junction switches to the voltage state. At a finite temperature the driving force fluctuates. If the junction's energy scale is small, the phase variable can undergo a macroscopic quantum tunneling (MQT) process at temperatures below the crossover temperature. Without a vortex trapped, the metastable state is not a potential minimum in space, but a potential minimum at zero phase difference. (orig.)

  20. Partial control of chaotic transients using escape times

    International Nuclear Information System (INIS)

    Sabuco, Juan; Zambrano, Samuel; Sanjuan, Miguel A F

    2010-01-01

    The partial control technique allows one to keep the trajectories of a dynamical system inside a region where there is a chaotic saddle and from which nearly all the trajectories diverge. Its main advantage is that this goal is achieved even if the corrections applied to the trajectories are smaller than the action of environmental noise on the dynamics, a counterintuitive result that is obtained by using certain safe sets. Using the Henon map as a paradigm, we show here the deep relationship between the safe sets and the sets of points with different escape times, the escape time sets. Furthermore, we show that it is possible to find certain extended safe sets that can be used instead of the safe sets in the partial control technique. Numerical simulations confirm our findings and show that in some situations, the use of extended safe sets can be more advantageous.

  1. The production and escape of nitrogen atoms on Mars

    Science.gov (United States)

    Fox, J. L.

    1993-01-01

    Updated rate coefficients and a revised ionosphere-thermosphere model are used to compute the production rates and densities of odd nitrogen species in the Martian atmosphere. Computed density profiles for N(4S), N(2D), N(2P), and NO are presented. The model NO densities are found to be about a factor of 2-3 less than those measured by the Viking 1 mass spectrometer. Revised values for the escape rates of N atoms from dissociative recombination and ionospheric reactions are also computed. Dissociative recombination is found to be comparable in importance to photodissociation at low solar activity, but it is still the most important escape mechanism for N-14 at high solar activity.

  2. Quantum and thermal phase escape in extended Josephson systems

    Energy Technology Data Exchange (ETDEWEB)

    Kemp, A.

    2006-07-12

    In this work I examine phase escape in long annular Josephson tunnel junctions. The sine-Gordon equation governs the dynamics of the phase variable along the junction. This equation supports topological soliton solutions, which correspond to quanta of magnetic flux trapped in the junction barrier. For such Josephson vortices an effective potential is formed by an external magnetic field, while a bias current acts as a driving force. Both together form a metastable potential well, which the vortex is trapped in. When the driving force exceeds the pinning force of the potential, the vortex escapes and the junction switches to the voltage state. At a finite temperature the driving force fluctuates. If the junction's energy scale is small, the phase variable can undergo a macroscopic quantum tunneling (MQT) process at temperatures below the crossover temperature. Without a vortex trapped, the metastable state is not a potential minimum in space, but a potential minimum at zero phase difference. (orig.)

  3. UNESCO to blame:Reality or easy escape?

    OpenAIRE

    Pereira Roders, A Ana; Grigolon, AB Anna

    2015-01-01

    “UNESCO to blame” is a trend often observed in scholarly works. In those studies UNESCO is accused to privilege Eurocentric standards on heritage conservation. Is this reality or an easy escape? Can this trend be noted in other UNESCO reference texts? This article seeks to answer this question by studying the two main inscription-based conventions and their contribution to heritage management, while performing a data analysis on the countries behind these conventions, and their roles over tim...

  4. The escape of natural satellites from Mercury and Venus

    International Nuclear Information System (INIS)

    Kumar, S.S.

    1977-01-01

    It is suggested that the slow rotations of Mercury and Venus may be connected with the absence of natural satellites around them. If Mercury or Venus possessed a satellite at the time of formation, the tidal evolution would have caused the satellite to recede. At a sufficiently large distance from the planet, the Sun's gravitational influence makes the satellite orbit unstable. The natural satellites of Mercury and Venus might have escaped as a consequence of this instability. (Auth.)

  5. Escape of natural satellites from Mercury and Venus

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S S [Virginia Univ., Charlottesville (USA)

    1977-09-01

    It is suggested that the slow rotations of Mercury and Venus may be connected with the absence of natural satellites around them. If Mercury or Venus possessed a satellite at the time of formation, the tidal evolution would have caused the satellite to recede. At a sufficiently large distance from the planet, the Sun's gravitational influence makes the satellite orbit unstable. The natural satellites of Mercury and Venus might have escaped as a consequence of this instability.

  6. ESCAPE: an integrated climate model for the EC

    International Nuclear Information System (INIS)

    Rotmans, J.

    1992-01-01

    A framework has been developed for the evaluation of policy options for climate change, called ESCAPE (Evaluation of Strategies to address Climate change by Adapting to and Preventing Emissions). ESCAPE consists of a suite of linked models which enables scenarios of greenhouse gas emissions to be constructed and their impact on global and regional climate and sea level and sectors of the European economy to be assessed. Conclusions resulting from simulations with the ESCAPE 1.1 model include: the major problem of a climate change for the EC is a sea level rise; Greece, Italy, Portugal and Spain will be faced with higher costs in the agricultural sector; worldwide implementation of an EC carbon tax leads to about 12% lower worldwide CO 2 emissions; to stabilize CO 2 emissions an Ecotax of 18 dollars per barrel would be required; and in all cases the rate of global temperature increase will be above the rate of 0.1 degree C per decade for the coming 40 years. 2 figs

  7. Anomalous barrier escape: The roles of noise distribution and correlation

    Science.gov (United States)

    Hu, Meng; Zhang, Jia-Ming; Bao, Jing-Dong

    2017-05-01

    We study numerically and analytically the barrier escape dynamics of a particle driven by an underlying correlated Lévy noise for a smooth metastable potential. A "quasi-monochrome-color" Lévy noise, i.e., the first-order derivative variable of a linear second-order differential equation subjected to a symmetric α-stable white Lévy noise, also called the harmonic velocity Lévy noise, is proposed. Note that the time-integral of the noise Green function of this kind is equal to zero. This leads to the existence of underlying negative time correlation and implies that a step in one direction is likely followed by a step in the other direction. By using the noise of this kind as a driving source, we discuss the competition between long flights and underlying negative correlations in the metastable dynamics. The quite rich behaviors in the parameter space including an optimum α for the stationary escape rate have been found. Remarkably, slow diffusion does not decrease the stationary rate while a negative correlation increases net escape. An approximate expression for the Lévy-Kramers rate is obtained to support the numerically observed dependencies.

  8. Transitions between three swimming gaits in Paramecium escape.

    Science.gov (United States)

    Hamel, Amandine; Fisch, Cathy; Combettes, Laurent; Dupuis-Williams, Pascale; Baroud, Charles N

    2011-05-03

    Paramecium and other protists are able to swim at velocities reaching several times their body size per second by beating their cilia in an organized fashion. The cilia beat in an asymmetric stroke, which breaks the time reversal symmetry of small scale flows. Here we show that Paramecium uses three different swimming gaits to escape from an aggression, applied in the form of a focused laser heating. For a weak aggression, normal swimming is sufficient and produces a steady swimming velocity. As the heating amplitude is increased, a higher acceleration and faster swimming are achieved through synchronized beating of the cilia, which begin by producing oscillating swimming velocities and later give way to the usual gait. Finally, escape from a life-threatening aggression is achieved by a "jumping" gait, which does not rely on the cilia but is achieved through the explosive release of a group of trichocysts in the direction of the hot spot. Measurements through high-speed video explain the role of trichocysts in defending against aggressions while showing unexpected transitions in the swimming of microorganisms. These measurements also demonstrate that Paramecium optimizes its escape pattern by taking advantage of its inertia.

  9. Effective climate-energy solutions, escape routes and peak oil

    International Nuclear Information System (INIS)

    Bergh, Jeroen C.J.M. van den

    2012-01-01

    Many well-intended climate-energy strategies are ineffective in the absence of serious environmental regulation. This holds, among others, for direct support of clean energy, voluntary energy conservation, technical standards on a limited set of products, unilateral stringent carbon pricing, and awaiting peak oil as a climate strategy. All of these suffer from “escape routes” that indirectly increase CO 2 emissions and thus make the original strategy ineffective. On the other hand, environmental regulation alone may lead to a myopia-bias, stimulating early dominance of cost-effective technologies and a focus on incremental innovations associated with such technologies rather than on radical innovations. Although adopting a partial viewpoint keeps the analysis simple, we urgently need a more inclusive systems perspective on climate solutions. This will allow the formulation of an effective climate policy package that addresses the various escape routes. - Highlights: ► Many well-intended climate-energy strategies are ineffective because of escape routes. ► In this context the relationship between peak oil and climate policy receives attention. ► Environmental regulation alone creates myopia-bias, the resolution of which requires technology-specific policies. ► To formulate an effective climate policy package an inclusive systems perspective is needed.

  10. Escape Geography--Developing Middle-School Students' Sense of Place.

    Science.gov (United States)

    Allen, Rodney F.; Molina, Laurie E. S.

    1992-01-01

    Suggests a social studies unit on escaping geography. Examines escape from dangerous places including an airliner, hotel fire, or war zone or from a social situation such as a boring speech or party. Describes historic escapes such as the Underground Railroad and the Berlin Wall. Lists learning strategies such as awareness of space and cognitive…

  11. Cobalt iron oxide nanoparticles induce cytotoxicity and regulate the apoptotic genes through ROS in human liver cells (HepG2).

    Science.gov (United States)

    Ahamed, Maqusood; Akhtar, Mohd Javed; Khan, M A Majeed; Alhadlaq, Hisham A; Alshamsan, Aws

    2016-12-01

    Cobalt iron oxide (CoFe 2 O 4 ) nanoparticles (CIO NPs) have been one of the most widely explored magnetic NPs because of their excellent chemical stability, mechanical hardness and heat generating potential. However, there is limited information concerning the interaction of CIO NPs with biological systems. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and apoptotic response of CIO NPs in human liver cells (HepG2). Diameter of crystalline CIO NPs was found to be 23nm with a band gap of 1.97eV. CIO NPs induced cell viability reduction and membrane damage, and degree of induction was dose- and time-dependent. CIO NPs were also found to induce oxidative stress revealed by induction of ROS, depletion of glutathione and lower activity of superoxide dismutase enzyme. Real-time PCR data has shown that mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were higher, while the expression level of anti-apoptotic gene bcl-2 was lower in cells following exposure to CIO NPs. Activity of caspase-3 and caspase-9 enzymes was also higher in CIO NPs exposed cells. Furthermore, co-exposure of N-acetyl-cysteine (ROS scavenger) efficiently abrogated the modulation of apoptotic genes along with the prevention of cytotoxicity caused by CIO NPs. Overall, we observed that CIO NPs induced cytotoxicity and apoptosis in HepG2 cells through ROS via p53 pathway. This study suggests that toxicity mechanisms of CIO NPs should be further investigated in animal models. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Synergistic effect of aluminum and ionizing radiation upon ultrastructure, oxidative stress and apoptotic alterations in Paneth cells of rat intestine.

    Science.gov (United States)

    Eltahawy, N A; Elsonbaty, S M; Abunour, S; Zahran, W E

    2017-03-01

    Environmental and occupational exposure to aluminum along with ionizing radiation results in serious health problems. This study was planned to investigate the impact of oxidative stress provoked by exposure to ionizing radiation with aluminum administration upon cellular ultra structure and apoptotic changes in Paneth cells of rat small intestine . Animals received daily aluminum chloride by gastric gavage at a dose 0.5 mg/Kg BW for 4 weeks. Whole body gamma irradiation was applied at a dose 2 Gy/week up to 8 Gy. Ileum malondialdehyde, advanced oxidative protein products, protein carbonyl and tumor necrosis factor-alpha were assessed as biomarkers of lipid peroxidation, protein oxidation and inflammation respectively along with superoxide dismutase, catalase, and glutathione peroxidase activities as enzymatic antioxidants. Moreover, analyses of cell cycle division and apoptotic changes were evaluated by flow cytometry. Intestinal cellular ultra structure was investigated using transmission electron microscope.Oxidative and inflammatory stresses assessment in the ileum of rats revealed that aluminum and ionizing radiation exposures exhibited a significant effect upon the increase in oxidative stress biomarkers along with the inflammatory marker tumor necrosis factor-α accompanied by a significant decreases in the antioxidant enzyme activities. Flow cytometric analyses showed significant alterations in the percentage of cells during cell cycle division phases along with significant increase in apoptotic cells. Ultra structurally, intestinal cellular alterations with marked injury in Paneth cells at the sites of bacterial translocation in the crypt of lumens were recorded. The results of this study have clearly showed that aluminum and ionizing radiation exposures induced apoptosis with oxidative and inflammatory disturbance in the Paneth cells of rat intestine, which appeared to play a major role in the pathogenesis of cellular damage. Furthermore, the

  13. Apoptotic potential and cell sensitivity to fractionated radiotherapy

    International Nuclear Information System (INIS)

    Rupnow, Brent A.; Murtha, Albert D.; Alarcon, Rodolfo M.; Giaccia, Amato J.; Knox, Susan J.

    1997-01-01

    Purpose/Objective: At present, the relationship between sensitivity to radiation-induced apoptosis and overall cellular radiosensitivity remains unclear. In particular, the relationship of apoptotic sensitivity to the survival of cells following fractionated irradiation has not been well studied. The purpose of the present study was to determine if increasing cell sensitivity to radiation-induced apoptosis would result in decreased clonogenic survival following single dose and fractionated irradiation in vitro. Materials and Methods: To address this, we chose a cell line (Rat-1MycER) in which the sensitivity to radiation-induced apoptosis could be altered by switching on or off the activity of a conditional c-Myc allele (c-MycER). The c-MycER construct expresses a full length c-Myc protein fused to a modified hormone binding domain of the estrogen receptor. Only in the presence of the estrogen analog 4-hydroxytamoxifen (4HT), does the conditional c-MycER become active. Apoptosis following irradiation in these cells (with and without c-MycER activation) was analyzed by flow cytometry to determine the percentage of cells undergoing apoptosis following various radiation doses and at different times after irradiation. Additionally, clonogenic survival analysis was performed following single radiation doses from 0 to 10 Gy and following five fractions of 2 or 4 Gy each. Survival of cells with and without c-MycER activation was compared. Furthermore, the effect of overexpressing the anti-apoptotic Bcl-2 gene on apoptosis induction and clonogenic survival of these cells was examined. Results: Rat-1MycER cells were strongly sensitized to radiation-induced apoptosis in a dose and time dependent manner when MycER was activated relative to cells treated without c-MycER activation. This c-Myc-mediated sensitivity to radiation-induced apoptosis was suppressed by overexpression of the anti-apoptotic protein Bcl-2. In addition to increasing apoptosis, activating c-MycER prior to

  14. The effects of escape from self and interpersonal relationship on the pathological use of Internet games.

    Science.gov (United States)

    Kwon, Jung-Hye; Chung, Chung-Suk; Lee, Jung

    2011-02-01

    The purpose of the present study was to examine whether Baumeister's escape from self theory may account for the pathological use of Internet games among Korean adolescents. A sample of 1,136 junior high school students completed measures assessing Internet game addiction (IGA), real-ideal self discrepancy, escape from self, current mood, peer relationships, perceived parent-child relationship, and parental supervision. IGA was significantly correlated with all of these variables. Multiple regression analysis showed that escape from self best explained the adolescents' IGA. A path model yielded significant paths from self-discrepancy to negative mood, from negative mood to escape from self, and from escape from self to IGA. These results support the validity of using the escape from self theory to explain the adolescents' IGA, thereby suggesting that adolescents become addicted to Internet games in an attempt to escape from self and reality.

  15. Protective effect of oestradiol in the coeliac ganglion against ovarian apoptotic mechanism on dioestrus.

    Science.gov (United States)

    Cynthia, Bronzi; Cristina, Daneri Becerra; Adriana, Vega Orozco; Belén, Delsouc María; María, Rastrilla Ana; Marilina, Casais; Zulema, Sosa

    2013-05-01

    The aims of this work were to investigate if oestradiol 10(-8)M in the incubation media of either the ovary alone (OV) or the ganglion compartment of an ex vivo coeliac ganglion-superior ovarian nerve-ovary system (a) modifies the release of ovarian progesterone (P4) and oestradiol (E2) on dioestrus II, and (b) modifies the ovarian gene expression of 3β-HSD and 20α-HSD enzymes and markers of apoptosis. The concentration of ovarian P4 release was measured in both experimental schemes, and ovarian P4 and E2 in the ex vivo system by RIA at different times. The expression of 3β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and antiapoptotic bcl-2 and proapoptotic bax by RT-PCR were determined. E2 added in the coeliac ganglion caused an increase in the ovarian release of the P4, E2 and 3β-HSD, while in the ovary incubation alone it decreased P4 and 3β-HSD but increased and 20α-HSD and bax/bcl-2 ratio. It is concluded that through a direct effect on the ovary, E2 promotes luteal regression in DII rats, but the addition of E2 in the coeliac ganglion does not have the same effect. The peripheral nervous system, through the superior ovarian nerve, has a protective effect against the apoptotic mechanism on DII. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Oxidative stress and apoptotic events during thermal stress in the symbiotic sea anemone, Anemonia viridis.

    Science.gov (United States)

    Richier, Sophie; Sabourault, Cécile; Courtiade, Juliette; Zucchini, Nathalie; Allemand, Denis; Furla, Paola

    2006-09-01

    Symbiosis between cnidarian and photosynthetic protists is widely distributed over temperate and tropical seas. These symbioses can periodically breakdown, a phenomenon known as cnidarian bleaching. This event can be irreversible for some associations subjected to acute and/or prolonged environmental disturbances, and leads to the death of the animal host. During bleaching, oxidative stress has been described previously as acting at molecular level and apoptosis is suggested to be one of the mechanisms involved. We focused our study on the role of apoptosis in bleaching via oxidative stress in the association between the sea anemone Anemonia viridis and the dinoflagellates Symbiodinium species. Characterization of caspase-like enzymes were conducted at the biochemical and molecular level to confirm the presence of a caspase-dependent apoptotic phenomenon in the cnidarian host. We provide evidence of oxidative stress followed by induction of caspase-like activity in animal host cells after an elevated temperature stress, suggesting the concomitant action of these components in bleaching.

  17. Pro-apoptotic effects of the flavonoid luteolin in rat H4IIE cells

    International Nuclear Information System (INIS)

    Michels, G.; Waetjen, W.; Niering, P.; Steffan, B.; Thi, Q.-H. Tran; Chovolou, Y.; Kampkoetter, A.; Bast, A.; Proksch, P.; Kahl, R.

    2005-01-01

    Polyphenols are ubiquitous substances in the diet. Their anti-oxidative, anti-inflammatory and anti-viral effects are of interest for human health, and polyphenols such as luteolin are used at high concentrations in food supplements. The aim of this project was to determine the intrinsic effects of luteolin in H4IIE rat hepatoma cells. Luteolin is relatively toxic, cell death was caused via induction of apoptosis as detected by DNA-ladder formation, by nuclear fragmentation and activation of apoptotic enzymes (caspase-2, -3/7, -9 and -8/10). Luteolin (250 μM, 24 h) increased the caspase-3/7 activity four-fold and the caspase-9 activity six-fold. In a time course experiment caspase-9 is activated after 6 h, while caspase-2 and -3/7 are activated after 12 h. After 24 h, caspase-8/10 also displays activation. We found a concentration-dependent increase in malondialdehyde release suggesting a prooxidative effect of luteolin. Furthermore, we analysed DNA strand break formation by luteolin and found a distinct increase of DNA strand breaks after incubation for 3 h with 100 μM luteolin, a concentration which induces oligonucleosomal DNA cleavage at 24 h. In conclusion, the sequence of events is compatible with the assumption that luteolin triggers the mitochondrial pathway of apoptosis, probably by inducing DNA damage

  18. PKCη confers protection against apoptosis by inhibiting the pro-apoptotic JNK activity in MCF-7 cells

    International Nuclear Information System (INIS)

    Rotem-Dai, Noa; Oberkovitz, Galia; Abu-Ghanem, Sara; Livneh, Etta

    2009-01-01

    Apoptosis is frequently regulated by different protein kinases including protein kinase C family enzymes. Both inhibitory and stimulatory effects were demonstrated for several of the different PKC isoforms. Here we show that the novel PKC isoform, PKCη, confers protection against apoptosis induced by the DNA damaging agents, UVC irradiation and the anti-cancer drug - Camptothecin, of the breast epithelial adenocarcinoma MCF-7 cells. The induced expression of PKCη in MCF-7 cells, under the control of the tetracycline-responsive promoter, resulted in increased cell survival and inhibition of cleavage of the apoptotic marker PARP-1. Activation of caspase-7 and 9 and the release of cytochrome c were also inhibited by the inducible expression of PKCη. Furthermore, JNK activity, required for apoptosis in MCF-7, as indicated by the inhibition of both caspase-7 cleavage and cytochrome c release from the mitochondria in the presence of the JNK inhibitor SP600125, was also suppressed by PKCη expression. Hence, in contrast to most PKC isoforms enhancing JNK activation, our studies show that PKCη is an anti-apoptotic protein, acting as a negative regulator of JNK activity. Thus, PKCη could represent a target for intervention aimed to reduce resistance to anti-cancer treatments.

  19. Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation.

    Science.gov (United States)

    Fuchs, Christiane; Rosner, Margit; Dolznig, Helmut; Mikula, Mario; Kramer, Nina; Hengstschläger, Markus

    2012-03-01

    Embryoid bodies (EBs) are three-dimensional multicellular aggregates allowing the in vitro investigation of stem-cell differentiation processes mimicking early embryogenesis. Human amniotic fluid stem (AFS) cells harbor high proliferation potential, do not raise the ethical issues of embryonic stem cells, have a lower risk for tumor development, do not need exogenic induction of pluripotency and are chromosomal stable. Starting from a single human AFS cell, EBs can be formed accompanied by the differentiation into cells of all three embryonic germ layers. Here, we report that siRNA-mediated knockdown of the endogenous tuberous sclerosis complex-2 (TSC2) gene product tuberin or of proline-rich Akt substrate of 40 kDa (PRAS40), the two major negative regulators of mammalian target of rapamycin (mTOR), leads to massive apoptotic cell death during EB development of human AFS cells without affecting the endodermal, mesodermal and ectodermal cell differentiation spectrum. Co-knockdown of endogenous mTOR demonstrated these effects to be mTOR-dependent. Our findings prove this enzyme cascade to be an essential anti-apoptotic gatekeeper of stem-cell differentiation during EB formation. These data allow new insights into the regulation of early stem-cell maintenance and differentiation and identify a new role of the tumor suppressor tuberin and the oncogenic protein PRAS40 with the relevance for a more detailed understanding of the pathogenesis of diseases associated with altered activities of these gene products.

  20. Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli.

    Science.gov (United States)

    Alsaleh, Ghada; Nehmar, Ramzi; Blüml, Stephan; Schleiss, Cédric; Ostermann, Eleonore; Dillenseger, Jean-Philippe; Sayeh, Amira; Choquet, Philippe; Dembele, Doulaye; Francois, Antoine; Salmon, Jean-Hugues; Paul, Nicodème; Schabbauer, Gernot; Bierry, Guillaume; Meyer, Alain; Gottenberg, Jacques-Eric; Haas, Gabrielle; Pfeffer, Sebastien; Vallat, Laurent; Sibilia, Jean; Bahram, Seiamak; Georgel, Philippe

    2016-08-01

    While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ). The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay. We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli. The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses. © 2016, American College of Rheumatology.

  1. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  2. 5-Lipoxygenase contributes to PPARγ activation in macrophages in response to apoptotic cells.

    Science.gov (United States)

    von Knethen, Andreas; Sha, Lisa K; Kuchler, Laura; Heeg, Annika K; Fuhrmann, Dominik; Heide, Heinrich; Wittig, Ilka; Maier, Thorsten J; Steinhilber, Dieter; Brüne, Bernhard

    2013-12-01

    Macrophage polarization to an anti-inflammatory phenotype upon contact with apoptotic cells is a contributing hallmark to immune suppression during the late phase of sepsis. Although the peroxisome proliferator-activated receptor γ (PPARγ) supports this macrophage phenotype switch, it remains elusive how apoptotic cells activate PPARγ. Assuming that a molecule causing PPARγ activation in macrophages originates in the cell membrane of apoptotic cells we analyzed lipid rafts from apoptotic, necrotic, and living human Jurkat T cells which showed the presence of 5-lipoxygenase (5-LO) in lipid rafts of apoptotic cells only. Incubating macrophages with lipid rafts of apoptotic, but not necrotic or living cells, induced PPAR responsive element (PPRE)-driven mRuby reporter gene expression in RAW 264.7 macrophages stably transduced with a 4xPPRE containing vector. Experiments with lipid rafts of apoptotic murine EL4 T cells revealed similar results. To verify the involvement of 5-LO in activating PPARγ in macrophages, Jurkat T cells were incubated with the 5-LO inhibitor MK-866 prior to induction of apoptosis, which failed to induce mRuby expression. Similar results were obtained with lipid rafts of apoptotic EL4 T cells preexposed to the 5-LO inhibitors zileuton and CJ-13610. Interestingly, Jurkat T cells overexpressing 5-LO failed to activate PPARγ in macrophages, while their 5-LO overexpressing apoptotic counterparts did. Our results suggest that during apoptosis 5-LO gets associated with lipid rafts and synthesizes ligands that in turn stimulate PPARγ in macrophages. © 2013.

  3. Escaping the Self: Identity, Group Identification and Violence

    Directory of Open Access Journals (Sweden)

    James Hardie-Bick

    2016-12-01

    Full Text Available This article draws on the early work of Erich Fromm. In Escape from Freedom Fromm (1969 [1941] directly addressed the psychological mechanisms of escape modern individuals employ to protect themselves from feelings of ontological insecurity and existential estrangement. The article builds on Fromm’s analysis by discussing the significance of his escape mechanisms for understanding the dynamic psychological attractions of identifying with entitative groups. Fromm’s work will be discussed in relation to Hogg’s recent work on uncertainty-identity theory. The aim of the article is to examine the advantages of combining Fromm’s psychoanalytic analysis with Hogg’s uncertainty-identity theory and to highlight the potential this approach has for understanding why groups engage in violent and destructive behaviour. Este artículo se inspira en las primeras obras de Erich Fromm. En El miedo a la libertad, Fromm (1969 [1941] abordó directamente los mecanismos psicológicos de evasión que los individuos modernos emplean para protegerse de los sentimientos de inseguridad ontológica y distanciamiento existencial. Este artículo se basa en el análisis de Fromm exponiendo el significado de sus mecanismos de evasión para entender las atracciones psicológicas dinámicas de identificación con grupos entitativos. Se analizará la obra de Fromm en relación con la obra reciente de Hogg sobre la teoría de incertidumbre identitaria. El objetivo del artículo es examinar las ventajas de combinar el análisis psicoanalítico de Fromm con la teoría de incertidumbre identitaria de Hogg, y destacar el potencial que tiene esta aproximación para comprender por qué los grupos adoptan un comportamiento violento y destructivo. DOWNLOAD THIS PAPER FROM SSRN: https://ssrn.com/abstract=2875737

  4. Escape trajectories of solar sails and general relativity

    Energy Technology Data Exchange (ETDEWEB)

    Kezerashvili, Roman Ya. [Physics Department, New York City College of Technology, City University of New York, 300 Jay Street, Brooklyn, NY 11201 (United States); Graduate School and University Center, City University of New York, 365 Fifth Avenue, New York, NY 10016 (United States); Vazquez-Poritz, Justin F., E-mail: jvazquez-poritz@citytech.cuny.ed [Physics Department, New York City College of Technology, City University of New York, 300 Jay Street, Brooklyn, NY 11201 (United States); Graduate School and University Center, City University of New York, 365 Fifth Avenue, New York, NY 10016 (United States)

    2009-11-16

    General relativity can have a significant impact on the long-range escape trajectories of solar sails deployed near the sun. For example, spacetime curvature in the vicinity of the sun can cause a solar sail traveling from about 4 solar radii to 2550 AU to be deflected by on the order of a million kilometers, and should therefore be taken into account at the beginning of the mission. There are a number of smaller general relativistic effects, such as frame dragging due to the slow rotation of the sun which can cause a deflection of more than one thousand kilometers.

  5. Diffusion escape through a cluster of small absorbing windows

    Energy Technology Data Exchange (ETDEWEB)

    Holcman, D [Department of Mathematics, Weizmann Institute of Science, Rehovot 76100 (Israel); Schuss, Z [Department of Mathematics, Tel-Aviv University, Tel-Aviv 69978 (Israel)

    2008-04-18

    We study the first eigenvalue of the Laplace equation in a bounded domain in R{sup d} (d=2,3) with mixed Neumann-Dirichlet (Zaremba) boundary conditions. The Neumann condition is imposed on most of the boundary and the Dirichlet boundary consists of a cluster of small windows. When the windows are well separated the first eigenvalue is asymptotically the sum of eigenvalues of mixed problems with a single Dirichlet window. However, when two or more Dirichlet windows cluster tightly together they interact nonlinearly. We compare our asymptotic approximation of the eigenvalue to the escape rate of simulated Brownian particles through the small windows.

  6. Chases and escapes the mathematics of pursuit and evasion

    CERN Document Server

    Nahin, Paul J

    2012-01-01

    We all played tag when we were kids. What most of us don't realize is that this simple chase game is in fact an application of pursuit theory, and that the same principles of games like tag, dodgeball, and hide-and-seek are also at play in military strategy, high-seas chases by the Coast Guard, and even romantic pursuits. In Chases and Escapes, Paul Nahin gives us the first complete history of this fascinating area of mathematics, from its classical analytical beginnings to the present day. Drawing on game theory, geometry, linear algebra, target-tracking algorithms, and much

  7. Experimental study of subsonic microjet escaping from a rectangular nozzle

    Science.gov (United States)

    Aniskin, V. M.; Maslov, A. A.; Mukhin, K. A.

    2016-10-01

    The first experiments on the subsonic laminar microjets escaping from the nozzles of rectangular shape are carried out. The nozzle size is 83.3x3823 microns. Reynolds number calculated by the nozzle height and the average flow velocity at the nozzle exit ranged from 58 to 154. The working gas was air at room temperature. The velocity decay and velocity fluctuations along the center line of the jet are determined. The fundamental difference between the laminar microjets characteristics and subsonic turbulent jets of macro size is shown. Based on measurements of velocity fluctuations it is shown the presence of laminar-turbulent transition in microjets and its location is determined.

  8. The age structure of selected countries in the ESCAP region.

    Science.gov (United States)

    Hong, S

    1982-01-01

    The study objective was to examine the age structure of selected countries in the Economic and Social Commission for Asia and the Pacific (ESCAP) region, using available data and frequently applied indices such as the population pyramid, aged-child ratio, and median age. Based on the overall picture of the age structure thus obtained, age trends and their implication for the near future were arrived at. Countries are grouped into 4 types based on the fertility and mortality levels. Except for Japan, Hong Kong, and Singapore, the age structure in the 18 ESCAP region countries changed comparatively little over the 1950-80 period. The largest structural change occurred in Singapore, where the proportion of children under age 15 in the population declined significantly from 41-27%, while that of persons 65 years and older more than doubled. This was due primarily to the marked decline in fertility from a total fertility rate (TFR) of 6.7-1.8 during the period. Hong Kong also had a similar major transformation during the same period: the proportion of the old age population increased 2 1/2 times, from 2.5-6.3%. The age structures of the 18 ESCAP countries varied greatly by country. 10 countries of the 2 high fertility and mortality types showed a similar young age structural pattern, i.e., they have higher dependency ratios, a higher proportion of children under 15 years, a lower proportion of population 65 years and older, lower aged-child ratios, and younger median ages than the average countries in the less developed regions of the world. With minimal changes over the 1950-80 period, the gap between these countries and the average of the less developed regions widened. Unlike these 10 (mostly South Asian) countries, moderately low fertility and mortality countries (China, Korea, and Sri Lanka) are located between the world average and the less developed region in most of the indices, particularly during the last decade. Although their rate of population aging is not

  9. Escape trajectories of solar sails and general relativity

    International Nuclear Information System (INIS)

    Kezerashvili, Roman Ya.; Vazquez-Poritz, Justin F.

    2009-01-01

    General relativity can have a significant impact on the long-range escape trajectories of solar sails deployed near the sun. For example, spacetime curvature in the vicinity of the sun can cause a solar sail traveling from about 4 solar radii to 2550 AU to be deflected by on the order of a million kilometers, and should therefore be taken into account at the beginning of the mission. There are a number of smaller general relativistic effects, such as frame dragging due to the slow rotation of the sun which can cause a deflection of more than one thousand kilometers.

  10. International Environmental Agreements: Emissions Trade, Safety Valves and Escape Clauses

    International Nuclear Information System (INIS)

    Karp, Larry; Zhao, Jinhua

    2010-01-01

    We explain how the structure of multi-national or multi-regional environmental agreements affect their chance of success. Trade in emissions permits has ambiguous and in some cases surprising effects on both the equilibrium level of abatement, and on the ability to persuade nations or regions to participate in environmental agreements. An escape clause policy and a safety valve policy have essentially the same properties when membership in environmental agreement is pre-determined, but they create markedly different effects on the incentives to join such an agreement. The two policies lead to a qualitative difference in the leverage that a potential member of the agreement exercises on other members

  11. The case of escape probability as linear in short time

    Science.gov (United States)

    Marchewka, A.; Schuss, Z.

    2018-02-01

    We derive rigorously the short-time escape probability of a quantum particle from its compactly supported initial state, which has a discontinuous derivative at the boundary of the support. We show that this probability is linear in time, which seems to be a new result. The novelty of our calculation is the inclusion of the boundary layer of the propagated wave function formed outside the initial support. This result has applications to the decay law of the particle, to the Zeno behaviour, quantum absorption, time of arrival, quantum measurements, and more.

  12. Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Steven T. Denham

    2018-02-01

    Full Text Available Cryptococcus neoformans is a common environmental saprophyte and human fungal pathogen that primarily causes disease in immunocompromised individuals. Similar to many environmentally acquired human fungal pathogens, C. neoformans initiates infection in the lungs. However, the main driver of mortality is invasive cryptococcosis leading to fungal meningitis. After C. neoformans gains a foothold in the lungs, a critical early step in invasion is transversal of the respiratory epithelium. In this review, we summarize current knowledge relating to pulmonary escape. We focus on fungal factors that allow C. neoformans to disseminate from the lungs via intracellular and extracellular routes.

  13. PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy

    Directory of Open Access Journals (Sweden)

    Byeon HJ

    2015-01-01

    Full Text Available Hyeong Jun Byeon,1 Insoo Kim,1 Ji Su Choi,1 Eun Seong Lee,2 Beom Soo Shin,3 Yu Seok Youn11Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 2Division of Biotechnology, The Catholic University of Korea, Bucheon-si, Republic of Korea; 3Department of Pharmacy, College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Republic of KoreaAbstract: The aim of the current study was to investigate the antitumor potential of poly(D,L-lactic-co-glycolic acid microspheres (PLGA MSs containing polyethylene glycol (PEG-conjugated (PEGylated tumor necrosis factor–related apoptosis-inducing ligand (PEG-TRAIL. PEG-TRAIL PLGA MSs were prepared by using a water-in-oil-in-water double-emulsion method, and the apoptotic activities of supernatants released from the PLGA MSs at days 1, 3, and 7 were examined. The antitumor effect caused by PEG-TRAIL PLGA MSs was evaluated in pancreatic Mia Paca-2 cell-xenografted mice. PEG-TRAIL PLGA MS was found to be spherical and 14.4±1.06 µm in size, and its encapsulation efficiency was significantly greater than that of TRAIL MS (85.7%±4.1% vs 43.3%±10.9%, respectively. The PLGA MS gradually released PEG-TRAIL for 14 days, and the released PEG-TRAIL was shown to have clear apoptotic activity in Mia Paca-2 cells, whereas TRAIL released after 1 day had a negligible activity. Finally, PEG-TRAIL PLGA MS displayed remarkably greater antitumor efficacy than blank or TRAIL PLGA MS in Mia Paca-2 cell-xenografted mice in terms of tumor volume and weight, apparently due to increased stability and well-retained apoptotic activity of PEG-TRAIL in PLGA MS. We believe that this PLGA MS system, combined with PEG-TRAIL, should be considered a promising candidate for treating pancreatic cancer.Keywords: Poly(D,L-lactic-co-glycolic acid, controlled release, PEGylation, TRAIL, pancreatic cancer

  14. European SpaceCraft for the study of Atmospheric Particle Escape (ESCAPE): a planetary mission to Earth, proposed in response to the ESA M5-call

    Science.gov (United States)

    Dandouras, I.; Yamauchi, M.; Rème, H.; De Keyser, J.; Marghitu, O.; Fazakerley, A.; Grison, B.; Kistler, L.; Milillo, A.; Nakamura, R.; Paschalidis, N.; Paschalis, A.; Pinçon, J.-L.; Sakanoi, T.; Wieser, M.; Wurz, P.; Yoshikawa, I.; Häggström, I.; Liemohn, M.; Tian, F.

    2017-09-01

    ESCAPE is a mission proposed in response to the ESA-M5 call that will quantitatively estimate the amount of escaping particles of the major atmospheric components (nitrogen and oxygen), as neutral and ionised species, escaping from the Earth as a magnetised planet. The goal is to understand the importance of each escape mechanism, its dependence on solar and geomagnetic activity, and to infer the history of the Earth's atmospheric composition over a long (geological scale) time period. Since the solar EUV and solar wind conditions during solar maximum at present are comparable to the solar minimum conditions 1-2 billion years ago, the escaping amount and the isotope and N/O ratios should be obtained as a function of external forcing (solar and geomagnetic conditions) to allow a scaling to the past. The result will be used as a reference to understand the atmospheric/ionospheric evolution of magnetised planets, which is essential for habitability.

  15. Myotonic dystrophy protein kinase (DMPK) induces actin cytoskeletal reorganization and apoptotic-like blebbing in lens cells

    Science.gov (United States)

    Jin, S.; Shimizu, M.; Balasubramanyam, A.; Epstein, H. F.

    2000-01-01

    DMPK, the product of the DM locus, is a member of the same family of serine-threonine protein kinases as the Rho-associated enzymes. In DM, membrane inclusions accumulate in lens fiber cells producing cataracts. Overexpression of DMPK in cultured lens epithelial cells led to apoptotic-like blebbing of the plasma membrane and reorganization of the actin cytoskeleton. Enzymatically active DMPK was necessary for both effects; inactive mutant DMPK protein did not produce either effect. Active RhoA but not constitutive GDP-state mutant protein produced similar effects as DMPK. The similar actions of DMPK and RhoA suggest that they may function in the same regulatory network. The observed effects of DMPK may be relevant to the removal of membrane organelles during normal lens differentiation and the retention of intracellular membranes in DM lenses. Copyright 2000 Wiley-Liss, Inc.

  16. Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

    2013-01-01

    Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

  17. Apoptotic and Nonapoptotic Activities of Pterostilbene against Cancer

    Directory of Open Access Journals (Sweden)

    Rong-Jane Chen

    2018-01-01

    Full Text Available Cancer is a major cause of death. The outcomes of current therapeutic strategies against cancer often ironically lead to even increased mortality due to the subsequent drug resistance and to metastatic recurrence. Alternative medicines are thus urgently needed. Cumulative evidence has pointed out that pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene, PS has excellent pharmacological benefits for the prevention and treatment for various types of cancer in their different stages of progression by evoking apoptotic or nonapoptotic anti-cancer activities. In this review article, we first update current knowledge regarding tumor progression toward accomplishment of metastasis. Subsequently, we review current literature regarding the anti-cancer activities of PS. Finally, we provide future perspectives to clinically utilize PS as novel cancer therapeutic remedies. We, therefore, conclude and propose that PS is one ideal alternative medicine to be administered in the diet as a nutritional supplement.

  18. New insights on the collisional escape of light neutrals from Mars

    Science.gov (United States)

    Gacesa, Marko; Zahnle, Kevin

    2017-04-01

    Photodissociative recombination (PDR) of atmospheric molecules on Mars is a major mechanism of production of hot (suprathermal) atoms with sufficient kinetic energy to either directly escape to space or to eject other atmospheric species. This collisional ejection mechanism is important for evaluating the escape rates of all light neutrals that are too heavy to escape via Jeans escape. In particular, it plays a role in estimating the total volume of escaped water constituents (i.e., O and H) from Mars, as well as influences evolution of the atmospheric [D]/[H] ratio1. We present revised estimates of total collisional escape rates of neutral light elements including H, He, and H2, based on recent (years 2015-2016) atmospheric density profiles obtained from the NASA Mars Atmosphere and Volatile Evolution (MAVEN) mission. We also estimate the contribution to the collisional escape from Energetic Neutral Atoms (ENAs) produced in charge-exchange of solar wind H+ and He+ ions with atmospheric gases2,3. Scattering of hot oxygen and atmospheric species of interest is modeled using fully-quantum reactive scattering formalism1,3. The escape rates are evaluated using a 1D model of the atmosphere supplemented with MAVEN measurements of the neutrals. Finally, new estimates of contributions of these non-thermal mechanisms to the estimated PDR escape rates from young Mars4 are presented. [1] M. Gacesa and V. Kharchenko, "Non-thermal escape of molecular hydrogen from Mars", Geophys. Res. Lett., 39, L10203 (2012). [2] N. Lewkow and V. Kharchenko, "Precipitation of Energetic Neutral Atoms and Escape Fluxes induced from the Mars Atmosphere", Astroph. J., 790, 98 (2014). [3] M. Gacesa, N. Lewkow, and V. Kharchenko, "Non-thermal production and escape of OH from the upper atmosphere of Mars", Icarus 284, 90 (2017). [4] J. Zhao, F. Tian, Y. Ni, and X. Huang, "DR-induced escape of O and C from early Mars", Icarus 284, 305 (2017).

  19. PARP Inhibition Restores Extrinsic Apoptotic Sensitivity in Glioblastoma

    Science.gov (United States)

    Karpel-Massler, Georg; Pareja, Fresia; Aimé, Pascaline; Shu, Chang; Chau, Lily; Westhoff, Mike-Andrew; Halatsch, Marc-Eric; Crary, John F.; Canoll, Peter; Siegelin, Markus D.

