WorldWideScience

Sample records for cellular radiation response

  1. Molecular targets in cellular response to ionizing radiation and implications in space radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Belli, M.; Tabocchini, M.A. [Istituto Superiore di Sanita, Rome (Italy). Physics Lab.; Sapora, O. [Istituto Superiore di Sanita, Rome (Italy). Comparative Toxicology Lab.

    2002-12-01

    DNA repair systems and cell cycle checkpoints closely co-operate in the attempt of maintaining the genomic integrity of cells damaged by ionizing radiation. DNA double-strand breaks (DSB) are considered as the most biologically important radiation-induced damage. Their spatial distribution and association with other types of damage depend on radiation quality. It is believed these features affect damage reparability, thus explaining the higher efficiency for cellular effects of densely ionizing radiation with respect to {gamma}-rays. DSB repair systems identified in mammalian cells are homologous recombination (HR), single-strand annealing (SSA) and non-homologous end-joining (NHEJ). Some enzymes may participate in more than one of these repair systems. DNA damage also triggers biochemical signals activating checkpoints responsible for delay in cell cycle progression that allows more time for repair. Those at G1/S and S phases prevent replication of damaged DNA and those at G2/M phase prevent segregation of changed chromosomes. Individuals with lack or alterations of genes involved in DNA DSB repair and cell cycle checkpoints exhibit syndromes characterized by genome instability and predisposition to cancer. Information reviewed in this paper on the basic mechanisms of cellular response to ionizing radiation indicates their importance for a number of issues relevant to protection of astronauts from space radiation. (author)

  2. Molecular events basic to cellular radiation response. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Kolodny, G.M.

    1976-01-01

    Studies on regulation of gene expression included research projects on turnover of ribosomal RNA, ribonuclease-resistant oligonucleotides, and reutilization of oligonucleotides. Studies on radiation effects on RNA included research projects on radioinduced strand breaks in RNA and radioinduced alterations in RNA nucleotides. Effects of vasopression on radiosensitivity were studied. Studies on amino acid-nucleic acid interactions included research projects on synthesis and spectroscopic analysis of nucleotide-amino acid covalently bonded model compound and intermolecular interactions between tryptophan and dinucleoside phosphates. (HLW)

  3. Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

    Energy Technology Data Exchange (ETDEWEB)

    Balajee, A.S.; Meador, J.A.; Su, Y.

    2011-03-24

    It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellular mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the

  4. Modeling of time-dose-LET effects in the cellular response to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Herr, Lisa Antje

    2015-07-20

    This work is dedicated to the elucidation of time-dose- and if applicable linear energy transfer (LET) effects in the cellular response to ion or photon radiation. In particular, the common concept of the Local Effect Model (LEM) and the Giant Loop Binary Lesion (GLOBLE) model, which explains cell survival probabilities on the hand of clustering of double-strand breaks (DSB) in micrometer-sized sub-structural units of the DNA, was investigated with regard to temporal aspects. In previous studies with the LEM and GLOBLE model, it has been demonstrated that the definition of two lesion classes, characterized by single or multiple DSB in a DNA giant loop, with two repair fidelities is adequate to comprehensively describe the dose dependence of the cellular response to instantaneous photon irradiation or ion irradiation with varying LET. Furthermore, with the GLOBLE model for photon radiation, it has been shown that the assignment of two repair time scales to the two lesion classes allows to adequately reproduce time-dose effects after photon irradiation with an arbitrary constant dose-rate. In this work, the results of four projects that strengthen the mechanistic consistency and the practical applicability of the LEM and GLOBLE model will be presented. First, it was found that the GLOBLE model is applicable to describe time-dose effects in the cellular response to two split photon doses and in the occurrence of deterministic radiation effects. Second, in a comparison of ten models for the temporal course of DSB rejoining, it was revealed that a bi-exponential approach, as suggested by the LEM and GLOBLE model, finds a relatively large support by 61 experimental data sets. Third, in a comparison of four kinetic photon cell survival models that was based on fits to 13 dose-rate experiments, it was shown that the GLOBLE model performs well with respect to e.g. accuracy, parsimony, reliability and other factors that characterize a good approach. Last but not least, the

  5. 7th International Workshop on Microbeam Probes of Cellular Radiation Response

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, David J.

    2009-07-21

    The extended abstracts that follow present a summary of the Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response, held at Columbia University’s Kellogg Center in New York City on March 15–17, 2006. These International Workshops on Microbeam Probes of Cellular Radiation Response have been held regularly since 1993 (1–5). Since the first workshop, there has been a rapid growth (see Fig. 1) in the number of centers developing microbeams for radiobiological research, and worldwide there are currently about 30 microbeams in operation or under development. Single-cell/single-particle microbeam systems can deliver beams of different ionizing radiations with a spatial resolution of a few micrometers down to a few tenths of a micrometer. Microbeams can be used to addressquestions relating to the effects of low doses of radiation (a single radiation track traversing a cell or group of cells), to probe subcellular targets (e.g. nucleus or cytoplasm), and to address questions regarding the propagation of information about DNA damage (for example, the radiation-induced bystander effect). Much of the recent research using microbeams has been to study low-dose effects and ‘‘non-targeted’’ responses such as bystander effects, genomic instability and adaptive responses. This Workshop provided a forum to assess the current state of microbeam technology and current biological applications and to discuss future directions for development, both technological and biological. Over 100 participants reviewed the current state of microbeam research worldwide and reported on new technological developments in the fields of both physics and biology.

  6. Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization.

    Science.gov (United States)

    Maier, Patrick; Hartmann, Linda; Wenz, Frederik; Herskind, Carsten

    2016-01-14

    During the last few decades, improvements in the planning and application of radiotherapy in combination with surgery and chemotherapy resulted in increased survival rates of tumor patients. However, the success of radiotherapy is impaired by two reasons: firstly, the radioresistance of tumor cells and, secondly, the radiation-induced damage of normal tissue cells located in the field of ionizing radiation. These limitations demand the development of drugs for either radiosensitization of tumor cells or radioprotection of normal tissue cells. In order to identify potential targets, a detailed understanding of the cellular pathways involved in radiation response is an absolute requirement. This review describes the most important pathways of radioresponse and several key target proteins for radiosensitization.