    2014-01-01

    Background Resistance to apoptosis is a paramount issue in the treatment of Glioblastoma (GBM). We show that targeting PARP by the small molecule inhibitors, Olaparib (AZD-2281) or PJ34, reduces proliferation and lowers the apoptotic threshold of GBM cells in vitro and in vivo. Methods The sensitizing effects of PARP inhibition on TRAIL-mediated apoptosis and potential toxicity were analyzed using viability assays and flow cytometry in established GBM cell lines, low-passage neurospheres and astrocytes in vitro. Molecular analyses included western blots and gene silencing. In vivo, effects on tumor growth were examined in a murine subcutaneous xenograft model. Results The combination treatment of PARP inhibitors and TRAIL led to an increased cell death with activation of caspases and inhibition of formation of neurospheres when compared to single-agent treatment. Mechanistically, pharmacological PARP inhibition elicited a nuclear stress response with up-regulation of down-stream DNA-stress response proteins, e.g., CCAAT enhancer binding protein (C/EBP) homology protein (CHOP). Furthermore, Olaparib and PJ34 increased protein levels of DR5 in a concentration and time-dependent manner. In turn, siRNA-mediated suppression of DR5 mitigated the effects of TRAIL/PARP inhibitor-mediated apoptosis. In addition, suppression of PARP-1 levels enhanced TRAIL-mediated apoptosis in malignant glioma cells. Treatment of human astrocytes with the combination of TRAIL/PARP inhibitors did not cause toxicity. Finally, the combination treatment of TRAIL and PJ34 significantly reduced tumor growth in vivo when compared to treatment with each agent alone. Conclusions PARP inhibition represents a promising avenue to overcome apoptotic resistance in GBM. PMID:25531448

  20. On the escape of pollutants from urban street canyons

    Energy Technology Data Exchange (ETDEWEB)

    Baik, J.J.; Kim, J.J. [Kwangju Inst. of Science and Technology (Korea). Dept. of Environmental Science and Engineering

    2002-07-01

    Pollutant transport from urban street canyons is numerically investigated using a two-dimensional flow and dispersion model. The ambient wind blows perpendicular to the street and passive pollutants are released at the street level. Results from the control experiment with a street aspect ratio of 1 show that at the roof level of the street canyon, the vertical turbulent flux of pollutants is upward everywhere and the vertical flux of pollutants by mean flow is upward or downward. The horizontally integrated vertical flux of pollutants by mean flow at the roof level of the street canyon is downward and its magnitude is much smaller than that by turbulent process. These results indicate that pollutants escape from the street canyon mainly by turbulent process and that the net effect of mean flow is to make some escaped pollutants reenter the street canyon. Further experiments with different inflow turbulence intensities, inflow wind speeds, and street aspect ratio confirm the findings from the control experiment. In the case of two isolated buildings, the horizontally integrated vertical flux of pollutants by mean flow is upward due to flow separation but the other main results are the same as those from the control experiment. (author)

  1. Ultra-fast Escape of a Octopus-inspired Rocket

    Science.gov (United States)

    Weymouth, Gabriel; Triantafyllou, Michael

    2013-11-01

    The octopus, squid, and other cephalopods inflate with water and then release a jet to accelerate in the opposite direction. This escape mechanism is particularly interesting in the octopus because they become initially quite bluff, yet this does not hinder them in achieving impressive bursts of speed. We examine this somewhat paradoxical maneuver using a simple deflating spheroid model in both potential and viscous flow. We demonstrate that the dynamic reduction of the width of the body completely changes the flow and forces acting on the escaping rocket in three ways. First, a body which reduces in size can generate an added mass thrust which counteracts the added mass inertia. Second, the motion of the shrinking wall acts similar to suction on a static wall, reducing separation and drag forces in a viscous fluid, but that this effects depends on the rate of size change. Third, using a combination of these two features it is possible to initially load the fluid with kinetic energy when heavy and bluff and then recover that energy when streamlined and light, enabling ultra-fast accelerations. As a notable example, these mechanisms allow a shrinking spheroid rocket in a heavy inviscid fluid to achieve speeds greater than an identical rocket in the vacuum of space. Southampton Marine and Maritime Institute.

  2. Lionfish misidentification circumvents an optimized escape response by prey.

    Science.gov (United States)

    McCormick, Mark I; Allan, Bridie J M

    2016-01-01

    Invasive lionfish represent an unprecedented problem in the Caribbean basin, where they are causing major changes to foodwebs and habitats through their generalized predation on fishes and invertebrates. To ascertain what makes the red lionfish ( Pterois volitans ) such a formidable predator, we examined the reaction of a native damselfish prey, the whitetail damsel ( Pomacentrus chrysurus ), to a repeatable startle stimulus once they had been forewarned of the sight or smell of lionfish. Fast-start responses were compared with prey forewarned of a predatory rockcod ( Cephalopholis microprion ), a corallivorous butterflyfish ( Chaetodon trifasctiatus ) and experimental controls. Forewarning of the sight, smell or a combination of the two cues from a rockcod led to reduced escape latencies and higher response distances, speed and maximal speed compared with controls, suggesting that forewarning primed the prey and enabled a more effective escape response. In contrast, forewarning of lionfish did not affect the fast-start kinematics measured, which were the same as in the control and non-predatory butterflyfish treatments. Lionfish appear to be able to circumvent mechanisms commonly used by prey to identify predators and were misclassified as non-predatory, and this is likely to contribute to their success as predators.

  3. Escape of charged particles from a neutron star

    International Nuclear Information System (INIS)

    Pelizzari, M.A.

    1976-01-01

    The theory of particle trajectories in an axisymmetric magnetic field, formulated by C. Stormer, can be extended to cover conservative force fields as well. As such, it is an ideal tool to study the escape of charged particles from a rapidly rotating neutron star, enabling one to determine the maximum range of their trajectories in space. With the aid of this theory, it is shown that a neutron star, rotating in a vacuum with rotation and magnetic axes aligned, will not evolve a perfectly conducting magnetosphere if the neutron star is the only source of charge. The sign of charge accelerated from the equatorial regions will be magnetically trapped to a toroidal region very near the star, and the opposite sign of charge, emerging from the polar regions, will escape from the magnetosphere until a critical stellar charge is reached, after which polar charges will be electrostatically bound to the magnetosphere. This selective magnetic trapping of one sign of charge, which prevents the formation of a stellar wind, is a consequence of the magnetic field's orientation relative to the internal charge density of the neutron star

  4. Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

    OpenAIRE

    Lim, Sung-Chul; Jeon, Ho Jong; Kee, Keun Hong; Lee, Mi Ja; Hong, Ran; Han, Song Iy

    2017-01-01

    Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL)....

  5. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

    DEFF Research Database (Denmark)

    Straten, Per thor; Andersen, Mads Hald; Andersen, Mads Hald

    2010-01-01

    Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death. They are all highly overexpressed in cancers of different origin in which they enhance the survival of the cancer cells. Consequently, they represent prime candidates for anti-ca...

  6. The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal

    Directory of Open Access Journals (Sweden)

    Hafner Martin

    2004-08-01

    Full Text Available Abstract Background Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse. Results Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr -/- mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide. Conclusion Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance.

  7. Relationship between apoptotic markers in semen from fertile men and demographic, hormonal and seminal characteristics

    DEFF Research Database (Denmark)

    Specht, Ina; Spanò, Marcello; Hougaard, Karin S

    2012-01-01

    and biological correlates of the pro-apoptotic marker Fas and the anti-apoptotic marker Bcl-xL in sperm cells of fertile men. Six hundred and four men from Greenland, Poland and Ukraine were consecutively enrolled during their pregnant wife's antenatal visits. Semen analysis was performed as recommended...

  8. Orbital and escape dynamics in barred galaxies - III. The 3D system: correlations between the basins of escape and the NHIMs

    Science.gov (United States)

    Zotos, Euaggelos E.; Jung, Christof

    2018-01-01

    The escape dynamics of the stars in a barred galaxy composed of a spherically symmetric central nucleus, a bar, a flat thin disc and a dark matter halo component is investigated by using a realistic three degrees of freedom (3-d.o.f.) dynamical model. Modern colour-coded diagrams are used for distinguishing between bounded and escaping motion. In addition, the smaller alignment index method is deployed for determining the regular, sticky or chaotic nature of bounded orbits. We reveal the basins of escape corresponding to the escape through the two symmetrical escape channels around the Lagrange points L2 and L3 and also we relate them with the corresponding distribution of the escape times of the orbits. Furthermore, we demonstrate how the stable manifolds, around the index-1 saddle points, accurately define the fractal basin boundaries observed in the colour-coded diagrams. The development scenario of the fundamental vertical Lyapunov periodic orbit is thoroughly explored for obtaining a more complete view of the unfolding of the singular behaviour of the dynamics at the cusp values of the parameters. Finally, we examine how the combination of the most important parameters of the bar (such as the semimajor axis and the angular velocity) influences the observed stellar structures (rings and spirals), which are formed by escaping stars guided by the invariant manifolds near the saddle points.

  9. Integrating geographical information and augmented reality techniques for mobile escape guidelines on nuclear accident sites

    International Nuclear Information System (INIS)

    Tsai, Ming-Kuan; Lee, Yung-Ching; Lu, Chung-Hsin; Chen, Mei-Hsin; Chou, Tien-Yin; Yau, Nie-Jia

    2012-01-01

    During nuclear accidents, when radioactive materials spread into the environment, the people in the affected areas should evacuate immediately. However, few information systems are available regarding escape guidelines for nuclear accidents. Therefore, this study constructs escape guidelines on mobile phones. This application is called Mobile Escape Guidelines (MEG) and adopts two techniques. One technique is the geographical information that offers multiple representations; the other is the augmented reality that provides semi-realistic information services. When this study tested the mobile escape guidelines, the results showed that this application was capable of identifying the correct locations of users, showing the escape routes, filtering geographical layers, and rapidly generating the relief reports. Users could evacuate from nuclear accident sites easily, even without relief personnel, since using slim devices to access the mobile escape guidelines is convenient. Overall, this study is a useful reference for a nuclear accident emergency response.

  10. Integrating geographical information and augmented reality techniques for mobile escape guidelines on nuclear accident sites.

    Science.gov (United States)

    Tsai, Ming-Kuan; Lee, Yung-Ching; Lu, Chung-Hsin; Chen, Mei-Hsin; Chou, Tien-Yin; Yau, Nie-Jia

    2012-07-01

    During nuclear accidents, when radioactive materials spread into the environment, the people in the affected areas should evacuate immediately. However, few information systems are available regarding escape guidelines for nuclear accidents. Therefore, this study constructs escape guidelines on mobile phones. This application is called Mobile Escape Guidelines (MEG) and adopts two techniques. One technique is the geographical information that offers multiple representations; the other is the augmented reality that provides semi-realistic information services. When this study tested the mobile escape guidelines, the results showed that this application was capable of identifying the correct locations of users, showing the escape routes, filtering geographical layers, and rapidly generating the relief reports. Users could evacuate from nuclear accident sites easily, even without relief personnel, since using slim devices to access the mobile escape guidelines is convenient. Overall, this study is a useful reference for a nuclear accident emergency response. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Gamma-ray escape peak characteristics of radiation-damaged reverse-electrode germanium coaxial detectors

    International Nuclear Information System (INIS)

    Pehl, R.H.; Hull, E.L.; Madden, N.W.; Xing Jingshu; Friesel, D.L.

    1996-01-01

    A comparison of the characteristics of full-energy gamma-ray peaks and their corresponding escape peaks when high energy photons interact in radiation damaged reverse-electrode (n-type) germanium coaxial detectors is presented. Coaxial detector geometry is the dominant factor, causing charge collection to be dramatically better for interactions occurring near the outer periphery of the detector as well as increasing of the probability of escape events occurring in this region. It follows that the resolution of escape peaks is better than that of ordinary gamma-ray peaks. This is experimentally verified. A nearly identical but undamaged detector exhibited significant Doppler broadening of single escape peaks. Because double escape events preferentially occur at outer radii, energy shifts of double escape reflect extremely small amounts of charge trapping in undamaged detectors. (orig.)

  12. Enzymes for improved biomass conversion

    Science.gov (United States)

    Brunecky, Roman; Himmel, Michael E.

    2016-02-02

    Disclosed herein are enzymes and combinations of the enzymes useful for the hydrolysis of cellulose and the conversion of biomass. Methods of degrading cellulose and biomass using enzymes and cocktails of enzymes are also disclosed.

  13. Escaping Electrons from Intense Laser-Solid Interactions as a Function of Laser Spot Size

    OpenAIRE

    Rusby, Dean; Gray, Ross; Butler, Nick; Dance, Rachel; Scott, Graeme; Bagnoud, Vincent; Zielbauer, Bernhard; McKenna, Paul; Neely, David

    2018-01-01

    The interaction of a high-intensity laser with a solid target produces an energetic distribution of electrons that pass into the target. These electrons reach the rear surface of the target creating strong electric potentials that act to restrict the further escape of additional electrons. The measurement of the angle, flux and spectra of the electrons that do escape gives insights to the initial interaction. Here, the escaping electrons have been measured using a differentially filtered imag...

  14. On the relative contributions of positive reinforcement and escape extinction in the treatment of food refusal.

    OpenAIRE

    Piazza, Cathleen C; Patel, Meeta R; Gulotta, Charles S; Sevin, Bari M; Layer, Stacy A

    2003-01-01

    We compared the effects of positive reinforcement alone, escape extinction alone, and positive reinforcement with escape extinction in the treatment of the food and fluid refusal of 4 children who had been diagnosed with a pediatric feeding disorder. Consumption did not increase when positive reinforcement was implemented alone. By contrast, consumption increased for all participants when escape extinction was implemented, independent of the presence or absence of positive reinforcement. Howe...

  15. Immobilized enzymes and cells

    Energy Technology Data Exchange (ETDEWEB)

    Bucke, C; Wiseman, A

    1981-04-04

    This article reviews the current state of the art of enzyme and cell immobilization and suggests advances which might be made during the 1980's. Current uses of immobilized enzymes include the use of glucoamylase in the production of glucose syrups from starch and glucose isomerase in the production of high fructose corn syrup. Possibilities for future uses of immobilized enzymes and cells include the utilization of whey and the production of ethanol.

  16. Profiling the orphan enzymes

    Science.gov (United States)

    2014-01-01

    The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called “orphan enzymes”. The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to “local orphan enzymes” that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new

  17. Antibody escape kinetics of equine infectious anemia virus infection of horses.

    Science.gov (United States)

    Schwartz, Elissa J; Nanda, Seema; Mealey, Robert H

    2015-07-01

    Lentivirus escape from neutralizing antibodies (NAbs) is not well understood. In this work, we quantified antibody escape of a lentivirus, using antibody escape data from horses infected with equine infectious anemia virus. We calculated antibody blocking rates of wild-type virus, fitness costs of mutant virus, and growth rates of both viruses. These quantitative kinetic estimates of antibody escape are important for understanding lentiviral control by antibody neutralization and in developing NAb-eliciting vaccine strategies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Sharks modulate their escape behavior in response to predator size, speed and approach orientation.

    Science.gov (United States)

    Seamone, Scott; Blaine, Tristan; Higham, Timothy E

    2014-12-01

    Escape responses are often critical for surviving predator-prey interactions. Nevertheless, little is known about how predator size, speed and approach orientation impact escape performance, especially in larger prey that are primarily viewed as predators. We used realistic shark models to examine how altering predatory behavior and morphology (size, speed and approach orientation) influences escape behavior and performance in Squalus acanthias, a shark that is preyed upon by apex marine predators. Predator models induced C-start escape responses, and increasing the size and speed of the models triggered a more intense response (increased escape turning rate and acceleration). In addition, increased predator size resulted in greater responsiveness from the sharks. Among the responses, predator approach orientation had the most significant impact on escapes, such that the head-on approach, as compared to the tail-on approach, induced greater reaction distances and increased escape turning rate, speed and acceleration. Thus, the anterior binocular vision in sharks renders them less effective at detecting predators approaching from behind. However, it appears that sharks compensate by performing high-intensity escapes, likely induced by the lateral line system, or by a sudden visual flash of the predator entering their field of view. Our study reveals key aspects of escape behavior in sharks, highlighting the modulation of performance in response to predator approach. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. Decompression illness in goats following simulated submarine escape: 1993-2006.

    Science.gov (United States)

    Seddon, F M; Thacker, J C; Fisher, A S; Jurd, K M; White, M G; Loveman, G A M

    2014-01-01

    The United Kingdom Ministry of Defence commissioned work to define the relationship between the internal pressure of a distressed submarine (DISSUB), the depth from which escape is made and the risk of decompression illness (DCI). The program of work used an animal model (goat) to define these risks and this paper reports the incidence and type of DCI observed. A total of 748 pressure exposures comprising saturation only, escape only or saturation followed by escape were conducted in the submarine escape simulator between 1993 and 2006. The DCI following saturation exposures was predominantly limb pain, whereas following escape exposures the DCI predominantly involved the central nervous system and was fast in onset. There was no strong relationship between the risk of DCI and the range of escape depths investigated. The risk of DCI incurred from escape following saturation was greater than that obtained by combining the risks for the independent saturation only, and escape only, exposures. The output from this program of work has led to improved advice on the safety of submarine escape.

  20. On the relative contributions of positive reinforcement and escape extinction in the treatment of food refusal.

    Science.gov (United States)

    Piazza, Cathleen C; Patel, Meeta R; Gulotta, Charles S; Sevin, Bari M; Layer, Stacy A

    2003-01-01

    We compared the effects of positive reinforcement alone, escape extinction alone, and positive reinforcement with escape extinction in the treatment of the food and fluid refusal of 4 children who had been diagnosed with a pediatric feeding disorder. Consumption did not increase when positive reinforcement was implemented alone. By contrast, consumption increased for all participants when escape extinction was implemented, independent of the presence or absence of positive reinforcement. However, the addition of positive reinforcement to escape extinction was associated with beneficial effects (e.g., greater decreases in negative vocalizations and inappropriate behavior) for some participants.

  1. On the relative contributions of noncontingent reinforcement and escape extinction in the treatment of food refusal.

    Science.gov (United States)

    Reed, Gregory K; Piazza, Cathleen C; Patel, Meeta R; Layer, Stacy A; Bachmeyer, Melanie H; Bethke, Stephanie D; Gutshall, Katharine A

    2004-01-01

    In the current investigation, we evaluated the relative effects of noncontingent reinforcement (NCR), escape extinction, and a combination of NCR and escape extinction as treatment for the feeding problems exhibited by 4 children. For each participant, consumption increased only when escape extinction was implemented, independent of whether NCR was present or absent. These results were consistent with prior research suggesting that positive reinforcement alone is insufficient for increasing consumption, and that escape extinction often is necessary to increase and maintain food acceptance. However, NCR appeared to decrease inappropriate behavior for some participants.

  2. Escape and avoidance learning in the earthworm Eisenia hortensis

    Directory of Open Access Journals (Sweden)

    W. Jeffrey Wilson

    2014-01-01

    Full Text Available Interest in instrumental learning in earthworms dates back to 1912 when Yerkes concluded that they can learn a spatial discrimination in a T-maze. Rosenkoetter and Boice determined in the 1970s that the “learning” that Yerkes observed was probably chemotaxis and not learning at all. We examined a different form of instrumental learning: the ability to learn both to escape and to avoid an aversive stimulus. Freely moving “master” worms could turn off an aversive white light by increasing their movement; the behavior of yoked controls had no effect on the light. We demonstrate that in as few as 12 trials the behavior of the master worms comes under the control of this contingency.

  3. Novel Anti-Melanoma Immunotherapies: Disarming Tumor Escape Mechanisms

    Directory of Open Access Journals (Sweden)

    Sivan Sapoznik

    2012-01-01

    Full Text Available The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies. We describe new immunomodulatory approaches currently in the development pipeline, focus on the novel CEACAM1 immune checkpoint, and compare its potential to the extensively described targets, CTLA4 and PD1. This paper combines multi-disciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles.

  4. The great escape: viral strategies to counter BST-2/tetherin.

    Directory of Open Access Journals (Sweden)

    Janet L Douglas

    2010-05-01

    Full Text Available The interferon-induced BST-2 protein has the unique ability to restrict the egress of HIV-1, Kaposi's sarcoma-associated herpesvirus (KSHV, Ebola virus, and other enveloped viruses. The observation that virions remain attached to the surface of BST-2-expressing cells led to the renaming of BST-2 as "tetherin". However, viral proteins such as HIV-1 Vpu, simian immunodeficiency virus Nef, and KSHV K5 counteract BST-2, thereby allowing mature virions to readily escape from infected cells. Since the anti-viral function of BST-2 was discovered, there has been an explosion of research into several aspects of this intriguing interplay between host and virus. This review focuses on recent work addressing the molecular mechanisms involved in BST-2 restriction of viral egress and the species-specific countermeasures employed by various viruses.

  5. Will 3552 Don Quixote escape from the Solar System?

    Directory of Open Access Journals (Sweden)

    Suryadi Siregar

    2011-05-01

    Full Text Available Asteroid 1983 SA, well known as 3552 Don Quixote, is one of Near Earth Asteroids (NEAs which is the most probable candidate for the cometary origin, or otherwise as Jupiter-Family-Comets (JFCs. The aim of this study is to investigate the possibility of 3552 Don Quixote to be ejected from the Solar System. This paper presents an orbital evolution of 100 hypothetical asteroids generated by cloning 3552 Don Quixote. Investigation of its orbital evolution is conducted by using the SWIFT subroutine package, where the gravitational perturbations of eight major planets in the Solar System are considered. Over very short time scales (220 kyr relative to the Solar System life time (10 Gyr, the asteroid 3552 Don Quixote gave an example of chaotic motion that can cause asteroid to move outward and may be followed by escaping from the Solar System. Probability of ejection within the 220 kyr time scale is 50%.

  6. The Anti-Apoptotic Properties of APEX1 in the Endothelium Require the First 20 Amino Acids and Converge on Thioredoxin-1.

    Science.gov (United States)

    Dyballa-Rukes, Nadine; Jakobs, Philipp; Eckers, Anna; Ale-Agha, Niloofar; Serbulea, Vlad; Aufenvenne, Karin; Zschauer, Tim-Christian; Rabanter, Lothar L; Jakob, Sascha; von Ameln, Florian; Eckermann, Olaf; Leitinger, Norbert; Goy, Christine; Altschmied, Joachim; Haendeler, Judith

    2017-04-20

    The APEX nuclease (multifunctional DNA repair enzyme) 1 (APEX1) has a disordered N-terminus, a redox, and a DNA repair domain. APEX1 has anti-apoptotic properties, which have been linked to both domains depending on cell type and experimental conditions. As protection against apoptosis is a hallmark of vessel integrity, we wanted to elucidate whether APEX1 acts anti-apoptotic in primary human endothelial cells and, if so, what the underlying mechanisms are. APEX1 inhibits apoptosis in endothelial cells by reducing Cathepsin D (CatD) cleavage, potentially by binding to the unprocessed form. Diminished CatD activation results in increased Thioredoxin-1 protein levels leading to reduced Caspase 3 activation. Consequently, apoptosis rates are decreased. This depends on the first twenty amino acids in APEX1, because APEX1 (21-318) induces CatD activity, decreases Thioredoxin-1 protein levels, and, thus, increases Caspase 3 activity and apoptosis. Along the same lines, APEX1 (1-20) inhibits Caspase 3 cleavage and apoptosis. Furthermore, re-expression of Thioredoxin-1 via lentiviral transduction rescues endothelial cells from APEX1 (21-318)-induced apoptosis. In an in vivo model of restenosis, which is characterized by oxidative stress, endothelial activation, and smooth muscle cell proliferation, Thioredoxin-1 protein levels are reduced in the endothelium of the carotids. APEX1 acts anti-apoptotic in endothelial cells. This anti-apoptotic effect depends on the first 20 amino acids of APEX1. As proper function of the endothelium during life span is a hallmark for individual health span, a detailed characterization of the functions of the APEX1N-terminus is required to understand all its cellular properties. Antioxid. Redox Signal. 26, 616-629.

  7. Host cell killing by the West Nile Virus NS2B-NS3 proteolytic complex: NS3 alone is sufficient to recruit caspase-8-based apoptotic pathway

    International Nuclear Information System (INIS)

    Ramanathan, Mathura P.; Chambers, Jerome A.; Pankhong, Panyupa; Chattergoon, Michael; Attatippaholkun, Watcharee; Dang, Kesen; Shah, Neelima; Weiner, David B.

    2006-01-01

    The West Nile Virus (WNV) non-structural proteins 2B and 3 (NS2B-NS3) constitute the proteolytic complex that mediates the cleavage and processing of the viral polyprotein. NS3 recruits NS2B and NS5 proteins to direct protease and replication activities. In an effort to investigate the biology of the viral protease, we cloned cDNA encoding the NS2B-NS3 proteolytic complex from brain tissue of a WNV-infected dead crow, collected from the Lower Merion area (Merion strain). Expression of the NS2B-NS3 gene cassette induced apoptosis within 48 h of transfection. Electron microscopic analysis of NS2B-NS3-transfected cells revealed ultra-structural changes that are typical of apoptotic cells including membrane blebbing, nuclear disintegration and cytoplasmic vacuolations. The role of NS3 or NS2B in contributing to host cell apoptosis was examined. NS3 alone triggers the apoptotic pathways involving caspases-8 and -3. Experimental results from the use of caspase-specific inhibitors and caspase-8 siRNA demonstrated that the activation of caspase-8 was essential to initiate apoptotic signaling in NS3-expressing cells. Downstream of caspase-3 activation, we observed nuclear membrane ruptures and cleavage of the DNA-repair enzyme, PARP in NS3-expressing cells. Nuclear herniations due to NS3 expression were absent in the cells treated with a caspase-3 inhibitor. Expression of protease and helicase domains themselves was sufficient to trigger apoptosis generating insight into the apoptotic pathways triggered by NS3 from WNV

  8. Initiating a watch list for Ebola virus antibody escape mutations

    Directory of Open Access Journals (Sweden)

    Craig R. Miller

    2016-02-01

    Full Text Available The 2014 Ebola virus (EBOV outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

  9. Initiating a watch list for Ebola virus antibody escape mutations.

    Science.gov (United States)

    Miller, Craig R; Johnson, Erin L; Burke, Aran Z; Martin, Kyle P; Miura, Tanya A; Wichman, Holly A; Brown, Celeste J; Ytreberg, F Marty

    2016-01-01

    The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

  10. Apoptotic activities of cardenolide glycosides from Asclepias subulata.

    Science.gov (United States)

    Rascón-Valenzuela, L A; Velázquez, C; Garibay-Escobar, A; Vilegas, W; Medina-Juárez, L A; Gámez-Meza, N; Robles-Zepeda, R E

    2016-12-04

    Asclepias subulata Decne. (Apocynaceae) is a shrub occurring in Sonora-Arizona desert. The ethnic groups of Sonora, Mexico, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer. To determine the cell death pathways that the cardenolide glycosides with antiproliferative activity found in the methanol extract of A. subulata are able to activate. The effect of cardenolide glycosides isolated of A. subulata on induction of apoptosis in cancer cells was evaluated through the measuring of several key events of apoptosis. A549 cells were treated for 12h with doses of 3.0, 0.2, 3.0 and 1.0µM of 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, respectively. Apoptotic and necrotic cell levels were measured by double staining with annexin V-FITC/PI. Mitochondrial membrane depolarization was examined through JC-1 staining. Apoptosis cell death and the apoptosis pathways activated by cardenolide glycosides isolated of A. subulata were further characterized by the measurement of caspase-3, caspase-8 and caspase-9 activity. Apoptotic assays showed that the four cardenolide glycosides isolated of A. subulata induced apoptosis in A549 cells, which was evidencing by phosphatidylserine externalization in 18.2%, 17.0%, 23.9% and 22.0% for 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, respectively, compared with 4.6% of control cells. Cell death was also associated with a decrease in mitochondrial membrane potential, which was more than 75% in the treated cultures respect to control. The activation of caspase-3 was observed in all cardenolide glycosides-treated cancer cells indicating the caspase-dependent apoptosis of A549 cells. Extrinsic and intrinsic apoptosis pathways were activated by cardenolide glycosides treatment at the doses tested. In this study was found that cardenolide glycosides, 12, 16-dihydroxicalotropin, calotropin

  11. Artificial Enzymes, "Chemzymes"

    DEFF Research Database (Denmark)

    Bjerre, Jeannette; Rousseau, Cyril Andre Raphaël; Pedersen, Lavinia Georgeta M

    2008-01-01

    Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models that successf......Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models...... that successfully perform Michaelis-Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called...... "Chemzymes", based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well...

  12. Magnetically responsive enzyme powders

    Energy Technology Data Exchange (ETDEWEB)

    Pospiskova, Kristyna, E-mail: kristyna.pospiskova@upol.cz [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Safarik, Ivo, E-mail: ivosaf@yahoo.com [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Department of Nanobiotechnology, Institute of Nanobiology and Structural Biology of GCRC, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic)

    2015-04-15

    Powdered enzymes were transformed into their insoluble magnetic derivatives retaining their catalytic activity. Enzyme powders (e.g., trypsin and lipase) were suspended in various liquid media not allowing their solubilization (e.g., saturated ammonium sulfate and highly concentrated polyethylene glycol solutions, ethanol, methanol, 2-propanol) and subsequently cross-linked with glutaraldehyde. Magnetic modification was successfully performed at low temperature in a freezer (−20 °C) using magnetic iron oxides nano- and microparticles prepared by microwave-assisted synthesis from ferrous sulfate. Magnetized cross-linked enzyme powders were stable at least for two months in water suspension without leakage of fixed magnetic particles. Operational stability of magnetically responsive enzymes during eight repeated reaction cycles was generally without loss of enzyme activity. Separation of magnetically modified cross-linked powdered enzymes from reaction mixtures was significantly simplified due to their magnetic properties. - Highlights: • Cross-linked enzyme powders were prepared in various liquid media. • Insoluble enzymes were magnetized using iron oxides particles. • Magnetic iron oxides particles were prepared by microwave-assisted synthesis. • Magnetic modification was performed under low (freezing) temperature. • Cross-linked powdered trypsin and lipase can be used repeatedly for reaction.

  13. Targeted enzyme prodrug therapies.

    Science.gov (United States)

    Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

    2010-09-01

    The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

  14. Enzymes in Fermented Fish.

    Science.gov (United States)

    Giyatmi; Irianto, H E

    Fermented fish products are very popular particularly in Southeast Asian countries. These products have unique characteristics, especially in terms of aroma, flavor, and texture developing during fermentation process. Proteolytic enzymes have a main role in hydrolyzing protein into simpler compounds. Fermentation process of fish relies both on naturally occurring enzymes (in the muscle or the intestinal tract) as well as bacteria. Fermented fish products processed using the whole fish show a different characteristic compared to those prepared from headed and gutted fish. Endogenous enzymes like trypsin, chymotrypsin, elastase, and aminopeptidase are the most involved in the fermentation process. Muscle tissue enzymes like cathepsins, peptidases, transaminases, amidases, amino acid decarboxylases, glutamic dehydrogenases, and related enzymes may also play a role in fish fermentation. Due to the decreased bacterial number during fermentation, contribution of microbial enzymes to proteolysis may be expected prior to salting of fish. Commercial enzymes are supplemented during processing for specific purposes, such as quality improvement and process acceleration. In the case of fish sauce, efforts to accelerate fermentation process and to improve product quality have been studied by addition of enzymes such as papain, bromelain, trypsin, pepsin, and chymotrypsin. © 2017 Elsevier Inc. All rights reserved.

  15. Non-apoptotic cell death associated with perturbations of macropinocytosis.

    Science.gov (United States)

    Maltese, William A; Overmeyer, Jean H

    2015-01-01

    Although macropinocytosis is widely recognized as a distinct form of fluid-phase endocytosis in antigen-presenting dendritic cells, it also occurs constitutively in many other normal and transformed cell types. Recent studies have established that various genetic or pharmacological manipulations can hyperstimulate macropinocytosis or disrupt normal macropinosome trafficking pathways, leading to accumulation of greatly enlarged cytoplasmic vacuoles. In some cases, this extreme vacuolization is associated with a unique form of non-apoptotic cell death termed "methuosis," from the Greek methuo (to drink to intoxication). It remains unclear whether cell death related to dysfunctional macropinocytosis occurs in normal physiological contexts. However, the finding that some types of cancer cells are particularly vulnerable to this unusual form of cell death has raised the possibility that small molecules capable of altering macropinosome trafficking or function might be useful as therapeutic agents against cancers that are resistant to drugs that work by inducing apoptosis. Herein we review examples of cell death associated with dysfunctional macropinocytosis and summarize what is known about the underlying mechanisms.

  16. Non-apoptotic cell death associated with perturbations of macropinocytosis

    Directory of Open Access Journals (Sweden)

    William A. Maltese

    2015-02-01

    Full Text Available Although macropinocytosis is widely recognized as a distinct form of fluid-phase endocytosis in antigen-presenting dendritic cells, it also occurs constitutively in many other normal and transformed cell types. Recent studies have established that various genetic or pharmacological manipulations can hyperstimulate macropinocytosis or disrupt normal macropinosome trafficking pathways, leading to accumulation of greatly enlarged cytoplasmic vacuoles. In some cases, this extreme vacuolization is associated with a unique form of non-apoptotic cell death termed ‘methuosis’, from the Greek methuo (to drink to intoxication. It remains unclear whether cell death related to dysfunctional macropinocytosis occurs in normal physiological contexts. However, the finding that some types of cancer cells are particularly vulnerable to this unusual form of cell death has raised the possibility that small molecules capable of altering macropinosome trafficking or function might be useful as therapeutic agents against cancers that are resistant to drugs that work by inducing apoptosis. Herein we review examples of cell death associated with dysfunctional macropinocytosis and summarize what is known about the underlying mechanisms.

  17. Calcein+/PI- as an early apoptotic feature in Leishmania.

    Science.gov (United States)

    Basmaciyan, Louise; Azas, Nadine; Casanova, Magali

    2017-01-01

    Although leishmaniases are responsible for high morbidity and mortality all over the world, no really satisfying treatment exists. Furthermore, the corresponding parasite Leishmania undergoes a very characteristic form of programmed cell death. Indeed, different stimuli can induce morphological and biochemical apoptotic-like features. However, the key proteins involved in mammal apoptosis, such as caspases and death receptors, are not encoded in the genome of this parasite. Currently, little is known about Leishmania apoptosis, notably owing to the lack of specific tools for programmed cell death analysis in these parasites. Furthermore, there is a need for a better understanding of Leishmania programmed cell death in order (i) to better understand the role of apoptosis in unicellular organisms, (ii) to better understand apoptosis in general through the study of an ancestral eukaryote, and (iii) to identify new therapeutic targets against leishmaniases. To advance understanding of apoptosis in Leishmania, in this study we developed a new tool based on the quantification of calcein and propidium iodide by flow cytometry. This double labeling can be employed to distinguish early apoptosis, late apoptosis and necrosis in Leishmania live cells with a very simple and rapid assay. This paper should, therefore, be of interest for people working on Leishmania and related parasites.

  18. Calcein+/PI- as an early apoptotic feature in Leishmania.

    Directory of Open Access Journals (Sweden)

    Louise Basmaciyan

    Full Text Available Although leishmaniases are responsible for high morbidity and mortality all over the world, no really satisfying treatment exists. Furthermore, the corresponding parasite Leishmania undergoes a very characteristic form of programmed cell death. Indeed, different stimuli can induce morphological and biochemical apoptotic-like features. However, the key proteins involved in mammal apoptosis, such as caspases and death receptors, are not encoded in the genome of this parasite. Currently, little is known about Leishmania apoptosis, notably owing to the lack of specific tools for programmed cell death analysis in these parasites. Furthermore, there is a need for a better understanding of Leishmania programmed cell death in order (i to better understand the role of apoptosis in unicellular organisms, (ii to better understand apoptosis in general through the study of an ancestral eukaryote, and (iii to identify new therapeutic targets against leishmaniases. To advance understanding of apoptosis in Leishmania, in this study we developed a new tool based on the quantification of calcein and propidium iodide by flow cytometry. This double labeling can be employed to distinguish early apoptosis, late apoptosis and necrosis in Leishmania live cells with a very simple and rapid assay. This paper should, therefore, be of interest for people working on Leishmania and related parasites.

  19. Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Andrys, C.; Krejsek, J.; Hamakova, K.; Kremlacek, J.; Palicka, V.; Ranna, D.; Fiala, Z. [Charles University Prague, Prague (Czech Republic). Faculty of Medicine

    2010-03-15

    Goeckerman therapy (GT) for psoriasis is based on cutaneous application of crude coal tar (polycyclic aromatic hydrocarbons (PAH)) and exposure to ultraviolet radiation (UVR). PAH and UVR are mutagenic, carcinogenic and immunotoxic agents that promote apoptosis. We evaluated dermal absorption of PAH as well as the genotoxic and apoptotic effects of GT in 20 patients with psoriasis, by determining numbers of chromosomal abnormalities in peripheral lymphocytes, and levels of 1-hydroxypyrene (1-OHP), p53 protein and soluble FasL (sFasL) in urine and/or blood, before and after GT. Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GT. Compared with pre-treatment levels, there was a significant increase in urine 1-OHP, indicating a high degree of dermal absorption of PAH (P <0.01). We also found a significant increase in the number of chromosomal abnormalities in peripheral blood lymphocytes (P <0.001), suggesting that GT is genotoxic; significantly increased p53 protein in plasma (P <0.05), an indicator of cell response to DNA damage; and significantly increased sFasL in serum (P <0.01), an indicator of apoptosis. The PASI score was significantly decreased after GT (P <0.001), confirming clinical benefit of this treatment. Our results demonstrate high dermal absorption of PAH during GT and provide evidence that GT promotes genotoxicity and apoptosis.

  20. Apoptotic induction of skin cancer cell death by plant extracts.

    Science.gov (United States)

    Thuncharoen, Walairat; Chulasiri, Malin; Nilwarangkoon, Sirinun; Nakamura, Yukio; Watanapokasin, Ramida

    2013-01-01

    The aim of the present study was to investigate the effects of plant extracts on cancer apoptotic induction. Human epidermoid carcinoma A431 cell line, obtained from the American Type Culture Collection (ATCC, Manassas, VA), was maintained in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37 degrees C, 5% carbon dioxide (CO2). Plant extract solutions were obtained from S & J international enterprises public company limited. These plant extracts include 50% hydroglycol extracts from Etlingera elatior (Jack) R.M.Smith (torch ginger; EE), Rosa damascene (damask rose; DR) and Rafflesia kerrii Meijer (bua phut; RM). The cell viability, time and dose dependency were determined by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. A431 cells were treated with the plant extracts and stained with Hoechst 33342 fluorescent staining dye. Cell viability was demonstrated by the inhibitory concentration 50% (IC50). The anti-proliferative effects were shown to be dependent on time and dose. Typical characteristics of apoptosis which are cell morphological changes and chromatin condensation were clearly observed. The plant extracts was shown to be effective for anti-proliferation and induction of apoptosis cell death in skin cancer cells. Therefore, mechanisms underlying the cell death and its potential use for treatment of skin cancer will be further studied.

  1. Apoptotic study in Graves disease treated with thyroid arterial embolization

    International Nuclear Information System (INIS)

    Zhao Wei; Gao Bulang; Yi Genfa

    2009-01-01

    The objective of this study was to investigate apoptosis in the thyroid of Graves disease (GD) induced by thyroid arterial embolization. Forty one patients with clinically and laboratorily ascertained GD were treated with thyroid arterial embolization and followed up for 3-54 months following embolization. Prior to embolization and at 1, 3, 6, 12 and 36 months following embolization, thyroid autoimmune antibodies were tested respectively, including thyroid stimulating antibody (TSAb), thyroglobulin antibody (TGAb) and thyroid microsomal antibody (TMAb). Thyroid biopsy was performed under the guidance of computed tomography for immunohistochemistry examination using semi-quantity analysis. The positive staining of Fas and FasL was mostly in the cytoplasma and cell membrane, the positive expression of Bax was mainly in the cytoplasma, and no positive expression of P53 was detected in the thyroid cells before embolization. After arterial embolziation, the positive cell number and staining degree of these genes were both greater than before embolization. The treatment method of thyroid arterial embolization can effectively enhance the positive expression of pro-apoptotic genes of Fas, FasL, Bax, Bcl-2 and P53 in GD thyroid, thus promoting apoptosis of GD thyroid and helping restore the thyroid size and function to normal conditions. (author)

  2. Genes of the mitochondrial apoptotic pathway in Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Noelia Estévez-Calvar

    Full Text Available Bivalves play vital roles in marine, brackish, freshwater and terrestrial habitats. In recent years, these ecosystems have become affected through anthropogenic activities. The ecological success of marine bivalves is based on the ability to modify their physiological functions in response to environmental changes. One of the most important mechanisms involved in adaptive responses to environmental and biological stresses is apoptosis, which has been scarcely studied in mollusks, although the final consequence of this process, DNA fragmentation, has been frequently used for pollution monitoring. Environmental stressors induce apoptosis in molluscan cells via an intrinsic pathway. Many of the proteins involved in vertebrate apoptosis have been recognized in model invertebrates; however, this process might not be universally conserved. Mytilus galloprovincialis is presented here as a new model to study the linkage between molecular mechanisms that mediate apoptosis and marine bivalve ecological adaptations. Therefore, it is strictly necessary to identify the key elements involved in bivalve apoptosis. In the present study, six mitochondrial apoptotic-related genes were characterized, and their gene expression profiles following UV irradiation were evaluated. This is the first step for the development of potential biomarkers to assess the biological responses of marine organisms to stress. The results confirmed that apoptosis and, more specifically, the expression of the genes involved in this process can be used to assess the biological responses of marine organisms to stress.

  3. The antiproliferative and apoptotic effects of apigenin on glioblastoma cells.

    Science.gov (United States)

    Stump, Trevor A; Santee, Brittany N; Williams, Lauren P; Kunze, Rachel A; Heinze, Chelsae E; Huseman, Eric D; Gryka, Rebecca J; Simpson, Denise S; Amos, Samson

    2017-07-01

    Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM. Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses. Our results showed that apigenin reduced cell viability and proliferation in a dose- and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL. Our results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM. © 2017 Royal Pharmaceutical Society.

  4. Biochemical and biophysical investigations of the interaction between human glucokinase and pro-apoptotic BAD.

    Science.gov (United States)

    Rexford, Alix; Zorio, Diego A R; Miller, Brian G

    2017-01-01

    The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD. Consistent with published reports, recombinant BAD displays high affinity for Bcl-xL (KD = 7 nM), and phosphorylation of BAD at S118, within the BH3 domain, abolishes this interaction. Unexpectedly, we do not detect association of recombinant, full-length BAD with recombinant human pancreatic GCK over a range of protein concentrations using various biochemical methods including size-exclusion chromatography, chemical cross-linking, analytical ultracentrifugation, and isothermal titration calorimetry. Furthermore, fluorescence polarization assays and isothermal titration calorimetry detect no direct interaction between GCK and BAD BH3 peptides. Kinetic characterization of GCK in the presence of high concentrations of recombinant BAD show modest (BAD BH3 peptides. These results raise questions as to the mechanism of action of stapled peptide analogs modeled after the BAD BH3 domain, which reportedly enhance the Vmax value of GCK and stimulate insulin release in BAD-deficient islets. Based on our results, we postulate that the BAD:GCK interaction, and any resultant regulatory effect(s) upon GCK activity, requires the participation of additional members of the mitochondrial complex.

  5. The Apoptotic Effects of the P300 Activator on Breast Cancer and Lung Fibroblast Cell Lines

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Salahshoor

    2013-10-01

    Full Text Available Background: P300 is an enzyme that acetylates histones during stress. It alsoacetylates several non-histone proteins, including P53 which is the most important tumorsuppressor gene. P53 plays an important role in the apoptosis of tumor cells. Hereby,this study describes the potency of cholera toxin B subunit as a P300 activator to induceapoptosis in a breast cancer cell line (MCF-7 and a lung fibroblast cell line (MRC-5as a non-tumorigenic control sample. Methods: MCF-7 and MRC-5 were cultured in RPMI-1640 and treated with orwithout cholera toxin B subunit at the concentration of 85.43 μmol/L, based on the half-maximal inhibitory concentration index at different times (24, 48 and 72 h. Thepercentage of apoptotic cells was measured by flow cytometry. Real-time quantitativeRT-PCR was performed to estimate the mRNA expression of P300 in MCF-7 and MRC-5 with cholera toxin B subunit at different times. We used the ELISA and Bradford proteintechniques to detect levels of total and acetylated P53 protein generated in MCF-7 andMRC-5. Results: Our findings indicated that the cholera toxin B subunit effectively andsignificantly induced more apoptosis in MCF-7 compared to MRC-5. We showed thatexpression of P300 up-regulated by increasing the time of the cholera toxin B subunittreatment in MCF-7 but not in MRC-5. In addition, the acetylated and total P53protein levels increased more in MCF-7 cells than in MRC-5 cells.Conclusion: Cholera toxin B subunit induced significant cell death in MCF-7, butit could be well tolerated in MRC-5. Therefore, cholera toxin B subunit can besuggested as an anti-cancer agent.

  6. APOPTOTIC, HEPATOPROTECTIVE AND ANTIOXIDANT POTENTIAL OF A TRIHERBAL FORMULATION AGAINST D-GALACTOSAMINE HEPATOTOXICITY

    Directory of Open Access Journals (Sweden)

    Onyekachi Ogbonnaya IROANYA

    2016-12-01

    Full Text Available A triherbal formulation prepared from hydroethanolic mixture of Gongronema latifolia, Ocimum gratissimum and Vernonia amygdalina leaves (GOV was evaluated to ascertain its heamatologic, hepatoprotective potentials, antioxidant properties and the fold increase in caspase 2, 3 and 9 activities against D-galactosamine-induced toxicity using Wistar albino rats. Forty-nine Wistar albino rats were divided equally into seven groups. Two control experiments which included normal rats treated with D-galactosamine and normal rats that received only distilled water. Three groups were treated with different doses of GOV extract (2, 4 and 8 g kg-1 b. wt while two groups received standard hepatoprotective drugs (Liv 52 and Silymarin for 13 days prior to intoxication with D-galactosamine. The activities of serum liver enzymes, concentrations of some biochemical analytes, effect on heamatologic parameters, antioxidant status and fold increase in caspase 2, 3 and 9 activities were monitored. HPTLC of GOV showed the presence of ascorbic acid, rutin, eugenol and β-sitosterol. Administration of GOV significantly (p<0.05 increased the Packed Cell Volume, Red Cell Count, Haemoglobin, White Blood Cell, platelet count, Mean Cell Haemoglobin, granulocytes and lymphocytes while the Mean Cell Volume and monocytes were significantly (p<0.05 depreciated dose dependently compared to the toxin control group. GOV dose dependently exhibited significant (p<0.05 decrease in levels of Alkaline phosphatase, Alanine aminotransferase, aspartate aminotransferase, L-γ-glutamyltransferase, Lactate dehydrogenase, cholesterol, creatinine, triglycerides, urea and Malondialdehyde. Subsequently, it significantly (p<0.05 increased the albumin, total protein, catalase, Glutathione Peroxidase, Reduced Glutathione, Glutathione-S-Transferase and Superoxide Dismutase levels. GOV significantly (p≤0.05 attenuated the fold increase in caspase 2, 3 and 9 activities compared to the toxin control

  7. Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis.

    Science.gov (United States)

    van Lent, P L; Licht, R; Dijkman, H; Holthuysen, A E; Berden, J H; van den Berg, W B

    2001-11-01

    Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex-mediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of apoptotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.

  8. Systems analysis of apoptotic priming in ovarian cancer identifies vulnerabilities and predictors of drug response.

    Science.gov (United States)

    Zervantonakis, Ioannis K; Iavarone, Claudia; Chen, Hsing-Yu; Selfors, Laura M; Palakurthi, Sangeetha; Liu, Joyce F; Drapkin, Ronny; Matulonis, Ursula; Leverson, Joel D; Sampath, Deepak; Mills, Gordon B; Brugge, Joan S

    2017-08-28

    The lack of effective chemotherapies for high-grade serous ovarian cancers (HGS-OvCa) has motivated a search for alternative treatment strategies. Here, we present an unbiased systems-approach to interrogate a panel of 14 well-annotated HGS-OvCa patient-derived xenografts for sensitivity to PI3K and PI3K/mTOR inhibitors and uncover cell death vulnerabilities. Proteomic analysis reveals that PI3K/mTOR inhibition in HGS-OvCa patient-derived xenografts induces both pro-apoptotic and anti-apoptotic signaling responses that limit cell killing, but also primes cells for inhibitors of anti-apoptotic proteins. In-depth quantitative analysis of BCL-2 family proteins and other apoptotic regulators, together with computational modeling and selective anti-apoptotic protein inhibitors, uncovers new mechanistic details about apoptotic regulators that are predictive of drug sensitivity (BIM, caspase-3, BCL-X L ) and resistance (MCL-1, XIAP). Our systems-approach presents a strategy for systematic analysis of the mechanisms that limit effective tumor cell killing and the identification of apoptotic vulnerabilities to overcome drug resistance in ovarian and other cancers.High-grade serous ovarian cancers (HGS-OvCa) frequently develop chemotherapy resistance. Here, the authors through a systematic analysis of proteomic and drug response data of 14 HGS-OvCa PDXs demonstrate that targeting apoptosis regulators can improve response of these tumors to inhibitors of the PI3K/mTOR pathway.

  9. European SpaceCraft for the study of Atmospheric Particle Escape (ESCAPE): a mission proposed in response to the ESA M5-call

    Science.gov (United States)

    Dandouras, Iannis; Yamauchi, Masatoshi; Rème, Henri; De Keyser, Johan; Marghitu, Octav; Fazakerley, Andrew; Grison, Benjamin; Kistler, Lynn; Milillo, Anna; Nakamura, Rumi; Paschalidis, Nikolaos; Paschalis, Antonis; Pinçon, Jean-Louis; Sakanoi, Takeshi; Wieser, Martin; Wurz, Peter; Yoshikawa, Ichiro; Häggström, Ingemar; Liemohn, Mike; Tian, Feng

    2017-04-01

    ESCAPE is a mission proposed in response to the ESA-M5 call that will quantitatively estimate the amount of escaping particles of the major atmospheric components (nitrogen and oxygen), as neutral and ionised species, escaping from the Earth as a magnetised planet. The spatial distribution and temporal variability of the flux of these species and their isotopic composition will be for the first time systematically investigated in an extended altitude range, from the exobase/upper ionosphere (500 km altitude) up to the magnetosphere. The goal is to understand the importance of each escape mechanism, its dependence on solar and geomagnetic activity, and to infer the history of the Earth's atmosphere over a long (geological scale) time period. Since the solar EUV and solar wind conditions during solar maximum at present are comparable to the solar minimum conditions 1-2 billion years ago, the escaping amount and the isotope and N/O ratios should be obtained as a function of external forcing (solar and geomagnetic conditions) to allow a scaling to the past. The result will be used as a reference to understand the atmospheric/ionospheric evolution of magnetised planets. To achieve this goal, a slowly spinning spacecraft is proposed equipped with a suite of instruments developed and supplied by an international consortium. These instruments will detect the upper atmosphere and magnetosphere escaping populations by a combination of in-situ measurements and of remote-sensing observations.

  10. Cytotoxic and Apoptotic Effect of Structurally Similar Flavonoids on Parental and Drug-Resistant Cells of a Human Cervical Carcinoma

    Directory of Open Access Journals (Sweden)

    Ksenija Durgo

    2009-01-01

    Full Text Available Flavonoids are phytochemicals characterized by a wide range of biological activities, including antioxidant activity, the ability to modulate enzyme or cell receptor activity patterns, and to interfere with essential biochemical pathways. Using HeLa cells of a human cervical carcinoma, and their drug-resistant HeLa CK subline, the effects of three structurally related flavonoids (quercetin, fisetin and luteolin have been examined, in terms of their: (i cytotoxicity, (ii influence on intracellular glutathione (GSH level, (iii influence on glutathione S-transferase (GST activity, and (iv influence on the expression of apoptosis-related genes (PARP, Bcl-2, survivin. Fisetin was more toxic to resistant HeLa CK cell line than to parental cell line, causing decreased expression of survivin in the same cell line. Concentrations of 5 μM of the examined flavonoids caused PARP degradation in parental cell line, leading HeLa cell line into apoptotic cell death. The same event was not determined in the resistant cell line. Fisetin and luteolin induce glutathione and GST in the resistant cell line, pointing to complex cellular effects which could be responsible for higher sensitivity of the resistant cell line in comparison with the parental cell line. Prooxidative nature of the investigated flavonoids was not detected, so free radical formation is not responsible for the induction of GSH, GST and proapoptotic enzymes.

  11. Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums

    Science.gov (United States)

    2010-01-01

    Everyday we turnover billions of cells. The quick, efficient, and immunologically silent disposal of the dying cells requires a coordinated orchestration of multiple steps, through which phagocytes selectively recognize and engulf apoptotic cells. Recent studies have suggested an important role for soluble mediators released by apoptotic cells that attract phagocytes (“find-me” signals). New information has also emerged on multiple receptors that can recognize phosphatidylserine, the key “eat-me” signal exposed on the surface of apoptotic cells. This perspective discusses recent exciting progress, gaps in our understanding, and the conflicting issues that arise from the newly acquired knowledge. PMID:20805564

  12. Escapement of Cape hakes under the fishing line of the Namibian ...

    African Journals Online (AJOL)

    The objective of this study was to establish whether Cape hakes Merluccius capensis and M. paradoxus escape under the fishing line and to identify any species or length dependence of escape rates. Experiments were carried out in Namibian waters during two cruises in October 2002 and October 2003. A collection bag ...

  13. The rate of immune escape vanishes when multiple immune responses control an HIV infection

    NARCIS (Netherlands)

    van Deutekom, Hanneke W. M.; Wijnker, Gilles; de Boer, Rob J.

    2013-01-01

    During the first months of HIV infection, the virus typically evolves several immune escape mutations. These mutations are found in epitopes in viral proteins and reduce the impact of the CD8⁺ T cells specific for these epitopes. Recent data show that only a subset of the epitopes escapes, that most

  14. Behavioral analyses of wind-evoked escape of the cricket, Gryllodes sigillatus.

    Science.gov (United States)

    Kanou, Masamichi; Konishi, Atsuko; Suenaga, Rie

    2006-04-01

    The wind-evoked escape behavior of the cricket Gryllodes sigillatus was investigated using an air puff stimulus. A high velocity air puff elicited the escape behavior in many crickets. The crickets tended to escape away from the stimulus source, but the direction was not accurately oriented 180 degrees from the stimulus. After bilateral cercal ablation, only a few crickets showed wind-evoked escape behavior, and their response rates did not increase even 19 days after ablation. Therefore, information on air motion detected by cercal filiform hairs is essential for triggering wind-evoked behavior. After unilateral cercal ablation, the 81.3% response rate of intact crickets decreased to 16.5%, that is, it decreased to almost 20% that of intact crickets. One week after unilateral cercal ablation, the response rate recovered to more than 60% that of intact crickets. However, the accuracy rate of the escape direction of G. sigillatus showed no change even immediately after the unilateral cercal ablation. Therefore, both cerci are not necessarily required to determine the escape direction. The behavioral characteristics of wind-evoked escape of G. sigillatus are compared with those of another species of cricket, Gryllus bimaculatus. The two species of cricket employ different strategies for wind-evoked escape.

  15. A Substantial Plume of Escaping Planetary Ions in the MSE Northern Hemisphere Observed by MAVEN

    Science.gov (United States)

    Dong, Y.; Fang, X.; Brain, D. A.; McFadden, J. P.; Halekas, J. S.; Connerney, J. E. P.; Curry, S.; Harada, Y.; Luhmann, J. G.; Jakosky, B. M.

    2015-12-01

    The Mars-solar wind interaction accelerates and transports planetary ions away from Mars through a number of processes, including pick-up by the electromagnetic fields. The Mars Atmospheric and Volatile EvolutioN (MAVEN) spacecraft has frequently detected strong escaping planetary ion fluxes in both tailward and upstream solar wind motional electric field directions since the beginning of its science phase in November 2014. Our statistical study using three-month MAVEN data from November 2014 through February 2015 illustrates a substantial plume-like escaping planetary ion population organized by the upstream electric field with strong fluxes widely distributed in the northern hemisphere of the Mars-Sun-Electric-field (MSE) coordinate system, which is generally consistent with model predictions. The plume constitutes an important planetary ion escape channel from the Martian atmosphere in addition to the tailward escape. The >25eV O+ escape rate through the plume is estimated to be ~35% of the tailward escape and ~25% of the total escape. We will compare the dynamics of the plume and tailward escaping ions based on their velocity-space distributions with respect to the electromagnetic fields. We will also discuss the variations of the plume characteristics between different ion species (O+, O2+, and CO2+) and from the effect of different solar wind and interplanetary magnetic field (IMF) conditions.

  16. Escaping blood-fed malaria mosquitoes minimize tactile detection without compromising on take-off speed

    NARCIS (Netherlands)

    Muijres, F.T.; Chang, S.W.; Veen, van W.G.; Spitzen, J.; Biemans, B.T.; Koehl, M.A.R.; Dudley, R.

    2017-01-01

    To escape after taking a blood meal, a mosquito must exert forces sufficiently high to take off when carrying a load roughly equal to its body weight, while simultaneously avoiding detection by minimizing tactile signals exerted on the host’s skin. We studied this trade-off between escape speed and

  17. Computer Self-Efficacy, Competitive Anxiety and Flow State: Escaping from Firing Online Game

    Science.gov (United States)

    Hong, Jon-Chao; Pei-Yu, Chiu; Shih, Hsiao-Feng; Lin, Pei-Shin; Hong, Jon-Chao

    2012-01-01

    Flow state in game playing affected by computer self-efficacy and game competitive anxiety was studied. In order to examine the effect of those constructs with high competition, this study select "Escaping from firing online game" which require college students to escape from fire and rescue people and eliminate the fire damage along the way of…

  18. Treatment of Escape-Maintained Behavior with Positive Reinforcement: The Role of Reinforcement Contingency and Density

    Science.gov (United States)

    Ingvarsson, Einar T.; Hanley, Gregory P.; Welter, Katherine M.

    2009-01-01

    Functional analyses suggested that the disruptive behavior of three preschool children was maintained by escape from demands. While keeping the escape contingency intact, we conducted (a) a density analysis in which the children earned preferred items for task completion according to two schedules that varied in reinforcement density, and (b) a…

  19. Plasma Clouds and Snowplows: Bulk Plasma Escape from Mars Observed by MAVEN

    Science.gov (United States)

    Halekas, J. S.; Brain, D. A.; Ruhunusiri, S.; McFadden, J. P.; Mitchell, D. L.; Mazelle, C.; Connerney, J. E. P.; Harada, Y.; Hara, T.; Espley, J. R.; hide

    2016-01-01

    We present initial Mars Atmosphere and Volatile EvolutioN (MAVEN) observations and preliminary interpretation of bulk plasma loss from Mars. MAVEN particle and field measurements show that planetary heavy ions derived from the Martian atmosphere can escape in the form of discrete coherent structures or "clouds." The ions in these clouds are unmagnetized or weakly magnetized, have velocities well above the escape speed, and lie directly downstream from magnetic field amplifications, suggesting a "snowplow" effect. This postulated escape process, similar to that successfully used to explain the dynamics of active gas releases in the solar wind and terrestrial magnetosheath, relies on momentum transfer from the shocked solar wind protons to the planetary heavy ions, with the electrons and magnetic field acting as intermediaries. Fluxes of planetary ions on the order of 10(exp 7)/sq cm/s can escape by this process, and if it operates regularly, it could contribute 10-20% of the current ion escape from Mars.

  20. Antarctic krill; assessment of mesh size selectivity and escape mortality from trawls

    DEFF Research Database (Denmark)

    Krafft, Bjørn A.; Krag, Ludvig Ahm; Herrmann, Bent

    2015-01-01

    Marine AS. The project will examine krill escape mortality from the codend during a full scale field experiment, model size selectivity and escape mortality in codends including different designs and assess the size selectivity in the trawl body forward of the codend. Based on end results from the preceding...... examinations we will be able to predict size selectivity and escape mortality from the entire trawl body with the appurtenant mortality for different trawl designs......This working paper presents the aims and methodology for a three-year-project (commenced in 2015) assessing size selectivity and escape mortality of Antarctic krill from trawl nets. The project is widely based on acquired experiences from a completed study Net Escapement of Antarctic krill...

  1. Highlights of the Global HIV-1 CSF Escape Consortium Meeting, 9 June 2016, Bethesda, MD, USA.

    Science.gov (United States)

    Joseph, Jeymohan; Cinque, Paola; Colosi, Deborah; Dravid, Ameet; Ene, Luminita; Fox, Howard; Gabuzda, Dana; Gisslen, Magnus; Beth Joseph, Sarah; Letendre, Scott; Mukerji, Shibani S; Nath, Avindra; Perez-Valero, Ignacio; Persaud, Deborah; Price, Richard W; Rao, Vasudev R; Sacktor, Ned; Swanstrom, Ronald; Winston, Alan; Wojna, Valerie; Wright, Edwina; Spudich, Serena

    2016-10-05

    CSF HIV escape is a recently recognised phenomenon that suggests that despite suppressive treatment, HIV RNA may be detected in the CNS compartment in some individuals. In rare cases this is associated with clinical neurological disease, while in most cases, neurological consequences are not apparent. Attempts at characterising the biological substrates of CSF escape and further investigating the neurological consequences need to be made to better understand the implications of this condition for the HIV cure agenda as well as for clinical outcomes. The Global CSF HIV-1 Escape Consortium meeting, convened by the US National Institute of Mental Health, was a first step to gather investigators from diverse sites to discuss opportunities for future collaborative work on this emerging issue. To better understand CSF HIV escape and allow cross-site data reconciliation, it will be useful to reach a consensus set of definitions of the distinct forms of CSF escape, without which concerted cross-site efforts are difficult.

  2. Improving the effectiveness of escape windows in directed Norway lobster Nephrops norvegicus trawl fisheries

    DEFF Research Database (Denmark)

    Madsen, Niels; Holst, René; Frandsen, Rikke

    2012-01-01

    A substantial improvement in the bycatch selectivity of Norway lobster Nephrops norvegicus trawls is required, particularly with respect to cod Gadus morhua , whose stocks are at low levels in several areas. Conventional escape windows are not adequate to properly release cod and other bycatch...... species caught in the trawls. To address this issue, we developed a novel sorting box concept consisting of a four-panel section with a window on the top in order to improve the escape of cod and other bycatch species through an escape window while retaining the target catch of Norway lobster. The concept....... The reduction in bycatch decreased with decreasing mesh size and increasing height of the sorting box. Escape of Norway lobster through the escape window was limited. A modified version of the sorting box concept was implemented in the Kattegat fishery from 2009 onwards...

  3. Mass fractionation during transonic escape and implications for loss of water from Mars and Venus

    International Nuclear Information System (INIS)

    Zahnle, K.J.; Kasting, J.F.

    1986-01-01

    Hydrodynamic escape of hydrogen from a planetary atmosphere can remove heavier gases as well as hydrogen, provided that the escape rate is sufficiently large. Analytic approximations for the degree of mass fractionation of a trace species during hydrodynamic escape are compared with accurate numerical solutions for the case of transonic outflow. The analytic approximations are most accurate when the ratio of molecular weights of the heavier and lighter constituents is large so that nonlinear terms in the momentum equation for the heavy constituent become small. The simplest analytic formula is readily generalized to the case where a heavy constituent is also a major species. Application of the generalized formula to hypothetical episodes of hydrodynamic escape from Venus and Mars suggests that both hydrogen and oxygen could have escaped; thus, substantial quantities of water may have been lost without the need to oxidize large amounts of the crust. 29 references

  4. Escape peak ratios in silicon X-ray charge coupled devices (CCDs)

    International Nuclear Information System (INIS)

    McCarthy, K.J.; Owens, A.; Keay, A.

    1997-01-01

    The intensity of the escape peak from the CCDs developed for the Joint European X-ray Telescope (JET-X) has been investigated over the energy range 2-10 keV. Both measured and calculated escape peak ratios (i.e., the ratio of counts in the escape peak to the sum of the counts in the escape and main peaks) are found to be in excellent agreement for all event sizes (i.e., single pixel events, 1 and 2 pixel events, etc.). Using a Monte Carlo simulation the escape peak ratio has been investigated as a function of pixel size and depletion depth. For completeness, we list the energy dependent parameterised forms for five CCDs used in three major astronomy missions. (orig.)

  5. The return of international labour migrants in the ESCAP Region.

    Science.gov (United States)

    1986-03-01

    The social phenomenon of massive temporary international labor migration from the ESCAP region has emerged extremely rapidly. Within 10 years, the number of persons from ESCAP countries grew from a negligible one to 3.5 million. Related research and government policies have lagged behind this latest surge in migration. Most research conducted has been small-scale and lacks an analytical or theoretical framework. Policy formulation for temporary labor migration is difficult because most of the rapid growth in the industry has occurred as a result of private efforts, with a minimum of government intervention. It is now difficult, for the government to provide effective regulations or measures to stimulate and assist the process. Regulations on compulsory remittances or overseas minimum wages have proved to be unrealistic and, if not rescinded, are routinely circumvented. The most effective policies to assist return migrants may not be those which are intended to do so, but those which control the earlier stages of the migration process, such as recruitment, working conditions, and banking arrangements. The most valuable policies may also include those affecting education, training, employment, and general socioeconomic growth. Governments are recommended to provide social services for migrants and their families who are experiencing problems, and to institute community programs in areas with a large number of labor migrants. Governmental efforts to promote forms of labor migration beneficial to the workers would be valuable and should include measures to identify overseas labor markets for employing its nationals, government ot government labor contracts, and government participation in joint-venture projects. International migration should be analyzed in the context of theories and social change in order for governments to formulate effective measures for the reintegration of returning workers. Labor migration on the current scale has many social implications for

  6. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    International Nuclear Information System (INIS)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand

    2013-01-01

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression

  7. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    Energy Technology Data Exchange (ETDEWEB)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Cook-Moreau, Jeanne [Université de Limoges, FR 3503 GEIST, UMR CNRS 7276 “Contrôle de la réponse immune B et lymphoproliférations”, Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Beneytout, Jean-Louis [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France)

    2013-04-15

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression.

  8. Antiproliferative and apoptotic activities of extracts of Asclepias subulata.

    Science.gov (United States)

    Rascón Valenzuela, Luisa Alondra; Jiménez Estrada, Manuel; Velázquez Contreras, Carlos Arturo; Garibay Escobar, Adriana; Medina Juárez, Luis Angel; Gámez Meza, Nohemi; Robles Zepeda, Ramón Enrique

    2015-01-01

    Asclepias subulata Decne. (Apocynaceae) is a shrub used in the Mexican traditional medicine for the treatment of cancer. The objective of this study was to evaluate the antiproliferative activity of methanol extract of aerial parts of A. subulata and its fractions against different cancer cell lines. Additionally, we analyzed the mechanism of action of the active fractions. Methanol extract fractions were prepared by serial extraction with n-hexane, ethyl acetate, and ethanol. The antiproliferative activity of methanol extract and its fractions was evaluated, against several murine (M12.C3.F6, RAW 264.7, and L929) and human (HeLa, A549, PC-3, LS 180, and ARPE-19) cell lines by the MTT assay, using concentrations of 0.4-400 µg/mL for 48 h. Ethanol and residual fractions were separated using silica gel column. Apoptosis induction of cancer cells was evaluated by Annexin and JC-1 staining using flow cytometry. Methanol extract and its fractions showed antiproliferative activity against all human cancer cell lines tested. Methanol extract had the highest antiproliferative activity on A549 and HeLa cells (IC50 values < 0.4 and 8.7 µg/mL, respectively). Ethanol and residual fractions exerted significant antiproliferative effect on A549 (IC50 < 0.4 µg/mL) and PC3 cells (IC50 1.4 and 5.1 µg/mL). Apoptotic assays showed that CEF7, CEF9, CRF6, and CRF5 fractions induced mitochondrial depolarization in A549 cells, 70, 73, 77, and 80%, respectively. Those fractions triggered the apoptosis mitochondrial pathway. Our data show that A. subulata extracts have potent antiproliferative properties on human cancer cell lines. This plant should be considered an important source of potent anticancer compounds.

  9. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC’s efficacy and mechanism of action. Results: ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. Conclusions: ARC treatment confers

  10. Effects of metamorphosis on the aquatic escape response of the two-lined salamander (Eurycea bislineata).

    Science.gov (United States)

    Azizi, Emanuel; Landberg, Tobias

    2002-03-01

    Although numerous studies have described the escape kinematics of fishes, little is known about the aquatic escape responses of salamanders. We compare the escape kinematics of larval and adult Eurycea bislineata, the two-lined salamander, to examine the effects of metamorphosis on aquatic escape performance. We hypothesize that shape changes associated with resorption of the larval tail fin at metamorphosis will affect aquatic locomotor performance. Escape responses were recorded using high-speed video, and the effects of life stage and total length on escape kinematics were analyzed statistically using analysis of covariance. Our results show that both larval and adult E. bislineata use a two-stage escape response (similar to the C-starts of fishes) that consists of a preparatory (stage 1) and a propulsive (stage 2) stroke. The duration of both kinematic stages and the distance traveled during stage 2 increased with total length. Both larval and adult E. bislineata had final escape trajectories that were directed away from the stimulus. The main kinematic difference between larvae and adults is that adults exhibit significantly greater maximum curvature during stage 1. Total escape duration and the distance traveled during stage 2 did not differ significantly between larvae and adults. Despite the significantly lower tail aspect ratio of adults, we found no significant decrease in the overall escape performance of adult E. bislineata. Our results suggest that adults may compensate for the decrease in tail aspect ratio by increasing their maximum curvature. These findings do not support the hypothesis that larvae exhibit better locomotor performance than adults as a result of stronger selective pressures on early life stages.

  11. Apoptotic action of peroxisome proliferator-activated receptor-gamma activation in human non small-cell lung cancer is mediated via proline oxidase-induced reactive oxygen species formation.

    Science.gov (United States)

    Kim, Ki Young; Ahn, Jin Hee; Cheon, Hyae Gyeong

    2007-09-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma ligands have been shown to inhibit human lung cancers by inducing apoptosis and differentiation. In the present study, we elucidated the apoptotic mechanism of PPARgamma activation in human lung cancers by using a novel PPARgamma agonist, 1-(trans-methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-(1H-indene-2-carboxylic acid ethyl ester (KR-62980), and rosiglitazone. PPARgamma activation selectively inhibited cell viability of non-small-cell lung cancer with little effect on small-cell lung cancer and normal lung cells. The cell death induced by PPARgamma activation presented apoptotic features of oligonucleosomal DNA fragmentation in A549 human non-small-cell lung cancer cell line. Reactive oxygen species (ROS) production was accompanied by increased expression of proline oxidase (POX), a redox enzyme expressed in mitochondria, upon incubation with the agonists. POX RNA interference treatment blocked PPARgamma-induced ROS formation and cytotoxicity, suggesting that POX plays a functional role in apoptosis through ROS formation. The apoptotic effects by the agonists were antagonized by bisphenol A diglycidyl ether, a PPARgamma antagonist, and by knockdown of PPARgamma expression, indicating the involvement of PPARgamma in these actions. The results of the present study suggest that PPARgamma activation induces apoptotic cell death in non-small-cell lung carcinoma mainly through ROS formation via POX induction.

  12. Enzymic lactose hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J J; Brand, J C

    1980-01-01

    Acid or enzymic hydrolysis can be used to hydrolyze lactose. Advantages of both are compared and details of enzymic hydrolysis using yeast or fungal enzymes given. The new scheme outlined involves recycling lactase. Because lactose and lactase react to ultrafiltration (UF) membranes differently separation is possible. Milk or milk products are ultrafiltered to separate a concentrate from a lactose-rich permeate which is treated with lactase in a reactor until hydrolysis reaches a required level. The lactase can be removed by UF as it does not permeate the membrane, and it is recycled back to the reactor. Permeate from the second UF stage may or may not be recombined with the concentrate from the first stage to produce a low lactose product (analysis of a typical low-lactose dried whole milk is given). Batch or continuous processes are explained and a batch process without enzyme recovery is discussed. (Refs. 4).

  13. Indicators: Sediment Enzymes

    Science.gov (United States)

    Sediment enzymes are proteins that are produced by microorganisms living in the sediment or soil. They are indicators of key ecosystem processes and can help determine which nutrients are affecting the biological community of a waterbody.

  14. Enzyme Vs. Extremozyme -32 ...

    Indian Academy of Sciences (India)

    Enzymes are biocatalytic protein molecules that enhance the rates of ... to physical forces (hydrogen bonds, hydrophobic 1, electrostatic and Van der ... conformation. In 1995 ... surface against 14.7% in Klenow poll (some of the hydrophobic.

  15. Evolutionary invasion and escape in the presence of deleterious mutations.

    Directory of Open Access Journals (Sweden)

    Claude Loverdo

    Full Text Available Replicators such as parasites invading a new host species, species invading a new ecological niche, or cancer cells invading a new tissue often must mutate to adapt to a new environment. It is often argued that a higher mutation rate will favor evolutionary invasion and escape from extinction. However, most mutations are deleterious, and even lethal. We study the probability that the lineage will survive and invade successfully as a function of the mutation rate when both the initial strain and an adaptive mutant strain are threatened by lethal mutations. We show that mutations are beneficial, i.e. a non-zero mutation rate increases survival compared to the limit of no mutations, if in the no-mutation limit the survival probability of the initial strain is smaller than the average survival probability of the strains which are one mutation away. The mutation rate that maximizes survival depends on the characteristics of both the initial strain and the adaptive mutant, but if one strain is closer to the threshold governing survival then its properties will have greater influence. These conclusions are robust for more realistic or mechanistic depictions of the fitness landscapes such as a more detailed viral life history, or non-lethal deleterious mutations.

  16. Human embryo immune escape mechanisms rediscovered by the tumor.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Riccobon, Angela; Ridolfi, Ruggero

    2009-01-01

    Towards the end of the 1990s, the two opposing theories on immunosurveillance and immunostimulation were extensively studied by researchers in an attempt to understand the complex mechanisms that regulate the relation between tumors and the host's immune system. Both theories probably have elements that would help us to comprehend how the host can induce anti-tumor clinical responses through stimulation of the immune system and which could also give us a deeper insight into the mechanisms of tumor immunosuppression. The model that most resembles the behavior of tumor cells in terms of growth, infiltration and suppression of the immune system of the environment in which they live is undoubtedly that of the embryonic cell. The fetus behaves like an allogenic transplant within the mother's body, using every means it has to escape from and defend itself against the mother's immune system. The majority of these mechanisms are the same as those found in tumor cells: antigenic loss, lack of expression of classic HLA-I molecules, production of immunosuppressive cytokines, induction of lack of expression of co-stimulatory molecules in antigen presenting cells, and induction of apoptosis in infiltrating lymphocytes, with activation of a type Th2 regulatory lymphocyte response. A careful and comparative study of key mechanisms capable of triggering tolerance or cytotoxicity in both embryonic and tumor cells could prove immensely valuable in designing new strategies for anti-tumor immunotherapy.

  17. Intertextuality in Novel: An Escape from Patriarchal Soliloquy

    Directory of Open Access Journals (Sweden)

    Nargess Bagheri

    2015-12-01

    Full Text Available Hypertextuality is one of the intertextual relationships introduced by Gerard Genette. According to him, hypertextuality includes all the relationships which the hypertext has with the previous text, i.e. the hypotext. However, he does not consider the relationship between these two texts to be in such a way that the hypertext is the interpretation of the hypotext. On the other hand, other theorizers including Bakhtin, regard the conversation between texts a way to escape a one-voiced and dominant discourse. From this viewpoint, the intertextual relationships of Sadegh Hedayat’s The Blind Owl, with Shahrnoush Parsipour’s The Blue Mind and Abbas Maroufi’s The Body of Farhad are in such a way that The Blind Owl can be regarded as a hypotext for the other 2 novels but these two novels interpret the text differently. The present study aims to examine the intertextual relationships between these 3 novels and explore how a multiple-voiced conversation is formed between them.

  18. Thermal and quantum escape of fractional Josephson vortices

    Energy Technology Data Exchange (ETDEWEB)

    Poehler, Hanna; Kienzle, Uta; Buckenmaier, Kai; Gaber, Tobias; Koelle, Dieter; Kleiner, Reinhold; Goldobin, Edward [Physikalisches Institut, Center for Collective Quantum Phenomena, Universitaet Tuebingen (Germany); Siegel, Michael [Institut fuer Mikro- und Nanoelektronische Systeme, Universitaet Karlsruhe (Germany)

    2009-07-01

    By using a pair of tiny current injectors one can create an arbitrary {kappa} discontinuity of the phase in a long Josephson junction (LJJ) and a fractional Josephson vortex (FJV), carrying a fraction {phi}/{phi}{sub 0}={kappa}/2{pi}{<=}1 of the magnetic flux quantum {phi}{sub 0}{approx}2.07 .10{sup -15} Wb, which is pinned at the discontinuity. If a bias current I, exceeds the critical value I{sub c}({kappa}), an integer fluxon is torn off the discontinuity and the LJJ switches to the voltage state. Due to thermal or quantum fluctuations this escape event may occur at I

  19. EUROGAM: A high efficiency escape suppressed spectrometer array

    Energy Technology Data Exchange (ETDEWEB)

    Nolan, P J [Liverpool Univ. (United Kingdom). Oliver Lodge Lab.

    1992-08-01

    EUROGAM is a UK-France collaboration to develop and build a high efficiency escape suppressed spectrometer array. The project has involved the development of both germanium (Ge) and bismuth germanate (BGO) detectors to produce crystals which are both bigger and have a more complex geometry. As a major investment for the future, the collaboration has developed a new electronics and data acquisition system based on the VXI and VME standards. The array will start its experimental programme in mid 1992 at the Nuclear Structure Facility at Daresbury, U.K. At this stage it will have a total photopeak efficiency (for 1.33 MeV gamma-rays) of {approx} 4.5%. This will give an improvement in sensitivity (relative to presently operating arrays) of a factor of about 10. When EUROGAM moves to France in mid 1993 its photopeak efficiency will have increased to about 8.5% which will result in an increase in sensitivity of a further factor of about 10. In this article I will concentrate on the array which will operate at Daresbury in 1992 and only briefly cover the developments which will take place for the full array before it is used in France in 1993. (author). 13 refs., 2 tabs., 10 figs.

  20. Imaging escape gated MPWC for hard X-ray astronomy

    Energy Technology Data Exchange (ETDEWEB)

    Ubertini, P.; Bazzano, A.; Boccaccini, L.; La Padula, C.; Mastropietro, M.; Patriarca, R.; Polcaro, V.F.; Barbareschi, L.; Perotti, F.; Villa, G.

    1983-11-15

    A scientific forward step in the hard X-ray and soft gamma-ray astronomy will only be possible with the use of a new generation of space borne instruments. Their main characteristics have to be the two-dimensional imaging capability over a large collecting area and the fine spectral resolution in order to discriminate between the weak signal coming from cosmic sources to be detected and the strong background induced by cosmic rays, in the space environment, on the detector. To reach this goal we have developed a new hard X-ray position sensitive proportional counter operating with the escape gate technique in the range 15-150 keV, to be used together with a pseudo-random coded mask in order to obtain sky images. The detector is a high pressure (5 bar) xenon-argon-isobutane filled chamber with a spatial resolution of 30x2 mm and a spectral resolution of 5% at 60 keV on the sensitive area of 3000 cm/sup 2/.

  1. Cellular Adhesion Promotes Prostate Cancer Cells Escape from Dormancy.

    Science.gov (United States)

    Ruppender, Nazanin; Larson, Sandy; Lakely, Bryce; Kollath, Lori; Brown, Lisha; Coleman, Ilsa; Coleman, Roger; Nguyen, Holly; Nelson, Peter S; Corey, Eva; Snyder, Linda A; Vessella, Robert L; Morrissey, Colm; Lam, Hung-Ming

    2015-01-01

    Dissemination of prostate cancer (PCa) cells to the bone marrow is an early event in the disease process. In some patients, disseminated tumor cells (DTC) proliferate to form active metastases after a prolonged period of undetectable disease known as tumor dormancy. Identifying mechanisms of PCa dormancy and reactivation remain a challenge partly due to the lack of in vitro models. Here, we characterized in vitro PCa dormancy-reactivation by inducing cells from three patient-derived xenograft (PDX) lines to proliferate through tumor cell contact with each other and with bone marrow stroma. Proliferating PCa cells demonstrated tumor cell-cell contact and integrin clustering by immunofluorescence. Global gene expression analyses on proliferating cells cultured on bone marrow stroma revealed a downregulation of TGFB2 in all of the three proliferating PCa PDX lines when compared to their non-proliferating counterparts. Furthermore, constitutive activation of myosin light chain kinase (MLCK), a downstream effector of integrin-beta1 and TGF-beta2, in non-proliferating cells promoted cell proliferation. This cell proliferation was associated with an upregulation of CDK6 and a downregulation of E2F4. Taken together, our data provide the first clinically relevant in vitro model to support cellular adhesion and downregulation of TGFB2 as a potential mechanism by which PCa cells may escape from dormancy. Targeting the TGF-beta2-associated mechanism could provide novel opportunities to prevent lethal PCa metastasis.

  2. EUROGAM: A high efficiency escape suppressed spectrometer array

    International Nuclear Information System (INIS)

    Nolan, P.J.

    1992-01-01

    EUROGAM is a UK-France collaboration to develop and build a high efficiency escape suppressed spectrometer array. The project has involved the development of both germanium (Ge) and bismuth germanate (BGO) detectors to produce crystals which are both bigger and have a more complex geometry. As a major investment for the future, the collaboration has developed a new electronics and data acquisition system based on the VXI and VME standards. The array will start its experimental programme in mid 1992 at the Nuclear Structure Facility at Daresbury, U.K. At this stage it will have a total photopeak efficiency (for 1.33 MeV gamma-rays) of ∼ 4.5%. This will give an improvement in sensitivity (relative to presently operating arrays) of a factor of about 10. When EUROGAM moves to France in mid 1993 its photopeak efficiency will have increased to about 8.5% which will result in an increase in sensitivity of a further factor of about 10. In this article I will concentrate on the array which will operate at Daresbury in 1992 and only briefly cover the developments which will take place for the full array before it is used in France in 1993. (author). 13 refs., 2 tabs., 10 figs

  3. Controlling ventilation for safe escape from coal mine fires

    Energy Technology Data Exchange (ETDEWEB)

    Wala, A M [University of Kentucky, Lexington, KY (United States). Mining Engineering Dept.

    1966-04-01

    If a fire occurs outby an underground coal mine section, the immediate safe evacuation of miners from the working section should always take precedence. Unfortunately, in many cases, the dedicated escapeway (escape routes) for the evacuation of the miners become contaminated by the byproducts of fire from the adjacent entries. The purpose of this paper is to present the ventilation-control process that would keep the escapeway free from contaminants and, thus, available for travel. A few scenarios of mine fires in longwall development panels are analysed and discussed. To perform these studies, a mine-fire simulator (MFS) was used. This (MFS) provides a dynamic representation of the fire`s progress (in real time) and gives a color-graphic visualization of the spready of oxygen, combustion products and temperature of the gases throughout the ventilation system. Also presented and discussed are ways in which the MFS can be used as a training and teaching tool for miners and particularly, for ventilation and safety specialists. 7 refs., 10 figs.

  4. ESCAPE. Energy Security and ClimAte Policy Evaluation

    International Nuclear Information System (INIS)

    Kessels, J.R.; Bakker, S.J.A.

    2005-05-01

    Climate change and energy supply security policy are currently not integrated in most countries, despite possible synergies. The ESCAPE approach suggests that linking climate change policy with security of energy supply could improve climate change policy at both a national and international level. The report explores the interaction between policies of energy security and climate change and the options of inclusion of energy security issues into national and international post-2012 climate negotiations. It emphasises the importance of the US in this regard and takes a close look at US energy policy documents. It appears that current US energy policy is not directed towards reducing its reliance on imported fossil fuel, even though the government has a strong preference for this. This study shows that measures to reduce import dependency are mostly synergetic with climate policy and gives some options that can be implemented. On an international level, linkages of energy security into post-2012 climate policy may be possible in sectoral bottom-up approaches or technology frameworks. As well, inclusion of a security of supply criterion in international emission trading instruments may provide potential benefits

  5. A Novel Mitochondria-Dependent Apoptotic Pathway (MAP) in Prostate Cancer (Pca) Cells

    National Research Council Canada - National Science Library

    Chandra, Dhyan

    2004-01-01

    ...) are also up-regulated (Chandra et al., J. Biol. Chem., 277, 50842-54; 2002). Later, when the apoptotic machinery is activated, I notice that there is prominent localization of active caspase-9 and -3 in the mitochondria...

  6. Overproduction of ligninolytic enzymes

    Science.gov (United States)

    Elisashvili, Vladimir; Kachlishvili, Eva; Torok, Tamas

    2014-06-17

    Methods, compositions, and systems for overproducing ligninolytic enzymes from the basidiomycetous fungus are described herein. As described, the method can include incubating a fungal strain of Cerrena unicolor IBB 303 in a fermentation system having growth medium which includes lignocellulosic material and then cultivating the fungal strain in the fermentation system under conditions wherein the fungus expresses the ligninolytic enzymes. In some cases, the lignocellulosic material is mandarin peel, ethanol production residue, walnut pericarp, wheat bran, wheat straw, or banana peel.

  7. Measurement of enzyme activity.

    Science.gov (United States)

    Harris, T K; Keshwani, M M

    2009-01-01

    To study and understand the nature of living cells, scientists have continually employed traditional biochemical techniques aimed to fractionate and characterize a designated network of macromolecular components required to carry out a particular cellular function. At the most rudimentary level, cellular functions ultimately entail rapid chemical transformations that otherwise would not occur in the physiological environment of the cell. The term enzyme is used to singularly designate a macromolecular gene product that specifically and greatly enhances the rate of a chemical transformation. Purification and characterization of individual and collective groups of enzymes has been and will remain essential toward advancement of the molecular biological sciences; and developing and utilizing enzyme reaction assays is central to this mission. First, basic kinetic principles are described for understanding chemical reaction rates and the catalytic effects of enzymes on such rates. Then, a number of methods are described for measuring enzyme-catalyzed reaction rates, which mainly differ with regard to techniques used to detect and quantify concentration changes of given reactants or products. Finally, short commentary is given toward formulation of reaction mixtures used to measure enzyme activity. Whereas a comprehensive treatment of enzymatic reaction assays is not within the scope of this chapter, the very core principles that are presented should enable new researchers to better understand the logic and utility of any given enzymatic assay that becomes of interest.

  8. BAD-mediated apoptotic pathway is associated with human cancer development.

    Science.gov (United States)

    Stickles, Xiaomang B; Marchion, Douglas C; Bicaku, Elona; Al Sawah, Entidhar; Abbasi, Forough; Xiong, Yin; Bou Zgheib, Nadim; Boac, Bernadette M; Orr, Brian C; Judson, Patricia L; Berry, Amy; Hakam, Ardeshir; Wenham, Robert M; Apte, Sachin M; Berglund, Anders E; Lancaster, Johnathan M

    2015-04-01

    The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive and invasive cancers of different types, such as ovarian, endometrial, breast and colon cancers in order to determine the associations between the BAD-mediated apoptotic pathway and cancer development. Immunofluorescence was used to compare the expression levels of phosphorylated BAD [pBAD (serine-112, -136 and -155)] in immortalized normal and invasive ovarian, colon and breast cancer cells. The expression of the BAD-mediated apoptotic pathway phosphatase, PP2C, was evaluated by RT-qPCR in the normal and ovarian cancer tissue samples. The growth-promoting effects of pBAD protein levels in the immortalized normal and cancer cells were assessed using siRNA depletion experiments with MTS assays. The expression of the BAD-mediated apoptotic pathway was associated with the development and/or progression of ovarian (n=106, pBAD-mediated apoptotic pathway is thus associated with the development of human cancers likely influenced by the protein levels of pBAD.

  9. Effects of Malnutrition on Neutrophil/Mononuclear Cell Apoptotic Functions in Children with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Cakir, Fatma Betul; Berrak, Su Gülsün; Aydogan, Gonul; Tulunay, Aysin; Timur, Cetin; Canpolat, Cengiz; Eksioglu Demiralp, Emel

    2017-04-01

    Recent studies claim that apoptosis may explain immune dysfunction observed in malnutrition. The objective of this study was to determine the effect of malnutrition on apoptotic functions of phagocytic cells in acute lymphoblastic leukemia (ALL). Twenty-eight ALL patients (13 with malnutrition) and thirty controls were enrolled. Neutrophil and mononuclear cell apoptosis of ALL patients and the control group were studied on admission before chemotherapy and repeated at a minimum of three months after induction of chemotherapy or when the nutritional status of leukemic children improved. The apoptotic functions of both ALL groups on admission were significantly lower than those of the control group. The apoptotic functions were lower in ALL patients with malnutrition than those in ALL patients without malnutrition, but this was not statistically significant. The repeated apoptotic functions of both ALL groups were increased to similar values with the control group. This increase was found to be statistically significant. The apoptotic functions in ALL patients were not found to be affected by malnutrition. However, after dietary intervention, increased apoptotic functions in both ALL patient groups deserve mentioning. Dietary intervention should always be recommended as malnutrition or cachexia leads to multiple complications. Enhanced apoptosis might originate also from remission state of cancer.