  7. Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization

    Directory of Open Access Journals (Sweden)

    Patrick Maier

    2016-01-01

    Full Text Available During the last few decades, improvements in the planning and application of radiotherapy in combination with surgery and chemotherapy resulted in increased survival rates of tumor patients. However, the success of radiotherapy is impaired by two reasons: firstly, the radioresistance of tumor cells and, secondly, the radiation-induced damage of normal tissue cells located in the field of ionizing radiation. These limitations demand the development of drugs for either radiosensitization of tumor cells or radioprotection of normal tissue cells. In order to identify potential targets, a detailed understanding of the cellular pathways involved in radiation response is an absolute requirement. This review describes the most important pathways of radioresponse and several key target proteins for radiosensitization.

  8. Space experiment "Cellular Responses to Radiation in Space (CellRad)": Hardware and biological system tests.

    Science.gov (United States)

    Hellweg, Christine E; Dilruba, Shahana; Adrian, Astrid; Feles, Sebastian; Schmitz, Claudia; Berger, Thomas; Przybyla, Bartos; Briganti, Luca; Franz, Markus; Segerer, Jürgen; Spitta, Luis F; Henschenmacher, Bernd; Konda, Bikash; Diegeler, Sebastian; Baumstark-Khan, Christa; Panitz, Corinna; Reitz, Günther

    2015-11-01

    One factor contributing to the high uncertainty in radiation risk assessment for long-term space missions is the insufficient knowledge about possible interactions of radiation with other spaceflight environmental factors. Such factors, e.g. microgravity, have to be considered as possibly additive or even synergistic factors in cancerogenesis. Regarding the effects of microgravity on signal transduction, it cannot be excluded that microgravity alters the cellular response to cosmic radiation, which comprises a complex network of signaling pathways. The purpose of the experiment "Cellular Responses to Radiation in Space" (CellRad, formerly CERASP) is to study the effects of combined exposure to microgravity, radiation and general space flight conditions on mammalian cells, in particular Human Embryonic Kidney (HEK) cells that are stably transfected with different plasmids allowing monitoring of proliferation and the Nuclear Factor κB (NF-κB) pathway by means of fluorescent proteins. The cells will be seeded on ground in multiwell plate units (MPUs), transported to the ISS, and irradiated by an artificial radiation source after an adaptation period at 0 × g and 1 × g. After different incubation periods, the cells will be fixed by pumping a formaldehyde solution into the MPUs. Ground control samples will be treated in the same way. For implementation of CellRad in the Biolab on the International Space Station (ISS), tests of the hardware and the biological systems were performed. The sequence of different steps in MPU fabrication (cutting, drilling, cleaning, growth surface coating, and sterilization) was optimized in order to reach full biocompatibility. Different coatings of the foil used as growth surface revealed that coating with 0.1 mg/ml poly-D-lysine supports cell attachment better than collagen type I. The tests of prototype hardware (Science Model) proved its full functionality for automated medium change, irradiation and fixation of cells. Exposure of

  9. Space experiment "Cellular Responses to Radiation in Space (CELLRAD)": Hardware and biological system tests

    Science.gov (United States)

    Hellweg, Christine E.; Dilruba, Shahana; Adrian, Astrid; Feles, Sebastian; Schmitz, Claudia; Berger, Thomas; Przybyla, Bartos; Briganti, Luca; Franz, Markus; Segerer, Jürgen; Spitta, Luis F.; Henschenmacher, Bernd; Konda, Bikash; Diegeler, Sebastian; Baumstark-Khan, Christa; Panitz, Corinna; Reitz, Günther

    2015-11-01

    One factor contributing to the high uncertainty in radiation risk assessment for long-term space missions is the insufficient knowledge about possible interactions of radiation with other spaceflight environmental factors. Such factors, e.g. microgravity, have to be considered as possibly additive or even synergistic factors in cancerogenesis. Regarding the effects of microgravity on signal transduction, it cannot be excluded that microgravity alters the cellular response to cosmic radiation, which comprises a complex network of signaling pathways. The purpose of the experiment "Cellular Responses to Radiation in Space" (CELLRAD, formerly CERASP) is to study the effects of combined exposure to microgravity, radiation and general space flight conditions on mammalian cells, in particular Human Embryonic Kidney (HEK) cells that are stably transfected with different plasmids allowing monitoring of proliferation and the Nuclear Factor κB (NF-κB) pathway by means of fluorescent proteins. The cells will be seeded on ground in multiwell plate units (MPUs), transported to the ISS, and irradiated by an artificial radiation source after an adaptation period at 0 × g and 1 × g. After different incubation periods, the cells will be fixed by pumping a formaldehyde solution into the MPUs. Ground control samples will be treated in the same way. For implementation of CELLRAD in the Biolab on the International Space Station (ISS), tests of the hardware and the biological systems were performed. The sequence of different steps in MPU fabrication (cutting, drilling, cleaning, growth surface coating, and sterilization) was optimized in order to reach full biocompatibility. Different coatings of the foil used as growth surface revealed that coating with 0.1 mg/ml poly-D-lysine supports cell attachment better than collagen type I. The tests of prototype hardware (Science Model) proved its full functionality for automated medium change, irradiation and fixation of cells. Exposure of

  10. Cellular Response to Irradiation

    Institute of Scientific and Technical Information of China (English)

    LIU Bo; YAN Shi-Wei

    2011-01-01

    To explore the nonlinear activities of the cellular signaling system composed of one transcriptional arm and one protein-interaction arm, we use an irradiation-response module to study the dynamics of stochastic interactions.It is shown that the oscillatory behavior could be described in a unified way when the radiation-derived signal and noise are incorporated.