  10. Apoptotic Effect of Nigella sativa on Human Lymphoma U937 Cells.

    Science.gov (United States)

    Arslan, Belkis Atasever; Isik, Fatma Busra; Gur, Hazal; Ozen, Fatih; Catal, Tunc

    2017-10-01

    Nigella sativa is from botanical Ranunculaceae family and commonly known as black seed. Apoptotic effect of N. sativa and its apoptotic signaling pathways on U937 lymphoma cells are unknown. In this study, we investigated selective cytotoxic and apoptotic effects of N. sativa extract and its apoptotic mechanisms on U937 cells. In addition, we also studied selective cytotoxic activity of thymoquinone that is the most active essential oil of N. sativa . Our results showed that N. sativa extract has selective cytotoxicity and apoptotic effects on U937 cells but not ECV304 control cells. However, thymoquinone had no significant cytotoxicity against on both cells. N. sativa extract increased significantly caspase-3, BAD, and p53 gene expressions in U937 cells. N. sativa may have anticancer drug potential and trigger p53-induced apoptosis in U937 lymphoma cells. This is the first study showing the apoptotic effect of Nigella sativa extract on U937 cells. Abbreviations used: CI: Cytotoxicity index, DMEM: Dulbecco's Modified Eagle Medium, HL: Hodgkin's lymphoma, MTT: 3-(4,5-dimethy lthiazol-2yl)-2,5-diphenyl tetrazolium bromide, RPMI: Roswell Park Memorial Institute medium.

  11. Proteomic analyses for profiling regulated proteins/enzymes by Fucus vesiculosus fucoidan in B16 melanoma cells: A combination of enzyme kinetics functional study.

    Science.gov (United States)

    Wang, Zhi-Jiang; Zheng, Li; Yang, Jun-Mo; Kang, Yani; Park, Yong-Doo

    2018-06-01

    Fucoidans are complex sulfated polysaccharides that have a wide range of biological activities. Previously, we reported the various effects of Fucus vesiculosus fucoidan on tyrosinase and B16 melanoma cells. In this study, to identify fucoidan-targeted proteins in B16 melanoma cells, we performed a proteomics study and integrated enzyme kinetics. We detected 19 candidate proteins dysregulated by fucoidan treatment. Among the probed proteins, the enzyme kinetics of two candidate enzymes, namely lactate dehydrogenase (LDH) as an upregulated protein and superoxide dismutase (SOD) as a downregulated enzyme, were determined. The enzyme kinetics results showed that Fucus vesiculosus fucoidan significantly inhibited LDH catalytic function while it did not affect SOD activity even at a high dose, while only slightly decreased activity (up to 10%) at a low dose. Based on our previous and present observations, fucoidan could inhibit B16 melanoma cells growth via regulating proteins/enzymes expression levels such as LDH and SOD known as cell survival biomarkers. Interestingly, both expression level and enzyme catalytic activity of LDH were regulated by fucoidan, which could directly induce the apoptotic effect on B16 melanoma cells along with SOD downregulation. This study highlights how combining proteomics with enzyme kinetics can yield valuable insights into fucoidan targets. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Means of escape provisions and evacuation simulation of public building in Malaysia and Singapore

    Science.gov (United States)

    Samad, Muna Hanim Abdul; Taib, Nooriati; Ying, Choo Siew

    2017-10-01

    The Uniform Building By-law 1984 of Malaysia is the legal document governing fire safety requirements in buildings. Its prescriptive nature has made the requirements out dated from the viewpoint of current performance based approach in most developed countries. The means of escape provisions is a critical requirement to safeguard occupants' safety in fire especially in public buildings. As stipulated in the UBBL 1984, the means of escape provisions includes sufficient escape routes, travel distance, protection of escape routes, etc. designated as means to allow occupants to escape within a safe period of time. This research aims at investigating the effectiveness of those provisions in public buildings during evacuation process involving massive crowd during emergencies. This research includes a scenario-based study on evacuation processes using two software i.e. PyroSim, a crowd modelling software to conduct smoke study and Pathfinder to stimulate evacuation model of building in Malaysia and Singapore as comparative study. The results show that the buildings used as case study were designed according to Malaysian UBBL 1984 and Singapore Firecode, 2013 respectively provide relative safe means of escape. The simulations of fire and smoke and coupled with simulation of evacuation have demonstrated that although there are adequate exits designated according to fire requirements, the impact of the geometry of atriums on the behavior of fire and smoke have significant effect on escape time especially for unfamiliar user of the premises.

  13. Measuring behaviours for escaping from house fires: use of latent variable models to summarise multiple behaviours.

    Science.gov (United States)

    Ploubidis, G B; Edwards, P; Kendrick, D

    2015-12-15

    This paper reports the development and testing of a construct measuring parental fire safety behaviours for planning escape from a house fire. Latent variable modelling of data on parental-reported fire safety behaviours and plans for escaping from a house fire and multivariable logistic regression to quantify the association between groups defined by the latent variable modelling and parental-report of having a plan for escaping from a house fire. Data comes from 1112 participants in a cluster randomised controlled trial set in children's centres in 4 study centres in the UK. A two class model provided the best fit to the data, combining responses to five fire safety planning behaviours. The first group ('more behaviours for escaping from a house fire') comprised 86% of participants who were most likely to have a torch, be aware of how their smoke alarm sounds, to have external door and window keys accessible, and exits clear. The second group ('fewer behaviours for escaping from a house fire') comprised 14% of participants who were less likely to report these five behaviours. After adjusting for potential confounders, participants allocated to the 'more behaviours for escaping from a house fire group were 2.5 times more likely to report having an escape plan (OR 2.48; 95% CI 1.59-3.86) than those in the "fewer behaviours for escaping from a house fire" group. Multiple fire safety behaviour questions can be combined into a single binary summary measure of fire safety behaviours for escaping from a house fire. Our findings will be useful to future studies wishing to use a single measure of fire safety planning behaviour as measures of outcome or exposure. NCT 01452191. Date of registration 13/10/2011.

  14. Quantifying the impact of human immunodeficiency virus-1 escape from cytotoxic T-lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ulrich D Kadolsky

    2010-11-01

    Full Text Available HIV-1 escape from the cytotoxic T-lymphocyte (CTL response leads to a weakening of viral control and is likely to be detrimental to the patient. To date, the impact of escape on viral load and CD4(+ T cell count has not been quantified, primarily because of sparse longitudinal data and the difficulty of separating cause and effect in cross-sectional studies. We use two independent methods to quantify the impact of HIV-1 escape from CTLs in chronic infection: mathematical modelling of escape and statistical analysis of a cross-sectional cohort. Mathematical modelling revealed a modest increase in log viral load of 0.051 copies ml(-1 per escape event. Analysis of the cross-sectional cohort revealed a significant positive association between viral load and the number of "escape events", after correcting for length of infection and rate of replication. We estimate that a single CTL escape event leads to a viral load increase of 0.11 log copies ml(-1 (95% confidence interval: 0.040-0.18, consistent with the predictions from the mathematical modelling. Overall, the number of escape events could only account for approximately 6% of the viral load variation in the cohort. Our findings indicate that although the loss of the CTL response for a single epitope results in a highly statistically significant increase in viral load, the biological impact is modest. We suggest that this small increase in viral load is explained by the small growth advantage of the variant relative to the wildtype virus. Escape from CTLs had a measurable, but unexpectedly low, impact on viral load in chronic infection.

  15. Seasonal variations of anti-/apoptotic and antioxidant proteins in the heart and gastrocnemius muscle of the water frog Pelophylax ridibundus.

    Science.gov (United States)

    Feidantsis, Konstantinos; Anestis, Andreas; Michaelidis, Basile

    2013-10-01

    In the present work we investigated the seasonal variations of apoptotic and antioxidant proteins in the heart and gastrocnemius muscle of the amphibian Pelophylax ridibundus. Particularly processes studied included the evaluation of hypoxia through the levels of transcriptional factor Hif-1α, of apoptosis through the determination of Bcl-2 and Bax, ubiquitin conjugates levels and the antioxidant defense through the determination of the activity of enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Due to a general metabolic depression during overwintering, levels of the above mentioned proteins and enzymes are generally retained at low levels of expression and activity in the examined tissues of P. ridibundus. On the other hand recovery from overwintering induces oxidative stress, followed by increased levels of the specific proteins and enzymes. A milder up-regulation of antioxidant enzymes during overwintering probably prepares P. ridibundus for oxidative stress during arousal. The seasonal activation of these mechanisms seems to protect this species from these unfavourable conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Escape of the martian protoatmosphere and initial water inventory.

    Science.gov (United States)

    Erkaev, N V; Lammer, H; Elkins-Tanton, L T; Stökl, A; Odert, P; Marcq, E; Dorfi, E A; Kislyakova, K G; Kulikov, Yu N; Leitzinger, M; Güdel, M

    2014-08-01

    Latest research in planet formation indicates that Mars formed within a few million years (Myr) and remained as a planetary embryo that never grew to a more massive planet. It can also be expected from dynamical models that most of Mars' building blocks consisted of material that formed in orbital locations just beyond the ice line which could have contained [Formula: see text] of H 2 O. By using these constraints, we estimate the nebula-captured and catastrophically outgassed volatile contents during the solidification of Mars' magma ocean and apply a hydrodynamic upper atmosphere model for the study of the soft X-ray and extreme ultraviolet (XUV) driven thermal escape of the martian protoatmosphere during the early active epoch of the young Sun. The amount of gas that has been captured from the protoplanetary disk into the planetary atmosphere is calculated by solving the hydrostatic structure equations in the protoplanetary nebula. Depending on nebular properties such as the dust grain depletion factor, planetesimal accretion rates and luminosities, hydrogen envelopes with masses [Formula: see text] to [Formula: see text] could have been captured from the nebula around early Mars. Depending on the before mentioned parameters, due to the planets low gravity and a solar XUV flux that was [Formula: see text] times stronger compared to the present value, our results indicate that early Mars would have lost its nebular captured hydrogen envelope after the nebula gas evaporated, during a fast period of [Formula: see text]. After the solidification of early Mars' magma ocean, catastrophically outgassed volatiles with the amount of [Formula: see text] H 2 O and [Formula: see text] CO 2 could have been lost during [Formula: see text], if the impact related energy flux of large planetesimals and small embryos to the planet's surface lasted long enough, that the steam atmosphere could have been prevented from condensing. If this was not the case, then our results suggest

  17. Escaping 1 MeV tritons in TFTR

    International Nuclear Information System (INIS)

    Zweben, S.J.; Strachan, J.D.; Boivin, R.; Cavallo, A.; Fredrickson, E.D.; McGuire, K.; Mynick, H.E.; White, R.B.

    1989-01-01

    1 MeV tritons created by D-D reactions can simulate the 'single-particle' behavior expected with 3.5 MeV D-T alphas, since the gyroradii and slowing-down of these two particles are similar. This paper describes measurements of the flux of escaping 1 MeV tritons from the TFTR plasma during high power D 0 →D neutral beam injection, and shows that in most cases the observed triton loss is consistent with the classical (single-particle) first-orbit loss model. In this model tritons are lost if their first orbit intersects the wall due to their large banana width, while almost all tritons confined on their first orbit should stay confined until thermalized. The triton detectors are ZnS(Ag) scintillator screens housed in light-tight boxes located just outside the plasma boundary at the bottom of the TFTR vessel. They are particle 'pinhole' cameras which can resolve the triton flux vs. pitch angle (to ±5 o ), energy (to ±50 %), and time (to <20 μsec). The 2-D images of triton flux onto these scintillators are optically coupled to either an intensified TV camera or to photomultiplyer tubes for fast time resolution. The soft x-ray background in an earlier prototype has been eliminated. Although there are presently 8 such detectors in TFTR, this paper discusses results from only the detector located just below the vessel center (R=259 cm, r=102 cm). Note that the '1 MeV triton' signal discussed below also has about a 30 % contribution from 3 MeV protons; however, since these two particles have identical gyroradii they should behave alike. 5 refs., 5 figs

  18. An analytical evaluation for spatial-dependent intra-pebble Dancoff factor and escape probability

    International Nuclear Information System (INIS)

    Kim, Songhyun; Kim, Hong-Chul; Kim, Jong Kyung; Kim, Soon Young; Noh, Jae Man

    2009-01-01

    The analytical evaluation of spatial-dependent intra-pebble Dancoff factors and their escape probabilities is pursued by the model developed in this study. Intra-pebble Dancoff factors and their escape probabilities are calculated as a function of fuel kernel radius, number of fuel kernels, and fuel region radius. The method in this study can be easily utilized to analyze the tendency of spatial-dependent intra-pebble Dancoff factor and spatial-dependent fuel region escape probability for the various geometries because it is faster than the MCNP method as well as good accuracy. (author)

  19. Random-walk enzymes

    Science.gov (United States)

    Mak, Chi H.; Pham, Phuong; Afif, Samir A.; Goodman, Myron F.

    2015-09-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C →U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics.

  20. Apoptotic DNA Degradation into Oligonucleosomal Fragments, but Not Apoptotic Nuclear Morphology, Relies on a Cytosolic Pool of DFF40/CAD Endonuclease*

    Science.gov (United States)

    Iglesias-Guimarais, Victoria; Gil-Guiñon, Estel; Gabernet, Gisela; García-Belinchón, Mercè; Sánchez-Osuna, María; Casanelles, Elisenda; Comella, Joan X.; Yuste, Victor J.

    2012-01-01

    Apoptotic cell death is characterized by nuclear fragmentation and oligonucleosomal DNA degradation, mediated by the caspase-dependent specific activation of DFF40/CAD endonuclease. Here, we describe how, upon apoptotic stimuli, SK-N-AS human neuroblastoma-derived cells show apoptotic nuclear morphology without displaying concomitant internucleosomal DNA fragmentation. Cytotoxicity afforded after staurosporine treatment is comparable with that obtained in SH-SY5Y cells, which exhibit a complete apoptotic phenotype. SK-N-AS cell death is a caspase-dependent process that can be impaired by the pan-caspase inhibitor q-VD-OPh. The endogenous inhibitor of DFF40/CAD, ICAD, is correctly processed, and dff40/cad cDNA sequence does not reveal mutations altering its amino acid composition. Biochemical approaches show that both SH-SY5Y and SK-N-AS resting cells express comparable levels of DFF40/CAD. However, the endonuclease is poorly expressed in the cytosolic fraction of healthy SK-N-AS cells. Despite this differential subcellular distribution of DFF40/CAD, we find no differences in the subcellular localization of both pro-caspase-3 and ICAD between the analyzed cell lines. After staurosporine treatment, the preferential processing of ICAD in the cytosolic fraction allows the translocation of DFF40/CAD from this fraction to a chromatin-enriched one. Therefore, the low levels of cytosolic DFF40/CAD detected in SK-N-AS cells determine the absence of DNA laddering after staurosporine treatment. In these cells DFF40/CAD cytosolic levels can be restored by the overexpression of their own endonuclease, which is sufficient to make them proficient at degrading their chromatin into oligonucleosome-size fragments after staurosporine treatment. Altogether, the cytosolic levels of DFF40/CAD are determinants in achieving a complete apoptotic phenotype, including oligonucleosomal DNA degradation. PMID:22253444

  1. Never ever? Characteristics, outcomes and motivations of patients who abscond or escape: A 5-year review of escapes and absconds from two medium and low secure forensic units.

    Science.gov (United States)

    Mezey, Gillian; Durkin, Catherine; Dodge, Liam; White, Sarah

    2015-12-01

    Absconds and escapes by psychiatric patients from secure forensic psychiatric settings create public anxiety and are poorly understood. To describe secure hospital patients who escape from within the secure perimeter or abscond, and test for differences between these groups. Escapes and absconds between 2008 and 2012 from the medium and low secure forensic psychiatric inpatient units of two London National Health Service Trusts were identified through the Trusts' databases. Demographic, offending, mental health and incident data were extracted from records for each. Seventy-seven incidents, involving 54 patients, were identified over the five years. These were 13 escapes involving 12 patients, representing a rate of 0.04 per 1000 bed days, and 64 absconds involving 42 patients, a rate of 0.26 per 1000 bed days; 15 (28%) patients were absent without leave more than once. Over half of the patients came back voluntarily within 24 hours of leaving. Over 50% of them had drunk alcohol or taken drugs while away from the unit. Escapees were more likely to be transferred prisoners and to have planned their escape, less likely to return to the unit voluntarily and away longer than patients who absconded. Offending was rare during unauthorised leave--just three offences among the 77 incidents; self-harm was more likely. Motives for absconding included: wanting freedom or drink or drugs, family worries and/or dissatisfaction with aspects of treatment. Escapes or absconding from secure healthcare units have different characteristics, but may best be prevented by convergent strategies. Relational security is likely to be as important for foiling plans for the former as it is for reducing boredom, building strong family support and managing substance misuse in the latter. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Trapped as a Group, Escape as a Team: Applying Gamification to Incorporate Team-building Skills Through an ‘Escape Room’ Experience

    Science.gov (United States)

    Lee, Hyunjoo; Rodriguez, Carlos; Rudner, Joshua; Chan, Teresa M; Papanagnou, Dimitrios

    2018-01-01

    Teamwork, a skill critical for quality patient care, is recognized as a core competency by the Accreditation Council for Graduate Medical Education (ACGME). To date, there is no consensus on how to effectively teach these skills in a forum that engages learners, immerses members in life-like activities, and builds both trust and rapport. Recreational ‘Escape Rooms’ have gained popularity in creating a life-like environment that rewards players for working together, solving puzzles, and completing successions of mind-bending tasks in order to effectively ‘escape the room’ in the time allotted. In this regard, escape rooms share many parallels with the multitasking and teamwork that is essential for a successful emergency department (ED) shift. A pilot group of nine emergency medicine (EM) residents and one senior EM faculty member underwent a commercial escape room as part of a team-building exercise in January 2018. The escape room required participants to practice teamwork, communication, task delegation, and critical thinking to tackle waves of increasingly complex puzzles, ranging from hidden objects, physical object assembly (i.e., jigsaw puzzles), and symbol matching. Activities required members to recognize and utilize the collective experiences, skills, knowledge base, and physical abilities of the group. After the game, players underwent a structured ‘game-master’ debriefing facilitated by an employee of the commercial escape room; this was followed by a post-event survey facilitated by a faculty member, which focused on participants’ feelings, experiences, and problem-solving techniques. Escape rooms afford learners the opportunity to engage in an activity that rewards teamwork and effective leadership through experiences that directly link to specific ACGME milestones and educational learning theories. EM participants were engaged in the activity and felt that the escape room reproduced an environment analogous to the ED. The debriefing

  3. Trapped as a Group, Escape as a Team: Applying Gamification to Incorporate Team-building Skills Through an 'Escape Room' Experience.

    Science.gov (United States)

    Zhang, Xiao Chi; Lee, Hyunjoo; Rodriguez, Carlos; Rudner, Joshua; Chan, Teresa M; Papanagnou, Dimitrios

    2018-03-02

    Teamwork, a skill critical for quality patient care, is recognized as a core competency by the Accreditation Council for Graduate Medical Education (ACGME). To date, there is no consensus on how to effectively teach these skills in a forum that engages learners, immerses members in life-like activities, and builds both trust and rapport. Recreational 'Escape Rooms' have gained popularity in creating a life-like environment that rewards players for working together, solving puzzles, and completing successions of mind-bending tasks in order to effectively 'escape the room' in the time allotted. In this regard, escape rooms share many parallels with the multitasking and teamwork that is essential for a successful emergency department (ED) shift. A pilot group of nine emergency medicine (EM) residents and one senior EM faculty member underwent a commercial escape room as part of a team-building exercise in January 2018. The escape room required participants to practice teamwork, communication, task delegation, and critical thinking to tackle waves of increasingly complex puzzles, ranging from hidden objects, physical object assembly (i.e., jigsaw puzzles), and symbol matching. Activities required members to recognize and utilize the collective experiences, skills, knowledge base, and physical abilities of the group. After the game, players underwent a structured 'game-master' debriefing facilitated by an employee of the commercial escape room; this was followed by a post-event survey facilitated by a faculty member, which focused on participants' feelings, experiences, and problem-solving techniques. Escape rooms afford learners the opportunity to engage in an activity that rewards teamwork and effective leadership through experiences that directly link to specific ACGME milestones and educational learning theories. EM participants were engaged in the activity and felt that the escape room reproduced an environment analogous to the ED. The debriefing that followed

  4. Effect of Apoptotic Cell Recognition on Macrophage Polarization and Mycobacterial Persistence

    Science.gov (United States)

    de Oliveira Fulco, Tatiana; Andrade, Priscila Ribeiro; de Mattos Barbosa, Mayara Garcia; Pinto, Thiago Gomes Toledo; Ferreira, Paula Fernandez; Ferreira, Helen; da Costa Nery, José Augusto; Real, Suzana Côrte; Borges, Valéria Matos; Moraes, Milton Ozório; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira

    2014-01-01

    Intracellular Mycobacterium leprae infection modifies host macrophage programming, creating a protective niche for bacterial survival. The milieu regulating cellular apoptosis in the tissue plays an important role in defining susceptible and/or resistant phenotypes. A higher density of apoptotic cells has been demonstrated in paucibacillary leprosy lesions than in multibacillary ones. However, the effect of apoptotic cell removal on M. leprae-stimulated cells has yet to be fully elucidated. In this study, we investigated whether apoptotic cell removal (efferocytosis) induces different phenotypes in proinflammatory (Mϕ1) and anti-inflammatory (Mϕ2) macrophages in the presence of M. leprae. We stimulated Mϕ1 and Mϕ2 cells with M. leprae in the presence or absence of apoptotic cells and subsequently evaluated the M. leprae uptake, cell phenotype, and cytokine pattern in the supernatants. In the presence of M. leprae and apoptotic cells, Mϕ1 macrophages changed their phenotype to resemble the Mϕ2 phenotype, displaying increased CD163 and SRA-I expression as well as higher phagocytic capacity. Efferocytosis increased M. leprae survival in Mϕ1 cells, accompanied by reduced interleukin-15 (IL-15) and IL-6 levels and increased transforming growth factor beta (TGF-β) and IL-10 secretion. Mϕ1 cells primed with M. leprae in the presence of apoptotic cells induced the secretion of Th2 cytokines IL-4 and IL-13 in autologous T cells compared with cultures stimulated with M. leprae or apoptotic cells alone. Efferocytosis did not alter the Mϕ2 cell phenotype or cytokine secretion profile, except for TGF-β. Based on these data, we suggest that, in paucibacillary leprosy patients, efferocytosis contributes to mycobacterial persistence by increasing the Mϕ2 population and sustaining the infection. PMID:25024361

  5. Matrix Metalloproteinase Enzyme Family

    Directory of Open Access Journals (Sweden)

    Ozlem Goruroglu Ozturk

    2013-04-01

    Full Text Available Matrix metalloproteinases play an important role in many biological processes such as embriogenesis, tissue remodeling, wound healing, and angiogenesis, and in some pathological conditions such as atherosclerosis, arthritis and cancer. Currently, 24 genes have been identified in humans that encode different groups of matrix metalloproteinase enzymes. This review discuss the members of the matrix metalloproteinase family and their substrate specificity, structure, function and the regulation of their enzyme activity by tissue inhibitors. [Archives Medical Review Journal 2013; 22(2.000: 209-220

  6. Exospheric density and escape fluxes of atomic isotopes on Venus and Mars

    International Nuclear Information System (INIS)

    Wallis, M.K.

    1978-01-01

    Energetic neutrals in dissociative recombinations near or above the exobase provided an important component of exospheric density and escape fluxes. Plasma thermal velocities provide the main contribution to the velocity spread and an exact integral for the escape flux applicable in marginal cases is found for a simple atmosphere and collisional cut-off. Atomic fragments from recombination of diatomic oxygen and nitrogen ions in the Venus and Mars atmospheres are examined and density integrals derived. The oxygen escape flux on Mars is half that previously estimated and there is very little isotope preference supplementing diffusive separation. However, escape of the heavier 15 N isotope is low by a factor two. Reinterpretation of its 75% enrichment as detected by Viking leads to a range 0.4-1.4 mbar for the primeval nitrogen content on Mars. (author)

  7. Inward contaminant leakage tests of the S-Tron Corporation emergency escape breathing device.

    Science.gov (United States)

    1992-04-01

    At the request of S-Tron Corporation, to support their contract with the U.S. Navy, performance tests of the Emergency Escape Breathing Device (EEBD) were conducted in the Environmental Physiology Research Section contaminant leakage chamber. Sulfur ...

  8. Escape windows to improve the size selectivity in the Baltic cod trawl fishery

    DEFF Research Database (Denmark)

    Madsen, Niels; Holst, René; Foldager, L.

    2002-01-01

    A rapid decrease of the stock of Baltic cod (Gadus morhua) has provided the incentive to improve the size selectivity in the trawl fishery. Use of escape windows is permitted in the legislation to give means of improving the size selectivity of cod as an alternative to a traditional standard codend....... The history of the use of escape windows in the Baltic Sea cod fishery is reviewed. The present escape windows do not function optimally. The objective of this new experiment was to compare an improved design of escape window, which is placed in the upper panel, with that of standard codend. Three standard...... of the codend selectivity was formulated to analyse the results and determine the effects of codend type, mesh size and other recorded variables. L50 and SR increased significantly with the mesh size. L50 was significantly increased and SR significantly reduced for a window codend with the same window mesh size...

  9. Optical escape factors for Doppler profiles in spherical, cylindrical and plane parallel geometries

    International Nuclear Information System (INIS)

    Otsuka, Masamoto.

    1977-12-01

    Optical escape factors for Doppler profiles in spherical, cylindrical and plane parallel geometries are tabulated over the range of optical depths from 10 -3 to 10 5 . Relations with the known formulae are discussed also. (auth.)

  10. Pizza or Pancake? Formation Models of Gas Escape Biosignatures in Terrestrial and Martian Sediments

    Science.gov (United States)

    Bonaccorsi, R.; Fairen, A. G.; Baker, L.; McKay, C. P.; Willson, D.

    2016-05-01

    Fine-grained sedimentary hollowed structures were imaged in Gale Crater, but no biomarkers identified to support biology. Our observation-based (gas escape) terrestrial model could inform on possible martian paleoenvironments at time of formation.

  11. Targeting the Anti-Apoptotic Protein c-FLIP for Cancer Therapy

    International Nuclear Information System (INIS)

    Safa, Ahmad R.; Pollok, Karen E.

    2011-01-01

    Cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) is a major resistance factor and critical anti-apoptotic regulator that inhibits tumor necrosis factor-alpha (TNF-alpha), Fas-L, and TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. c-FLIP is expressed as long (c-FLIP L ), short (c-FLIP S ), and c-FLIP R splice variants in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 in a ligand-dependent and-independent fashion, which in turn prevents death-inducing signaling complex (DISC) formation and subsequent activation of the caspase cascade. Moreover, c-FLIP L and c-FLIP S are known to have multifunctional roles in various signaling pathways, as well as activating and/or upregulating several cytoprotective signaling molecules. Upregulation of c-FLIP has been found in various tumor types, and its downregulation has been shown to restore apoptosis triggered by cytokines and various chemotherapeutic agents. Hence, c-FLIP is an important target for cancer therapy. For example, small interfering RNAs (siRNAs) that specifically knockdown the expression of c-FLIP L in diverse human cancer cell lines augmented TRAIL-induced DISC recruitment and increased the efficacy of chemotherapeutic agents, thereby enhancing effector caspase stimulation and apoptosis. Moreover, small molecules causing degradation of c-FLIP as well as decreasing mRNA and protein levels of c-FLIP L and c-FLIP S splice variants have been found, and efforts are underway to develop other c-FLIP-targeted cancer therapies. This review focuses on (1) the functional role of c-FLIP splice variants in preventing apoptosis and inducing cytokine and drug resistance; (2) the molecular mechanisms that regulate c-FLIP expression; and (3) strategies to inhibit c-FLIP expression and function

  12. The surface science of enzymes

    DEFF Research Database (Denmark)

    Rod, Thomas Holm; Nørskov, Jens Kehlet

    2002-01-01

    One of the largest challenges to science in the coming years is to find the relation between enzyme structure and function. Can we predict which reactions an enzyme catalyzes from knowledge of its structure-or from its amino acid sequence? Can we use that knowledge to modify enzyme function......? To solve these problems we must understand in some detail how enzymes interact with reactants from its surroundings. These interactions take place at the surface of the enzyme and the question of enzyme function can be viewed as the surface science of enzymes. In this article we discuss how to describe...... catalysis by enzymes, and in particular the analogies between enzyme catalyzed reactions and surface catalyzed reactions. We do this by discussing two concrete examples of reactions catalyzed both in nature (by enzymes) and in industrial reactors (by inorganic materials), and show that although analogies...

  13. The relationship between migration and development in the ESCAP region.

    Science.gov (United States)

    Skeldon, R

    1991-01-01

    The relationship between migration and development in the ESCAP region including southeast and south Asian countries and the Pacific island of Fiji, Papua New Guinea, Vanuatu, Kiribati, Samoa, and the Solomon Islands is discussed in terms of mobility transition and origin and destination factors. The changing patterns of mobility in Asia are further delineated in the discussion of internal movements and international movement. Emigration in the smaller countries of the Pacific are treated separately. Future predictions are that the Asia Pacific region will experience continued fertility decline and stabilization of low rates over the next 20 years. The declines will result in slow labor force growth, and increased demand for labor in traditional core and neocore countries as defined and presented in table form by Friedman will be heightened. International movements are likely to increase in large urban areas within destination countries. Tokyo and Singapore are the principal cities in Asia. Tokyo by restrictive government policy has limited immigration, but future labor shortages of unskilled labor from southeast Asia and China are expected. Singapore is already dependent on foreign labor by 10%. Current labor shortages have led to the creation of a growth triangle between Singapore, Indonesia, and Malaysia. Other cities expected to emerge as primary cities in international regional complexes with spillover into the hinterlands include the Hong Kong, Guangzhou, and Macau triangle in the Pearl River delta, Taipei and Seoul, and possibly Kuala Lumpur. Internal migration is expected to increase in the capital cities of Bangkok, Manila,j and centers such as Shanghai, Beijing, and other large cities of southeast Asia. These cities will be linked through the flows of skilled international migrants, which began in the 1960s and is expected to become a future major flow. Recreational and resource niches will be left in much of the Pacific, the Himalayan Kingdoms, and

  14. Outlet strut fracture and leaflet escape of Bjork-Shiley convexo-concave valve.

    Science.gov (United States)

    Uchino, Gaku; Yoshida, Hideo; Sakoda, Naoya; Hattori, Shigeru; Kawabata, Takuya; Saiki, Munehiro; Fujita, Yasufumi; Yunoki, Keiji; Hisamochi, Kunikazu; Mine, Yoshinari

    2017-06-01

    Prosthetic valve fracture is a serious complication and may arise in patient post-valve replacement. We experienced an outlet strut fracture and leaflet escape of a Bjork-Shiley convexo-concave valve. We performed an emergency redo mitral valve replacement and successfully retrieved the fractured strut and escaped leaflet from superficial femoral artery and the abdominal aorta. The patient showed an uneventful postoperative recovery.

  15. Inhibition of chaotic escape from a potential well using small parametric modulations

    International Nuclear Information System (INIS)

    Chacon, R.; Balibrea, F.; Lopez, M.A.

    1996-01-01

    It is shown theoretically for the first time that, depending on its period, amplitude, and initial phase, a periodic parametric modulation can suppress a chaotic escape from a potential well. The instance of the Helmholtz oscillator is used to demonstrate, by means of Melnikov close-quote s method, that parametric modulations of the linear or quadratic potential terms inhibit chaotic escape when certain resonance conditions are met. copyright 1996 American Institute of Physics

  16. A Direct Simulation Monte Carlo Model Of Thermal Escape From Titan

    Science.gov (United States)

    Johnson, Robert E.; Tucker, O. J.

    2008-09-01

    Recent analysis of density profiles vs. altitude from the Ion Neutral Mass Spectrometer (INMS) on Cassini (Waite et al. 2005) suggest Titan could have loss a significant amount of atmosphere in 4 Gyr at present escape rates (e.g., Johnson 2008). Strobel 2008 applied a slow hydrodynamic escape model to Titan's atmosphere using solar heating below the exobase to drive upward thermal conduction and power escape. However, near the exobase continuum models become problematic as a result of the increasing rarefaction in the atmosphere. The microscopic nature of DSMC is directly suitable to model atmosphere flow in nominal exobase region (e.g., Michael et. al. 2005). Our Preliminary DSMC models have shown no evidence for slow hydrodynamic escape of N2 and CH4 from Titan's atmosphere using boundary conditions normalized to the atmospheric properties in Strobel (2008). In this paper we use a 1D radial Direct Simulation Monte Carlo (DSMC) model of heating in Titan's upper atmosphere to estimate the escape rate as a function of the Jean's parameter. In this way we can test under what conditions the suggested deviations from Jeans escape would occur. In addition, we will be able to extract the necessary energy deposition to power the heavy molecule loss rates suggested in recent models (Strobel 2008; Yelle et. al. 2008). Michael, M. Johnson, R.E. 2005 Energy Deposition of pickup ions and heating of Titan's atmosphere. Planat. Sp. Sci. 53, 1510-1514 Johnson, R.E., "Sputtering and Heating of Titan's Upper Atmosphere", Proc Royal Soc. (London) (2008) Strobel, D.F. 2008 Titan's hydrodynamically escaping atmosphere. Icarus 193, 588-594 Yelle, R.V., J. Cui and I. C.F. Muller-Wodarg 2008 Methane Escape from Titan's Atmosphere. J. Geophys. Res in press Waite, J.H., Jr., Niemann, H.B., Yelle, R.V. et al. 2005 Ion Neutral Mass Spectrometer Results from the First Flyby of Titan. Science 308, 982-986

  17. Efektivitas Celah Pelolosan (Escape Gap) Pada Alat Tangkap Pengilar Untuk Menunjang Kelestarian Sumberdaya Ikan

    OpenAIRE

    Rezeki, Silka Tria; Syofyan, Irwandy; ', Isnaniah

    2017-01-01

    The research was conducted during of March until June 2016 in Kampar River and Laboratory of Fishing Gear and Material Faculty of Fisheries and Marine Science University of Riau. The study aim to determine the extent effectivenes of escape gap. The method used are survey and experiment method. The results of this study shown that the circles escape gap can pass the larva of fish with a value of the effectiveness has 0.89

  18. Magnetically responsive enzyme powders

    Czech Academy of Sciences Publication Activity Database

    Pospišková, K.; Šafařík, Ivo

    2015-01-01

    Roč. 380, APR 2015 (2015), s. 197-200 ISSN 0304-8853 R&D Projects: GA MŠk(CZ) LD13021 Institutional support: RVO:67179843 Keywords : enzyme powders * cross-linking * magnetic modification * magnetic separation * magnetic iron oxides particles * microwave-assisted synthesis Subject RIV: CE - Biochemistry Impact factor: 2.357, year: 2015

  19. Enzyme with rhamnogalacturonase activity.

    NARCIS (Netherlands)

    Kofod, L.V.; Andersen, L.N.; Dalboge, H.; Kauppinen, M.S.; Christgau, S.; Heldt-Hansen, H.P.; Christophersen, C.; Nielsen, P.M.; Voragen, A.G.J.; Schols, H.A.

    1998-01-01

    An enzyme exhibiting rhamnogalacturonase activity, capable of cleaving a rhamnogalacturonan backbone in such a manner that galacturonic acids are left as the non-reducing ends, and which exhibits activity on hairy regions from a soy bean material and/or on saponified hairy regions from a sugar beet

  20. Implantable enzyme amperometric biosensors.

    Science.gov (United States)

    Kotanen, Christian N; Moussy, Francis Gabriel; Carrara, Sandro; Guiseppi-Elie, Anthony

    2012-05-15

    The implantable enzyme amperometric biosensor continues as the dominant in vivo format for the detection, monitoring and reporting of biochemical analytes related to a wide range of pathologies. Widely used in animal studies, there is increasing emphasis on their use in diabetes care and management, the management of trauma-associated hemorrhage and in critical care monitoring by intensivists in the ICU. These frontier opportunities demand continuous indwelling performance for up to several years, well in excess of the currently approved seven days. This review outlines the many challenges to successful deployment of chronically implantable amperometric enzyme biosensors and emphasizes the emerging technological approaches in their continued development. The foreign body response plays a prominent role in implantable biotransducer failure. Topics considering the approaches to mitigate the inflammatory response, use of biomimetic chemistries, nanostructured topographies, drug eluting constructs, and tissue-to-device interface modulus matching are reviewed. Similarly, factors that influence biotransducer performance such as enzyme stability, substrate interference, mediator selection and calibration are reviewed. For the biosensor system, the opportunities and challenges of integration, guided by footprint requirements, the limitations of mixed signal electronics, and power requirements, has produced three systems approaches. The potential is great. However, integration along the multiple length scales needed to address fundamental issues and integration across the diverse disciplines needed to achieve success of these highly integrated systems, continues to be a challenge in the development and deployment of implantable amperometric enzyme biosensor systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Advances in enzyme bioelectrochemistry

    Directory of Open Access Journals (Sweden)

    ANDRESSA R. PEREIRA

    Full Text Available ABSTRACT Bioelectrochemistry can be defined as a branch of Chemical Science concerned with electron-proton transfer and transport involving biomolecules, as well as electrode reactions of redox enzymes. The bioelectrochemical reactions and system have direct impact in biotechnological development, in medical devices designing, in the behavior of DNA-protein complexes, in green-energy and bioenergy concepts, and make it possible an understanding of metabolism of all living organisms (e.g. humans where biomolecules are integral to health and proper functioning. In the last years, many researchers have dedicated itself to study different redox enzymes by using electrochemistry, aiming to understand their mechanisms and to develop promising bioanodes and biocathodes for biofuel cells as well as to develop biosensors and implantable bioelectronics devices. Inside this scope, this review try to introduce and contemplate some relevant topics for enzyme bioelectrochemistry, such as the immobilization of the enzymes at electrode surfaces, the electron transfer, the bioelectrocatalysis, and new techniques conjugated with electrochemistry vising understand the kinetics and thermodynamics of redox proteins. Furthermore, examples of recent approaches in designing biosensors and biofuel developed are presented.

  2. Cold-Adapted Enzymes

    Science.gov (United States)

    Georlette, D.; Bentahir, M.; Claverie, P.; Collins, T.; D'amico, S.; Delille, D.; Feller, G.; Gratia, E.; Hoyoux, A.; Lonhienne, T.; Meuwis, M.-a.; Zecchinon, L.; Gerday, Ch.

    In the last few years, increased attention has been focused on enzymes produced by cold-adapted micro-organisms. It has emerged that psychrophilic enzymes represent an extremely powerful tool in both protein folding investigations and for biotechnological purposes. Such enzymes are characterised by an increased thermosensitivity and, most of them, by a higher catalytic efficiency at low and moderate temperatures, when compared to their mesophilic counterparts. The high thermosensitivity probably originates from an increased flexibility of either a selected area of the molecular edifice or the overall protein structure, providing enhanced abilities to undergo conformational changes during catalysis at low temperatures. Structure modelling and recent crystallographic data have allowed to elucidate the structural parameters that could be involved in this higher resilience. It was demonstrated that each psychrophilic enzyme adopts its own adaptive strategy. It appears, moreover, that there is a continuum in the strategy of protein adaptation to temperature, as the previously mentioned structural parameters are implicated in the stability of thermophilic proteins. Additional 3D crystal structures, site-directed and random mutagenesis experiments should now be undertaken to further investigate the stability-flexibility-activity relationship.

  3. Embedded enzymes catalyse capture

    Science.gov (United States)

    Kentish, Sandra

    2018-05-01

    Membrane technologies for carbon capture can offer economic and environmental advantages over conventional amine-based absorption, but can suffer from limited gas flux and selectivity to CO2. Now, a membrane based on enzymes embedded in hydrophilic pores is shown to exhibit combined flux and selectivity that challenges the state of the art.

  4. Photoperiodism and Enzyme Activity

    Science.gov (United States)

    Queiroz, Orlando; Morel, Claudine

    1974-01-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system. PMID:16658749

  5. ISFET based enzyme sensors

    NARCIS (Netherlands)

    van der Schoot, Bart H.; Bergveld, Piet

    1987-01-01

    This paper reviews the results that have been reported on ISFET based enzyme sensors. The most important improvement that results from the application of ISFETs instead of glass membrane electrodes is in the method of fabrication. Problems with regard to the pH dependence of the response and the

  6. Apoptotic cells can induce non-autonomous apoptosis through the TNF pathway

    Science.gov (United States)

    Pérez-Garijo, Ainhoa; Fuchs, Yaron; Steller, Hermann

    2013-01-01

    Apoptotic cells can produce signals to instruct cells in their local environment, including ones that stimulate engulfment and proliferation. We identified a novel mode of communication by which apoptotic cells induce additional apoptosis in the same tissue. Strong induction of apoptosis in one compartment of the Drosophila wing disc causes apoptosis of cells in the other compartment, indicating that dying cells can release long-range death factors. We identified Eiger, the Drosophila tumor necrosis factor (TNF) homolog, as the signal responsible for apoptosis-induced apoptosis (AiA). Eiger is produced in apoptotic cells and, through activation of the c-Jun N-terminal kinase (JNK) pathway, is able to propagate the initial apoptotic stimulus. We also show that during coordinated cell death of hair follicle cells in mice, TNF-α is expressed in apoptotic cells and is required for normal cell death. AiA provides a mechanism to explain cohort behavior of dying cells that is seen both in normal development and under pathological conditions. DOI: http://dx.doi.org/10.7554/eLife.01004.001 PMID:24066226

  7. Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

    Directory of Open Access Journals (Sweden)

    Mariana Raineri

    Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

  8. Enhancing usability of augmented-reality-based mobile escape guidelines for radioactive accidents

    International Nuclear Information System (INIS)

    Tsai, Ming-Kuan; Yau, Nie-Jia

    2013-01-01

    When radioactive accidents occur, modern tools in information technology for emergency response are good solutions to reduce the impact. Since few information-technology-based applications were developed for people during radioactive accidents, a previous study (Tsai et al., 2012) proposed augmented-reality-based mobile escape guidelines. However, because of the lack of transparent escape routes and indoor escape guidelines, the usability of the guidelines is limited. Therefore, this study introduces route planning and mobile three-dimensional (3D) graphics techniques to address the identified problems. The proposed approach could correctly present the geographical relationship from user locations to the anticipated shelters, and quickly show the floor-plan drawings as users are in the buildings. Based on the testing results, in contrast to the previous study, this study offered better escape routes, when the participants performed self-evacuation in outdoor and indoor environments. Overall, this study is not only a useful reference for similar studies, but also a beneficial tool for emergency response during radioactive accidents. -- Highlights: ► Enhancing the efficiency when people escape from radioactive accidents. ► The spatial relationship is transparently displayed in real time. ► In contrast to a previous study, this study offers better escape guidelines

  9. Escaping and repairing behaviors of the termite Odontotermes formosanus (Blattodea: Termitidae in response to disturbance

    Directory of Open Access Journals (Sweden)

    Hongpeng Xiong

    2018-03-01

    Full Text Available The escaping behavior of termites has been documented under laboratory conditions; however, no study has been conducted in a field setting due to the difficulty of observing natural behaviors inside wood or structures (e.g., nests, tunnels, etc.. The black-winged termite, Odontotermes formosanus (Shiraki, is a subterranean macrotermitine species which builds extensive mud tubes on tree trunks. In the present study, 41 videos (totaling ∼2,700 min were taken on 22 colonies/subcolonies of O. formosanus after their mud tubes were partially damaged by hand. In general, termites consistently demonstrated three phases of escape, including initiation (wandering near the mud-tube breach, individual escaping (single termites moving downward, and massive, unidirectional escaping flows (groups of termites moving downward. Downward moving and repairing were the dominant behavioral activities of individuals and were significantly more frequent than upward moving, turning/backward moving, or wandering. Interestingly, termites in escaping flows moved significantly faster than escaping individuals. Repairing behavior was observed shortly after the disturbance, and new mud tubes were preferentially constructed from the bottom up. When predators (i.e., ants were present, however, termites stopped moving and quickly sealed the mud-tube openings by capping the broken ends. Our study provides an interesting example that documents an animal (besides humans simultaneously carrying out pathway repairs and emergency evacuation without congestion.

  10. Escaping and repairing behaviors of the termite Odontotermes formosanus (Blattodea: Termitidae) in response to disturbance.

    Science.gov (United States)

    Xiong, Hongpeng; Chen, Xuan; Wen, Yuzhen; Layne, Michael; Sun, Zhaohui; Ma, Tao; Wen, Xiujun; Wang, Cai

    2018-01-01

    The escaping behavior of termites has been documented under laboratory conditions; however, no study has been conducted in a field setting due to the difficulty of observing natural behaviors inside wood or structures (e.g., nests, tunnels, etc.). The black-winged termite, Odontotermes formosanus (Shiraki), is a subterranean macrotermitine species which builds extensive mud tubes on tree trunks. In the present study, 41 videos (totaling ∼2,700 min) were taken on 22 colonies/subcolonies of O. formosanus after their mud tubes were partially damaged by hand. In general, termites consistently demonstrated three phases of escape, including initiation (wandering near the mud-tube breach), individual escaping (single termites moving downward), and massive, unidirectional escaping flows (groups of termites moving downward). Downward moving and repairing were the dominant behavioral activities of individuals and were significantly more frequent than upward moving, turning/backward moving, or wandering. Interestingly, termites in escaping flows moved significantly faster than escaping individuals. Repairing behavior was observed shortly after the disturbance, and new mud tubes were preferentially constructed from the bottom up. When predators (i.e., ants) were present, however, termites stopped moving and quickly sealed the mud-tube openings by capping the broken ends. Our study provides an interesting example that documents an animal (besides humans) simultaneously carrying out pathway repairs and emergency evacuation without congestion.

  11. Heat-induced symmetry breaking in ant (Hymenoptera: Formicidae escape behavior.

    Directory of Open Access Journals (Sweden)

    Yuan-Kai Chung

    Full Text Available The collective egress of social insects is important in dangerous situations such as natural disasters or enemy attacks. Some studies have described the phenomenon of symmetry breaking in ants, with two exits induced by a repellent. However, whether symmetry breaking occurs under high temperature conditions, which are a common abiotic stress, remains unknown. In our study, we deposited a group of Polyrhachis dives ants on a heated platform and counted the number of escaping ants with two identical exits. We discovered that ants asymmetrically escaped through two exits when the temperature of the heated platform was >32.75°C. The degree of asymmetry increased linearly with the temperature of the platform. Furthermore, the higher the temperature of heated platform was, the more ants escaped from the heated platform. However, the number of escaping ants decreased for 3 min when the temperature was higher than the critical thermal limit (39.46°C, which is the threshold for ants to endure high temperature without a loss of performance. Moreover, the ants tended to form small groups to escape from the thermal stress. A preparatory formation of ant grouping was observed before they reached the exit, indicating that the ants actively clustered rather than accidentally gathered at the exits to escape. We suggest that a combination of individual and grouping ants may help to optimize the likelihood of survival during evacuation.

  12. Flowing water affects fish fast-starts: escape performance of the Hawaiian stream goby, Sicyopterus stimpsoni.

    Science.gov (United States)

    Diamond, Kelly M; Schoenfuss, Heiko L; Walker, Jeffrey A; Blob, Richard W

    2016-10-01

    Experimental measurements of escape performance in fishes have typically been conducted in still water; however, many fishes inhabit environments with flow that could impact escape behavior. We examined the influences of flow and predator attack direction on the escape behavior of fish, using juveniles of the amphidromous Hawaiian goby Sicyopterus stimpsoni In nature, these fish must escape ambush predation while moving through streams with high-velocity flow. We measured the escape performance of juvenile gobies while exposing them to a range of water velocities encountered in natural streams and stimulating fish from three different directions. Frequency of response across treatments indicated strong effects of flow conditions and attack direction. Juvenile S. stimpsoni had uniformly high response rates for attacks from a caudal direction (opposite flow); however, response rates for attacks from a cranial direction (matching flow) decreased dramatically as flow speed increased. Mechanical stimuli produced by predators attacking in the same direction as flow might be masked by the flow environment, impairing the ability of prey to detect attacks. Thus, the likelihood of successful escape performance in fishes can depend critically on environmental context. © 2016. Published by The Company of Biologists Ltd.

  13. Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy.

    Science.gov (United States)

    Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Høgset, Anders; Selbo, Pål Kristian

    2015-05-28

    The cancer stem cell (CSC) marker CD133 is an attractive target to improve antitumor therapy. We have used photochemical internalization (PCI) for the endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133-saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which generates reactive oxygen species upon light-activation causing a rupture of the vesicle membranes and endosomal escape of entrapped drugs. Here we show that AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation and induced 100% inhibition of cell viability and colony forming ability at the highest light doses, whereas no cytotoxicity was obtained in the absence of light. Efficient PCI-based CD133-targeting was in addition demonstrated in the stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin induced mainly necrosis and a minimal apoptotic response based on assessing cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in S phase arrest and reduced LC3-II conversion compared to control treatments. Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II conversion, indicating a termination of the autophagic flux in WiDr cells. For the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor response was observed after PCIAC133-saporin. The present PCI-based endosomal escape technology represents a minimally invasive strategy for spatio-temporal, light-controlled targeting of CD133+ cells in localized primary tumors or metastasis. Copyright © 2015

  14. The Enzyme Function Initiative†

    Science.gov (United States)

    Gerlt, John A.; Allen, Karen N.; Almo, Steven C.; Armstrong, Richard N.; Babbitt, Patricia C.; Cronan, John E.; Dunaway-Mariano, Debra; Imker, Heidi J.; Jacobson, Matthew P.; Minor, Wladek; Poulter, C. Dale; Raushel, Frank M.; Sali, Andrej; Shoichet, Brian K.; Sweedler, Jonathan V.

    2011-01-01

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily-specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include: 1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation); 2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia; 3) computational and bioinformatic tools for using the strategy; 4) provision of experimental protocols and/or reagents for enzyme production and characterization; and 5) dissemination of data via the EFI’s website, enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal and pharmaceutical efforts. PMID

  15. The Enzyme Function Initiative.

    Science.gov (United States)

    Gerlt, John A; Allen, Karen N; Almo, Steven C; Armstrong, Richard N; Babbitt, Patricia C; Cronan, John E; Dunaway-Mariano, Debra; Imker, Heidi J; Jacobson, Matthew P; Minor, Wladek; Poulter, C Dale; Raushel, Frank M; Sali, Andrej; Shoichet, Brian K; Sweedler, Jonathan V

    2011-11-22

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include (1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation), (2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia, (3) computational and bioinformatic tools for using the strategy, (4) provision of experimental protocols and/or reagents for enzyme production and characterization, and (5) dissemination of data via the EFI's Website, http://enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal, and pharmaceutical efforts.

  16. PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling.

    Science.gov (United States)

    Monterisi, Stefania; Lobo, Miguel J; Livie, Craig; Castle, John C; Weinberger, Michael; Baillie, George; Surdo, Nicoletta C; Musheshe, Nshunge; Stangherlin, Alessandra; Gottlieb, Eyal; Maizels, Rory; Bortolozzi, Mario; Micaroni, Massimo; Zaccolo, Manuela

    2017-05-02

    cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle. The function and regulation of these domains remain largely unknown. Here, we describe a novel cAMP/PKA signalling domain localised at mitochondrial membranes and regulated by PDE2A2. Using pharmacological and genetic approaches combined with real-time FRET imaging and high resolution microscopy, we demonstrate that in rat cardiac myocytes and other cell types mitochondrial PDE2A2 regulates local cAMP levels and PKA-dependent phosphorylation of Drp1. We further demonstrate that inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death.

  17. Asymmetric Synthesis and Evaluation of Danshensu-Cysteine Conjugates as Novel Potential Anti-Apoptotic Drug Candidates

    Science.gov (United States)

    Pan, Li-Long; Wang, Jie; Jia, Yao-Ling; Zheng, Hong-Ming; Wang, Yang; Zhu, Yi-Zhun

    2014-01-01

    We have previously reported that the danshensu-cysteine conjugate N-((R)-3-benzylthio-1-methoxy-1-oxo-2-propanyl)-2-acetoxy-3-(3,4-diacetoxyphenyl) propanamide (DSC) is a potent anti-oxidative and anti-apoptotic agent. Herein, we further design and asymmetrically synthesize two diastereoisomers of DSC and explore their potential bioactivities. Our results show that DSC and its two diastereoisomers exert similar protective effects in hydrogen peroxide (H2O2)-induced cellular injury in SH-SY5Y cells, as evidenced by the increase of cell viability, superoxide dismutase (SOD), and reduced glutathione (GSH) activity, and glutathione peroxidase (GPx) expression, and the decrease of cellular morphological changes and nuclear condensation, lactate dehydrogenase (LDH) release, and malondialdehyde (MDA) production. In H2O2-stimulated human umbilical vein endothelial cells (HUVEC), DSC concentration-dependently attenuates H2O2-induced cell death, LDH release, mitochondrial membrane potential collapse, and modulates the expression of apoptosis-related proteins (Bcl-2, Bax, caspase-3, and caspase-9). Our results provide strong evidence that DSC and its two diastereoisomers have similar anti-oxidative activity and that DSC exerts significant vascular-protective effects, at least in part, through inhibition of apoptosis and modulation of endogenous antioxidant enzymes. PMID:25551606

  18. Effects of Downregulation of MicroRNA-181a on H2O2-Induced H9c2 Cell Apoptosis via the Mitochondrial Apoptotic Pathway

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    Lei Wang

    2014-01-01

    Full Text Available Glutathione peroxidase-1 (GPx1 is a pivotal intracellular antioxidant enzyme that enzymatically reduces hydrogen peroxide to water to limit its harmful effects. This study aims to identify a microRNA (miRNA that targets GPx1 to maintain redox homeostasis. Dual luciferase assays combined with mutational analysis and immunoblotting were used to validate the bioinformatically predicted miRNAs. We sought to select miRNAs that were responsive to oxidative stress induced by hydrogen peroxide (H2O2 in the H9c2 rat cardiomyocyte cell line. Quantitative real-time PCR (qPCR demonstrated that the expression of miR-181a in H2O2-treated H9c2 cells was markedly upregulated. The downregulation of miR-181a significantly inhibited H2O2-induced cellular apoptosis, ROS production, the increase in malondialdehyde (MDA levels, the disruption of mitochondrial structure, and the activation of key signaling proteins in the mitochondrial apoptotic pathway. Our results suggest that miR-181a plays an important role in regulating the mitochondrial apoptotic pathway in cardiomyocytes challenged with oxidative stress. MiR-181a may represent a potential therapeutic target for the treatment of oxidative stress-associated cardiovascular diseases.

  19. To the nucleolar density and size in apoptotic human leukemic myeloblasts produced in vitro by Trichostatin A

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    K Smetana

    2009-08-01

    Full Text Available The present study was designed to provide more information on nucleoli in apoptotic cells, which were represented in the present study by cultured leukemic myeloblasts (Kasumi-1 cells. The apoptotic process in these cells was produced by trichostatin A (TSA that is a histone deacetylase inhibitor with strong cytostatic effects. The selected TSA concentration added to cultures facilitated to study apoptotic and notapoptotic cells in one and the same specimen. The nucleolar diameter and density were determined using computer assisted measurement and densitometry in specimens stained for RNA. In comparison with not-apoptotic cells, in apoptotic cells, nucleolar mean diameter did not change significantly and nucleolar RNA density was also not apparently different. On the other hand, the cytoplasmic RNA density in apoptotic cells was markedly reduced. Thus it seemed to be possible that the transcribed RNA remained “frozen” within the nucleolus but its transport to the cytoplasm decreased or stopped. However, the possibility of the RNA degradation in the cytoplasm of apoptotic cells based on the present study cannot be eliminated. At this occasion it should be added that AgNORs reflecting nucleolar biosynthetic and cell proliferation activity in apoptotic cells decreased in number or disappeared. The presented results also indicated that large nucleoli intensely stained for RNA need not be necessarily related to the high nucleolar biosynthetic or cell proliferation activity and may be also present in apoptotic cells responding to the cytostatic treatment.

  20. Androgen receptor in early apoptotic follicles in the porcine ovary at pregnancy.

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    Zbigniew Tabarowski

    2006-09-01

    Full Text Available Localization of androgen receptor (AR was investigated in ovarian follicles developing and undergoing atresia during pregnancy in the pig. Immunohistochemical staining was conducted on ovarian antral follicles isolated on different days of gestation: 10, 18, 32, 50, 70, and 90. Paraffin sections were also subjected to in situ DNA labeling. TUNEL staining revealed the presence of positive follicles on all days of pregnancy but the amount of atretic follicles increased with time. However, even on day 90 of gestation many follicles were normal, with no signs of atresia. In atretic follicles, apoptotic cells were localized predominantly in the granulosa while theca was much less affected. Atretic follicles with many apoptotic cells were negative for AR. Nuclear immunostaining for AR was positive in follicles with limited amount of apoptotic cells. The same relationship was observed in ovarian follicles isolated at various days of pregnancy.

  1. Targeting apoptotic machinery as approach for anticancer therapy: Smac mimetics as anticancer agents

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    Nevine M.Y. Elsayed

    2015-06-01

    Full Text Available Apoptosis is a chief regulator of cellular homeostasis. Impairment of apoptotic machinery is a main characteristic of several diseases such as cancer, where the evasion of apoptosis is a cardinal hallmark of cancer. Apoptosis is regulated by contribution of pro- and anti- apoptotic proteins, where caspases are the main executioners of the apoptotic machinery. IAP (inhibitors of apoptosis proteins is a family of endogenous inhibitors of apoptosis, which perform their function through interference with the function of caspases. Smac (second mitochondria-derived activator of caspases is endogenous inhibitor of IAPs, thus it is one of the major proapoptotic endogenous proteins. Thus, the development of Smac mimetics has evolved as an approach for anticancer therapy. Several Smac mimetic agents have been introduced to clinical trial such as birinapanet 12. Herein, the history of development of Smac mimetics along with the recent development in this field is briefly discussed.

  2. Expression of caspase-3 gene in apoptotic HL-60 cell and different human tumor cell lines

    International Nuclear Information System (INIS)

    Li Xiaoming; Song Tianbao

    1999-01-01

    Objective: To research the expression of caspase-3 gene in the apoptotic and the control HL-60 cells and in the different human tumor cell lines. Methods: Caspase-3 mRNA in the control and γ-radiation-induced apoptotic HL-60 cells, and in the 6 types of human tumor cell lines, was analysed by Northern blot. Results: The caspase-3 gene transcript was more highly expressed in leukemia cells HL-60, CEM, K562 and neuroblastoma SH-SY5Y than in cervical adenocarcinoma HeLa and breast carcinoma MCF7, and more highly in the radiation-induced apoptotic HL-60 than in the control HL-60 cells. Conclusion: The high level of expression of caspase-3 may aid the efforts to understand the tumor cell sensitivity to radiation, apoptosis and its inherent ability to survive

  3. Anti-apoptotic peptides protect against radiation-induced cell death

    International Nuclear Information System (INIS)

    McConnell, Kevin W.; Muenzer, Jared T.; Chang, Kathy C.; Davis, Chris G.; McDunn, Jonathan E.; Coopersmith, Craig M.; Hilliard, Carolyn A.; Hotchkiss, Richard S.; Grigsby, Perry W.; Hunt, Clayton R.

    2007-01-01

    The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues

  4. Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis

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    Sun Zujun

    2012-05-01

    Full Text Available Abstract Background Toll-like receptor 4 (TLR4 is expressed on immune cells as a sensor that recognizes lipopolysaccharide (LPS, a microbial conserved component. It has recently been determined that the expression of TLR4 is also found in various types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral squamous cell carcinoma (OSCC treatment. However, the mechanisms responsible for cisplatin resistance are not well understood. Results The present study was designed to elucidate the role of TLR4 expression in human OSCC regarding immune escape and apoptotic resistance to cisplatin. TLR4 and the myeloid differentiation primary response gene 88 (MyD88 were highly expressed in OSCC cell lines. Upon LPS stimulation both NF-κB and p38 MAPK pathways were activated in OSCC cell lines, followed by the production of large quantities of IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells (HIOECs. OSCC cell lines were found to be resistant to cisplatin-mediated apoptosis after pretreatment with LPS. Conclusions Our results suggested that TLR4 was functionally expressed in human OSCC cells and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might thus elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC.

  5. Single Nucleotide Polymorphisms in Selected Apoptotic Genes and BPDE-Induced Apoptotic Capacity in Apparently Normal Primary Lymphocytes: A Genotype-Phenotype Correlation Analysis

    International Nuclear Information System (INIS)

    Hu, Z.; Li, Ch.; Chen, K.; Wang, L.E.; Sturgis, E.M.; Spitz, M.R.; Wei, Q.; Sturgis, E.M.

    2008-01-01

    Apoptotic capacity (AC) in primary lymphocytes may be a marker for cancer susceptibility, and functional single nucleotide polymorphisms (SNPs) in genes involved in apoptotic pathways may modulate cellular AC in response to DNA damage. To further examine the correlation between apoptotic genotypes and phenotype, we geno typed 14 published SNPs in 11 apoptosis-related genes (i.e., p53, Bcl-2, BAX, CASP9, DR4, Fas, FasL, CASP8, CASP10, CASP3, and CASP7) and assessed the AC in response to benzo[a]pyrene-7,8-9,10-diol epoxide (BPDE) in cultured primary lymphocytes from 172 cancer-free subjects. We found that among these 14 SNPs, R72P, intron 3 16-bp del/ins, and intron 6 G>A in , −938C>A in Bcl-2, and I522L in CASP10 were significant predictors of the BPDE-induced lymphocytic AC in single-locus analysis. In the combined analysis of the three variants, we found that the individuals with the diplotypes carrying 0-1 copy of the common R-del-G haplotype had higher AC values compared to other genotypes. Although the study size may not have the statistical power to detect the role of other SNPs in AC, our findings suggest that some SNPs in genes involved in the intrinsic apoptotic pathway may modulate lymphocytic AC in response to BPDE exposure in the general population. Larger studies are needed to validate these findings for further studying individual susceptibility to cancer and other apoptosis-related diseases

  6. Tributyltin induces apoptotic signaling in hepatocytes through pathways involving the endoplasmic reticulum and mitochondria

    International Nuclear Information System (INIS)

    Grondin, Melanie; Marion, Michel; Denizeau, Francine; Averill-Bates, Diana A.

    2007-01-01

    Tri-n-butyltin is a widespread environmental toxicant, which accumulates in the liver. This study investigates whether tri-n-butyltin induces pro-apoptotic signaling in rat liver hepatocytes through pathways involving the endoplasmic reticulum and mitochondria. Tri-n-butyltin activated the endoplasmic reticulum pathway of apoptosis, which was demonstrated by the activation of the protease calpain, its translocation to the plasma membrane, followed by cleavage of the calpain substrates, cytoskeletal protein vinculin, and caspase-12. Caspase-12 is localized to the cytoplasmic side of the endoplasmic reticulum and is involved in apoptosis mediated by the endoplasmic reticulum. Tri-n-butyltin also caused translocation of the pro-apoptotic proteins Bax and Bad from the cytosol to mitochondria, as well as changes in mitochondrial membrane permeability, events which can activate the mitochondrial death pathway. Tri-n-butyltin induced downstream apoptotic events in rat hepatocytes at the nuclear level, detected by chromatin condensation and by confocal microscopy using acridine orange. We investigated whether the tri-n-butyltin-induced pro-apoptotic events in hepatocytes could be linked to perturbation of intracellular calcium homeostasis, using confocal microscopy. Tri-n-butyltin caused changes in intracellular calcium distribution, which were similar to those induced by thapsigargin. Calcium was released from a subcellular compartment, which is likely to be the endoplasmic reticulum, into the cytosol. Cytosolic acidification, which is known to trigger apoptosis, also occurred and involved the Cl - /HCO 3 - exchanger. Pro-apoptotic events in hepatocytes were inhibited by the calcium chelator, Bapta-AM, and by a calpain inhibitor, which suggests that changes in intracellular calcium homeostasis are involved in tri-n-butyltin-induced apoptotic signaling in rat hepatocytes

  7. The effect of bystander medium on the apoptotic process in HPV-G cells

    International Nuclear Information System (INIS)

    Maguire, P.; Lyng, F.; Seymour, C.; Mothersill, C.

    2003-01-01

    Full text: It has been shown in recent years that in both in vivo and in vitro situations irradiated cells cause what is known as the bystander effect. This presently unknown factor causes chromosomal aberrations, initiation of apoptosis and reduced clonogenic survival. Using the medium transfer method to study the bystander effect, this study investigated early events in the apoptotic cascade, which leads to cell death in cells receiving medium from irradiated cells but which were not themselves irradiated. Medium from irradiated ( 0.005Gy to 5Gy) human HPV G keratinocytes was harvested one hour after irradiation, sterile filtered and transferred on to unirradiated HPV-G cells. The appearance of apoptotic markers in the apoptotic cascade was monitored over a period of 48 hours following medium transfer. These apoptotic markers include loss of mitochondrial membrane potential, cytochrome c release and the activity of the death inducing caspase 3. Clonogenic survival of HPV-G cells over a nine day period was also monitored to assess the final survival of the cells. A TUNEL assay, which indicated the level of apoptosis over a 72 hour period after exposure to bystander medium was also performed. Data collected in this study indicates that for very low doses (0.005Gy) the appearance of well-characterised early 'apoptotic' markers such as changes in mitochondrial membrane potential doesn't mean the cell has committed to the apoptotic cascade leading to cell death. This has been illustrated for bystander medium from 0.005Gy irradiated cells, which causes mitochondrial membrane potential depolarisation after six-hour exposure but little difference has been noted for clonogenic survival for exposure to 0.005Gy bystander medium from that of the control. The results may help clarify how cells sector to death or survival following receipt of a signal from a radiation event

  8. Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells.

    Science.gov (United States)

    Lim, Sung-Chul; Jeon, Ho Jong; Kee, Keun Hong; Lee, Mi Ja; Hong, Ran; Han, Song Iy

    2017-05-01

    Andrographolide, a natural compound isolated from Andrographis paniculata , has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL). Exposure of GC cells to andrographolide altered the expression level of several growth-inhibiting and apoptosis-regulating proteins, including death receptors. It was demonstrated that activity of the TRAIL-R2 (DR5) pathway was critical in the development of andrographolide-mediated rhTRAIL sensitization, since its inhibition significantly reduced the extent of apoptosis induced by the combination of rhTRAIL and andrographolide. In addition, andrographolide increased reactive oxygen species (ROS) generation in a dose-dependent manner. N-acetyl cysteine prevented andrographolide-mediated DR5 induction and the apoptotic effect induced by the combination of rhTRAIL and andrographolide. Collectively, the present study demonstrated that andrographolide enhances TRAIL-induced apoptosis through induction of DR5 expression. This effect appears to involve ROS generation in GCs.

  9. Effect of hrHPV infection on anti-apoptotic gene and pro-apoptotic gene expression in cervical cancer tissue

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    Min-Er Tang

    2016-09-01

    Full Text Available Objective: To study the effect of hrHPV infection on anti-apoptotic gene and pro-apoptotic gene expression in cervical cancer tissue. Methods: A total of 56 patients with cervical cancer, 94 cases of patients with cervical intraepithelial neoplasia and 48 cases of patients with chronic cervicitis who were treated in our hospital from May 2013 to December 2015 were selected for study and included in malignant group, precancerous lesion group and benign group respectively. hrHPV infection as well as the expression of anti-apoptotic genes and proapoptotic genes in cervical tissue were detected. Results: hrHPV infection rate and viral load in cervical tissue of malignant group were significantly higher than those of precancerous lesion group and benign group; P27 and p16 levels in cervical tissue of malignant group were significantly lower than those of precancerous lesion group and benign group, and K-ras, c-myc, Prdx4 and TNFAIP8 levels were significantly higher than those of precancerous lesion group and benign group; the greater the HPV virus load, the lower the p27 and p16 levels and the higher the K-ras, c-myc, Prdx4 and TNFAIP8 levels in cervical tissue. Conclusions: hrHPV infection can result in tumor suppressor genes p27 and p16 expression deletion and increase the expression of proto-oncogene and apoptosis-inhibiting genes, and it is associated with the occurrence and development of cervical cancer.

  10. Different immunophenotypical apoptotic profiles characterise megakaryocytes of essential thrombocythaemia and primary myelofibrosis.

    Science.gov (United States)

    Florena, A M; Tripodo, C; Di Bernardo, A; Iannitto, E; Guarnotta, C; Porcasi, R; Ingrao, S; Abbadessa, V; Franco, V

    2009-04-01

    Essential thrombocythaemia (ET) and primary myelofibrosis (PMF) share some clinical and pathological features, but show different biological behaviour and prognosis. The latest contributions to understanding the nature of these disorders have focused on bone marrow microenvironment remodelling and proliferative stress, recognising megakaryocytes (MKCs) as "key-cells". The aim of this study was to investigate the apoptotic profile of ET and PMF MKCs in order to further characterise the biology of these disorders. Bone marrow biopsy samples from 30 patients with ET, and 30 patients with PMF, were immunophenotypically studied for the expression of pro-apoptotic (Fas, Fas-L, Bax, Bad) and anti-apoptotic (Bcl-2, Bcl-XL, hTERT (human telomerase reverse transcriptase)) molecules and the "executioner" molecule caspase-3. The fraction of MKCs undergoing apoptosis was assessed by deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Only the mitochondrial pathway seemed to be involved in MKC apoptosis. The anti-apoptotic molecule Bcl-XL was predominantly found in ET MKCs (50.5% of ET MKCs versus 35% of PMF MKCs; p = 0.036), while pro-apoptotic molecules Bax and Bad showed a prevalent expression in PMF MKCs (30.5% of ET MKCs versus 55% of PMF MKCs; 41% of ET MKCs versus 52% of PMF MKCs; p = 0.001 and p = 0.068, respectively). A significant fraction of PMF MKCs were committed to apoptosis according to caspase-3 expression and TUNEL, while only few ET cells were committed to apoptosis. hTERT was significantly more expressed in PMF (32% of ET MKCs versus 46% of PMF MKCs; p = 0.022), in agreement with the proliferative nature of this disease. It was found that ET and PMF MKCs, which barely differ in terms of morphology and aggregation, are characterised by markedly different apoptotic profiles. The rather high apoptotic fraction of PMF was able to support the fibrotic nature of this process, while the anti-apoptotic profile of ET cells fits well with their "steady

  11. Apoptotic Cells Induced Signaling for Immune Homeostasis in Macrophages and Dendritic Cells

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    Uriel Trahtemberg

    2017-10-01

    Full Text Available Inefficient and abnormal clearance of apoptotic cells (efferocytosis contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs, and contributes to maintenance of peripheral tolerance. As many as 3 × 108 cells undergo apoptosis every hour in our bodies, and one of the primary “eat me” signals expressed by apoptotic cells is phosphatidylserine (PtdSer. Apoptotic cells themselves are major contributors to the “anti-inflammatory” nature of the engulfment process, some by secreting thrombospondin-1 (TSP-1 or adenosine monophosphate and possibly other immune modulating “calm-down” signals that interact with macrophages and DCs. Apoptotic cells also produce “find me” and “tolerate me” signals to attract and immune modulate macrophages and DCs that express specific receptors for some of these signals. Neither macrophages nor DCs are uniform, and each cell type may variably express membrane proteins that function as receptors for PtdSer or for opsonins like complement or opsonins that bind to PtdSer, such as protein S and growth arrest-specific 6. Macrophages and DCs also express scavenger receptors, CD36, and integrins that function via bridging molecules such as TSP-1 or milk fat globule-EGF factor 8 protein and that differentially engage in various multi-ligand interactions between apoptotic cells and phagocytes. In this review, we describe the anti-inflammatory and pro-homeostatic nature of apoptotic cell interaction with the immune system. We do not review some forms of immunogenic cell death. We summarize the known apoptotic cell signaling events in macrophages and DCs that are related to toll-like receptors, nuclear factor kappa B, inflammasome, the lipid

  12. Temporal and ontogenetic variation in the escape response of Ameiva festiva (Squamata, Teiidae

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    Lattanzio

    2014-08-01

    Full Text Available Several factors have been shown to affect lizard escape behavior (flight initiation distance or FID, the distance between predator and prey when the prey initiates escape. Patterns of daily activity, such as foraging or movement behavior, vary with respect to time of day, supporting that escape responses may vary temporally as well. However, there remains scant information regarding the effects of time of day on FID. During peak activity, FID may decrease due to increased cost of giving up resources (e.g., prey or potential mates. An alternative hypothesis is that FID may increase because lizard activity in general may serve to alert a predator in advance of its approach. A lizard in this scenario may be favored to flee sooner rather than later. Moreover, juvenile and adult lizards of multiple species may differ in behavioral, ecological, and morphological traits that could influence escape decisions. I tested the effects of time of day (in 30-min intervals and age (juvenile or adult on the FID of a tropical whiptail lizard, Ameiva festiva in Costa Rica. I found that A. festiva escape responses varied with time of day such that in general, their FID decreased throughout the day. In addition, I observed a peak in FID from mid to late-morning that matches published estimates of peak activity times for A. festiva. Overall, juvenile A. festiva initiated an escape response sooner than adults, which may be related to differences in perceived risk associated with differences in size and predator experience between the two age groups. I conclude that escape responses may be contingent on both the activity level of the animal at the time of approach and its age.

  13. Escape Excel: A tool for preventing gene symbol and accession conversion errors.

    Science.gov (United States)

    Welsh, Eric A; Stewart, Paul A; Kuenzi, Brent M; Eschrich, James A

    2017-01-01

    Microsoft Excel automatically converts certain gene symbols, database accessions, and other alphanumeric text into dates, scientific notation, and other numerical representations. These conversions lead to subsequent, irreversible, corruption of the imported text. A recent survey of popular genomic literature estimates that one-fifth of all papers with supplementary gene lists suffer from this issue. Here, we present an open-source tool, Escape Excel, which prevents these erroneous conversions by generating an escaped text file that can be safely imported into Excel. Escape Excel is implemented in a variety of formats (http://www.github.com/pstew/escape_excel), including a command line based Perl script, a Windows-only Excel Add-In, an OS X drag-and-drop application, a simple web-server, and as a Galaxy web environment interface. Test server implementations are accessible as a Galaxy interface (http://apostl.moffitt.org) and simple non-Galaxy web server (http://apostl.moffitt.org:8000/). Escape Excel detects and escapes a wide variety of problematic text strings so that they are not erroneously converted into other representations upon importation into Excel. Examples of problematic strings include date-like strings, time-like strings, leading zeroes in front of numbers, and long numeric and alphanumeric identifiers that should not be automatically converted into scientific notation. It is hoped that greater awareness of these potential data corruption issues, together with diligent escaping of text files prior to importation into Excel, will help to reduce the amount of Excel-corrupted data in scientific analyses and publications.

  14. Comparative pick-up ion distributions at Mars and Venus: Consequences for atmospheric deposition and escape

    Science.gov (United States)

    Curry, Shannon M.; Luhmann, Janet; Ma, Yingjuan; Liemohn, Michael; Dong, Chuanfei; Hara, Takuya

    2015-09-01

    Without the shielding of a substantial intrinsic dipole magnetic field, the atmospheres of Mars and Venus are particularly susceptible to similar atmospheric ion energization and scavenging processes. However, each planet has different attributes and external conditions controlling its high altitude planetary ion spatial and energy distributions. This paper describes analogous test particle simulations in background MHD fields that allow us to compare the properties and fates, precipitation or escape, of the mainly O+ atmospheric pick-up ions at Mars and Venus. The goal is to illustrate how atmospheric and planetary scales affect the upper atmospheres and space environments of our terrestrial planet neighbors. The results show the expected convection electric field-related hemispheric asymmetries in both precipitation and escape, where the degree of asymmetry at each planet is determined by the planetary scale and local interplanetary field strength. At Venus, the kinetic treatment of O+ reveals a strong nightside source of precipitation while Mars' crustal fields complicate the simple asymmetry in ion precipitation and drive a dayside source of precipitation. The pickup O+ escape pattern at both Venus and Mars exhibits low energy tailward escape, but Mars exhibits a prominent, high energy 'polar plume' feature in the hemisphere of the upward convection electric field while the Venus ion wake shows only a modest poleward concentration. The overall escape is larger at Venus than Mars (2.1 ×1025 and 4.3 ×1024 at solar maximum, respectively), but the efficiency (likelihood) of O+ escaping is 2-3 times higher at Mars. The consequences of these comparisons for pickup ion related atmospheric energy deposition, loss rates, and detection on spacecraft including PVO, VEX, MEX and MAVEN are considered. In particular, both O+ precipitation and escape show electric field controlled asymmetries that grow with energy, while the O+ fluxes and energy spectra at selected spatial

  15. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL response.

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    Ryan M Troyer

    2009-04-01

    Full Text Available Human lymphocyte antigen (HLA-restricted CD8(+ cytotoxic T lymphocytes (CTL target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs.

  16. Unsteady motion: escape jumps in planktonic copepods, their kinematics and energetics

    Science.gov (United States)

    Kiørboe, Thomas; Andersen, Anders; Langlois, Vincent J.; Jakobsen, Hans H.

    2010-01-01

    We describe the kinematics of escape jumps in three species of 0.3–3.0 mm-sized planktonic copepods. We find similar kinematics between species with periodically alternating power strokes and passive coasting and a resulting highly fluctuating escape velocity. By direct numerical simulations, we estimate the force and power output needed to accelerate and overcome drag. Both are very high compared with those of other organisms, as are the escape velocities in comparison to startle velocities of other aquatic animals. Thus, the maximum weight-specific force, which for muscle motors of other animals has been found to be near constant at 57 N (kg muscle)−1, is more than an order of magnitude higher for the escaping copepods. We argue that this is feasible because most copepods have different systems for steady propulsion (feeding appendages) and intensive escapes (swimming legs), with the muscular arrangement of the latter probably adapted for high force production during short-lasting bursts. The resulting escape velocities scale with body length to power 0.65, different from the size-scaling of both similar sized and larger animals moving at constant velocity, but similar to that found for startle velocities in other aquatic organisms. The relative duration of the pauses between power strokes was observed to increase with organism size. We demonstrate that this is an inherent property of swimming by alternating power strokes and pauses. We finally show that the Strouhal number is in the range of peak propulsion efficiency, again suggesting that copepods are optimally designed for rapid escape jumps. PMID:20462876

  17. Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

    International Nuclear Information System (INIS)

    Ahmed, Maha A.E.

    2015-01-01

    The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10 mg/kg/week, I.M.), taurine (100 mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. - Highlights: • Nandrolone decanoate (ND) disrupts sperm profile and steroidogenesis in rats. • ND upregulates gene expression of inflammatory and apoptotic markers. • Taurine normalizes sperm profile and serum testosterone level

  18. Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Maha A.E., E-mail: mahapharm@yahoo.com

    2015-02-01

    The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10 mg/kg/week, I.M.), taurine (100 mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. - Highlights: • Nandrolone decanoate (ND) disrupts sperm profile and steroidogenesis in rats. • ND upregulates gene expression of inflammatory and apoptotic markers. • Taurine normalizes sperm profile and serum testosterone level

  19. Nosema ceranae escapes fumagillin control in honey bees.

    Directory of Open Access Journals (Sweden)

    Wei-Fone Huang

    2013-03-01

    Full Text Available Fumagillin is the only antibiotic approved for control of nosema disease in honey bees and has been extensively used in United States apiculture for more than 50 years for control of Nosema apis. It is toxic to mammals and must be applied seasonally and with caution to avoid residues in honey. Fumagillin degrades or is diluted in hives over the foraging season, exposing bees and the microsporidia to declining concentrations of the drug. We showed that spore production by Nosema ceranae, an emerging microsporidian pathogen in honey bees, increased in response to declining fumagillin concentrations, up to 100% higher than that of infected bees that have not been exposed to fumagillin. N. apis spore production was also higher, although not significantly so. Fumagillin inhibits the enzyme methionine aminopeptidase2 (MetAP2 in eukaryotic cells and interferes with protein modifications necessary for normal cell function. We sequenced the MetAP2 gene for apid Nosema species and determined that, although susceptibility to fumagillin differs among species, there are no apparent differences in fumagillin binding sites. Protein assays of uninfected bees showed that fumagillin altered structural and metabolic proteins in honey bee midgut tissues at concentrations that do not suppress microsporidia reproduction. The microsporidia, particularly N. ceranae, are apparently released from the suppressive effects of fumagillin at concentrations that continue to impact honey bee physiology. The current application protocol for fumagillin may exacerbate N. ceranae infection rather than suppress it.

  20. Intrinsic and extrinsic apoptotic pathways are involved in rat testis by cold water immersion-induced acute and chronic stress.

    Science.gov (United States)

    Juárez-Rojas, Adriana Lizbeth; García-Lorenzana, Mario; Aragón-Martínez, Andrés; Gómez-Quiroz, Luis Enrique; Retana-Márquez, María del Socorro

    2015-01-01

    Testicular apoptosis is activated by stress, but it is not clear which signaling pathway is activated in response to stress. The aim of this study was to investigate whether intrinsic, extrinsic, or both apoptotic signaling pathways are activated by acute and chronic stress. Adult male rats were subjected to cold water immersion-induced stress for 1, 20, 40, and 50 consecutive days. The seminiferous tubules:apoptotic cell ratio was assayed on acute (1 day) and chronic (20, 40, 50 days) stress. Apoptotic markers, including cleaved-caspase 3 and 8, the pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were also determined after acute and chronic stress induction. Additionally, epididymal sperm quality was evaluated, as well as corticosterone and testosterone levels. An increase in tubule apoptotic cell count percentage after an hour of acute stress and during chronic stress induction was observed. The apoptotic cells rate per tubule increment was only detected one hour after acute stress, but not with chronic stress. Accordingly, there was an increase in Bax, cleaved caspase-8 and caspase-3 pro-apoptotic proteins with a decrease of anti-apoptotic Bcl-2 in both acutely and chronically stressed male testes. In addition, sperm count, viability, as well as total and progressive motility were low in chronically stressed males. Finally, the levels of corticosterone increased whereas testosterone levels decreased in chronically stressed males. Activation of the extrinsic apoptotic pathway was shown by cleaved caspase-8 increase whereas the intrinsic apoptotic pathway activation was determined by the increase of Bax, along with Bcl-2 decrease, making evident a cross-talk between these two pathways with the activation of caspase-3. These results suggest that both acute and chronic stress can potentially activate the intrinsic/extrinsic apoptosis pathways in testes. Chronic stress also reduces the quality of epididymal spermatozoa, possibly due to a decrease in testosterone.

  1. Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner.

    Science.gov (United States)

    Leno-Durán, E; Ruiz-Magaña, M J; Muñoz-Fernández, R; Requena, F; Olivares, E G; Ruiz-Ruiz, C

    2014-10-10

    Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)? Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC. The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood. The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated. DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay. DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants. Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis. The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua

  2. Reduced IRE1α mediates apoptotic cell death by disrupting calcium homeostasis via the InsP3 receptor.

    Science.gov (United States)

    Son, S M; Byun, J; Roh, S-E; Kim, S J; Mook-Jung, I

    2014-04-17

    The endoplasmic reticulum (ER) is not only a home for folding and posttranslational modifications of secretory proteins but also a reservoir for intracellular Ca(2+). Perturbation of ER homeostasis contributes to the pathogenesis of various neurodegenerative diseases, such as Alzheimer's and Parkinson diseases. One key regulator that underlies cell survival and Ca(2+) homeostasis during ER stress responses is inositol-requiring enzyme 1α (IRE1α). Despite extensive studies on this ER membrane-associated protein, little is known about the molecular mechanisms by which excessive ER stress triggers cell death and Ca(2+) dysregulation via the IRE1α-dependent signaling pathway. In this study, we show that inactivation of IRE1α by RNA interference increases cytosolic Ca(2+) concentration in SH-SY5Y cells, leading to cell death. This dysregulation is caused by an accelerated ER-to-cytosolic efflux of Ca(2+) through the InsP3 receptor (InsP3R). The Ca(2+) efflux in IRE1α-deficient cells correlates with dissociation of the Ca(2+)-binding InsP3R inhibitor CIB1 and increased complex formation of CIB1 with the pro-apoptotic kinase ASK1, which otherwise remains inactivated in the IRE1α-TRAF2-ASK1 complex. The increased cytosolic concentration of Ca(2+) induces mitochondrial production of reactive oxygen species (ROS), in particular superoxide, resulting in severe mitochondrial abnormalities, such as fragmentation and depolarization of membrane potential. These Ca(2+) dysregulation-induced mitochondrial abnormalities and cell death in IRE1α-deficient cells can be blocked by depleting ROS or inhibiting Ca(2+) influx into the mitochondria. These results demonstrate the importance of IRE1α in Ca(2+) homeostasis and cell survival during ER stress and reveal a previously unknown Ca(2+)-mediated cell death signaling between the IRE1α-InsP3R pathway in the ER and the redox-dependent apoptotic pathway in the mitochondrion.

  3. Nifedipine treatment reduces resting calcium concentration, oxidative and apoptotic gene expression, and improves muscle function in dystrophic mdx mice.

    Directory of Open Access Journals (Sweden)

    Francisco Altamirano

    Full Text Available Duchenne Muscular Dystrophy (DMD is a recessive X-linked genetic disease, caused by mutations in the gene encoding dystrophin. DMD is characterized in humans and in mdx mice by a severe and progressive destruction of muscle fibers, inflammation, oxidative/nitrosative stress, and cell death. In mdx muscle fibers, we have shown that basal ATP release is increased and that extracellular ATP stimulation is pro-apoptotic. In normal fibers, depolarization-induced ATP release is blocked by nifedipine, leading us to study the potential therapeutic effect of nifedipine in mdx muscles and its relation with extracellular ATP signaling. Acute exposure to nifedipine (10 µM decreased [Ca(2+]r, NF-κB activity and iNOS expression in mdx myotubes. In addition, 6-week-old mdx mice were treated with daily intraperitoneal injections of nifedipine, 1 mg/Kg for 1 week. This treatment lowered the [Ca(2+]r measured in vivo in the mdx vastus lateralis. We demonstrated that extracellular ATP levels were higher in adult mdx flexor digitorum brevis (FDB fibers and can be significantly reduced after 1 week of treatment with nifedipine. Interestingly, acute treatment of mdx FDB fibers with apyrase, an enzyme that completely degrades extracellular ATP to AMP, reduced [Ca(2+]r to a similar extent as was seen in FDB fibers after 1-week of nifedipine treatment. Moreover, we demonstrated that nifedipine treatment reduced mRNA levels of pro-oxidative/nitrosative (iNOS and gp91(phox/p47(phox NOX2 subunits and pro-apoptotic (Bax genes in mdx diaphragm muscles and lowered serum creatine kinase (CK levels. In addition, nifedipine treatment increased muscle strength assessed by the inverted grip-hanging test and exercise tolerance measured with forced swimming test in mdx mice. We hypothesize that nifedipine reduces basal ATP release, thereby decreasing purinergic receptor activation, which in turn reduces [Ca(2+]r in mdx skeletal muscle cells. The results in this work open new

  4. NRSA enzyme decomposition model data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microbial enzyme activities measured at more than 2000 US streams and rivers. These enzyme data were then used to predict organic matter decomposition and microbial...

  5. Cellulase enzyme and biomass utilization

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... human population grows and economic development. However, the current .... conditions and the production cost of the related enzyme system. Therefore ... Given the importance of this enzyme to these so many industries,.

  6. Vacuolar processing enzyme: an executor of plant cell death.

    Science.gov (United States)

    Hara-Nishimura, Ikuko; Hatsugai, Noriyuki; Nakaune, Satoru; Kuroyanagi, Miwa; Nishimura, Mikio

    2005-08-01

    Apoptotic cell death in animals is regulated by cysteine proteinases called caspases. Recently, vacuolar processing enzyme (VPE) was identified as a plant caspase. VPE deficiency prevents cell death during hypersensitive response and cell death of limited cell layers at the early stage of embryogenesis. Because plants do not have macrophages, dying cells must degrade their materials by themselves. VPE plays an essential role in the regulation of the lytic system of plants during the processes of defense and development. VPE is localized in the vacuoles, unlike animal caspases, which are localized in the cytosol. Thus, plants might have evolved a regulated cellular suicide strategy that, unlike animal apoptosis, is mediated by VPE and the vacuoles.