  11. Assessment of the cellular and electrophysiological response of cardiomyocytes to radiation

    Science.gov (United States)

    Helm, Alexander; Ritter, Sylvia; Durante, Marco; Friess, Johannes; Thielemann, Christiane; Mr; Frank, Simon

    Cardiac disease is considered as a late effect resulting from an exposure during long-term space missions. Yet, the underlying mechanisms and the impact of radiation quality and dose are not well understood. To address this topic, we used cardiomyocytes derived from mouse embryonic stem cells (mESC) as a model system. This model has already been successfully used for cardiotoxicity screening of new drugs. Both, the cellular and electrophysiological response to X-ray irradiation were examined. Cellular endpoints such as the induction of micronuclei, apoptosis, number of binucleated cells and expression of connexin43 (Cx 43) were analyzed by standard techniques. For electrophysiological studies a microelectrode array (MEA) was used allowing non-invasive recordings of electrical signals such as signal amplitude and shape, beat rate and conduction velocity. Data analysis was performed using the MATLAB based software DrCell. As a first approach, cardiomyocytes were generated by differentiation of mESC via the formation of embryoid bodies. However, the system proved to be unsuitable due to large intra- and inter-sample variations. In consecutive experiments we used commercially available Cor.At cells, i.e. a pure culture of mESC derived cardiomyocytes. For the analysis of cellular and electrophysiological endpoints Cor.At cells were seeded onto chamber slides or MEA chips, respectively. Irradiation with 0.5 and 2 Gy X-rays (250 kV, 16 mA) was performed two days after seeding. At that time cardiomyocytes are electrically coupled through gap junctions and form a spontaneously beating network. Samples were examined up to four days after exposure. Analysis of the electrophysiological data revealed only minor differences between controls and X-irradiated samples indicating the functionality of cardiomyocytes is not within the dose range examined. Currently, further experiments are performed to statistically verify this finding. Additionally, the expression of Cx 43, a major

  12. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  13. Inhibiting the NF-kappaB pathway to assess its function in the cellular response to space radiation

    Science.gov (United States)

    Koch, Kristina; Baumstark-Khan, Christa; Hellweg, Christine; Testard, Isabelle; Reitz, Guenther

    2012-07-01

    Radiation is regarded as one of the limiting factors for space missions. Therefore the cellular radiation response needs to be studied in order to estimate risks and to develop appropriate countermeasures. Exposure of human cells to ionizing radiation can provoke cell cycle arrest, leading to cellular senescence or premature differentiation, and different types of cell death. Previous heavy ion experiments have shown that the Nuclear Factor κB (NF-κB) pathway is activated by fluences that can be reached during long-term missions and thereby NF-κB was identified as an important modulating factor in the cellular radiation response. It could improve cellular survival after exposure to high radiation doses and influence the cancer risk of astronauts. The classical and the genotoxic stress induced NF-κB pathway result in nuclear translocation of the p65/p50 dimer. Both pathways might contribute to the cellular radiation response. Chemical inhibitors were tested to suppress the NF-κB pathway in recombinant HEK-pNF-κB-d2EGFP/Neo cells. The efficacy and cytotoxicity of the inhibitors targeting different elements of the NF-κB pathway were analyzed and found mostly inappropriate as inhibitors were partly cytotoxic or unspecific. Alternatively a functional knock-out of RelA (p65) was used to identify the contribution of the NF-κB pathway to different cellular outcomes. Small hairpin RNA constructs (shRNA) were transfected into the HEK-pNF-κB-d2EGFP/Neo cell line. Their functionality was assessed by quantitative Reverse Transcriptase real-time PCR (qRT-PCR) to verify that the RelA mRNA amount was reduced by more than 80% in the knock-down cells The original cell line had been stably transfected with a reporter system to monitor NF-κB activation by measuring destabilized Enhanced Green Fluorescent Protein (d2EGFP)-expression. It was shown that after 18 hours d2EGFP reaches its highest expression level after activation of NF-κB and can be measured by FACS analysis

  14. Coordination between p21 and DDB2 in the cellular response to UV radiation.

    Directory of Open Access Journals (Sweden)

    Hao Li

    Full Text Available The tumor suppressor p53 guides the cellular response to DNA damage mainly by regulating expression of target genes. The cyclin-dependent kinase inhibitor p21, which is induced by p53, can both arrest the cell cycle and inhibit apoptosis. Interestingly, p53-inducible DDB2 (damaged-DNA binding protein 2 promotes apoptosis by mediating p21 degradation after ultraviolet (UV-induced DNA damage. Here, we developed an integrated model of the p53 network to explore how the UV-irradiated cell makes a decision between survival and death and how the activities of p21 and DDB2 are modulated. By numerical simulations, we found that p53 is activated progressively and the promoter selectivity of p53 depends on its concentration. For minor DNA damage, p53 settles at an intermediate level. p21 is induced by p53 to arrest the cell cycle via inhibiting E2F1 activity, allowing for DNA repair. The proapoptotic genes are expressed at low levels. For severe DNA damage, p53 undergoes a two-phase behavior and accumulates to high levels in the second phase. Consequently, those proapoptotic proteins accumulate remarkably. Bax activates the release of cytochrome c, while DDB2 promotes the degradation of p21, which leads to activation of E2F1 and induction of Apaf-1. Finally, the caspase cascade is activated to trigger apoptosis. We revealed that the downregulation of p21 is necessary for apoptosis induction and PTEN promotes apoptosis by amplifying p53 activation. This work demonstrates that how the dynamics of the p53 network can be finely regulated through feed-forward and feedback loops within the network and emphasizes the importance of p21 regulation in the DNA damage response.

  15. Influence of Dose Rate on the Cellular Response to Low- and High-LET Radiations.

    Science.gov (United States)

    Wozny, Anne-Sophie; Alphonse, Gersende; Battiston-Montagne, Priscillia; Simonet, Stéphanie; Poncet, Delphine; Testa, Etienne; Guy, Jean-Baptiste; Rancoule, Chloé; Magné, Nicolas; Beuve, Michael; Rodriguez-Lafrasse, Claire

    2016-01-01

    Nowadays, head and neck squamous cell carcinoma (HNSCC) treatment failure is mostly explained by locoregional progression or intrinsic radioresistance. Radiotherapy (RT) has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy, which modify the dose rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a dose rate variation during conventional RT or carbon ion hadrontherapy treatment in order to improve the therapeutic care of patient. In this regard, two HNSCC cell lines were irradiated with photons or 72 MeV/n carbon ions at a dose rate of 0.5, 2, or 10 Gy/min. For both radiosensitive and radioresistant cells, the change in dose rate significantly affected cell survival in response to photon exposure. This variation of radiosensitivity was associated with the number of initial and residual DNA double-strand breaks (DSBs). By contrast, the dose rate change did not affect neither cell survival nor the residual DNA DSBs after carbon ion irradiation. As a result, the relative biological efficiency at 10% survival increased when the dose rate decreased. In conclusion, in the RT treatment of HNSCC, it is advised to remain very careful when modifying the classical schemes toward altered fractionation. At the opposite, as the dose rate does not seem to have any effects after carbon ion exposure, there is less need to adapt hadrontherapy treatment planning during active system irradiation.