  7. Sterol glycosyltransferases--the enzymes that modify sterols.

    Science.gov (United States)

    Chaturvedi, Pankaj; Misra, Pratibha; Tuli, Rakesh

    2011-09-01

    Sterols are important components of cell membranes, hormones, signalling molecules and defense-related biotic and abiotic chemicals. Sterol glycosyltransferases (SGTs) are enzymes involved in sterol modifications and play an important role in metabolic plasticity during adaptive responses. The enzymes are classified as a subset of family 1 glycosyltransferases due to the presence of a signature motif in their primary sequence. These enzymes follow a compulsory order sequential mechanism forming a ternary complex. The diverse applications of sterol glycosides, like cytotoxic and apoptotic activity, anticancer activity, medicinal values, anti-stress roles and anti-insect and antibacterial properties, draws attention towards their synthesis mechanisms. Many secondary metabolites are derived from sterol pathways, which are important in defense mechanisms against pathogens. SGTs in plants are involved in changed sensitivity to stress hormones and their agrochemical analogs and changed tolerance to biotic and abiotic stresses. SGTs that glycosylate steroidal hormones, such as brassinosteroids, function as growth and development regulators in plants. In terms of metabolic roles, it can be said that SGTs occupy important position in plant metabolism and may offer future tools for crop improvement.

  8. Extinction Correction Significantly Influences the Estimate of the Lyα Escape Fraction

    Science.gov (United States)

    An, Fang Xia; Zheng, Xian Zhong; Hao, Cai-Na; Huang, Jia-Sheng; Xia, Xiao-Yang

    2017-02-01

    The Lyα escape fraction is a key measure to constrain the neutral state of the intergalactic medium and then to understand how the universe was fully reionized. We combine deep narrowband imaging data from the custom-made filter NB393 and the {{{H}}}2S1 filter centered at 2.14 μm to examine the Lyα emitters and Hα emitters at the same redshift z = 2.24. The combination of these two populations allows us to determine the Lyα escape fraction at z = 2.24. Over an area of 383 arcmin2 in the Extended Chandra Deep Field South (ECDFS), 124 Lyα emitters are detected down to NB393 = 26.4 mag at the 5σ level, and 56 Hα emitters come from An et al. Of these, four have both Lyα and Hα emissions (LAHAEs). We also collect the Lyα emitters and Hα emitters at z = 2.24 in the COSMOS field from the literature, and increase the number of LAHAEs to 15 in total. About one-third of them are AGNs. We measure the individual/volumetric Lyα escape fraction by comparing the observed Lyα luminosity/luminosity density to the extinction-corrected Hα luminosity/luminosity density. We revisit the extinction correction for Hα emitters using the Galactic extinction law with color excess for nebular emission. We also adopt the Calzetti extinction law together with an identical color excess for stellar and nebular regions to explore how the uncertainties in extinction correction affect the estimate of individual and global Lyα escape fractions. In both cases, an anti-correlation between the Lyα escape fraction and dust attenuation is found among the LAHAEs, suggesting that dust absorption is responsible for the suppression of the escaping Lyα photons. However, the estimated Lyα escape fraction of individual LAHAEs varies by up to ˜3 percentage points between the two methods of extinction correction. We find the global Lyα escape fraction at z = 2.24 to be (3.7 ± 1.4)% in the ECDFS. The variation in the color excess of the extinction causes a discrepancy of ˜1 percentage point

  9. Energy transfer in O collisions with He isotopes and helium escape from Mars

    Science.gov (United States)

    Bovino, S.; Zhang, P.; Kharchenko, V.; Dalgarno, A.

    2010-12-01

    Helium is one of the dominant constituents in the upper atmosphere of Mars [1]. Thermal (Jeans’) escape of He is negligible on Mars [2] and major mechanism of escape is related to the collisional ejection of He atoms by energetic oxygen. Collisional ejection dominates over ion-related mechanisms [3] and evaluation of the escape flux of neutral He becomes an important issue. The dissociative recombination of O2+ is considered to be the major source of energetic oxygen atoms [4]. We report accurate data on energy-transfer collisions between hot oxygen atoms and the atmospheric helium gas. Angular dependent scattering cross sections for elastic collisions of O(3P) and O(1D) atoms with helium gas have been calculated quantum mechanically and found to be surprisingly similar. Cross sections, computed for collisions with both helium isotopes, 3He and 4He, have been used to construct the kernel of the Boltzmann equation, describing the energy relaxation of hot oxygen atoms. Computed rates of energy transfer in O + He collisions have been used to evaluate the flux of He atoms escaping from the Mars atmosphere at different solar conditions. We have identified atmospheric layers mostly responsible for production of the He escape flux. Our results are consistent with recent data from Monte Carlo simulations of the escape of O atoms: strong angular anisotropy of atomic cross sections leads to an increased transparency of the upper atmosphere for escaping O flux [5] and stimulate the collisional ejection of He atoms. References [1] Krasnopolsky, V. A., and G. R. Gladstone (2005), Helium on Mars and Venus: EUVE observations and modeling, Icarus, 176, 395. [2] Chassefiere E. and F. Leblanc (2004), Mars atmospheric escape and evolution; interaction with the solar wind, Planetary and Space Science, 52, 1039 [3] Krasnopolsky, V. (2010), Solar activity variations of thermospheric temperatures on Mars and a problem of CO in the lower atmoshpere, Icarus, 207, 638. [4] Fox, J. L

  10. Non-thermal escape rates of atmospheric H and D from Mars using MAVEN data

    Science.gov (United States)

    Gacesa, M.; Zahnle, K. J.

    2017-12-01

    Geological evidence suggests that an ocean of liquid water existed on Mars until at least middle to late Noachian era (4.1 to 3.8 Ga) and possibly, at least episodically, as late as Hesperian. Between 67% and 87% of the total primordial amount of water, equal to about 70 to 110 meters equivalent (spread over the entire Mars' surface), is believed to have escape to space, while about 35 meters remains on or beneath the surface as water ice. Establishing better constraints on these numbers and identifying the responsible atmospheric loss processes remains the major objective of NASA's Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. The ratio of atmospheric Deuterium and Hydrogen (D/H) on Mars is one of the best indicators of water loss to space. While majority of H and D escape through thermal Jeans escape, up to 10% of D can escape to space via non-thermal mechanisms, such as collisions with superthermal neutral atoms. In this study, we present new estimates of non-thermal escape rates of light molecules of interest to the water evolution, including H2, HD, OH, and OD, based on recent measurements of atmospheric density and temperature profiles by MAVEN. The escape mechanisms considered include photochemical sources of hot O, as well as collisions with energetic neutral atoms produced in charge-exchange of solar wind ions with atmospheric gases1,2. Energy transport and escape rates are modeled using quantum reactive scattering formalism3 and seasonal variations are illustrated. Finally, a simple estimate of the role of the non-thermal escape mechanisms in previous eras is given. We conclude that D escape rates can be affected by the non-thermal processes with consequences on the estimates of primordial water inventory based on the D/H ratio. [1] N. Lewkow and V. Kharchenko, Astroph. J., 790, 98 (2014) [2] M. Gacesa, N. Lewkow, V. Kharchenko, Icarus 284, 90 (2017) [3] M. Gacesa and V. Kharchenko, Geophys. Res. Lett., 39, L10203 (2012)

  11. Injury rate in a helicopter underwater escape trainer (HUET) from 2005-2012.

    Science.gov (United States)

    Brooks, Christopher J; MacDonald, Conor V; Gibbs, Peter N A

    2014-08-01

    Helicopter underwater escape training (HUET) carries a potential for injury and this paper identifies the injury rate. A marine survival training school registry of all students trained between 2005-2012 in HUET and the coinciding accident records were examined. There were 8902 students trained in a helicopter underwater escape simulator for a total of 59,245 underwater escapes. There were 40 cases where only first-aid was required and 3 serious injuries (a laceration requiring 5 sutures, 1 dislocated shoulder, and 1 water aspiration requiring hospitalization). There were no deaths and no problems reported with using the Emergency Breathing System (EBS) or Air Pocket. Of the injuries, 11 were due to the student using a poor escape technique. The overall probability of injury was 0.74 per 1000 ascents. In HUET training, there is a very low injury rate with almost no significant severity. Although not scientifically proven, this would suggest that the low incident rate is due to good medical screening and the attention given by instructors to anxious students. Compared to other training such as diving, parachute jumping, and submarine escape training, the rate of injury was considerably lower.

  12. Escape from Telomere-Driven Crisis Is DNA Ligase III Dependent

    Directory of Open Access Journals (Sweden)

    Rhiannon E. Jones

    2014-08-01

    Full Text Available Short dysfunctional telomeres are capable of fusion, generating dicentric chromosomes and initiating breakage-fusion-bridge cycles. Cells that escape the ensuing cellular crisis exhibit large-scale genomic rearrangements that drive clonal evolution and malignant progression. We demonstrate that there is an absolute requirement for fully functional DNA ligase III (LIG3, but not ligase IV (LIG4, to facilitate the escape from a telomere-driven crisis. LIG3- and LIG4-dependent alternative (A and classical (C nonhomologous end-joining (NHEJ pathways were capable of mediating the fusion of short dysfunctional telomeres, both displaying characteristic patterns of microhomology and deletion. Cells that failed to escape crisis exhibited increased proportions of C-NHEJ-mediated interchromosomal fusions, whereas those that escaped displayed increased proportions of intrachromosomal fusions. We propose that the balance between inter- and intrachromosomal telomere fusions dictates the ability of human cells to escape crisis and is influenced by the relative activities of A- and C-NHEJ at short dysfunctional telomeres.

  13. How Hospitable Are Space Weather Affected Habitable Zones? The Role of Ion Escape

    Energy Technology Data Exchange (ETDEWEB)

    Airapetian, Vladimir S.; Glocer, Alex; Khazanov, George V.; Danchi, William C. [NASA/GSFC, Greenbelt, MD (United States); Loyd, R. O. P.; France, Kevin [University of Colorado/LASP, Boulder, CO (United States); Sojka, Jan [Utah State University, Logan, UT (United States); Liemohn, Michael W. [University of Michigan, Ann Arbor, MI (United States)

    2017-02-10

    Atmospheres of exoplanets in the habitable zones around active young G-K-M stars are subject to extreme X-ray and EUV (XUV) fluxes from their host stars that can initiate atmospheric erosion. Atmospheric loss affects exoplanetary habitability in terms of surface water inventory, atmospheric pressure, the efficiency of greenhouse warming, and the dosage of the UV surface irradiation. Thermal escape models suggest that exoplanetary atmospheres around active K-M stars should undergo massive hydrogen escape, while heavier species including oxygen will accumulate forming an oxidizing atmosphere. Here, we show that non-thermal oxygen ion escape could be as important as thermal, hydrodynamic H escape in removing the constituents of water from exoplanetary atmospheres under supersolar XUV irradiation. Our models suggest that the atmospheres of a significant fraction of Earth-like exoplanets around M dwarfs and active K stars exposed to high XUV fluxes will incur a significant atmospheric loss rate of oxygen and nitrogen, which will make them uninhabitable within a few tens to hundreds of Myr, given a low replenishment rate from volcanism or cometary bombardment. Our non-thermal escape models have important implications for the habitability of the Proxima Centauri’s terrestrial planet.

  14. Enhanced Endosomal Escape by Light-Fueled Liquid-Metal Transformer.

    Science.gov (United States)

    Lu, Yue; Lin, Yiliang; Chen, Zhaowei; Hu, Quanyin; Liu, Yang; Yu, Shuangjiang; Gao, Wei; Dickey, Michael D; Gu, Zhen

    2017-04-12

    Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal. When coated with graphene quantum dots (GQDs), the resulting nanospheres demonstrate the ability to absorb and convert photoenergy to drive the simultaneous phase separation and morphological transformation of the inner liquid-metal core. The morphological transformation from nanospheres to hollow nanorods with a remarkable change of aspect ratio can physically disrupt the endosomal membrane to promote endosomal escape of payloads. This metal-based nanotransformer equipped with GQDs provides a new strategy for facilitating effective endosomal escape to achieve spatiotemporally controlled drug delivery with enhanced efficacy.

  15. Escape rate for nonequilibrium processes dominated by strong non-detailed balance force

    Science.gov (United States)

    Tang, Ying; Xu, Song; Ao, Ping

    2018-02-01

    Quantifying the escape rate from a meta-stable state is essential to understand a wide range of dynamical processes. Kramers' classical rate formula is the product of an exponential function of the potential barrier height and a pre-factor related to the friction coefficient. Although many applications of the rate formula focused on the exponential term, the prefactor can have a significant effect on the escape rate in certain parameter regions, such as the overdamped limit and the underdamped limit. There have been continuous interests to understand the effect of non-detailed balance on the escape rate; however, how the prefactor behaves under strong non-detailed balance force remains elusive. In this work, we find that the escape rate formula has a vanishing prefactor with decreasing friction strength under the strong non-detailed balance limit. We both obtain analytical solutions in specific examples and provide a derivation for more general cases. We further verify the result by simulations and propose a testable experimental system of a charged Brownian particle in electromagnetic field. Our study demonstrates that a special care is required to estimate the effect of prefactor on the escape rate when non-detailed balance force dominates.

  16. How Hospitable Are Space Weather Affected Habitable Zones? The Role of Ion Escape

    International Nuclear Information System (INIS)

    Airapetian, Vladimir S.; Glocer, Alex; Khazanov, George V.; Danchi, William C.; Loyd, R. O. P.; France, Kevin; Sojka, Jan; Liemohn, Michael W.

    2017-01-01

    Atmospheres of exoplanets in the habitable zones around active young G-K-M stars are subject to extreme X-ray and EUV (XUV) fluxes from their host stars that can initiate atmospheric erosion. Atmospheric loss affects exoplanetary habitability in terms of surface water inventory, atmospheric pressure, the efficiency of greenhouse warming, and the dosage of the UV surface irradiation. Thermal escape models suggest that exoplanetary atmospheres around active K-M stars should undergo massive hydrogen escape, while heavier species including oxygen will accumulate forming an oxidizing atmosphere. Here, we show that non-thermal oxygen ion escape could be as important as thermal, hydrodynamic H escape in removing the constituents of water from exoplanetary atmospheres under supersolar XUV irradiation. Our models suggest that the atmospheres of a significant fraction of Earth-like exoplanets around M dwarfs and active K stars exposed to high XUV fluxes will incur a significant atmospheric loss rate of oxygen and nitrogen, which will make them uninhabitable within a few tens to hundreds of Myr, given a low replenishment rate from volcanism or cometary bombardment. Our non-thermal escape models have important implications for the habitability of the Proxima Centauri’s terrestrial planet.

  17. Hydrogen escape from Mars enhanced by deep convection in dust storms

    Science.gov (United States)

    Heavens, Nicholas G.; Kleinböhl, Armin; Chaffin, Michael S.; Halekas, Jasper S.; Kass, David M.; Hayne, Paul O.; McCleese, Daniel J.; Piqueux, Sylvain; Shirley, James H.; Schofield, John T.

    2018-02-01

    Present-day water loss from Mars provides insight into Mars's past habitability1-3. Its main mechanism is thought to be Jeans escape of a steady hydrogen reservoir sourced from odd-oxygen reactions with near-surface water vapour2, 4,5. The observed escape rate, however, is strongly variable and correlates poorly with solar extreme-ultraviolet radiation flux6-8, which was predicted to modulate escape9. This variability has recently been attributed to hydrogen sourced from photolysed middle atmospheric water vapour10, whose vertical and seasonal distribution is only partly characterized and understood11-13. Here, we report multi-annual observational estimates of water content and dust and water transport to the middle atmosphere from Mars Climate Sounder data. We provide strong evidence that the transport of water vapour and ice to the middle atmosphere by deep convection in Martian dust storms can enhance hydrogen escape. Planet-encircling dust storms can raise the effective hygropause (where water content rapidly decreases to effectively zero) from 50 to 80 km above the areoid (the reference equipotential surface). Smaller dust storms contribute to an annual mode in water content at 40-50 km that may explain seasonal variability in escape. Our results imply that Martian atmospheric chemistry and evolution can be strongly affected by the meteorology of the lower and middle atmosphere of Mars.

  18. Escape Distance in Ground-Nesting Birds Differs with Individual Level of Camouflage.

    Science.gov (United States)

    Wilson-Aggarwal, Jared K; Troscianko, Jolyon T; Stevens, Martin; Spottiswoode, Claire N

    2016-08-01

    Camouflage is one of the most widespread antipredator strategies in the animal kingdom, yet no animal can match its background perfectly in a complex environment. Therefore, selection should favor individuals that use information on how effective their camouflage is in their immediate habitat when responding to an approaching threat. In a field study of African ground-nesting birds (plovers, coursers, and nightjars), we tested the hypothesis that individuals adaptively modulate their escape behavior in relation to their degree of background matching. We used digital imaging and models of predator vision to quantify differences in color, luminance, and pattern between eggs and their background, as well as the plumage of incubating adult nightjars. We found that plovers and coursers showed greater escape distances when their eggs were a poorer pattern match to the background. Nightjars sit on their eggs until a potential threat is nearby, and, correspondingly, they showed greater escape distances when the pattern and color match of the incubating adult's plumage-rather than its eggs-was a poorer match to the background. Finally, escape distances were shorter in the middle of the day, suggesting that escape behavior is mediated by both camouflage and thermoregulation.

  19. Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis

    NARCIS (Netherlands)

    Frodermann, Vanessa; van Puijvelde, Gijs H M; Wierts, Laura; Lagraauw, H Maxime; Foks, Amanda C; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

    2015-01-01

    Modulation of immune responses may form a powerful approach to treat atherosclerosis. It was shown that clearance of apoptotic cells results in tolerance induction to cleared Ags by dendritic cells (DCs); however, this seems impaired in atherosclerosis because Ag-specific tolerance is lacking. This

  20. Cytotoxicity and apoptotic effects of nickel oxide nanoparticles in cultured HeLa cells

    Directory of Open Access Journals (Sweden)

    Kezban Ada

    2010-04-01

    Full Text Available The aim of this study was to observe the cytotoxicity and apoptotic effects of nickel oxide nanoparticles on humancervix epithelioid carcinoma cell line (HeLa. Nickel oxide precursors were synthesized by an nickel sulphate-excess ureareaction in boiling aqueous solution. The synthesized NiO nanoparticles (<200 nm were investigated by X-ray diffractionanalysis and transmission electron microscopy techniques. For cytotoxicity experiments, HeLa cells were incubated in50-500 μg/mL NiO for 2, 6, 12 and 16 hours. The viable cells were counted with a haemacytometer using light microscopy.The cytotoxicity was observed low in 50-200 μg/mL concentration for 16 h, but high in 400-500 μg/mL concentration for2-6 h. HeLa cells' cytoplasm membrane was lysed and detached from the well surface in 400 μg/mL concentration NiOnanoparticles. Double staining and M30 immunostaining were performed to quantify the number of apoptotic cells in cultureon the basis of apoptotic cell nuclei scores. The apoptotic effect was observed 20% for 16 h incubation.

  1. Expression of defender against apoptotic death (DAD-1) in iris and dianthus petals

    NARCIS (Netherlands)

    Kop, van der D.A.M.; Ruys, G.; Dees, D.; Schoot, van der C.; Boer, de A.D.; Doorn, van W.G.

    2003-01-01

    The gene defender against apoptotic death (DAD-1) prevents programmed cell death in animal cells. We investigated the expression pattern of DAD-1 in petals of iris (Iris x hollandica cv. Blue Magic) and carnation (Dianthus caryophyllus cv. Etarro). DAD-1 expression in Iris petals was strongly

  2. Antiproliferative and Pro-apoptotic activities of the stem bark of ...

    African Journals Online (AJOL)

    Persea americana (Lauraceae) have been used in traditional medicine for a wide range of illness and some of these uses have been proven scientifically. The aim of this present study is to screen for the phytochemical content, determine the proximate parameter and determine the antiproliferative and apoptotic effects of ...

  3. Apoptotic and free radical scavenging properties of the methanolic extract of Gentianella alborosea.

    Science.gov (United States)

    Acero, Nuria; Llinares, Francisco; Galán de Mera, Antonio; Oltra, Beatriz; Muñoz-Mingarro, Dolores

    2006-09-01

    Gentianella alborosea ("Hercampure") is a Peruvian species used in folk medicine for the treatment of a variety of health disorders. We tested the free radical scavenging (DPPH) and induction of apoptosis on a human uterus tumor cell line (HeLa) by its methanolic extract. The results showed a noticeable radical scavenging activity and a dose-dependent apoptotic effect.

  4. Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dae-Hee, E-mail: leedneo@gmail.com [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Dong-Wook [Department of Microbiology, Immunology, and Cancer Biology, University of VA (United States); Jung, Chang-Hwa [Division of Metabolism and Functionality Research, Korea Food Research Institute (Korea, Republic of); Lee, Yong J. [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Park, Daeho, E-mail: daehopark@gist.ac.kr [School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)

    2014-09-15

    Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway.

  5. Antitumor and apoptotic effects of cucurbitacin a in A-549 lung ...

    African Journals Online (AJOL)

    Background: The main aim of this study was to demonstrate the antitumor potential of cucurbitacin A on A-549 NSCLC (non-small cell lung cancer cells). The effects of Cucurbitacin A on apoptotic induction, cell physic, cell cycle failure and m-TOR/PI3K/Akt signalling pathway were also investigated in the present study.

  6. The calcimimetic R-568 induces apoptotic cell death in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Cheng Guangming

    2009-07-01

    Full Text Available Abstract Background Increased serum level of parathyroid hormone (PTH was found in metastatic prostate cancers. Calcimimetic R-568 was reported to reduce PTH expression, to suppress cell proliferation and to induce apoptosis in parathyroid cells. In this study, we investigated the effect of R-568 on cellular survival of prostate cancer cells. Methods Prostate cancer cell lines LNCaP and PC-3 were used in this study. Cellular survival was determined with MTT, trypan blue exclusion and fluorescent Live/Death assays. Western blot assay was utilized to assess apoptotic events induced by R-568 treatment. JC-1 staining was used to evaluate mitochondrial membrane potential. Results In cultured prostate cancer LNCaP and PC-3 cells, R-568 treatment significantly reduced cellular survival in a dose- and time-dependent manner. R-568-induced cell death was an apoptotic event, as evidenced by caspase-3 processing and PARP cleavage, as well as JC-1 color change in mitochondria. Knocking down calcium sensing receptor (CaSR significantly reduced R-568-induced cytotoxicity. Enforced expression of Bcl-xL gene abolished R-568-induced cell death, while loss of Bcl-xL expression led to increased cell death in R-568-treated LNCaP cells,. Conclusion Taken together, our data demonstrated that calcimimetic R-568 triggers an intrinsic mitochondria-related apoptotic pathway, which is dependent on the CaSR and is modulated by Bcl-xL anti-apoptotic pathway.

  7. Chlamydia pneumoniae hides inside apoptotic neutrophils to silently infect and propagate in macrophages.

    Directory of Open Access Journals (Sweden)

    Jan Rupp

    Full Text Available BACKGROUND: Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae. METHODOLOGY/PRINCIPAL FINDINGS: We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ss production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-alpha response. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest that C. pneumoniae uses neutrophil granulocytes to be silently taken up by long-lived macrophages, which allows for efficient propagation and immune protection within the human host.

  8. Involvement of caspase-dependent and -independent apoptotic pathways in cisplatin-induced apoptosis

    Science.gov (United States)

    Liu, Lei; Zhang, Yingjie; Wang, Xianwang

    2009-02-01

    Cisplatin, an efficient anticancer agent, can trigger multiple apoptotic pathways in cancer cells. However, the signal transduction pathways in response to cisplatin-based chemotherapy are complicated, and the mechanism is not fully understood. In current study, we showed that, during cisplatin-induced apoptosis of human lung adenocarcinoma cells, both the caspase-dependent and -independent pathways were activated. Herein, we reported that after cisplatin treatment, the activities of caspase-9/-3 were sharply increased; pre-treatment with Z-LEHD-fmk (inhibitor of caspase-9), Z-DEVD-fmk (inhibitor of caspase-3), and Z-VAD-fmk (a pan-caspase inhibitor) increased cell viability and decreased apoptosis, suggesting that caspase-mediated apoptotic pathway was activated following cisplatin treatment. Confocal imaging of the cells transfected with AIF-GFP demonstrated that AIF release occurred about 9 h after cisplatin treatment. The event proceeded progressively over time, coinciding with a nuclear translocation and lasting for more than 2 hours. Down-regulation of AIF by siRNA also significantly increased cell viability and decreased apoptosis, these results suggested that AIF-mediated caspase-independent apoptotic pathway was involved in cispatin-induced apoptosis. In conclusion, the current study demonstrated that both caspase-dependent and -independent apoptotic pathways were involved in cisplatin-induced apoptosis in human lung adenocarcinoma cells.

  9. Withaferin A Suppresses Anti-apoptotic BCL2, Bcl-xL, XIAP and ...

    African Journals Online (AJOL)

    apoptotic genes, BCL2, Bcl-xL, XIAP and Survivin), in cervical carcinoma cells. Methods: Annexin V-FITC/propidium iodide (PI) staining was used for the investigation of cell apoptosis. RNA RNeasy Kits was used to isolate RNA and Omniscript ...

  10. Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

    International Nuclear Information System (INIS)

    Lee, Dae-Hee; Kim, Dong-Wook; Jung, Chang-Hwa; Lee, Yong J.; Park, Daeho

    2014-01-01

    Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway

  11. The anti-apoptotic activity associated with phosphatidylinositol transfer protein α activates the MAPK and Akt/PKB pathway

    NARCIS (Netherlands)

    Schenning, M.; Goedhart, J.; Gadella (jr.), T.W.J.; Avram, D.; Wirtz, K.W.A.; Snoek, G.T.

    2008-01-01

    The conditioned medium (CM) from mouse NIH3T3 fibroblast cells overexpressing phosphatidylinositol transfer protein α (PI-TPα; SPIα cells) demonstrates an increased anti-apoptotic activity compared with CM from wild type NIH3T3 (wtNIH3T3) cells. As previously shown, the anti-apoptotic activity acts

  12. Dynamic release of nuclear RanGTP triggers TPX2-dependent microtubule assembly during the apoptotic execution phase.

    Science.gov (United States)

    Moss, David K; Wilde, Andrew; Lane, Jon D

    2009-03-01

    During apoptosis, the interphase microtubule network is dismantled then later replaced by a novel, non-centrosomal microtubule array. These microtubules assist in the peripheral redistribution of nuclear fragments in the apoptotic cell; however, the regulation of apoptotic microtubule assembly is not understood. Here, we demonstrate that microtubule assembly depends upon the release of nuclear RanGTP into the apoptotic cytoplasm because this process is blocked in apoptotic cells overexpressing dominant-negative GDP-locked Ran (T24N). Actin-myosin-II contractility provides the impetus for Ran release and, consequently, microtubule assembly is blocked in blebbistatin- and Y27632-treated apoptotic cells. Importantly, the spindle-assembly factor TPX2 (targeting protein for Xklp2), colocalises with apoptotic microtubules, and siRNA silencing of TPX2, but not of the microtubule motors Mklp1 and Kid, abrogates apoptotic microtubule assembly. These data provide a molecular explanation for the assembly of the apoptotic microtubule network, and suggest important similarities with the process of RanGTP- and TPX2-mediated mitotic spindle formation.

  13. In vitro evidence for participation of DEC-205 expressed by thymic cortical epithelial cells in clearance of apoptotic thymocytes.

    NARCIS (Netherlands)

    Small, M; Kraal, G.

    2003-01-01

    Binding of apoptotic cells was compared after incubation of thymocytes with two clones of murine thymic stromal cells to which CD4(+)/CD8(+) thymocytes attach. With the BA/10, but not the BA/2, clone, thymocytes with apoptotic morphology were bound irreversibly. These tightly bound thymocytes were

  14. Thermoresponsive pegylated bubble liposome nanovectors for efficient siRNA delivery via endosomal escape

    KAUST Repository

    Alamoudi, Kholod; Martins, Patricia; Croissant, Jonas G.; Patil, Sachin; Omar, Haneen; Khashab, Niveen M.

    2017-01-01

    Improving the delivery of siRNA into cancer cells via bubble liposomes. Designing a thermoresponsive pegylated liposome through the introduction of ammonium bicarbonate salt into liposomes so as to control their endosomal escape for gene therapy.A sub-200 nm nanovector was fully characterized and examined for cellular uptake, cytotoxicity, endosomal escape and gene silencing.The siRNA-liposomes were internalized into cancer cells within 5 min and then released siRNAs in the cytosol prior to lysosomal degradation upon external temperature elevation. This was confirmed by confocal bioimaging and gene silencing reaching up to 90% and further demonstrated by the protein inhibition of both target genes.The thermoresponsiveness of ammonium bicarbonate containing liposomes enabled the rapid endosomal escape of the particles and resulted in an efficient gene silencing.

  15. European policymaking on the tobacco advertising ban: the importance of escape routes.

    Science.gov (United States)

    Adamini, Sandra; Versluis, Esther; Maarse, Hans

    2011-01-01

    This article analyses the European Union policymaking process regarding tobacco advertising. While others already highlighted the importance of intergovernmental bargaining between member states to explain the outcome of the tobacco advertising case, the main aim of this article is to identify the use of escape routes by the Commission, the European Parliament, the Council and interest groups that played an important role in overcoming the deadlock. When looking at the different institutions that structure policymaking, we argue that indeed focusing on escape routes provides a clear insight in the process and in what strategies were necessary to 'make Europe work'. In the end, it appears to be a combination of escape routes that resulted in the final decision.

  16. Thermoresponsive pegylated bubble liposome nanovectors for efficient siRNA delivery via endosomal escape

    KAUST Repository

    Alamoudi, Kholod

    2017-05-19

    Improving the delivery of siRNA into cancer cells via bubble liposomes. Designing a thermoresponsive pegylated liposome through the introduction of ammonium bicarbonate salt into liposomes so as to control their endosomal escape for gene therapy.A sub-200 nm nanovector was fully characterized and examined for cellular uptake, cytotoxicity, endosomal escape and gene silencing.The siRNA-liposomes were internalized into cancer cells within 5 min and then released siRNAs in the cytosol prior to lysosomal degradation upon external temperature elevation. This was confirmed by confocal bioimaging and gene silencing reaching up to 90% and further demonstrated by the protein inhibition of both target genes.The thermoresponsiveness of ammonium bicarbonate containing liposomes enabled the rapid endosomal escape of the particles and resulted in an efficient gene silencing.

  17. HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

    Science.gov (United States)

    Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

    2010-12-15

    Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

  18. Mass fractionation of noble gases in diffusion-limited hydrodynamic hydrogen escape

    International Nuclear Information System (INIS)

    Zahnle, K.; Pollack, J.B.; Kasting, J.F.

    1990-01-01

    The theory of mass fractionation by hydrogen is presently extended to atmospheres in which hydrogen is not the major constituent. This theoretical framework is applied to three different cases. In the first, it is shown that the fractionation of terrestrial atmospheric neon with respect to mantle neon is explainable as a consequence of diffusion-limited hydrogen escape from a steam atmosphere toward the end of the accretion process. In the second, the anomalously high Ar-38/Ar-36 ratio of Mars is shown to be due to hydrodynamic fractionation by a vigorously escaping and very pure hydrogen wind. In the last case, it is speculated that the currently high Martian D/H ratio emerged during the hydrodynamic escape phase which fractionated Ar. 35 refs

  19. Unsteady motion: escape jumps in planktonic copepods, their kinematics and energetics

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Andersen, Anders Peter; Langlois, Vincent J.

    2010-01-01

    velocities in other aquatic organisms. The relative duration of the pauses between power strokes was observed to increase with organism size. We demonstrate that this is an inherent property of swimming by alternating power strokes and pauses. We finally show that the Strouhal number is in the range of peak......We describe the kinematics of escape jumps in three species of 0.3–3.0 mm-sized planktonic copepods. We find similar kinematics between species with periodically alternating power strokes and passive coasting and a resulting highly fluctuating escape velocity. By direct numerical simulations, we...... estimate the force and power output needed to accelerate and overcome drag. Both are very high compared with those of other organisms, as are the escape velocities in comparison to startle velocities of other aquatic animals. Thus, the maximum weight-specific force, which for muscle motors of other animals...

  20. Optimization of a Compton-suppression system by escape-peak ratio

    International Nuclear Information System (INIS)

    Niu, H.; Chao, J.H.; Wu, S.-C.

    1996-01-01

    A Compton-suppression system consisting of an HPGe central detector surrounded by eight BGO scintillators in an annular geometry was assembled. This system is dedicated to in-beam γ-ray measurements. The ratios of full-energy to single-escape peak and full-energy of double-escape peak, at γ-rays of 2754, 4443 and 6130 keV, were used to derive associated suppression factors in order to optimize detection conditions of the system. The suppression factors derived both from the escape peak ratios and the corresponding peak-to-Compton ratios of the γ-ray spectra are compared and discussed. This optimization technique may be of great significance for analyzing complicated spectra, where high-energy γ-rays are considered for analytical use. (Author)

  1. New insights into the apoptotic process in mollusks: characterization of caspase genes in Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Alejandro Romero

    2011-02-01

    Full Text Available Apoptosis is an essential biological process in the development and maintenance of immune system homeostasis. Caspase proteins constitute the core of the apoptotic machinery and can be categorized as either initiators or effectors of apoptosis. Although the genes encoding caspase proteins have been described in vertebrates and in almost all invertebrate phyla, there are few reports describing the initiator and executioner caspases or the modulation of their expression by different stimuli in different apoptotic pathways in bivalves. In the present work, we characterized two initiator and four executioner caspases in the mussel Mytilus galloprovincialis. Both initiators and executioners showed structural features that make them different from other caspase proteins already described. Evaluation of the genes' tissue expression patterns revealed extremely high expression levels within the gland and gills, where the apoptotic process is highly active due to the clearance of damaged cells. Hemocytes also showed high expression values, probably due to of the role of apoptosis in the defense against pathogens. To understand the mechanisms of caspase gene regulation, hemocytes were treated with UV-light, environmental pollutants and pathogen-associated molecular patterns (PAMPs and apoptosis was evaluated by microscopy, flow cytometry and qPCR techniques. Our results suggest that the apoptotic process could be tightly regulated in bivalve mollusks by overexpression/suppression of caspase genes; additionally, there is evidence of caspase-specific responses to pathogens and pollutants. The apoptotic process in mollusks has a similar complexity to that of vertebrates, but presents unique features that may be related to recurrent exposure to environmental changes, pollutants and pathogens imposed by their sedentary nature.

  2. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis

    Science.gov (United States)

    Millet, Arnaud; Martin, Katherine R.; Bonnefoy, Francis; Saas, Philippe; Mocek, Julie; Alkan, Manal; Terrier, Benjamin; Kerstein, Anja; Tamassia, Nicola; Satyanarayanan, Senthil Kumaran; Ariel, Amiram; Ribeil, Jean-Antoine; Guillevin, Loïc; Cassatella, Marco A.; Mueller, Antje; Thieblemont, Nathalie; Lamprecht, Peter; Mouthon, Luc; Perruche, Sylvain; Witko-Sarsat, Véronique

    2015-01-01

    Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology. PMID:26436651

  3. H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptotic response

    Science.gov (United States)

    Bland, David A; Suarez, Giovanni; Beswick, Ellen J; Sierra, Johanna C; Reyes, Victor E

    2006-01-01

    AIM: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. METHODS: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in a marked reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. CONCLUSION: The results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that the crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells. PMID:16981259

  4. Foveolar cells phagocytose apoptotic neutrophils in chronic active Helicobacter pylori gastritis.

    Science.gov (United States)

    Caruso, R A; Fedele, F; Di Bella, C; Mazzon, E; Rigoli, L

    2012-11-01

    The recognition and removal of apoptotic inflammatory cells by tissue macrophages and non-professional phagocytes, in a process called efferocytosis, is required for resolution of inflammation and is actively anti-inflammatory. We have previously demonstrated phagocytosis of apoptotic neutrophils by tumor cells in human gastric carcinoma, but to date, there have been no studies investigating this process in chronic active Helicobacter pylori gastritis. Biopsy specimens from 28 subjects with or without H. pylori infection and active inflammation were examined and graded according to the updated Sydney system. Light microscopy, electron microscopy, and Terminal Deoxynucleotidyltransferase-Mediated UTP End Labeling staining were used to identify apoptosis. H. pylori infection was detected by histology and by molecular assay in 16 out of 28 cases. DNA from paraffin-embedded gastric biopsies was amplified using primers specific for cagA, for the cag "empty site" as well as for the s and m alleles of vacA. The more virulent cagA-positive strains were found in five out of nine patients with chronic active gastritis. The vacA s1/m1 and s2/m1 genotypes were more common in nine patients with chronic active gastritis, while the vacA s2/m2 genotype was more frequent in seven patients with chronic inactive gastritis. Apoptotic neutrophils were also detected within the cytoplasmic vacuoles of the foveolar cells of nine cases with chronic active gastritis. Transmission electron micrographs revealed further apoptotic neutrophils within spacious phagosomes of foveolar cells in a similar manner to those described in late-phase efferocytosis both in vivo and in vitro. These new observations expand the morphological spectrum of gastritis in patients infected with more virulent H. pylori strains, compatible with an anti-inflammatory role for the gastric epithelial cells in their removal of apoptotic neutrophils during active chronic gastritis.

  5. Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells.

    Science.gov (United States)

    Yajima, Ichiro; Uemura, Noriyuki; Nizam, Saika; Khalequzzaman, Md; Thang, Nguyen D; Kumasaka, Mayuko Y; Akhand, Anwarul A; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2012-06-01

    Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

  6. Ion transport in a human lens epithelial cell line exposed to hyposmotic and apoptotic stress.

    Science.gov (United States)

    Chimote, Ameet A; Adragna, Norma C; Lauf, Peter K

    2010-04-01

    Membrane transport changes in human lens epithelial (HLE-B3) cells under hyposmotic and apoptotic stress were compared. Cell potassium content, K(i), uptake of the K congener rubidium, Rb(i), and water content were measured after hyposmotic stress induced by hypotonicity, and apoptotic stress by the protein-kinase inhibitor staurosporine (STP). Cell water increased in hyposmotic (150 mOsm) as compared to isosmotic (300 mOsm) balanced salt solution (BSS) by >2-fold at 5 min and decreased within 15 min to baseline values accompanied by a 40% K(i) loss commensurate with cell swelling and subsequent cell shrinkage likely due to regulatory volume decrease (RVD). Loss of K(i), and accompanying water, and Rb(i) uptake in hyposmotic BSS were prevented by clotrimazole (CTZ) suggesting water shifts associated with K and Rb flux via intermediate conductance K (IK) channels, also detected at the mRNA and protein level. In contrast, 2 h after 2 microM STP exposure, the cells lost approximately 40% water and approximately 60% K(i), respectively, consistent with apoptotic volume decrease (AVD). Indeed, water and K(i) loss was at least fivefold greater after hyposmotic than after apoptotic stress. High extracellular K and 2 mM 4-aminopyridine (4-AP) but not CTZ significantly reduced apoptosis. Annexin labeling phosphatidylserine (PS) at 15 min suggested loss of lipid asymmetry. Quantitative PCR revealed significant IK channel expression during prolonged hyposmotic stress. Results suggest in HLE-B3 cells, IK channels likely partook in and were down regulated after RVD, whereas pro-apoptotic STP-activation of 4-AP-sensitive voltage-gated K channels preceded or accompanied PS externalization before subsequent apoptosis. J. Cell. Physiol. 223: 110-122, 2010. (c) 2009 Wiley-Liss, Inc.

  7. Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape.

    Directory of Open Access Journals (Sweden)

    Katharine J Bar

    Full Text Available Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, antibody adsorptions and virus-entry assays, we found evidence in three subjects of neutralizing antibody (Nab responses as early as 2 weeks post-seroconversion, with Nab titers as low as 1∶20 to 1∶50 (IC(50 selecting for virus escape. In each of the subjects, Nabs targeted different regions of the HIV-1 envelope (Env in a strain-specific, conformationally sensitive manner. In subject CH40, virus escape was first mediated by mutations in the V1 region of the Env, followed by V3. HIV-1 specific monoclonal antibodies from this subject mapped to an immunodominant region at the base of V3 and exhibited neutralizing patterns indistinguishable from polyclonal antibody responses, indicating V1-V3 interactions within the Env trimer. In subject CH77, escape mutations mapped to the V2 region of Env, several of which selected for alterations of glycosylation. And in subject CH58, escape mutations mapped to the Env outer domain. In all three subjects, initial Nab recognition was followed by sequential rounds of virus escape and Nab elicitation, with Nab escape variants exhibiting variable costs to replication fitness. Although delayed in comparison with autologous CD8 T-cell responses, our findings show that Nabs appear earlier in HIV-1 infection than previously recognized, target diverse sites on HIV-1 Env, and impede virus replication at surprisingly low titers. The unexpected in vivo sensitivity of early transmitted/founder virus to Nabs raises the possibility that similarly low concentrations of vaccine-induced Nabs could impair virus acquisition in natural HIV-1 transmission, where the risk of infection is low and the number of viruses responsible for transmission and productive clinical

  8. MAVEN Observations of Escaping Planetary Ions from the Martian Atmosphere: Mass, Velocity, and Spatial Distributions

    Science.gov (United States)

    Dong, Yaxue; Fang, Xiaohua; Brain, D. A.; McFadden, James P.; Halekas, Jasper; Connerney, Jack

    2015-04-01

    The Mars-solar wind interaction accelerates and transports planetary ions away from the Martian atmosphere through a number of processes, including ‘pick-up’ by electromagnetic fields. The MAVEN spacecraft has made routine observations of escaping planetary ions since its arrival at Mars in September 2014. The SupraThermal And Thermal Ion Composition (STATIC) instrument measures the ion energy, mass, and angular spectra. It has detected energetic planetary ions during most of the spacecraft orbits, which are attributed to the pick-up process. We found significant variations in the escaping ion mass and velocity distributions from the STATIC data, which can be explained by factors such as varying solar wind conditions, contributions of particles from different source locations and different phases during the pick-up process. We also study the spatial distributions of different planetary ion species, which can provide insight into the physics of ion escaping process and enhance our understanding of atmospheric erosion by the solar wind. Our results will be further interpreted within the context of the upstream solar wind conditions measured by the MAVEN Solar Wind Ion Analyzer (SWIA) instrument and the magnetic field environment measured by the Magnetometer (MAG) instrument. Our study shows that the ion spatial distribution in the Mars-Sun-Electric-Field (MSE) coordinate system and the velocity space distribution with respect to the local magnetic field line can be used to distinguish the ions escaping through the polar plume and those through the tail region. The contribution of the polar plume ion escape to the total escape rate will also be discussed.

  9. Escape of O(3P), O(1D), and O(1S) from the Martian atmosphere

    Science.gov (United States)

    Fox, Jane L.; Hać, Aleksander B.

    2018-01-01

    We have computed here the escape probabilities, fluxes and rates for hot O atoms that are initially produced in the ground state and the first two excited metastable states, O(1D)and O(1S), in the Martian thermosphere by dissociative recombination of O2+. In order to compare our results with those of our previous calculations and with those of others, we have employed here the pre-MAVEN models that we have used previously. To compute the escape probabilities, we have employed the Monte Carlo escape code that has been described previously, but we here use for the first time energy-dependent elastic cross sections for collisions of the energetic O atoms with each of the twelve background species in our model. We also incorporate three mechanisms that interchange identities of the O(3P) and O(1D) atoms, including collisional excitation of O(3P) to O(1D), quenching of O(1D) to O(3P), and excitation exchange of O(1D) with O(3P). We find that the escape probabilities of O atoms that are produced initially as O(1D) are reduced compared to those in which these processes are not included, but the escape probabilities of O atoms that are initially produced as O(3P) are not significantly reduced. As a guide for our future research and those of other investigators, we review here what is known about the interactions of O atoms with other species in which the energies of the O atoms are altered, and several other sources of hot and escaping O, many of which have been suggested by other investigators. We will incorporate these data in a future MAVEN-like model.

  10. Enzyme recycling in lignocellulosic biorefineries

    DEFF Research Database (Denmark)

    Jørgensen, Henning; Pinelo, Manuel

    2017-01-01

    platform. Cellulases are the most important enzymes required in this process, but the complex nature of lignocellulose requires several other enzymes (hemicellulases and auxiliary enzymes) for efficient hydrolysis. Enzyme recycling increases the catalytic productivity of the enzymes by reusing them...... for several batches of hydrolysis, and thereby reduces the overall cost associated with the hydrolysis. Research on this subject has been ongoing for many years and several promising technologies and methods have been developed and demonstrated. But only in a very few cases have these technologies been...... upscaled and tested in industrial settings, mainly because of many difficulties with recycling of enzymes from the complex lignocellulose hydrolyzate at industrially relevant conditions, i.e., high solids loadings. The challenges are associated with the large number of different enzymes required...

  11. Characterising Complex Enzyme Reaction Data.

    Directory of Open Access Journals (Sweden)

    Handan Melike Dönertaş

    Full Text Available The relationship between enzyme-catalysed reactions and the Enzyme Commission (EC number, the widely accepted classification scheme used to characterise enzyme activity, is complex and with the rapid increase in our knowledge of the reactions catalysed by enzymes needs revisiting. We present a manual and computational analysis to investigate this complexity and found that almost one-third of all known EC numbers are linked to more than one reaction in the secondary reaction databases (e.g., KEGG. Although this complexity is often resolved by defining generic, alternative and partial reactions, we have also found individual EC numbers with more than one reaction catalysing different types of bond changes. This analysis adds a new dimension to our understanding of enzyme function and might be useful for the accurate annotation of the function of enzymes and to study the changes in enzyme function during evolution.

  12. Rejecting escape events in large volume Ge detectors by a pulse shape selection procedure

    International Nuclear Information System (INIS)

    Del Zoppo, A.; Agodi, C.; Alba, R.; Bellia, G.; Coniglione, R.; Loukachine, K.; Maiolino, C.; Migneco, E.; Piattelli, P.; Santonocito, D.; Sapienza, P.

    1993-01-01

    The dependence of the response to γ-rays of a large volume Ge detector on the interval width of a selected initial rise pulse slope is investigated. The number of escape events associated with a small pulse slope is found to be greater than the corresponding number of full energy events. An escape event rejection procedure based on the observed correlation between energy deposition and pulse shape is discussed. Such a procedure seems particularly suited for the design of highly granular large volume Ge detector arrays. (orig.)

  13. Four-channel ZnS scintillator measurements of escaping tritons in TFTR

    International Nuclear Information System (INIS)

    Zweben, S.J.

    1988-10-01

    A four-channel scintillation detector capable of measuring tritons, protons, and alphas escaping from a tokamak plasma was operated during the 1986 run period of the Tokamak Fusion Test Reactor (TFTR). Signals consistent with the expected 1 MeV triton behavior have been observed during deuterium operation. Backgrounds associated with neutrons, gammas, and soft x-rays have been evaluated in situ. Such a detector should be capable of measuring escaping alphas during the D/T phase of TFTR. 16 refs., 10 figs

  14. Tumor suppressor genes that escape from X-inactivation contribute to cancer sex bias

    OpenAIRE

    Dunford, Andrew; Weinstock, David M.; Savova, Virginia; Schumacher, Steven E.; Cleary, John P.; Yoda, Akinori; Sullivan, Timothy J.; Hess, Julian M.; Gimelbrant, Alexander A.; Beroukhim, Rameen; Lawrence, Michael S.; Getz, Gad; Lane, Andrew A.

    2016-01-01

    There is a striking and unexplained male predominance across many cancer types. A subset of X chromosome (chrX) genes can escape X-inactivation, which would protect females from complete functional loss by a single mutation. To identify putative “Escape from X-Inactivation Tumor Suppressor” (EXITS) genes, we compared somatic alterations from >4100 cancers across 21 tumor types for sex bias. Six of 783 non-pseudoautosomal region (PAR) chrX genes (ATRX, CNKSR2, DDX3X, KDM5C, KDM6A, and MAGEC3) ...

  15. Four-channel ZnS scintillator measurements of escaping tritons in TFTR

    Energy Technology Data Exchange (ETDEWEB)

    Zweben, S.J.

    1988-10-01

    A four-channel scintillation detector capable of measuring tritons, protons, and alphas escaping from a tokamak plasma was operated during the 1986 run period of the Tokamak Fusion Test Reactor (TFTR). Signals consistent with the expected 1 MeV triton behavior have been observed during deuterium operation. Backgrounds associated with neutrons, gammas, and soft x-rays have been evaluated in situ. Such a detector should be capable of measuring escaping alphas during the D/T phase of TFTR. 16 refs., 10 figs.

  16. Sound attenuation and preferred music in the treatment of problem behavior maintained by escape from noise.

    Science.gov (United States)

    Kettering, Tracy L; Fisher, Wayne W; Kelley, Michael E; LaRue, Robert H

    2018-06-06

    We examined the extent to which different sounds functioned as motivating operations (MO) that evoked problem behavior during a functional analysis for two participants. Results suggested that escape from loud noises reinforced the problem behavior for one participant and escape from arguing reinforced problem behavior for the other participant. Noncontingent delivery of preferred music through sound-attenuating headphones decreased problem behavior without the use of extinction for both participants. We discuss the results in terms of the abolishing effects of the intervention. © 2018 Society for the Experimental Analysis of Behavior.

  17. Measuring the Enzyme Activity of Arabidopsis Deubiquitylating Enzymes.

    Science.gov (United States)

    Kalinowska, Kamila; Nagel, Marie-Kristin; Isono, Erika

    2016-01-01

    Deubiquitylating enzymes, or DUBs, are important regulators of ubiquitin homeostasis and substrate stability, though the molecular mechanisms of most of the DUBs in plants are not yet understood. As different ubiquitin chain types are implicated in different biological pathways, it is important to analyze the enzyme characteristic for studying a DUB. Quantitative analysis of DUB activity is also important to determine enzyme kinetics and the influence of DUB binding proteins on the enzyme activity. Here, we show methods to analyze DUB activity using immunodetection, Coomassie Brilliant Blue staining, and fluorescence measurement that can be useful for understanding the basic characteristic of DUBs.

  18. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ganusov, Vitaly V [Los Alamos National Laboratory; Korber, Bette M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

  19. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

    International Nuclear Information System (INIS)

    Kampa, Marilena; Boskou, Dimitrios; Gravanis, Achille; Castanas, Elias; Alexaki, Vassilia-Ismini; Notas, George; Nifli, Artemissia-Phoebe; Nistikaki, Anastassia; Hatzoglou, Anastassia; Bakogeorgou, Efstathia; Kouimtzoglou, Elena; Blekas, George

    2004-01-01

    The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production). The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system. Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action

  20. Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by reduction of iPLA{sub 2} activity

    Energy Technology Data Exchange (ETDEWEB)

    Takatani-Nakase, Tomoka, E-mail: nakase@mukogawa-u.ac.jp; Takahashi, Koichi, E-mail: koichi@mukogawa-u.ac.jp

    2015-07-17

    Caspase-independent, non-apoptotic cell death is an important therapeutic target in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit cytoprotective effects on the ischemic heart, but the mechanisms are poorly understood. In this research, we found that pretreatment of leptin strongly suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on cardiomyocytes. Leptin was also shown to significantly inhibit the activity of iPLA{sub 2}, which is considered to play crucial roles in non-apoptotic cell death, resulting in effective prevention of ischemia-induced myocyte death. These findings provide the first evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death. - Highlights: • Myocardial ischemia-model induces in caspase-independent, non-apoptotic cell death. • Leptin strongly inhibits ischemic-augmented non-apoptotic cell death. • Leptin reduces iPLA{sub 2} activity, leading to avoidance of non-apoptotic cell death.

  1. Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by reduction of iPLA2 activity

    International Nuclear Information System (INIS)

    Takatani-Nakase, Tomoka; Takahashi, Koichi

    2015-01-01

    Caspase-independent, non-apoptotic cell death is an important therapeutic target in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit cytoprotective effects on the ischemic heart, but the mechanisms are poorly understood. In this research, we found that pretreatment of leptin strongly suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on cardiomyocytes. Leptin was also shown to significantly inhibit the activity of iPLA 2 , which is considered to play crucial roles in non-apoptotic cell death, resulting in effective prevention of ischemia-induced myocyte death. These findings provide the first evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death. - Highlights: • Myocardial ischemia-model induces in caspase-independent, non-apoptotic cell death. • Leptin strongly inhibits ischemic-augmented non-apoptotic cell death. • Leptin reduces iPLA 2 activity, leading to avoidance of non-apoptotic cell death

  2. Enzyme Molecules in Solitary Confinement

    Directory of Open Access Journals (Sweden)

    Raphaela B. Liebherr

    2014-09-01

    Full Text Available Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  3. DGAT enzymes and triacylglycerol biosynthesis

    Science.gov (United States)

    Yen, Chi-Liang Eric; Stone, Scot J.; Koliwad, Suneil; Harris, Charles; Farese, Robert V.

    2008-01-01

    Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, and the use of molecular tools, including mice deficient in either enzyme, has shed light on their functions. Although DGAT enzymes are involved in TG synthesis, they have distinct protein sequences and differ in their biochemical, cellular, and physiological functions. Both enzymes may be useful as therapeutic targets for diseases. Here we review the current knowledge of DGAT enzymes, focusing on new advances since the cloning of their genes, including possible roles in human health and diseases. PMID:18757836

  4. Enzyme stabilization for pesticide degradation

    Energy Technology Data Exchange (ETDEWEB)

    Rivers, D.B.; Frazer, F.R. III; Mason, D.W.; Tice, T.R.

    1988-01-01

    Enzymes offer inherent advantages and limitations as active components of formulations used to decontaminate soil and equipment contaminated with toxic materials such as pesticides. Because of the catalytic nature of enzymes, each molecule of enzyme has the potential to destroy countless molecules of a contaminating toxic compound. This degradation takes place under mild environmental conditions of pH, temperature, pressure, and solvent. The basic limitation of enzymes is their degree of stability during storage and application conditions. Stabilizing methods such as the use of additives, covalent crosslinking, covalent attachment, gel entrapment, and microencapsulation have been directed developing an enzyme preparation that is stable under extremes of pH, temperature, and exposure to organic solvents. Initial studies were conducted using the model enzymes subtilisin and horseradish peroxidase.

  5. Application of escape probability to line transfer in laser-produced plasmas

    International Nuclear Information System (INIS)

    Lee, Y.T.; London, R.A.; Zimmerman, G.B.; Haglestein, P.L.

    1989-01-01

    In this paper the authors apply the escape probability method to treat transfer of optically thick lines in laser-produced plasmas in plan-parallel geometry. They investigate the effect of self-absorption on the ionization balance and ion level populations. In addition, they calculate such effect on the laser gains in an exploding foil target heated by an optical laser. Due to the large ion streaming motion in laser-produced plasmas, absorption of an emitted photon occurs only over the length in which the Doppler shift is equal to the line width. They find that the escape probability calculated with the Doppler shift is larger compared to the escape probability for a static plasma. Therefore, the ion streaming motion contributes significantly to the line transfer process in laser-produced plasmas. As examples, they have applied escape probability to calculate transfer of optically thick lines in both ablating slab and exploding foil targets under irradiation of a high-power optical laser

  6. Retrieval of a leaflet escaped in a Tri-technologies bileaflet mechanical prosthetic valve.

    Science.gov (United States)

    Cianciulli, Tomás F; Lax, Jorge A; Saccheri, María C; Guidoin, Robert; Salvado, César M; Fernández, Adrián J; Prezioso, Horacio A

    2008-01-01

    The escape of the prosthetic heart valve disc is one of the causes of prosthetic dysfunction that requires emergency surgery. The removal of the embolized disc should be carried out because of the risk of a progressive extrusion on the aortic wall. Several imaging techniques can be used for the detection of the missing disc localization. In this report we describe a 32-year-old man who underwent mitral valve replacement with a Tri-technologies bileaflet valve three years ago, and was admitted in cardiogenic shock. Transesophageal echocardiography showed acute-onset massive mitral regurgitation. The patient underwent emergency replacement of the prosthetic valve. Only one of the two leaflets remained in the removed prosthetic valve. The missing leaflet could not be found within the cardiac cavity. The abdominal fluoroscopic study and plain radiography were unable to detect the escaped leaflet. The abdominal computed tomography scan and the ultrasound showed the escaped leaflet in the terminal portion of the aortic bifurcation. To retrieve the embolized disc laparotomy and aortotomy were performed three months later. The escaped leaflet shows a fracture of one of the pivot systems caused by structural failure. This kind of failure mode is usually the result of high stress concentration.

  7. Extended exposure to elevated temperature affects escape response behaviour in coral reef fishes

    Directory of Open Access Journals (Sweden)

    Donald T. Warren

    2017-08-01

    Full Text Available The threat of predation, and the prey’s response, are important drivers of community dynamics. Yet environmental temperature can have a significant effect on predation avoidance techniques such as fast-start performance observed in marine fishes. While it is known that temperature increases can influence performance and behaviour in the short-term, little is known about how species respond to extended exposure during development. We produced a startle response in two species of damselfish, the lemon damsel Pomacentrus moluccensis, and the Ambon damselfish Pomacentrus amboinensis, by the repeated use of a drop stimulus. We show that the length of thermal exposure of juveniles to elevated temperature significantly affects this escape responses. Short-term (4d exposure to warmer temperature affected directionality and responsiveness for both species. After long-term (90d exposure, only P. moluccensis showed beneficial plasticity, with directionality returning to control levels. Responsiveness also decreased in both species, possibly to compensate for higher temperatures. There was no effect of temperature or length of exposure on latency to react, maximum swimming speed, or escape distance suggesting that the physical ability to escape was maintained. Evidence suggests that elevated temperature may impact some fish species through its effect on the behavioural responses while under threat rather than having a direct influence on their physical ability to perform an effective escape response.

  8. On the escape transition of a tethered Gaussian chain; exact results in two conjugate ensembles

    NARCIS (Netherlands)

    Skvortsov, A.M.; Klushin, L.I.; Leermakers, F.A.M.

    2006-01-01

    Upon compression between two pistons an end-tethered polymer chain undergoes an abrupt transition from a confined coil state to an inhomogeneous flower-like conformation that is partially escaped from the gap. In the thermodynamic limit the system demonstrates a first-order phase transition. A

  9. Self-consciousness and binge eating in college women : an escape from rumination?

    NARCIS (Netherlands)

    Dalley, Simon; Donofrio, Stacey

    2014-01-01

    Background: Binge-eating is a highly distressing symptom that has been found to co-occur with other symptoms of eating disorders such as bulimia nervosa. One perspective of binge eating is that it is an attempt to escape high levels of aversive self-consciousness. A primary aim of this study is to

  10. Race as/and the Trace of the Ghost: Jurisprudential Escapism ...

    African Journals Online (AJOL)

    Secondly, how the escape from those legal texts evinces, or perhaps even facilitated, a certain evasion of, or anxiety towards the horizontal application of the Bill of Rights which explicitly proscribes overt (racial) discrimination by private non-state actors. And thirdly, how by following a formalist legal approach, one in which ...

  11. A trouser bag experiment that quantify by-catch species escaping ...

    African Journals Online (AJOL)

    Sea fishing trials were conducted to quantify by-catch species escaping from a modified shrimp trawl codend and retained in a trouser bag. Modification was by inserting a rectangular aluminum frame excluder device with bar spacing of 20mm at the anterior bunt. Thirty replicate landings showed that; Drepane africana have ...

  12. Educational Gaming for Pharmacy Students - Design and Evaluation of a Diabetes-themed Escape Room.

    Science.gov (United States)

    Eukel, Heidi N; Frenzel, Jeanne E; Cernusca, Dan

    2017-09-01

    Objective. To design an educational game that will increase third-year professional pharmacy students' knowledge of diabetes mellitus disease management and to evaluate their perceived value of the game. Methods. Faculty members created an innovative educational game, the diabetes escape room. An authentic escape room gaming environment was established through the use of a locked room, an escape time limit, and game rules within which student teams completed complex puzzles focused on diabetes disease management. To evaluate the impact, students completed a pre-test and post-test to measure the knowledge they've gained and a perception survey to identify moderating factors that could help instructors improve the game's effectiveness and utility. Results. Students showed statistically significant increases in knowledge after completion of the game. A one-sample t -test indicated that students' mean perception was statistically significantly higher than the mean value of the evaluation scale. This statically significant result proved that this gaming act offers a potential instructional benefit beyond its novelty. Conclusion. The diabetes escape room proved to be a valuable educational game that increased students' knowledge of diabetes mellitus disease management and showed a positive perceived overall value by student participants.

  13. Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

    International Nuclear Information System (INIS)

    Rudneva, Irina A.; Timofeeva, Tatiana A.; Ignatieva, Anna V.; Shilov, Aleksandr A.; Krylov, Petr S.; Ilyushina, Natalia A.; Kaverin, Nikolai V.

    2013-01-01

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropic effects

  14. The upstream escape of energized solar wind protons from the bow shock

    International Nuclear Information System (INIS)

    Greenstadt, E.W.

    1975-01-01

    Recently, there have been some systematic observations of backstreaming protons at the Earth's bow shock with parallel velocity components and total energies much too high to be associated with the usual long-period upstream waves or to be produced by Sonnerup's simple reflection process (Lin et al., 1974), and these protons (30-100keV) were attributed to some unknown acceleration mechanism in the upstream region. The observations of Lof et al. involved protons in high pitch angle, and, although their reasons for favoring an upstream acceleration were quite different, it may seem intuitive that high pitch angle particles would have difficulty escaping the shock, especially at large field-normal angles. Such an inference would superficially support the notion of energization outside the bow shock. It seems worthwhile therefore to examine the extent to which the geometry of individual particle motion alone might select among reflected particles those that can escape upstream and those that cannot. In this paper the geometry of escape is described and some simple numerical examples are worked out for a few special cases. It is found that protons with rather high energies and pitch angles can escape the shock at only marginally quasi-parallel field orientations (i.e., thetasub(nB) approximately 50 0 ), even if they have quite moderate speeds parallel to B. (Auth.)

  15. Measurement of p-odd asymmetry of fragment escape in ternary fission of plutonium 239

    International Nuclear Information System (INIS)

    Belozerov, A.V.; Vodennikov, B.D.; Danilyan, G.V.; Korobkina, E.I.; Pavlov, V.S.; Pevchev, Yu.F.; Sadchikov, A.G.

    1988-01-01

    Values of effects of parity nonconservation in binary and ternary fission of plutonium 239 by polarized thermal neutrons were measured simultaneously. The ratio of asymmetry coefficient (AC) of ternary fission to the AC of binary fission was equal to 0.67+-0.20. The obtained result testifies to insignificant disagreement of AC of fragment escape in studied fission types

  16. A New Window into Escaping Exoplanet Atmospheres: 10830 Å Line of Helium

    Science.gov (United States)

    Oklopčić, Antonija; Hirata, Christopher M.

    2018-03-01

    Observational evidence for escaping exoplanet atmospheres has been obtained for a few exoplanets to date. It comes from strong transit signals detected in the ultraviolet, most notably in the wings of the hydrogen Lyα (Lyα) line. However, the core of the Lyα line is often heavily affected by interstellar absorption and geocoronal emission, limiting the information about the atmosphere that can be extracted from that part of the spectrum. Transit observations in atomic lines that are (a) sensitive enough to trace the rarefied gas in the planetary wind and (b) do not suffer from significant extinction by the interstellar medium could enable more detailed observations, and thus provide better constraints on theoretical models of escaping atmospheres. The absorption line of a metastable state of helium at 10830 Å could satisfy both of these conditions for some exoplanets. We develop a simple 1D model of escaping planetary atmospheres containing hydrogen and helium. We use it to calculate the density profile of helium in the 23S metastable excited state and the expected in-transit absorption at 10830 Å for two exoplanets known to have escaping atmospheres. Our results indicate that exoplanets similar to GJ 436b and HD 209458b should exhibit enhanced transit depths at 10830 Å, with ∼8% and ∼2% excess absorption in the line core, respectively.

  17. Enhanced escape rate for Hg 254 nm resonance radiation in fluorescent lamps

    International Nuclear Information System (INIS)

    Lawler, James E; Raizen, Mark G

    2013-01-01

    The potential of the low-cost MAGIS isotopic separation method to improve fluorescent lamp efficacy is explored using resonance radiation transport simulations. New Hg isotopic mixes are discovered that yield escape rates for 254 nm Hg I resonance radiation equal to 117% to 122% of the rate for a natural isotopic mix under the same lamp conditions. (paper)

  18. Identification of a Peptide-Pheromone that Enhances Listeria monocytogenes Escape from Host Cell Vacuoles

    Science.gov (United States)

    Xayarath, Bobbi; Alonzo, Francis; Freitag, Nancy E.

    2015-01-01

    Listeria monocytogenes is a Gram-positive facultative intracellular bacterial pathogen that invades mammalian cells and escapes from membrane-bound vacuoles to replicate within the host cell cytosol. Gene products required for intracellular bacterial growth and bacterial spread to adjacent cells are regulated by a transcriptional activator known as PrfA. PrfA becomes activated following L. monocytogenes entry into host cells, however the signal that stimulates PrfA activation has not yet been defined. Here we provide evidence for L. monocytogenes secretion of a small peptide pheromone, pPplA, which enhances the escape of L. monocytogenes from host cell vacuoles and may facilitate PrfA activation. The pPplA pheromone is generated via the proteolytic processing of the PplA lipoprotein secretion signal peptide. While the PplA lipoprotein is dispensable for pathogenesis, bacteria lacking the pPplA pheromone are significantly attenuated for virulence in mice and have a reduced efficiency of bacterial escape from the vacuoles of nonprofessional phagocytic cells. Mutational activation of PrfA restores virulence and eliminates the need for pPplA-dependent signaling. Experimental evidence suggests that the pPplA peptide may help signal to L. monocytogenes its presence within the confines of the host cell vacuole, stimulating the expression of gene products that contribute to vacuole escape and facilitating PrfA activation to promote bacterial growth within the cytosol. PMID:25822753

  19. Increased metabolic turnover rate and transcapillary escape rate of albumin in long-term juvenile diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, N; Sander, E

    1975-01-01

    The metabolic turnover rate and transcapillary escape rate of albumin were studied with 131I-labelled human albumin in nine patients with long-term diabetes mellitus. Retinopathy was present in all patients and nephropathy in four. Plasma albumin concentration and plasma volume were reduced (P...

  20. 50 CFR Figure 12 to Part 223 - Escape Opening & Cover Dimensions for 71-inch TED

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Escape Opening & Cover Dimensions for 71-inch TED 12 Figure 12 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 12 Figure 12 to...

  1. 50 CFR Figure 13 to Part 223 - Single Grid Hard TED Escape Opening

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Single Grid Hard TED Escape Opening 13 Figure 13 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 13 Figure 13 to Part 223—Singl...

  2. X-ray escape effects in Si, Ge, and NaI detectors

    International Nuclear Information System (INIS)

    Brunner, G.

    1989-01-01

    A 3-parameter representation of the type x = K 1 [1 -L(ln(1 + 1/L))] together with L = K 2 E K 3 is recommended for the escape to parent peak ratio. Parameter values are provided for Si, Ge, and NaI detectors. Scattering, which has been neglected up to now, is included. (author)

  3. Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

    Energy Technology Data Exchange (ETDEWEB)

    Rudneva, Irina A.; Timofeeva, Tatiana A.; Ignatieva, Anna V.; Shilov, Aleksandr A.; Krylov, Petr S. [D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation); Ilyushina, Natalia A., E-mail: Natalia.Ilyushina@fda.hhs.gov [FDA CDER, 29 Lincoln Drive, Bethesda, MD 20892 (United States); Kaverin, Nikolai V., E-mail: nik.kaverin@gmail.com [D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation)

    2013-12-15

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropic effects.

  4. Workshop on agricultural and agro-industrial residue utilization in the ESCAP region

    Energy Technology Data Exchange (ETDEWEB)

    Vimal, O P

    1980-02-01

    A summary of the workshop held at Pattaya, Thailand is given at which the present status of both technological and non-technical aspects of utilization of agricultural and industrial residues in the ESCAP region are reviewed. A course of action was recommended whereby national programmes could develop and international assistance be focussed through follow up activities.

  5. Genetic evidence of hybridization between Onothera wolfii (Wolf's evening primrose) and O. glaziovana, a garden escape

    Science.gov (United States)

    Jennifer DeWoody; Leonel Arguello; David Imper; Robert D. Westfall; Valerie D. Hipkins

    2008-01-01

    Isozyme analysis of the rare Oenothera wolfii (Wolf's evening primrose) and the garden escape, O. glazioviana, indicates that hybridization between these species may be more widespread than morphological evidence indicates. Although both species contained low amounts of genetic variation, unique alleles were identified in...

  6. GAMMA-RAY EMISSION OF ACCELERATED PARTICLES ESCAPING A SUPERNOVA REMNANT IN A MOLECULAR CLOUD

    International Nuclear Information System (INIS)

    Ellison, Donald C.; Bykov, Andrei M.

    2011-01-01

    We present a model of gamma-ray emission from core-collapse supernovae (SNe) originating from the explosions of massive young stars. The fast forward shock of the supernova remnant (SNR) can accelerate particles by diffusive shock acceleration (DSA) in a cavern blown by a strong, pre-SN stellar wind. As a fundamental part of nonlinear DSA, some fraction of the accelerated particles escape the shock and interact with a surrounding massive dense shell producing hard photon emission. To calculate this emission, we have developed a new Monte Carlo technique for propagating the cosmic rays (CRs) produced by the forward shock of the SNR, into the dense, external material. This technique is incorporated in a hydrodynamic model of an evolving SNR which includes the nonlinear feedback of CRs on the SNR evolution, the production of escaping CRs along with those that remain trapped within the remnant, and the broadband emission of radiation from trapped and escaping CRs. While our combined CR-hydro-escape model is quite general and applies to both core collapse and thermonuclear SNe, the parameters we choose for our discussion here are more typical of SNRs from very massive stars whose emission spectra differ somewhat from those produced by lower mass progenitors directly interacting with a molecular cloud.

  7. Theoretical UV absorption spectra of hydrodynamically escaping O2/CO2-rich exoplanetary atmospheres

    International Nuclear Information System (INIS)

    Gronoff, G.; Mertens, C. J.; Norman, R. B.; Maggiolo, R.; Wedlund, C. Simon; Bell, J.; Bernard, D.; Parkinson, C. J.; Vidal-Madjar, A.

    2014-01-01

    Characterizing Earth- and Venus-like exoplanets' atmospheres to determine if they are habitable and how they are evolving (e.g., equilibrium or strong erosion) is a challenge. For that endeavor, a key element is the retrieval of the exospheric temperature, which is a marker of some of the processes occurring in the lower layers and controls a large part of the atmospheric escape. We describe a method to determine the exospheric temperature of an O 2 - and/or CO 2 -rich transiting exoplanet, and we simulate the respective spectra of such a planet in hydrostatic equilibrium and hydrodynamic escape. The observation of hydrodynamically escaping atmospheres in young planets may help constrain and improve our understanding of the evolution of the solar system's terrestrial planets' atmospheres. We use the dependency of the absorption spectra of the O 2 and CO 2 molecules on the temperature to estimate the temperature independently of the total absorption of the planet. Combining two observables (two parts of the UV spectra that have a different temperature dependency) with the model, we are able to determine the thermospheric density profile and temperature. If the slope of the density profile is inconsistent with the temperature, then we infer the hydrodynamic escape. We address the question of the possible biases in the application of the method to future observations, and we show that the flare activity should be cautiously monitored to avoid large biases.

  8. DWARF GALAXIES WITH IONIZING RADIATION FEEDBACK. I. ESCAPE OF IONIZING PHOTONS

    International Nuclear Information System (INIS)

    Kim, Ji-hoon; Krumholz, Mark R.; Goldbaum, Nathan J.; Wise, John H.; Turk, Matthew J.; Abel, Tom

    2013-01-01

    We describe a new method for simulating ionizing radiation and supernova feedback in the analogs of low-redshift galactic disks. In this method, which we call star-forming molecular cloud (SFMC) particles, we use a ray-tracing technique to solve the radiative transfer equation for ultraviolet photons emitted by thousands of distinct particles on the fly. Joined with high numerical resolution of 3.8 pc, the realistic description of stellar feedback helps to self-regulate star formation. This new feedback scheme also enables us to study the escape of ionizing photons from star-forming clumps and from a galaxy, and to examine the evolving environment of star-forming gas clumps. By simulating a galactic disk in a halo of 2.3 × 10 11 M ☉ , we find that the average escape fraction from all radiating sources on the spiral arms (excluding the central 2.5 kpc) fluctuates between 0.08% and 5.9% during a ∼20 Myr period with a mean value of 1.1%. The flux of escaped photons from these sources is not strongly beamed, but manifests a large opening angle of more than 60° from the galactic pole. Further, we investigate the escape fraction per SFMC particle, f esc (i), and how it evolves as the particle ages. We discover that the average escape fraction f esc is dominated by a small number of SFMC particles with high f esc (i). On average, the escape fraction from an SFMC particle rises from 0.27% at its birth to 2.1% at the end of a particle lifetime, 6 Myr. This is because SFMC particles drift away from the dense gas clumps in which they were born, and because the gas around the star-forming clumps is dispersed by ionizing radiation and supernova feedback. The framework established in this study brings deeper insight into the physics of photon escape fraction from an individual star-forming clump and from a galactic disk

  9. Automated guidance algorithms for a space station-based crew escape vehicle.

    Science.gov (United States)

    Flanary, R; Hammen, D G; Ito, D; Rabalais, B W; Rishikof, B H; Siebold, K H

    2003-04-01

    An escape vehicle was designed to provide an emergency evacuation for crew members living on a space station. For maximum escape capability, the escape vehicle needs to have the ability to safely evacuate a station in a contingency scenario such as an uncontrolled (e.g., tumbling) station. This emergency escape sequence will typically be divided into three events: The first separation event (SEP1), the navigation reconstruction event, and the second separation event (SEP2). SEP1 is responsible for taking the spacecraft from its docking port to a distance greater than the maximum radius of the rotating station. The navigation reconstruction event takes place prior to the SEP2 event and establishes the orbital state to within the tolerance limits necessary for SEP2. The SEP2 event calculates and performs an avoidance burn to prevent station recontact during the next several orbits. This paper presents the tools and results for the whole separation sequence with an emphasis on the two separation events. The first challenge includes collision avoidance during the escape sequence while the station is in an uncontrolled rotational state, with rotation rates of up to 2 degrees per second. The task of avoiding a collision may require the use of the Vehicle's de-orbit propulsion system for maximum thrust and minimum dwell time within the vicinity of the station vicinity. The thrust of the propulsion system is in a single direction, and can be controlled only by the attitude of the spacecraft. Escape algorithms based on a look-up table or analytical guidance can be implemented since the rotation rate and the angular momentum vector can be sensed onboard and a-priori knowledge of the position and relative orientation are available. In addition, crew intervention has been provided for in the event of unforeseen obstacles in the escape path. The purpose of the SEP2 burn is to avoid re-contact with the station over an extended period of time. Performing this maneuver requires

  10. Estimating Collisionally-Induced Escape Rates of Light Neutrals from Early Mars

    Science.gov (United States)

    Gacesa, M.; Zahnle, K. J.

    2016-12-01

    Collisions of atmospheric gases with hot oxygen atoms constitute an important non-thermal mechanism of escape of light atomic and molecular species at Mars. In this study, we present revised theoretical estimates of non-thermal escape rates of neutral O, H, He, and H2 based on recent atmospheric density profiles obtained from the NASA Mars Atmosphere and Volatile Evolution (MAVEN) mission and related theoretical models. As primary sources of hot oxygen, we consider dissociative recombination of O2+ and CO2+ molecular ions. We also consider hot oxygen atoms energized in primary and secondary collisions with energetic neutral atoms (ENAs) produced in charge-exchange of solar wind H+ and He+ ions with atmospheric gases1,2. Scattering of hot oxygen and atmospheric species of interest is modeled using fully-quantum reactive scattering formalism3. This approach allows us to construct distributions of vibrationally and rotationally excited states and predict the products' emission spectra. In addition, we estimate formation rates of excited, translationally hot hydroxyl molecules in the upper atmosphere of Mars. The escape rates are calculated from the kinetic energy distributions of the reaction products using an enhanced 1D model of the atmosphere for a range of orbital and solar parameters. Finally, by considering different scenarios, we estimate the influence of these escape mechanisms on the evolution of Mars's atmosphere throughout previous epochs and their impact on the atmospheric D/H ratio. M.G.'s research was supported by an appointment to the NASA Postdoctoral Program at the NASA Ames Research Center, administered by Universities Space Research Association under contract with NASA. 1N. Lewkow and V. Kharchenko, "Precipitation of Energetic Neutral Atoms and Escape Fluxes induced from the Mars Atmosphere", Astroph. J., 790, 98 (2014) 2M. Gacesa, N. Lewkow, and V. Kharchenko, "Non-thermal production and escape of OH from the upper atmosphere of Mars", arXiv:1607

  11. Direct comparison of enzyme histochemical and immunohistochemical methods to localize an enzyme

    NARCIS (Netherlands)

    van Noorden, Cornelis J. F.

    2002-01-01

    Immunohistochemical localization of enzymes is compared directly with localization of enzyme activity with (catalytic) enzyme histochemical methods. The two approaches demonstrate principally different aspects of an enzyme. The immunohistochemical method localizes the enzyme protein whether it is

  12. Huperzine A ameliorates damage induced by acute myocardial infarction in rats through antioxidant, anti-apoptotic and anti-inflammatory mechanisms.

    Science.gov (United States)

    Sui, Xizhong; Gao, Changqing

    2014-01-01

    Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats.

  13. Enzyme Mimics: Advances and Applications.

    Science.gov (United States)

    Kuah, Evelyn; Toh, Seraphina; Yee, Jessica; Ma, Qian; Gao, Zhiqiang

    2016-06-13

    Enzyme mimics or artificial enzymes are a class of catalysts that have been actively pursued for decades and have heralded much interest as potentially viable alternatives to natural enzymes. Aside from having catalytic activities similar to their natural counterparts, enzyme mimics have the desired advantages of tunable structures and catalytic efficiencies, excellent tolerance to experimental conditions, lower cost, and purely synthetic routes to their preparation. Although still in the midst of development, impressive advances have already been made. Enzyme mimics have shown immense potential in the catalysis of a wide range of chemical and biological reactions, the development of chemical and biological sensing and anti-biofouling systems, and the production of pharmaceuticals and clean fuels. This Review concerns the development of various types of enzyme mimics, namely polymeric and dendrimeric, supramolecular, nanoparticulate and proteinic enzyme mimics, with an emphasis on their synthesis, catalytic properties and technical applications. It provides an introduction to enzyme mimics and a comprehensive summary of the advances and current standings of their applications, and seeks to inspire researchers to perfect the design and synthesis of enzyme mimics and to tailor their functionality for a much wider range of applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Phage lytic enzymes: a history.

    Science.gov (United States)

    Trudil, David

    2015-02-01

    There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of 'bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well (Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specific disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay (Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes-from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

  15. Escape of HIV-1-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk--a pivotal role of HMGB1.

    Directory of Open Access Journals (Sweden)

    Marie-Thérèse Melki

    2010-04-01

    Full Text Available Early stages of Human Immunodeficiency Virus-1 (HIV-1 infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK cells and dendritic cells (DCs. Immature DCs (iDCs capture HIV-1 through specific receptors and can disseminate the infection to lymphoid tissues following their migration, which is associated to a maturation process. This process is dependent on NK cells, whose role is to keep in check the quality and the quantity of DCs undergoing maturation. If DC maturation is inappropriate, NK cells will kill them ("editing process" at sites of tissue inflammation, thus optimizing the adaptive immunity. In the context of a viral infection, NK-dependent killing of infected-DCs is a crucial event required for early elimination of infected target cells. Here, we report that NK-mediated editing of iDCs is impaired if DCs are infected with HIV-1. We first addressed the question of the mechanisms involved in iDC editing, and we show that cognate NK-iDC interaction triggers apoptosis via the TNF-related apoptosis-inducing ligand (TRAIL-Death Receptor 4 (DR4 pathway and not via the perforin pathway. Nevertheless, once infected with HIV-1, DC(HIV become resistant to NK-induced TRAIL-mediated apoptosis. This resistance occurs despite normal amounts of TRAIL released by NK cells and comparable DR4 expression on DC(HIV. The escape of DC(HIV from NK killing is due to the upregulation of two anti-apoptotic molecules, the cellular-Flice like inhibitory protein (c-FLIP and the cellular inhibitor of apoptosis 2 (c-IAP2, induced by NK-DC(HIV cognate interaction. High-mobility group box 1 (HMGB1, an alarmin and a key mediator of NK-DC cross-talk, was found to play a pivotal role in NK-dependent upregulation of c-FLIP and c-IAP2 in DC(HIV. Finally, we demonstrate that restoration of DC(HIV susceptibility to NK-induced TRAIL killing can be obtained either by silencing c-FLIP and c-IAP2 by specific

  16. [The rise of enzyme engineering in China].

    Science.gov (United States)

    Li, Gaoxiang

    2015-06-01

    Enzyme engineering is an important part of the modern biotechnology. Industrial biocatalysis is considered the third wave of biotechnology following pharmaceutical and agricultural waves. In 25 years, China has made a mighty advances in enzyme engineering research. This review focuses on enzyme genomics, enzyme proteomics, biosynthesis, microbial conversion and biosensors in the Chinese enzyme engineering symposiums and advances in enzyme preparation industry in China.

  17. Evaluation of K x-ray escape and crosstalk in CdTe detectors and multi-channel detectors

    International Nuclear Information System (INIS)

    Ohtsuchi, Tetsuro; Ohmori, Koichi; Tsutsui, Hiroshi; Baba, Sueki

    1995-01-01

    The simple structure of CdTe semiconductor detectors facilitates their downsizing, and their possible application to radiographic sensors has been studied. The escape of K X-rays from these detectors increases with reduction of their dimensions and affects the measurements of X- and gamma-ray spectra. K X-rays also produce crosstalk in multi-channel detectors with adjacent channels. Therefore, K X-rays which escape from the detector elements degrade both the precision of energy spectra and spatial resolution. The ratios of escape peak integrated counts to total photon counts for various sizes of CdTe single detectors were calculated for gamma rays using the Monte Carlo method. Also, escape and crosstalk ratios were simulated for the CdTe multi-channel detectors. The theoretical results were tested experimentally for 59.54-keV gamma rays from a 241 Am radioactive source. Results showed that escape ratios for single detectors were strongly dependent on element size and thickness. The escape and crosstalk ratios increased with closer channel pitch. The calculated results showed a good agreement with the experimental data. The calculations made it clear that K X-rays which escaped to neighboring channels induced crosstalk more frequently at smaller channel pitch in multichannel detectors. A radiation shielding grid which blocked incident photons between the boundary channels was also tested by experiment and by calculation. It was effective in reducing the probability of escape and crosstalk

  18. Escapism among players of MMORPGs--conceptual clarification, its relation to mental health factors, and development of a new measure.

    Science.gov (United States)

    Hagström, David; Kaldo, Viktor

    2014-01-01

    Previous studies show that the concept of escapism needs to be clarified and that its relation to problematic online gaming and other factors needs further examination. This study uses well-established, basic learning theory to clarify the concept of escapism, and examines its relation to problematic gaming, psychological distress, and satisfaction with life among players of massively multiplayer online role-playing games (MMORPGs). MMORPG players (n=201) answered an online questionnaire where these factors were measured and correlated with a previously developed scale on motivation to play (MTPI), including extra items to cover positive and negative aspects of escapism. Factor analysis and construct validation show that positive aspects of escapism are theoretically and empirically unstable and that escapism is best clarified as purely "negative escapism," corresponding to playing being negatively reinforced as a way of avoiding everyday hassles and distress. Negative escapism had a stronger relationship to symptoms of Internet addiction, psychological distress, and life satisfaction than other variables and other more positive motivations to play. Future studies should use the revised subscale for escapism (in the MTPI-R) presented in the present study, for example when screening for Internet addiction.

  19. Centering Single Cells in Microgels via Delayed Crosslinking Supports Long-Term 3D Culture by Preventing Cell Escape

    NARCIS (Netherlands)

    Kamperman, Tom; Henke, Sieger; Visser, Claas Willem; Karperien, Marcel; Leijten, Jeroen

    2017-01-01

    Single-cell-laden microgels support physiological 3D culture conditions while enabling straightforward handling and high-resolution readouts of individual cells. However, their widespread adoption for long-term cultures is limited by cell escape. In this work, it is demonstrated that cell escape is

  20. Data from: Escaping blood-fed malaria mosquitoes minimize tactile detection without compromising on take-off speed

    NARCIS (Netherlands)

    Muijres, F.T.; Chang, S.W.; Veen, van W.G.; Spitzen, J.; Biemans, Bart; Koehl, M.A.R.; Dudley, R.

    2017-01-01

    To escape after taking a blood meal, a mosquito must exert forces sufficiently high to take off when carrying a load roughly equal to its body weight, while simultaneously avoiding detection by minimizing tactile signals exerted on the host's skin. We studied this trade-off between escape speed and

  1. Comparing Effective Treatments for Attention-Maintained and Escape- Maintained Behaviors in Children with Behavior Disorders: Brief Review and Analysis

    OpenAIRE

    Lauren Worcester; T. F. McLaughlin

    2013-01-01

    This literature review compares treatment for attention-maintainedversus escape maintained aberrant behavior in children with behavior disorders. Specifically, studies utilizing time out procedures, differential reinforcement procedures, noncontingent reinforcement, and functional communication training are discussed. It was found that these are effective treatments for attention-maintained behaviors; while escape extinction, positive and negative reinforcement, functional communication trai...

  2. Variation of NO2 and NOx concentrations between and within 36 European study areas: Results from the ESCAPE study

    NARCIS (Netherlands)

    Cyrys, J.; Eeftens, M.R.|info:eu-repo/dai/nl/315028300; Heinrich, J.; Ampe, C.; Armengaud, A.; Beelen, R.; Bellander, T.; Beregszaszi, T.; Birk, M.; Cesaroni, G.; Cirach, M.; de Hoogh, K.; de Nazelle, A.; de Vocht, F.; Declercq, C.; Dėdelė, A.; Dimakopoulou, K.; Eriksen, K.; Galassi, C.; Grąulevičienė, R.; Grivas, G.; Gruzieva, O.; Gustafsson, A.H.; Hoffmann, B.; Iakovides, M.; Ineichen, A.; Krämer, U.; Lanki, T.; Lozano, P.; Madsen, C.; Meliefste, K.; Modig, L.; Mölter, A.; Mosler, G.; Nieuwenhuijsen, M.; Nonnemacher, M.; Oldenwening, M.; Peters, A.; Pontet, S.; Probst-Hensch, N.; Quass, U.; Raaschou-Nielsen, O.; Ranzi, A.; Sugiri, D.; Stephanou, E.G.; Taimisto, P.; Tsai, M-Y.; Vaskövi, É.; Villani, S.; Wang, M.|info:eu-repo/dai/nl/345480279; Brunekreef, B.|info:eu-repo/dai/nl/067548180; Hoek, G.|info:eu-repo/dai/nl/069553475

    2012-01-01

    The ESCAPE study (European Study of Cohorts for Air Pollution Effects) investigates long-term effects of exposure to air pollution on human health in Europe. This paper documents the spatial variation of measured NO2 and NOx concentrations between and within 36 ESCAPE study areas across Europe. In

  3. Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells.