  16. INFLUENCE OF DOSE RATE ON THE CELLULAR RESPONSE TO LOW- AND HIGH-LET RADIATIONS

    Directory of Open Access Journals (Sweden)

    Anne-Sophie eWozny

    2016-03-01

    Full Text Available Nowadays, head and neck squamous cell carcinoma (HNSCC treatment failure is mostly explained by loco-regional progression or intrinsic radioresistance. Radiotherapy has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy which modify the dose-rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a dose rate variation during conventional radiotherapy or carbon ion hadrontherapy treatment in order to improve the therapeutic care of patient. In this regard, two HNSCC cell lines were irradiated with photons or 72MeV/n carbon ions at a dose rate of 0.5, 2 or 10Gy/min.For both radiosensitive and radioresistant cells, the change in dose rate significantly affected cell survival in response to photon exposure, this variation of radiosensitivity was associated to the number of initial and residual DNA double-strand breaks. By contrast, the dose rate change did not affect neither cell survival nor the residual DNA double-strand breaks after carbon ion irradiation. As a result, the Relative Biological Efficiency at 10% survival increased when the dose rate decreased.In conclusion, in the radiotherapy treatment of HNSCC, it is advised to remain very careful when modifying the classical schemes towards altered-fractionation. At the opposite, as the dose rate does not seem to have any effects after carbon ion exposure, there is less need to adapt hadrontherapy treatment planning during active system irradiation

  17. Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.

    Directory of Open Access Journals (Sweden)

    Gillian D McFeat

    Full Text Available Exposure to ultraviolet (UV light can cause significant damage to mammalian cells and, although the spectrum of damage produced varies with the wavelength of UV, all parts of the UV spectrum are recognised as being detrimental to human health. Characterising the cellular response to different wavelengths of UV therefore remains an important aim so that risks and their moderation can be evaluated, in particular in relation to the initiation of skin cancer. The p53 tumour suppressor protein is central to the cellular response that protects the genome from damage by external agents such as UV, thus reducing the risk of tumorigenesis. In response to a variety of DNA damaging agents including UV light, wild-type p53 plays a role in mediating cell-cycle arrest, facilitating apoptosis and stimulating repair processes, all of which prevent the propagation of potentially mutagenic defects. In this study we examined the induction of p53 protein and its influence on the survival of primary mouse fibroblasts exposed to different wavelengths of UV light. UVC was found to elevate p53 protein and its sequence specific DNA binding capacity. Unexpectedly, UVA treatment failed to induce p53 protein accumulation or sequence specific DNA binding. Despite this, UVA exposure of wild-type cells induced a p53 dependent G1 cell cycle arrest followed by a wave of p53 dependent apoptosis, peaking 12 hours post-insult. Thus, it is demonstrated that the elements of the p53 cellular response evoked by exposure to UV radiation are wavelength dependent. Furthermore, the interrelationship between various endpoints is complex and not easily predictable. This has important implications not only for understanding the mode of action of p53 but also for the use of molecular endpoints in quantifying exposure to different wavelengths of UV in the context of human health protection.

  18. Mitochondrial-Derived Oxidants and Cellular Responses to Low Dose/Low LET Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Spitz, Douglas R.

    2009-11-09

    Exposure to ionizing radiation results in the immediate formation of free radicals and other reactive oxygen species (ROS). It has been assumed that the subsequent injury processes leading to genomic instability and carcinogenesis following radiation, derive from the initial oxidative damage caused by these free radicals and ROS. It is now becoming increasingly obvious that metabolic oxidation/reduction (redox) reactions can be altered by irradiation leading to persistent increases in steady-state levels of intracellular free radicals and ROS that contribute to the long term biological effects of radiation exposure by causing chronic oxidative stress. The objective during the last period of support (DE-FG02-05ER64050; 5/15/05-12/31/09) was to determine the involvement of mitochondrial genetic defects in metabolic oxidative stress and the biological effects of low dose/low LET radiation. Aim 1 was to determine if cells with mutations in succinate dehydrogenase (SDH) subunits C and D (SDHC and SDHD in mitochondrial complex II) demonstrated increases in steady-state levels of reactive oxygen species (ROS; O2•- and H2O2) as well as demonstrating increased sensitivity to low dose/low LET radiation (10 cGy) in cultured mammalian cells. Aim #2 was to determine if mitochondrially-derived ROS contributed to increased sensitivity to low dose/low LET radiation in mammalian cells containing mutations in SDH subunits. Aim #3 was to determine if a causal relationship existed between increases in mitochondrial ROS production, alterations in electron transport chain proteins, and genomic instability in the progeny of irradiated cells. Evidence gathered in the 2005-2009 period of support demonstrated that mutations in genes coding for mitochondrial electron transport chain proteins (ETC); either Succinate Dehydrogenase (SDH) subunit C (SDHC) or subunit D (SDHD); caused increased ROS production, increased genomic instability, and increased sensitivity to low dose/low LET radiation

  19. Cellular response to ionizing radiations: a study of the roles of physics and biology. [Neutrons (14 MeV); X radiation

    Energy Technology Data Exchange (ETDEWEB)

    DeWyngaert, J.K.

    1982-01-01

    A study of the complementary roles of physics and biology in determining the response of cellular systems to ionizing radiations has been conducted. Upon exposure to radiation, a cell responds in a binary (yes/no) manner in terms of its proliferative ability (survival). The relationship between the survival probability and absorbed dose may then be examined in terms of relevant physical and biological parameters. The approach to these studies was to vary the physics and biology independently and observe separately their influences upon the measured effect. Unique to these studies was the use of heterogeneous tumor systems. These are solid tumors found to consist of genetically related but identifiably distinct populations of cells. The two heterogeneous systems studied, a murine system consisting of four subpopulations and a human tumor system with two subpopulations, were exposed to graded doses of 14 MeV neutrons or x-rays and their effectiveness in inducing cell lethality compared. A further examination of the radiation effect involved a study at the chemical level, measuring the ability of oxygen to potentiate the damage produced by photon irradiation. To summarize, the physics, biology and the environment have all been varied, and the systematics of the responses studied. The data were analyzed within the formalisms of the dual theory of radiation action, the repair-misrepair model, and the repair saturation model of cell killing. The change in survival curve shape and the increased effectiveness in cell killing for higher Linear Energy Transfer (LET) radiations (neutrons vs. x-rays) are discussed in relation to explanations in terms of either physical or biochemical processes.

  20. Absolute quantification of acetylation and phosphorylation of the histone variant H2AX upon ionizing radiation reveals distinct cellular responses in two cancer cell lines.

    Science.gov (United States)

    Matsuda, Shun; Furuya, Kanji; Ikura, Masae; Matsuda, Tomonari; Ikura, Tsuyoshi

    2015-11-01

    Histone modifications change upon the cellular response to ionizing radiation, and their cellular amounts could reflect the DNA damage response activity. We previously reported a sensitive and reliable method for the absolute quantification of γH2AX within cells, using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The technique has broad adaptability to a variety of biological systems and can quantitate different modifications of histones. In this study, we applied it to quantitate the levels of γH2AX and K5-acetylated H2AX, and to compare the radiation responses between two cancer cell lines: HeLa and U-2 OS. The two cell lines have distinct properties in terms of their H2AX modifications. HeLa cells have relatively high γH2AX (3.1 %) against the total H2AX even in un-irradiated cells, while U-2 OS cells have an essentially undetectable level (nearly 0 %) of γH2AX. In contrast, the amounts of acetylated histones are lower in HeLa cells (9.3 %) and higher in U-2 OS cells (24.2 %) under un-irradiated conditions. Furthermore, after ionizing radiation exposure, the time-dependent increases and decreases in the amounts of histone modifications differed between the two cell lines, especially at the early time points. These results suggest that each biological system has distinct kinase/phosphatase and/or acetylase/deacetylase activities. In conclusion, for the first time, we have succeeded in simultaneously monitoring the absolute amounts of phosphorylated and acetylated cellular H2AX after ionizing radiation exposure. This multi-criteria assessment enables precise comparisons of the effects of radiation between any biological systems.

  1. Cellular Effects of Electromagnetic Radiation.

    Science.gov (United States)

    2014-09-26

    8217-- - - .- . - .- ’*-_- - 7 - r - .STUDIES OF EXPOSURE TO AMPLITUDE-MODULATED FIELDS The electromagnetic fields to which naval personnel are exposed tend to...radiation) ,.- Biological effects of electromagnetic fields , 20. ABSTRACT (Contimee an revers side II neceesmv aiId identify by Wek numbe") , .P-Giant...cells of characean algae were examined for electrophysiological sequelae to acute electromagnetic field irradiation at 10 mW/cm Carrier frequencies

  2. Defining molecular and cellular responses after low and high linear energy transfer radiations to develop biomarkers of carcinogenic risk or therapeutic outcome.

    Science.gov (United States)

    Story, Michael; Ding, Liang-hao; Brock, William A; Ang, K Kian; Alsbeih, Ghazi; Minna, John; Park, Seongmi; Das, Amit

    2012-11-01

    The variability in radiosensitivity across the human population is governed in part by genetic factors. The ability to predict therapeutic response, identify individuals at greatest risk for adverse clinical responses after therapeutic radiation doses, or identify individuals at high risk for carcinogenesis from environmental or medical radiation exposures has a medical and economic impact on both the individual and society at large. As radiotherapy incorporates particles, particularly particles larger than protons, into therapy, the need for such discriminators, (i.e., biomarkers) will become ever more important. Cellular assays for survival, DNA repair, or chromatid/chromosomal analysis have been used to identify at-risk individuals, but they are not clinically applicable. Newer approaches, such as genome-wide analysis of gene expression or single nucleotide polymorphisms and small copy number variations within chromosomes, are examples of technologies being applied to the discovery process. Gene expression analysis of primary or immortalized human cells suggests that there are distinct gene expression patterns associated with radiation exposure to both low and high linear energy transfer radiations and that those most radiosensitive are discernible by their basal gene expression patterns. However, because the genetic alterations that drive radio response may be subtle and cumulative, the need for large sample sizes of specific cell or tissue types is required. A systems biology approach will ultimately be necessary. Potential biomarkers from cell lines or animal models will require validation in a human setting where possible and before being considered as a credible biomarker some understanding of the molecular mechanism is necessary.

  3. Important role of catalase in the cellular response of the budding yeast Saccharomyces cerevisiae exposed to ionizing radiation.

    Science.gov (United States)

    Nishimoto, Takuto; Furuta, Masakazu; Kataoka, Michihiko; Kishida, Masao

    2015-03-01

    Ionizing radiation indirectly causes oxidative stress in cells via reactive oxygen species (ROS), such as hydroxyl radicals (OH(-)) generated by the radiolysis of water. We investigated how the catalase function was affected by ionizing radiation and analyzed the phenotype of mutants with a disrupted catalase gene in Saccharomyces cerevisiae exposed to radiation. The wild-type yeast strain and isogenic mutants with disrupted catalase genes were exposed to various doses of (60)Co gamma-rays. There was no difference between the wild-type strain and the cta1 disruption mutant following exposure to gamma-ray irradiation. In contrast, there was a significant decrease in the ctt1 disruption mutant, suggesting that this strain exhibited decreased survival on gamma-ray exposure compared with other strains. In all three strains, stationary phase cells were more tolerant to the exposure of gamma-rays than exponential phase cells, whereas the catalase activity in the wild-type strain and cta1 disruption mutant was higher in the stationary phase than in the exponential phase. These data suggest a correlation between catalase activity and survival following gamma-ray exposure. However, this correlation was not clear in the ctt1 disruption mutant, suggesting that other factors are involved in the tolerance to ROS induced by irradiation.

  4. Cellular immune responses to HIV

    Science.gov (United States)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  5. The insect cellular immune response

    Institute of Scientific and Technical Information of China (English)

    Michael R. Strand

    2008-01-01

    The innate immune system of insects is divided into humoral defenses that include the production of soluble effector molecules and cellular defenses like phagocytosis and encapsulation that are mediated by hemocytes. This review summarizes current understanding of the cellular immune response. Insects produce several terminally differentiated types of hemocytes that are distinguished by morphology, molecular and antigenic markers, and function. The differentiated hemocytes that circulate in larval or nymphal stage insects arise from two sources: progenitor cells produced during embryogenesis and mesodermally derived hematopoietic organs. Regulation of hematopoiesis and hemocyte differentiation also involves several different signaling pathways. Phagocytosis and encapsulation require that hemocytes first recognize a given target as foreign followed by activation of downstream signaling and effector responses. A number of humoral and cellular receptors have been identified that recognize different microbes and multicellular parasites. In turn, activation of these receptors stimulates a number of signaling pathways that regulate different hemocyte functions. Recent studies also identify hemocytes as important sources of a number of humoral effector molecules required for killing different foreign invaders.