    Science.gov (United States)

    Ramakrishnan, P; Kahn, D A; Baltimore, D

    2011-04-01

    Thymocyte development is a tightly controlled multi-step process involving selective elimination of self-reactive and non-functional T cells by apoptosis. This developmental process depends on signaling by Notch, IL-7 and active glucose metabolism. In this study, we explored the requirement of glucose for thymocyte survival and found that in addition to metabolic regulation, glucose leads to the expression of anti-apoptotic genes. Under hyperglycemic conditions, both mouse and human thymocytes demonstrate enhanced survival. We show that glucose-induced anti-apoptotic genes are dependent on NF-κB p65 because high glucose is unable to attenuate normal ongoing apoptosis of thymocytes isolated from p65 knockout mice. Furthermore, we demonstrate that in vivo hyperglycemia decreases apoptosis of thymocytes allowing for survival of potentially self-reactive thymocytes. These results imply that hyperglycemic conditions could contribute to the development of autoimmunity through dysregulated thymic selection. © 2011 Macmillan Publishers Limited

  4. Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis.

    Science.gov (United States)

    Someya, Shinichi; Yamasoba, Tatsuya; Weindruch, Richard; Prolla, Tomas A; Tanokura, Masaru

    2007-10-01

    Presbycusis is characterized by an age-related progressive decline of auditory function, and arises mainly from the degeneration of hair cells or spiral ganglion (SG) cells in the cochlea. Here we show that caloric restriction suppresses apoptotic cell death in the mouse cochlea and prevents late onset of presbycusis. Calorie restricted (CR) mice, which maintained body weight at the same level as that of young control (YC) mice, retained normal hearing and showed no cochlear degeneration. CR mice also showed a significant reduction in the number of TUNEL-positive cells and cleaved caspase-3-positive cells relative to middle-age control (MC) mice. Microarray analysis revealed that CR down-regulated the expression of 24 apoptotic genes, including Bak and Bim. Taken together, our findings suggest that loss of critical cells through apoptosis is an important mechanism of presbycusis in mammals, and that CR can retard this process by suppressing apoptosis in the inner ear tissue.

  5. Cell-Centric View of Apoptosis and Apoptotic Cell Death-Inducing Antitumoral Strategies

    Directory of Open Access Journals (Sweden)

    Maria Dolores Boyano

    2011-03-01

    Full Text Available Programmed cell death and especially apoptotic cell death, occurs under physiological conditions and is also desirable under pathological circumstances. However, the more we learn about cellular signaling cascades, the less plausible it becomes to find restricted and well-limited signaling pathways. In this context, an extensive description of pathway-connections is necessary in order to point out the main regulatory molecules as well as to select the most appropriate therapeutic targets. On the other hand, irregularities in programmed cell death pathways often lead to tumor development and cancer-related mortality is projected to continue increasing despite the effort to develop more active and selective antitumoral compounds. In fact, tumor cell plasticity represents a major challenge in chemotherapy and improvement on anticancer therapies seems to rely on appropriate drug combinations. An overview of the current status regarding apoptotic pathways as well as available chemotherapeutic compounds provides a new perspective of possible future anticancer strategies.

  6. Proposed Pharmacological Countermeasures Against Apoptotic Cell Death in Experimental Models Mimicking Space Environment Damage

    Science.gov (United States)

    Lulli, Matteo; Papucci, Laura; Witort, Ewa; Donnini, Martino; Lapucci, Andrea; Lazzarano, Stefano; Mazzoni, Tiziano; Simoncini, Madine; Falciani, Piergiuseppe; Capaccioli, Sergio

    2008-06-01

    Several damaging agents have been suggested to affect human vision during long term space travels. Recently, apoptosis induced by DNA-damaging agents has emerged as frequent pathogenetic mechanism of ophthalmologic pathologies. Here, we propose two countermeasures: coenzyme Q10 and bcl-2 downregulation preventing antisense oligoribonucleotides (ORNs), aimed to inhibit cellular apoptotic death. Our studies have been carried out on retina and neuronal cultured cells treated with the following apoptotic stimuli mimicking space environment: a several-day exposure to either 3H-labeled tymidine or to the genotoxic drug doxorubicin, UV irradiation, hypoxia and glucose/growth factor starvation (Locke medium). The preliminary results clearly indicate that CoQ10, as well as bcl-2 down-regulation preventing ORNs, significantly counteract apoptosis in response to different DNA damaging agents in cultured eye and in neuronal cells. This supports the possibility that both could be optimal countermeasures against ophthalmologic lesions during space explorations.

  7. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States.

    Science.gov (United States)

    Brueggemann, Angela B; Pai, Rekha; Crook, Derrick W; Beall, Bernard

    2007-11-01

    The heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the United States (US) in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990), but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s) at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny), recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.

  8. Characterization of extra-solar planets and their atmospheres (Spectroscopy of transits and atmospheric escape)

    International Nuclear Information System (INIS)

    Bourrier, Vincent

    2014-01-01

    Hot Jupiters are exo-planets so close to their star that their atmosphere can lose gas because of hydrodynamic escape. Transiting gaseous giants are an excellent way to understand this mechanism, but it is necessary to study other types of planets to determine its impact on the exo-planetary population. This thesis aims at using transit spectroscopy to observe the atmosphere of several exo-planets, to study their properties and to contribute to the characterization of hydrodynamic escape. UV lines observed with the Hubble telescope are analyzed with the numerical model of upper atmospheres we developed. Using the Ly-α line we identify energetic and dynamical interactions between the atmospheres of the hot Jupiters HD209458b and HD189733b and their stars. We study the dependence of the escape on the environment of a planet and on its physical properties, through the observation of a super-Earth and a warm Jupiter in the 55 Cnc system. Using observations of HD209458b, we show that magnesium lines are a window on the region of formation of hydrodynamic escape. We study the potential of transit spectroscopy in the near-UV to detect new cases of atmospheric escape. This mechanism is fostered by the proximity of a planet to its star, which makes it even more important to understand the formation and migration processes that can be traced in the alignment of a planetary system. Using measures from the spectrographs HARPS-N and SOPHIE we study the alignments of 55 Cnc e and the Kepler candidate KOI 12.01, whose planetary nature we also seek to validate. (author)

  9. Acute Mitral Valve Dysfunction Due to Escape of Prosthetic Mechanical Leaflet and Peripheral Leaftlet Embolization.

    Science.gov (United States)

    Calik, Eyup Serhat; Limandal, Husnu Kamil; Arslan, Umit; Tort, Mehmet; Yildiz, Ziya; Bayram, Ednan; Dag, Ozgur; Kaygin, Mehmet Ali; Erkut, Bilgehan

    2015-12-14

    Leaflet escape of prosthetic valve is rare but potentially life threatening. Early diagnosis is essential on account of avoiding mortality, and emergency surgical correction is compulsory. This complication has previously been reported for both monoleaflet and bileaflet valve models. A 30-year-old man who had undergone mitral valve replacement with a bileaflet valve 8 years prior at another center was admitted with acute-onset with cardiogenic shock as an emergency case. Transthoracic echocardiograms showed acute-starting severe mitral regurgitation associated with prosthetic mitral valve. There was a suspicious finding of a single prosthetic mitral leaflet. But the problem related with the valve wasn't specifically determined. The patient underwent emergent surgery for replacement of the damaged prosthetic valves immediately. There was no tissue impingement and thrombosis, one of the two leaflets was absent, and there were no signs of endocarditis or pannus formation in the prosthetic valve. The missing leaflet could not be found within the cardiac cavity. The abdominal fluoroscopic study and plain radiography were unable to detect the escaped leaflet during surgery. The damaged valve was removed and a replacement 29 mm bileaflet mechanical valve was inserted by right lateral thoracotomy. After post-operative week one, the abdominal computed tomography scan and the ultrasound showed the escaped leaflet in the left femoral artery. Fifteen days after the surgery the escaped leaflet was removed safely from the left femoral artery and the patient made a complete recovery. The escaped leaflet showed a fracture of one of the pivot systems caused by structural failure. Early cardiac surgery should be applied because of life-threatening problems.

  10. A convergent and essential interneuron pathway for Mauthner-cell-mediated escapes.

    Science.gov (United States)

    Lacoste, Alix M B; Schoppik, David; Robson, Drew N; Haesemeyer, Martin; Portugues, Ruben; Li, Jennifer M; Randlett, Owen; Wee, Caroline L; Engert, Florian; Schier, Alexander F

    2015-06-01

    The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an additional, convergent pathway that is essential for the M-cell-mediated startle behavior in larval zebrafish. It is composed of excitatory interneurons called spiral fiber neurons, which project to the M-cell axon hillock. By in vivo calcium imaging, we found that spiral fiber neurons are active in response to aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral ablations of spiral fiber neurons largely eliminate short-latency escapes. Unilateral spiral fiber neuron ablations shift the directionality of escapes and indicate that spiral fiber neurons excite the M-cell in a lateralized manner. Their optogenetic activation increases the probability of short-latency escapes, supporting the notion that spiral fiber neurons help activate M-cell-mediated startle behavior. These results reveal that spiral fiber neurons are essential for the function of the M-cell in response to sensory cues and suggest that convergent excitatory inputs that differ in their input location and timing ensure reliable activation of the M-cell, a feedforward excitatory motif that may extend to other neural circuits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Space Weathering of Super-Earths: Model Simulations of Exospheric Sodium Escape from 61 Virgo b

    Energy Technology Data Exchange (ETDEWEB)

    Yoneda, M.; Berdyugina, S.; Kuhn, J. [Kiepenheuer Institute for Solar Physics, Schöneckstraße 6, 79104 Freiburg im Breisgau (Germany)

    2017-10-01

    Rocky exoplanets are expected to be eroded by space weather in a similar way as in the solar system. In particular, Mercury is one of the dramatically eroded planets whose material continuously escapes into its exosphere and further into space. This escape is well traced by sodium atoms scattering sunlight. Due to solar wind impact, micrometeorite impacts, photo-stimulated desorption and thermal desorption, sodium atoms are released from surface regolith. Some of these released sodium atoms are escaping from Mercury’s gravitational-sphere. They are dragged anti-Sun-ward and form a tail structure. We expect similar phenomena on exoplanets. The hot super-Earth 61 Vir b orbiting a G3V star at only 0.05 au may show a similar structure. Because of its small separation from the star, the sodium release mechanisms may be working more efficiently on hot super-Earths than on Mercury, although the strong gravitational force of Earth-sized or even more massive planets may be keeping sodium atoms from escaping from the planet. Here, we performed model simulations for Mercury (to verify our model) and 61 Vir b as a representative super-Earth. We have found that sodium atoms can escape from this exoplanet due to stellar wind sputtering and micrometeorite impacts, to form a sodium tail. However, in contrast to Mercury, the tail on this hot super-Earth is strongly aligned with the anti-starward direction because of higher light pressure. Our model suggests that 61 Vir b seems to have an exo-base atmosphere like that of Mercury.

  12. Space Weathering of Super-Earths: Model Simulations of Exospheric Sodium Escape from 61 Virgo b

    International Nuclear Information System (INIS)

    Yoneda, M.; Berdyugina, S.; Kuhn, J.

    2017-01-01

    Rocky exoplanets are expected to be eroded by space weather in a similar way as in the solar system. In particular, Mercury is one of the dramatically eroded planets whose material continuously escapes into its exosphere and further into space. This escape is well traced by sodium atoms scattering sunlight. Due to solar wind impact, micrometeorite impacts, photo-stimulated desorption and thermal desorption, sodium atoms are released from surface regolith. Some of these released sodium atoms are escaping from Mercury’s gravitational-sphere. They are dragged anti-Sun-ward and form a tail structure. We expect similar phenomena on exoplanets. The hot super-Earth 61 Vir b orbiting a G3V star at only 0.05 au may show a similar structure. Because of its small separation from the star, the sodium release mechanisms may be working more efficiently on hot super-Earths than on Mercury, although the strong gravitational force of Earth-sized or even more massive planets may be keeping sodium atoms from escaping from the planet. Here, we performed model simulations for Mercury (to verify our model) and 61 Vir b as a representative super-Earth. We have found that sodium atoms can escape from this exoplanet due to stellar wind sputtering and micrometeorite impacts, to form a sodium tail. However, in contrast to Mercury, the tail on this hot super-Earth is strongly aligned with the anti-starward direction because of higher light pressure. Our model suggests that 61 Vir b seems to have an exo-base atmosphere like that of Mercury.

  13. Enzyme structure, enzyme function and allozyme diversity in ...

    African Journals Online (AJOL)

    In estimates of population genetic diversity based on allozyme heterozygosity, some enzymes are regularly more variable than others. Evolutionary theory suggests that functionally less important molecules, or parts of molecules, evolve more rapidly than more important ones; the latter enzymes should then theoretically be ...

  14. Effects of Cigarette Smoke Condensate on Oxidative Stress, Apoptotic Cell Death, and HIV Replication in Human Monocytic Cells.

    Directory of Open Access Journals (Sweden)

    Pss Rao

    Full Text Available While cigarette smoking is prevalent amongst HIV-infected patients, the effects of cigarette smoke constituents in cells of myeloid lineage are poorly known. Recently, we have shown that nicotine induces oxidative stress through cytochrome P450 (CYP 2A6-mediated pathway in U937 monocytic cells. The present study was designed to examine the effect of cigarette smoke condensate (CSC, which contains majority of tobacco constituents, on oxidative stress, cytotoxicity, expression of CYP1A1, and/or HIV-1 replication in HIV-infected (U1 and uninfected U937 cells. The effects of CSC on induction of CYP1 enzymes in HIV-infected primary macrophages were also analyzed. The results showed that the CSC-mediated increase in production of reactive oxygen species (ROS in U937 cells is dose- and time-dependent. Moreover, CSC treatment was found to induce cytotoxicity in U937 cells through the apoptotic pathway via activation of caspase-3. Importantly, pretreatment with vitamin C blocked the CSC-mediated production of ROS and induction of caspase-3 activity. In U1 cells, acute treatment of CSC increased ROS production at 6H (>2-fold and both ROS (>2 fold and HIV-1 replication (>3-fold after chronic treatment. The CSC mediated effects were associated with robust induction in the expression of CYP1A1 mRNA upon acute CSC treatment of U937 and U1 cells (>20-fold, and upon chronic CSC treatment to U1 cells (>30-fold. In addition, the CYP1A1 induction in U937 cells was mediated through the aromatic hydrocarbon receptor pathway. Lastly, CSC, which is known to increase viral replication in primary macrophages, was also found to induce CYP1 enzymes in HIV-infected primary macrophages. While mRNA levels of both CYP1A1 and CYP1B1 were elevated following CSC treatment, only CYP1B1 protein levels were increased in HIV-infected primary macrophages. In conclusion, these results suggest a possible association between oxidative stress, CYP1 expression, and viral replication in

  15. Increased endothelial apoptotic cell density in human diabetic erectile tissue--comparison with clinical data.

    Science.gov (United States)

    Costa, Carla; Soares, Raquel; Castela, Angela; Adães, Sara; Hastert, Véronique; Vendeira, Pedro; Virag, Ronald

    2009-03-01

    Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). Establish an index of ACD and correlate those results with patient clinical data. Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.

  16. Apoptotic factors in physiological and pathological processes of teeth and periodontal tissues – literature review

    Directory of Open Access Journals (Sweden)

    Orzedala-Koszel Urszula

    2014-12-01

    Full Text Available Apoptosis is a physiological process that occurs in the human body throughout the entire life span. This process can be seen in the tissues of the stomatognathic system. A disorder in such programmed cell death processes leads to the development of pathological lesions. Among these are inflammation, osteolytic lesions and neoplastic hyperplasia. We put forward that future studies should concentrate on how to use the knowledge of apoptotic processes and their inhibitors in therapeutic processes involving the stomatognathic system.

  17. Reemergence of apoptotic cells between fractionated doses in irradiated murine tumors

    International Nuclear Information System (INIS)

    Meyn, R.E.; Hunter, N.R.; Milas, L.

    1994-01-01

    The purpose of this investigation was to follow up our previous studies on the development of apoptosis in irradiated murine tumors by testing whether an apoptotic subpopulation of cells reemerges between fractionated exposures. Mice bearing a murine ovarian carcinoma, OCa-I, were treated in vivo with two fractionation protocols: two doses of 12.5 Gy separated by various times out to 5 days and multiple daily fractions of 2.5 Gy. Animals were killed 4 h after the last dose in each protocol, and the percent apoptosis was scored from stained histological sections made from the irradiated tumors according to the specific features characteristic of this mode of cell death. The 12.5+12.5 Gy protocol yielded a net total percent apoptosis of about 45% when the two doses were separated by 5 days (total dose = 25 Gy), whereas the 2.5 Gy per day protocol yielded about 50% net apoptotic cells when given for 5 days (total dose = 12.5 Gy). These values are to be compared to the value of 36% apoptotic cells that is yielded by large single doses (> 25 Gy). Thus, these results indicate that an apoptotic subpopulation of cells reemerged between the fractions in both protocols, but the kinetics appeared to be delayed in the 12.5+12.5 Gy vs. the multiple 2.5 Gy protocol. This reemergence of cells with the propensity for radiation-induced apoptosis between fractionated exposures is consistent with a role for this mode of cell death in the response of tumors to radiotherapy and may represent the priming of a new subpopulation of tumor cells for apoptosis as part of normal tumor homeostasis to counterbalance cell division. 25 refs., 3 figs., 1 tab

  18. Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under ER stress conditions.

    Science.gov (United States)

    Deegan, Shane; Saveljeva, Svetlana; Logue, Susan E; Pakos-Zebrucka, Karolina; Gupta, Sanjeev; Vandenabeele, Peter; Bertrand, Mathieu J M; Samali, Afshin

    2014-01-01

    Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells.

  19. Pro- and anti-apoptotic CD95 signaling in T cells

    Directory of Open Access Journals (Sweden)

    Janssen Ottmar

    2011-04-01

    Full Text Available Abstract The TNF receptor superfamily member CD95 (Fas, APO-1, TNFRSF6 is known as the prototypic death receptor in and outside the immune system. In fact, many mechanisms involved in apoptotic signaling cascades were solved by addressing consequences and pathways initiated by CD95 ligation in activated T cells or other "CD95-sensitive" cell populations. As an example, the binding of the inducible CD95 ligand (CD95L to CD95 on activated T lymphocytes results in apoptotic cell death. This activation-induced cell death was implicated in the control of immune cell homeostasis and immune response termination. Over the past years, however, it became evident that CD95 acts as a dual function receptor that also exerts anti-apoptotic effects depending on the cellular context. Early observations of a potential non-apoptotic role of CD95 in the growth control of resting T cells were recently reconsidered and revealed quite unexpected findings regarding the costimulatory capacity of CD95 for primary T cell activation. It turned out that CD95 engagement modulates TCR/CD3-driven signal initiation in a dose-dependent manner. High doses of immobilized CD95 agonists or cellular CD95L almost completely silence T cells by blocking early TCR-induced signaling events. In contrast, under otherwise unchanged conditions, lower amounts of the same agonists dramatically augment TCR/CD3-driven activation and proliferation. In the present overview, we summarize these recent findings with a focus on the costimulatory capacity of CD95 in primary T cells and discuss potential implications for the T cell compartment and the interplay between T cells and CD95L-expressing cells including antigen-presenting cells.

  20. Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

    Science.gov (United States)

    Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

    2011-12-01

    Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Characterization of the enhanced apoptotic response to azidothymidine by pharmacological inhibition of NF-kB.

    Science.gov (United States)

    Matteucci, Claudia; Minutolo, Antonella; Marino-Merlo, Francesca; Grelli, Sandro; Frezza, Caterina; Mastino, Antonio; Macchi, Beatrice

    2015-04-15

    The present study addresses the issue of enhanced apoptotic response to AZT following co-treatment with an NF-kB inhibitor. To investigate this issue, different cell lines were assayed for susceptibility to AZT-mediated apoptosis without or with the addition of the NF-kB inhibitor Bay-11-7085. For further investigation, U937 cells were selected as good-responder cells to the combination treatment with 32 or 128 μM AZT, and 1 μM Bay-11-7085. Inhibition of NF-kB activation by Bay-11-7085 in cells treated with AZT was assayed through Western blot analysis of p65 expression and by EMSA. Involvement of the mitochondrial pathway of apoptosis in mechanisms underlying the improved effect of AZT following Bay-11-7085 co-treatment, was evaluated by assaying the cytochrome c release and the mitochondrial membrane potential (MMP) status using the JC-1 dye. Moreover, the transcriptional activity of both anti- and pro-apoptotic genes in U937 cells after combination treatment was quantitatively evaluated through real-time PCR. We found that the combined treatment induced high levels of cytochrome c release and of MMP collapse in association with evident changes in the expression of both anti- and pro-apoptotic genes of the Bcl-2 family. Overexpression of Bcl-2 significantly suppressed the sensitization of U937 cells to an enhanced apoptotic response to AZT following co-treatment with the NF-kB inhibitor. The new findings suggest that a combination regimen based on AZT plus an NF-kB inhibitor could represent a new chemotherapeutic tool for retrovirus-related pathologies.

  2. Early radiation effects in highly apoptotic murine lymphoma xenografts monitored by 31P magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Sakurai, Hideyuki; Mitsuhashi, Norio; Murata, Osamu; Kitamoto, Yoshizumi; Saito, Yoshihiro; Hasegawa, Masatoshi; Akimoto, Tetsuo; Takahashi, Takeo; Nasu, Sachiko; Niibe, Hideo

    1998-01-01

    Purpose: Phosphorus-31 magnetic resonance spectra ( 31 P-MRS) were obtained from highly apoptotic murine lymphoma xenografts before and up to 24 hr following graded doses of radiation ranging from 2 to 30 Gy. Radiation-induced apoptosis was also estimated up to 24 hr by scoring apoptotic cells in tumor tissue. Methods and Materials: Highly apoptotic murine lymphoma cells, EL4, were subcutaneously transplanted into C57/BL mice. At 7 days after transplantation, radiation was given to the tumor with a single dose at 3, 10, and 30 Gy. The β-ATP/Pi, PME/Pi, and β-ATP/PME values were calculated from the peak area of each spectrum. Radiation-induced apoptosis was scored with counting apoptotic cells on hematoxylin and eosin stained specimens (%apoptosis). Results: The values of % apoptosis 4, 8, and 24 hr after radiation were 21.8, 19.6, and 4.6% at 3 Gy, 35.1, 25.6, and 14.8% at 10 Gy, 38.4, 38.0, and 30.6% at 30 Gy, respectively (cf. 4.4% in control). There was no correlation between early change in β-ATP/Pi and % apoptosis at 4 hr after radiation when most of the apoptosis occurred. An early decrease in PME/Pi was observed at 4 hr after radiation dose at 30 Gy. For each dose, the values of β-ATP/Pi 24 hr after radiation were inversely related to radiation dose. Conclusion: The increase in β-ATP/Pi observed by 31 P-MRS was linked to the degree of histological recovery from radiation-induced apoptosis

  3. Computational enzyme design: transitioning from catalytic proteins to enzymes.

    Science.gov (United States)

    Mak, Wai Shun; Siegel, Justin B

    2014-08-01

    The widespread interest in enzymes stem from their ability to catalyze chemical reactions under mild and ecologically friendly conditions with unparalleled catalytic proficiencies. While thousands of naturally occurring enzymes have been identified and characterized, there are still numerous important applications for which there are no biological catalysts capable of performing the desired chemical transformation. In order to engineer enzymes for which there is no natural starting point, efforts using a combination of quantum chemistry and force-field based protein molecular modeling have led to the design of novel proteins capable of catalyzing chemical reactions not catalyzed by naturally occurring enzymes. Here we discuss the current status and potential avenues to pursue as the field of computational enzyme design moves forward. Published by Elsevier Ltd.

  4. Immobilized enzymes: understanding enzyme - surface interactions at the molecular level.

    Science.gov (United States)

    Hoarau, Marie; Badieyan, Somayesadat; Marsh, E Neil G

    2017-11-22

    Enzymes immobilized on solid supports have important and industrial and medical applications. However, their uses are limited by the significant reductions in activity and stability that often accompany the immobilization process. Here we review recent advances in our understanding of the molecular level interactions between proteins and supporting surfaces that contribute to changes in stability and activity. This understanding has been facilitated by the application of various surface-sensitive spectroscopic techniques that allow the structure and orientation of enzymes at the solid/liquid interface to be probed, often with monolayer sensitivity. An appreciation of the molecular interactions between enzyme and surface support has allowed the surface chemistry and method of enzyme attachement to be fine-tuned such that activity and stability can be greatly enhanced. These advances suggest that a much wider variety of enzymes may eventually be amenable to immobilization as green catalysts.

  5. Stability of Enzymes in Granular Enzyme Products for Laundry Detergents

    DEFF Research Database (Denmark)

    Biran, Suzan; Bach, Poul; Simonsen, Ole

    Enzymes have long been of interest to the detergent industry due to their ability to improve the cleaning efficiency of synthetic detergents, contribute to shortening washing times, and reduce energy and water consumption, provision of environmentally friendlier wash water effluents and fabric care....... However, incorporating enzymes in detergent formulations gives rise to numerous practical problems due to their incompatibility with and stability against various detergent components. In powdered detergent formulations, these issues can be partly overcome by physically isolating the enzymes in separate...... particles. However, enzymes may loose a significant part of their activity over a time period of several weeks. Possible causes of inactivation of enzymes in a granule may be related to the release of hydrogen peroxide from the bleaching chemicals in a moisture-containing atmosphere, humidity, autolysis...

  6. Enzymes in Human Milk.

    Science.gov (United States)

    Dallas, David C; German, J Bruce

    2017-01-01

    Milk proteins are a complex and diverse source of biological activities. Beyond their function, intact milk proteins also act as carriers of encrypted functional sequences that, when released as peptides, exert biological functions, including antimicrobial and immunomodulatory activity, which could contribute to the infant's competitive success. Research has now revealed that the release of these functional peptides begins within the mammary gland itself. A complex array of proteases produced in mother's milk has been shown to be active in the milk, releasing these peptides. Moreover, our recent research demonstrates that these milk proteases continue to digest milk proteins within the infant's stomach, possibly even to a larger extent than the infant's own proteases. As the neonate has relatively low digestive capacity, the activity of milk proteases in the infant may provide important assistance to digesting milk proteins. The coordinated release of these encrypted sequences is accomplished by selective proteolytic action provided by an array of native milk proteases and infant-produced enzymes. The task for scientists is now to discover the selective advantages of this protein-protease-based peptide release system. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  7. Sesamol induced apoptotic effect in lung adenocarcinoma cells through both intrinsic and extrinsic pathways.

    Science.gov (United States)

    Siriwarin, Boondaree; Weerapreeyakul, Natthida

    2016-07-25

    Sesamol is a phenolic lignan found in sesame seeds (Sesamum indicum L.) and sesame oil. The anticancer effects and molecular mechanisms underlying its apoptosis-inducing effect were investigated in human lung adenocarcinoma (SK-LU-1) cells. Sesamol inhibited SK-LU-1 cell growth with an IC50 value of 2.7 mM and exhibited less toxicity toward normal Vero cells after 48 h of treatment (Selective index = 3). Apoptotic bodies-the hallmark of apoptosis-were observed in sesamol-treated SK-LU-1 cells, stained with DAPI. Sesamol increased the activity of caspase 8, 9, and 3/7, indicating that apoptotic cell death occurred through both extrinsic and intrinsic pathways. Sesamol caused the loss of mitochondrial transmembrane potential signifying intrinsic apoptosis induction. Decreasing Bid expression revealed crosstalk between the intrinsic and extrinsic apoptotic pathways; demonstrating clearly that sesamol induces apoptosis through both pathways in human lung adenocarcinoma (SK-LU-1) cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Melatonin modulates inflammatory response and suppresses burn-induced apoptotic injury

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    Ganka Bekyarova

    2017-04-01

    Full Text Available Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p. was applied immediately after 30% of total body surface area (TBSA burns on male Wistar rats. The level of malondialdehyde (MDA as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry the expression Ki67 proliferative marker was investigated. Results: Hepatic MDA and TNF-α levels increased significantly following burns without any change in IL-10 level. Intracellular vacuolization, hepatic cell degeneration and apoptosis occurred in rats after burns. The number of apoptotic cells was increased whereas no significant increase in Ki67 proliferative marker. Melatonin decreased the MDA and TNF-α content and increased the IL-10 level. It also limited the degenerative changes and formation of apoptotic cells in rat liver but did not increase expression of the marker of proliferation. In conclusion, our data show that melatonin relieves burn-induced hepatic damage associated with modulation of the proinflammatory/anti-inflammatory balance, mitigation of lipid peroxidation and hepatic apoptosis.

  9. Antitumor effects of traditional Chinese medicine targeting the cellular apoptotic pathway

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    Xu HL

    2015-05-01

    Full Text Available Huanli Xu,1 Xin Zhao,2 Xiaohui Liu,1 Pingxiang Xu,1 Keming Zhang,2 Xiukun Lin11Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, 2Department of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation Army, Beijing, People’s Republic of ChinaAbstract: Defects in apoptosis are common phenomena in many types of cancer and are also a critical step in tumorigenesis. Targeting the apoptotic pathway has been considered an intriguing strategy for cancer therapy. Traditional Chinese medicine (TCM has been used in the People’s Republic of China for thousands of years, and many of the medicines have been confirmed to be effective in the treatment of a number of tumors. With increasing cancer rates worldwide, the antitumor effects of TCMs have attracted more and more attention globally. Many of the TCMs have been shown to have antitumor activity through multiple targets, and apoptosis pathway-related targets have been extensively studied and defined to be promising. This review focuses on several antitumor TCMs, especially those with clinical efficacy, based on their effects on the apoptotic signaling pathway. The problems with and prospects of development of TCMs as anticancer agents are also presented.Keywords: traditional Chinese medicine, antitumor effects, apoptotic pathway

  10. Vitamin-C protect ethanol induced apoptotic neuro degeneration in postnatal rat brain

    International Nuclear Information System (INIS)

    Naseer, M.I.; Najeebullah; Ikramullah; Zubair, H.; Hassan, M.; Yang, B.C.

    2010-01-01

    Objective: To evaluate ethanol effects to induced activation of caspsae-3, and to observe the protective effects of Vitamin C (vit-C) on ethanol-induced apoptotic neuro degeneration in rat cortical area of brain. Methodology: Administration of a single dose of ethanol in 7-d postnatal (P7) rats triggers activation of caspase-3 and widespread apoptotic neuronal death. Western blot analysis, cells counting and Nissl staining were used to elucidate possible protective effect of vit-C against ethanol-induced apoptotic neuro degeneration in brain. Results: The results showed that ethanol significantly increased caspase-3 expression and neuronal apoptosis. Furthermore, the co-treatment of vit-C along with ethanol showed significantly decreased expression of caspase-3 as compare to control group. Conclusion: Our findings indicate that vit-C can prevent some of the deleterious effect of ethanol on developing rat brain when given after ethanol exposure and can be used as an effective protective agent for Fetal Alcohol Syndrome (FAS). (author)

  11. Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway in anterior pituitary cells.

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    Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Cabilla, Jimena P; Duvilanski, Beatriz H

    2007-03-01

    We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.

  12. Apoptotic effects of bovine apo-lactoferrin on HeLa tumor cells.

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    Luzi, Carla; Brisdelli, Fabrizia; Iorio, Roberto; Bozzi, Argante; Carnicelli, Veronica; Di Giulio, Antonio; Lizzi, Anna Rita

    2017-01-01

    Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12.5 μM). Western blot analysis showed that key apoptotic regulators including Bax, Bcl-2, Sirt1, Mcl-1, and PARP-1 were modulated by 1.25 μM of apo-bLf. In the same cell line, apo-bLf induced apoptosis together with poly (ADP-ribose) polymerase cleavage, caspase activation, and a significant drop of NAD + . In addition, apo-bLf-treated HeLa cells showed a marked increase of reactive oxygen species level and a significant GSH depletion. On the whole, apo-bLf triggered apoptosis of HeLa cells upon oxygen radicals burst and GSH decrease. Copyright © 2017 John Wiley & Sons, Ltd.

  13. BAG1: the guardian of anti-apoptotic proteins in acute myeloid leukemia.

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    Sanja Aveic

    Full Text Available BCL2 associated Athano-Gene 1 (BAG1 is a multifunctional protein that has been described to be involved in different cell processes linked to cell survival. It has been reported as deregulated in diverse cancer types. Here, BAG1 protein was found highly expressed in children with acute myeloid leukemia at diagnosis, and in a cohort of leukemic cell lines. A silencing approach was used for determining BAG1's role in AML, finding that its down-regulation decreased expression of BCL2, BCL-XL, MCL1, and phospho-ERK1/2, all proteins able to sustain leukemia, without affecting the pro-apoptotic protein BAX. BAG1 down-regulation was also found to increase expression of BAG3, whose similar activity was able to compensate the loss of function of BAG1. BAG1/BAG3 co-silencing caused an enhanced cell predisposition to death in cell lines and also in primary AML cultures, affecting the same proteins. Cell death was CASPASE-3 dependent, was accompanied by PARP cleavage and documented by an increased release of pro-apoptotic molecules Smac/DIABLO and Cytochrome c. BAG1 was found to directly maintain BCL2 and to protect MCL1 from proteasomal degradation by controlling USP9X expression, which appeared to be its novel target. Finally, BAG1 was found able to affect leukemia cell fate by influencing the expression of anti-apoptotic proteins crucial for AML maintenance.

  14. Apoptotic-cell-derived membrane microparticles and IFN-α induce an inflammatory immune response.

    Science.gov (United States)

    Niessen, Anna; Heyder, Petra; Krienke, Stefan; Blank, Norbert; Tykocinski, Lars-Oliver; Lorenz, Hanns-Martin; Schiller, Martin

    2015-07-15

    A dysregulation in the clearance of apoptotic material is considered a major pathogenetic factor for the emergence of autoimmune diseases. Apoptotic-cell-derived membrane microparticles (AdMPs), which are released from the cell surface during apoptosis, have been implicated in the pathogenesis of autoimmunity. Also of importance are cytokines, such as interferon-α (IFN-α), which is known to be a major player in patients with systemic lupus erythematosus (SLE). This study investigates the combined effect of AdMPs and IFN-α on professional phagocytes. In the presence of IFN-α, phagocytosis of AdMPs by human monocytes was significantly increased in a dose-dependent manner. The combination of AdMPs and raised IFN-α concentrations resulted in an increase in the secretion of pro-inflammatory cytokines and an upregulation of surface molecule expression involved in antigen uptake. In addition, macrophage polarisation was shifted towards a more inflammatory type of cell. The synergism between IFN-α and AdMPs seemed to be mediated by an upregulation of phosphorylated STAT1. Our results indicate that IFN-α, together with AdMPs, amplify the initiation and maintenance of inflammation. This mechanism might especially play a crucial role in disorders with a defective clearance of apoptotic material. © 2015. Published by The Company of Biologists Ltd.

  15. Kinetics of apoptotic markers in exogeneously induced apoptosis of EL4 cells.

    Science.gov (United States)

    Jessel, Robert; Haertel, Steffen; Socaciu, Carmen; Tykhonova, Svetlana; Diehl, Horst A

    2002-01-01

    We investigated the time-dependence of apoptotic events in EL4 cells by monitoring plasma membrane changes in correlation to DNA fragmentation and cell shrinkage. We applied three apoptosis inducers (staurosporine, tubericidine and X-rays) and we looked at various markers to follow the early-to-late apoptotic events: phospholipid translocation (identified through annexin V-fluorescein assay and propidium iodide), lipid package (via merocyanine assay), membrane fluidity and anisotropy (via fluorescent measurements), DNA fragmentation by the fluorescence-labeling test and cell size measurements. The different apoptotic inducers caused different reactions of the cells: staurosporine induced apoptosis most rapidly in a high number of cells, tubercidine triggered apoptosis only in the S phase cells, while X-rays caused a G2/M arrest and subsequently apoptosis. Loss of lipid asymmetry is promptly detectable after one hour of incubation time. The phosphatidylserine translocation, decrease of lipid package and anisotropy, and the increase of membrane fluidity appeared to be based on the same process of lipid asymmetry loss. Therefore, the DNA fragmentation and the cell shrinkage appear to be parallel and independent processes running on different time scales but which are kinetically inter-related. The results indicate different signal steps to apoptosis dependent on inducer characteristics but the kinetics of "early-to-late" apoptosis appears to be a fixed program.

  16. p53 dependent apoptotic cell death induces embryonic malformation in Carassius auratus under chronic hypoxia.

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    Paramita Banerjee Sawant

    Full Text Available Hypoxia is a global phenomenon affecting recruitment as well as the embryonic development of aquatic fauna. The present study depicts hypoxia induced disruption of the intrinsic pathway of programmed cell death (PCD, leading to embryonic malformation in the goldfish, Carrasius auratus. Constant hypoxia induced the early expression of pro-apoptotic/tumor suppressor p53 and concomitant expression of the cell death molecule, caspase-3, leading to high level of DNA damage and cell death in hypoxic embryos, as compared to normoxic ones. As a result, the former showed delayed 4 and 64 celled stages and a delay in appearance of epiboly stage. Expression of p53 efficiently switched off expression of the anti-apoptotic Bcl-2 during the initial 12 hours post fertilization (hpf and caused embryonic cell death. However, after 12 hours, simultaneous downregulation of p53 and Caspase-3 and exponential increase of Bcl-2, caused uncontrolled cell proliferation and prevented essential programmed cell death (PCD, ultimately resulting in significant (p<0.05 embryonic malformation up to 144 hpf. Evidences suggest that uncontrolled cell proliferation after 12 hpf may have been due to downregulation of p53 abundance, which in turn has an influence on upregulation of anti-apoptotic Bcl-2. Therefore, we have been able to show for the first time and propose that hypoxia induced downregulation of p53 beyond 12 hpf, disrupts PCD and leads to failure in normal differentiation, causing malformation in gold fish embryos.

  17. Apoptotic intrinsic pathway proteins predict survival in canine cutaneous mast cell tumours.

    Science.gov (United States)

    Barra, C N; Macedo, B M; Cadrobbi, K G; Pulz, L H; Huete, G C; Kleeb, S R; Xavier, J G; Catão-Dias, J L; Nishiya, A T; Fukumasu, H; Strefezzi, R F

    2018-03-01

    Mast cell tumours (MCTs) are the most frequent canine round cell neoplasms and show variable biological behaviours with high metastatic and recurrence rates. The disease is treated surgically and wide margins are recommended. Adjuvant chemotherapy and radiotherapy used in this disease cause DNA damage in neoplastic cells, which is aimed to induce apoptotic cell death. Resisting cell death is a hallmark of cancer, which contributes to the development and progression of tumours. The aim of this study was to investigate the expression of the proteins involved in the apoptotic intrinsic pathway and to evaluate their potential use as prognostic markers for canine cutaneous MCTs. Immunohistochemistry for BAX, BCL2, APAF1, Caspase-9, and Caspase-3 was performed in 50 canine cases of MCTs. High BAX expression was associated with higher mortality rate and shorter survival. BCL2 and APAF1 expressions offered additional prognostic information to the histopathological grading systems. The present results indicate that variations in the expression of apoptotic proteins are related to malignancy of cutaneous MCTs in dogs. © 2017 John Wiley & Sons Ltd.

  18. DUOX enzyme activity promotes AKT signalling in prostate cancer cells.

    Science.gov (United States)

    Pettigrew, Christopher A; Clerkin, John S; Cotter, Thomas G

    2012-12-01

    Reactive oxygen species (ROS) and oxidative stress are related to tumour progression, and high levels of ROS have been observed in prostate tumours compared to normal prostate. ROS can positively influence AKT signalling and thereby promote cell survival. The aim of this project was to establish whether the ROS generated in prostate cancer cells positively regulate AKT signalling and enable resistance to apoptotic stimuli. In PC3 cells, dual oxidase (DUOX) enzymes actively generate ROS, which inactivate phosphatases, thereby maintaining AKT phosphorylation. Inhibition of DUOX by diphenylene iodium (DPI), intracellular calcium chelation and small-interfering RNA (siRNA) resulted in lower ROS levels, lower AKT and glycogen synthase kinase 3β (GSK3β) phosphorylation, as well as reduced cell viability and increased susceptibility to apoptosis stimulating fragment (FAS) induced apoptosis. This report shows that ROS levels in PC3 cells are constitutively maintained by DUOX enzymes, and these ROS positively regulate AKT signalling through inactivating phosphatases, leading to increased resistance to apoptosis.

  19. Design and synthesis of thienopyrimidine urea derivatives with potential cytotoxic and pro-apoptotic activity against breast cancer cell line MCF-7.

    Science.gov (United States)

    Abdelhaleem, Eman F; Abdelhameid, Mohammed K; Kassab, Asmaa E; Kandeel, Manal M

    2018-01-01

    A series of novel tetrahydrobenzothieno[2,3-d]pyrimidine urea derivatives was synthesized according to fragment-based design strategy. They were evaluated for their anticancer activity against MCF-7 cell line. Three compounds 9c, 9d and 11b showed 1.5-1.03 folds more potent anticancer activity than doxorubicin. In this study, a promising multi-sited enzyme small molecule inhibitor 9c, which showed the most potent anti-proliferative activity, was identified. The anti-proliferative activity of this compound appears to correlate well with its ability to inhibit topoisomerase II (IC 50  = 9.29 μM). Moreover, compound 9c showed excellent VEGFR-2 inhibitory activity, at the sub-micromolar level with IC 50 value 0.2 μM, which is 2.1 folds more potent than sorafenib. Moreover, activation of damage response pathway of the DNA leads to cell cycle arrest at G2/M phase, accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining, indicating that cell death proceeds through an apoptotic mechanism. Compound 9c showed potent pro-apoptotic effect through induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the expression of the tumor suppressor gene p53, elevation in Bax/BCL-2 ratio and a significant increase in the level of active caspase-3. Quantitative structure-activity relationship (QSAR) studies delivered equations of five 3D descriptors with R 2  = 0.814. This QSAR model provides an effective technique for understanding the observed antitumor properties and thus could be adopted for developing effective lead structures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Human Adipose-Derived Stem Cells Delay Retinal Degeneration in Royal College of Surgeons Rats Through Anti-Apoptotic and VEGF-Mediated Neuroprotective Effects.

    Science.gov (United States)

    Li, Z; Wang, J; Gao, F; Zhang, J; Tian, H; Shi, X; Lian, C; Sun, Y; Li, W; Xu, J-Y; Li, P; Zhang, J; Gao, Z; Xu, J; Wang, F; Lu, L; Xu, G-T

    2016-01-01

    Stem cell therapy is a promising therapeutic approach for retinal degeneration (RD). Our study investigated the effects of human adipose derived stem cell (hADSCs) on Royal College of Surgeons (RCS) rats. Green fluorescent protein (GFP)-labeled hADSCs were transplanted subretinally into RCS rats at postnatal (PN) 21 days to explore potential therapeutic effects, while adeno-associated viral vector (AAV2)-vascular endothelial growth factor (VEGF) and siVEGF-hADSCs were used to aid the mechanistic dissections. Visual function was evaluated by Electroretinogram (ERG) recording. Potential transdifferentiations were examined by Immunofluorescence (IF) and gene expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Apoptotic retinal cells were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay and the cytokines secreted by hADSCs were measured by Enzyme-linked Immunosorbent Assay (ELISA). The visual function of RCS rats began to decrease one week after their eyes opened at PN week 3 and almost lost in PN 5 weeks, accompanied by the loss of retinal outer nuclear layer (ONL). Subretinal transplantation of hADSCs significantly improved the visual function 2 weeks after the transplantation and such therapeutic effect persisted up to 8 weeks after the treatment (PN 11 weeks), with 3-4 rows of photoreceptors remained in the ONL and reduced apoptosis. Consistent with these phenotypic changes, the gene expression of rod photoreceptor markers Rhodopsin (Rho), Crx and Opsin (Opn1) in RCS rats showed obvious decreasing trends over time after PN 3 weeks, but were elevated with hADSC treatment. hADSC transplantation also repressed the expressions of Bax, Bak and Caspase 3, but not the expression of anti-apoptotic genes, including Bcl-2 and Bcl-XL. Finally, substantial VEGF, hepatocyte growth factor (HGF) and pigment epithelium-derived factor (PEDF) secretions from hADSCs were detected, while endogenous