  6. DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2013-07-10

    DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was associated with persistent MRE11, γH2AX, RAD51 foci at 2 h after irradiation. Persistent MRE11 and RAD51 foci were also evident 24 h after 0.2 Gy. MSH2 significantly enhances cell radiosensitivity to low dose IR.

  7. Thermal effects of radiation from cellular telephones

    Science.gov (United States)

    Wainwright, Peter

    2000-08-01

    A finite element thermal model of the head has been developed to calculate temperature rises generated in the brain by radiation from cellular telephones and similar electromagnetic devices. A 1 mm resolution MRI dataset was segmented semiautomatically, assigning each volume element to one of ten tissue types. A finite element mesh was then generated using a fully automatic tetrahedral mesh generator developed at NRPB. There are two sources of heat in the model: firstly the natural metabolic heat production; and secondly the power absorbed from the electromagnetic field. The SAR was derived from a finite difference time domain model of the head, coupled to a model `mobile phone', namely a quarter-wavelength antenna mounted on a metal box. The steady-state temperature distribution was calculated using the standard Pennes `bioheat equation'. In the normal cerebral cortex the high blood perfusion rate serves to provide an efficient cooling mechanism. In the case of equipment generally available to the public, the maximum temperature rise found in the brain was about 0.1 °C. These results will help in the further development of criteria for exposure guidelines, and the technique developed may be used to assess temperature rises associated with SARs for different types of RF exposure.

  8. Molecular mechanism of cellular reception of ionizing radiation and of activation of signal transduction pathway

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Keiji [Nagasaki Univ. (Japan). Faculty of Pharmaceutical Sciences

    1997-03-01

    The author reviewed what in cells receives ionizing radiation as a stress and which signal transduction pathway is activated to induce the stress reaction in the following order: Activation of protein kinase C (PKC) pathway by radiation, activation of MAP kinase superfamily by radiation, induction of p53 function by radiation, and radiation exposure and stress reaction pathway. Conclusion was as follows: Cellular receptors to radiation can be cell membrane and DNA. Membrane reception of radiation induces activation of tyrosine kinase and sphingomyelinase, which resulting in activation of PKC- and MAP kinase-mediated signal transduction. The signal generated in the nucleus participates in regulation of cell cycle and in DNA repair. Therefore, it seems that irradiation of ionizing radiation gives energy to various cellular receptor sites as well as DNA, which generate various independent signals to be transduced and accumulated in the nucleus, and leading to cellular response. (K.H.). 63 refs.

  9. Identification of human genes involved in cellular responses to ionizing radiation: molecular and cellular studies of gene encoding the p68 helicase in mammalian cells; Identification de genes humains impliques dans la reponse cellulaire aux radiations ionisantes: etudes moleculaire et cellulaire du gene codant l'helicase p68 dans les cellules de mammiferes

    Energy Technology Data Exchange (ETDEWEB)

    Menaa, F.

    2003-12-15

    Cells submitted to genotoxic factors -like IR- activate several and important mechanisms such as repair, cell cycle arrest or 'apoptosis' to maintain genetic integrity. So, the damaged cells will induce many and different genes. The human transcriptome analysis by 'SSH' method in a human breast carcinoma cell line MCF7 {gamma}-irradiated versus not irradiated, allowed to identify about one hundred genes. Among of these genes, we have focused our study on a radio-induced gene encoding the p68 helicase. In the conditions of irradiation used, our results show that the kinetic and the regulation of this gene expression differs between the nature of radiations used. Indeed, in {gamma}-irradiated mammalian cells, ATM, a protein kinase activated by DSB and IR, is required to induce quickly P68 gene via the important transcription factor p53 stabilized by IR. In the case of UVC-irradiated cells, the P68 gene induction is late and the intracellular signalling pathway that lead to this induction is independent from the p53 protein. Finally, we show that the p68 protein under-expression is responsible for an increased radiosensitivity of MCF7 cells. Consequently, we can postulate that the p68 protein is involved in cellular responses to radiations to reduce the increased radiosensitivity of cells exposed to {gamma}-rays. (author)

  10. Dynamic modeling of cellular response to DNA damage based on p53 stress response networks

    Institute of Scientific and Technical Information of China (English)

    Jinpeng Qi; Yongsheng Ding; Shihuang Shao

    2009-01-01

    Under acute perturbations from the outside, cells can trigger self-defensive mechanisms to fight against genome stress. To investigate the cellular response to continuous ion radiation (IR), a dynamic model for p53 stress response networks at the cellular level is proposed. The model can successfully be used to simulate the dynamic processes of double-strand breaks (DSBs) generation and their repair, switch-like ataxia telangiectasia mutated (ATM) activation, oscillations occurring in the p53-MDM2 feedback loop, as well as toxins elimination triggered by p53 stress response networks. Especially, the model can predict the plausible outcomes of cellular response under different IR dose regimes.

  11. Cellular responses to environmental DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.

  12. Autophagy in human skin fibroblasts: Comparison between young and aged cells and evaluation of its cellular rhythm and response to Ultraviolet A radiation.

    Science.gov (United States)

    Pernodet, Nadine; Dong, Kelly; Pelle, Edward

    2016-01-01

    Autophagic mechanisms play critical roles in cell maintenance. Damaged organelles that are not removed by autophagosomes, which act by engulfing and degrading these cellular components, have been linked to various pathologies. Recently, the progression of aging has also been correlated to a compromised autophagic response. Here, we report for the first time a significant reduction in autophagic levels in synchronized aged normal human skin fibroblasts as compared to young fibroblasts. We measured a 77.9% reduction in autophagy as determined by reverse transcription-polymerase chain reaction for LC3B expression, a microtubule-associated protein correlated to late stage autophagosome formation. In addition, we visualized these same changes by immunocytofluorescence with antibodies directed against LC3B. By harvesting synchronized, as well as unsynchronized cells over time, we were also able to measure for the first time a nighttime peak in autophagy that was present in young but absent in aged fibroblasts. Finally, since human skin is constantly subjected to environmentally induced oxidative stress from sunlight, we exposed fibroblasts to 10 J/cm2 ultraviolet A and found, in good agreement with current literature, not only that irradiation could partially reactivate autophagy in the aged cells, but also that this increase was phase shifted earlier from its endogenous temporal pattern because of its loss of synchronization with circadian rhythm.

  13. Characterizing heterogeneous cellular responses to perturbations.

    Science.gov (United States)

    Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

    2008-12-01

    Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

  14. A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis

    DEFF Research Database (Denmark)

    Villumsen, Bine H; Danielsen, Jannie R; Povlsen, Lou;

    2013-01-01

    Centriolar satellites are small, granular structures that cluster around centrosomes, but whose biological function and regulation are poorly understood. We show that centriolar satellites undergo striking reorganization in response to cellular stresses such as UV radiation, heat shock...

  15. Cellular and molecular level responses after radiofrequency radiation exposure, alone or in combination with x-rays or chemicals. Final report, 1 April 1991-30 September 1994

    Energy Technology Data Exchange (ETDEWEB)

    Meltz, M.L.; Natarajan, M.; Prasad, A.V.

    1995-02-21

    This project was initiated to explore the potential bioeffects of microwave radiation, alone or in combination with ionizing radiation and chemicals. Over the time period of the project, an automated thermal control system, to be used for maintaining the temperature in tissue culture medium during microwave exposures, was designed, constructed, and software was created. While this was underway during the project period, numerous positive control biological experiments were performed on two different cell types, the Epstein Barr Virus transformed 244B human lymphoblastoid cell, and the freshly isolated peripheral human lymphocyte. The 244B cells were used to address the question of whether a physical agent, ionizing radiation, at low doses where cells would predominantly remain viable, would induce the DNA binding protein NF-kB, and/or four immediate early genes (IEG) (protooncogenes).

  16. Dynamics of active cellular response under stress

    Science.gov (United States)

    de, Rumi; Zemel, Assaf; Safran, Samuel

    2008-03-01

    Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. Using a simple theoretical model that includes the forces due to both the mechanosensitive nature of cells and the elastic response of the matrix, we predict the dynamics of orientation of cells. The model predicts many features observed in measurements of cellular forces and orientation including the increase with time of the forces generated by cells in the absence of applied stress and the consequent decrease of the force in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material can be used to distinguish systems in which cell activity is controlled by stress from those where cell activity is controlled by strain. Reference: Nature Physics, vol. 3, pp 655 (2007).

  17. Complex cellular responses to reactive oxygen species.

    Science.gov (United States)

    Temple, Mark D; Perrone, Gabriel G; Dawes, Ian W

    2005-06-01

    Genome-wide analyses of yeast provide insight into cellular responses to reactive oxygen species (ROS). Many deletion mutants are sensitive to at least one ROS, but no one oxidant is representative of 'oxidative stress' despite the widespread use of a single compound such as H(2)O(2). This has major implications for studies of pathological situations. Cells have a range of mechanisms for maintaining resistance that involves either induction or repression of many genes and extensive remodeling of the transcriptome. Cells have constitutive defense systems that are largely unique to each oxidant, but overlapping, inducible repair systems. The pattern of the transcriptional response to a particular ROS depends on its concentration, and 'classical' antioxidant systems that are induced by high concentrations of ROS can be repressed when cells adapt to low concentrations of ROS.

  18. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure.

    Science.gov (United States)

    Franco, A; Ciccarelli, M; Sorriento, D; Napolitano, L; Fiordelisi, A; Trimarco, B; Durante, M; Iaccarino, G

    2016-05-01

    High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism.

  19. Molecular events basic to cellular radiation response

    Energy Technology Data Exchange (ETDEWEB)

    Kolodny, G. M.

    1979-09-01

    The initiation and control of the division process in normal cells is studied to gain insight into changes in these regards caused by x-irradiation and neoplasia. The Primer Hypothesis for eukaryotic gene regulation proposes that small molecular weight RNA acts as primer for new RNA synthesis by hybridizing with DNA and there initiating the transcription of a new RNA chain. The experiments reported here indicate that small molecular weight RNA will induce the production of new proteins. These results are consistent with the Primer Hypothesis, and demonstrate that RNA can be taken up from the media by cells in culture and can induce in vitro the production of differentiated cell products. (ACR)

  20. Cellular immune responses towards regulatory cells.

    Science.gov (United States)

    Larsen, Stine Kiær

    2016-01-01

    This thesis describes the results from two published papers identifying spontaneous cellular immune responses against the transcription factors Foxp3 and Foxo3. The tumor microenvironment is infiltrated by cells that hinder effective tumor immunity from developing. Two of these cell types, which have been linked to a bad prognosis for patients, are regulatory T cells (Treg) and tolerogenic dendritic cells (DC). Tregs inhibit effector T cells from attacking the tumor through various mechanisms, including secreted factors and cell-to-cell contact. Tregs express the transcription factor Foxp3, which is necessary for their development and suppressive activities. Tolerogenic DCs participate in creating an environment in the tumor where effector T cells become tolerant towards the tumor instead of attacking it. The transcription factor Foxo3 was recently described to be highly expressed by tolerogenic DCs and to programme their tolerogenic influence. This thesis describes for the first time the existence of spontaneous cellular immune responses against peptides derived from Foxp3 and Foxo3. We have detected the presence of cytotoxic T cells that recognise these peptides in an HLA-A2 restricted manner in cancer patients and for Foxp3 in healthy donors as well. In addition, we have demonstrated that the Foxp3- and Foxo3-specific CTLs recognize Foxp3- and Foxo3-expressing cancer cell lines and importantly, suppressive immune cells, namely Tregs and in vitro generated DCs. Cancer immunotherapy is recently emerging as an important treatment modality improving the survival of selected patients. The current progress is largely owing to targeting of the immune suppressive milieu that is dominating the tumor microenvironment. This is being done through immune checkpoint blockade with CTLA-4 and PD-1/PD-L1 antibodies and through lymphodepleting conditioning of patients and ex vivo activation of TILs in adoptive cell transfer. Several strategies are being explored for depletion of

  1. Maintenance of radiation-induced intestinal fibrosis: Cellular and molecular features

    Institute of Scientific and Technical Information of China (English)

    Valérie Haydont; Marie-Catherine Vozenin-Brotons

    2007-01-01

    Recent advances in cell and molecular radiobiology clearly showed that tissue response to radiation injury cannot be restricted to a simple cell-killing process, but depends upon continuous and integrated pathogenic processes, involving cell differentiation and crosstalk between the various cellular components of the tissue within the extracellular matrix. Thus, the prior concept of primary cell target in which a single-cell type (whatever it's epithelial or endothelial cells) dictates the whole tissue response to radiation injury has to be replaced by the occurrence of coordinated multicellular response that may either lead to tissue recovery or to sequel development. In this context, the present review will focus on the maintenance of the radiation-induced wound healing and fibrogenic signals triggered by and through the microenvironment toward the mesencnymal cell compartment, and will highlight how sequential and sustained modifications in cell phenotypes will in cascade modify cell-to-cell interactions and tissue composition.

  2. Nicotinamide prevents ultraviolet radiation-induced cellular energy loss.

    Science.gov (United States)

    Park, Joohong; Halliday, Gary M; Surjana, Devita; Damian, Diona L

    2010-01-01

    UV radiation is carcinogenic by causing mutations in the skin and also by suppressing cutaneous antitumor immunity. We previously found nicotinamide (vitamin B3) to be highly effective at reducing UV-induced immunosuppression in human volunteers, with microarray studies on in vivo irradiated human skin suggesting that nicotinamide normalizes subsets of apoptosis, immune function and energy metabolism-related genes that are downregulated by UV exposure. Using human adult low calcium temperature keratinocytes, we further investigated nicotinamide's effects on cellular energy metabolism. We found that nicotinamide prevented UV-induced cellular ATP loss and protected against UV-induced glycolytic blockade. To determine whether nicotinamide alters the effects of UV-induced oxidative stress posttranslationally, we also measured UV-induced reactive oxygen species (ROS). Nicotinamide had no effect on ROS formation, and at the low UV doses used in these studies, equivalent to ambient daily sun exposure, there was no evidence of apoptosis. Hence, nicotinamide appears to exert its UV protective effects on the skin via its role in cellular energy pathways.

  3. Cellular neoplastic transformation induced by 916 MHz microwave radiation.

    Science.gov (United States)

    Yang, Lei; Hao, Dongmei; Wang, Minglian; Zeng, Yi; Wu, Shuicai; Zeng, Yanjun

    2012-08-01

    There has been growing concern about the possibility of adverse health effects resulting from exposure to microwave radiations, such as those emitted by mobile phones. The purpose of this study was to investigate the cellular neoplastic transformation effects of electromagnetic fields. 916 MHz continuous microwave was employed in our study to simulate the electromagnetic radiation of mobile phone. NIH/3T3 cells were adopted in our experiment due to their sensitivity to carcinogen or cancer promoter in environment. They were divided randomly into one control group and three microwave groups. The three microwave groups were exposed to 916 MHz EMF for 2 h per day with power density of 10, 50, and 90 w/m(2), respectively, in which 10 w/m(2) was close to intensity near the antenna of mobile phone. The morphology and proliferation of NIH/3T3 cells were examined and furthermore soft agar culture and animal carcinogenesis assay were carried out to determine the neoplastic promotion. Our experiments showed NIH/3T3 cells changed in morphology and proliferation after 5-8 weeks exposure and formed clone in soft agar culture after another 3-4 weeks depending on the exposure intensity. In the animal carcinogenesis study, lumps developed on the back of SCID mice after being inoculated into exposed NIH/3T3 cells for more than 4 weeks. The results indicate that microwave radiation can promote neoplastic transformation of NIH/3T3cells.

  4. Mitochondria as Sub-cellular Targets of Space Radiation

    Science.gov (United States)

    Hei, Tom; Zhang, Bo; Davidson, Mercy

    High linear energy transfer (LET) radiation including alpha particles and heavy ions is the major type of radiation find in space and is considered a potential health risk for astronauts. Even though the chance that these high LET particles traversing through the cytoplasm of cells is higher than that through the nuclei, the contribution of targeted cytoplasmic irradiation, to the induction of genomic instability and other chromosomal damages induced by high LET radiation is not known. Mitochondria are the sole energy center of a cell and normal mitochondria are highly dynamic organelles that move along microtubules or microfilaments and continuously fuse and divide in healthy cells. A balance between mitochondrial fusion and fission is essential to maintain normal mitochondrial function. Targeted cytoplasmic irradiation by high LET alpha particles induced DNA oxidative damage and double strand breaks in wild type rho+ human small airway epithelial (SAE) cells. Furthermore, there was a significant increase in autophagy and micronuclei, which is an indication of genomic instability, together with the activation of nuclear factor kappa-B (NF-kappaB) and mitochondrial inducible nitric oxide synthase (iNOS) signaling pathways in rho+ SAE cells. In contrast, SAE cells with depleted mitochondrial DNA (rho0) and, therefore, no oxidative metabolic functions, exhibited a significantly lower response to these same endpoints examined after cytoplasmic irradiation with high LET alpha particles. The results indicate that normal mitochondrial function is essential in mediating radiation induced genotoxic damages in mammalian cells. Furthermore, the findings may shed some light in the design of countermeasures for space radiation protection.

  5. Mechanistic Modelling of DNA Repair and Cellular Survival Following Radiation-Induced DNA Damage

    Science.gov (United States)

    McMahon, Stephen J.; Schuemann, Jan; Paganetti, Harald; Prise, Kevin M.

    2016-09-01

    Characterising and predicting the effects of ionising radiation on cells remains challenging, with the lack of robust models of the underlying mechanism of radiation responses providing a significant limitation to the development of personalised radiotherapy. In this paper we present a mechanistic model of cellular response to radiation that incorporates the kinetics of different DNA repair processes, the spatial distribution of double strand breaks and the resulting probability and severity of misrepair. This model enables predictions to be made of a range of key biological endpoints (DNA repair kinetics, chromosome aberration and mutation formation, survival) across a range of cell types based on a set of 11 mechanistic fitting parameters that are common across all cells. Applying this model to cellular survival showed its capacity to stratify the radiosensitivity of cells based on aspects of their phenotype and experimental conditions such as cell cycle phase and plating delay (correlation between modelled and observed Mean Inactivation Doses R2 > 0.9). By explicitly incorporating underlying mechanistic factors, this model can integrate knowledge from a wide range of biological studies to provide robust predictions and may act as a foundation for future calculations of individualised radiosensitivity.

  6. Cellular immune responses to respiratory viruses

    NARCIS (Netherlands)

    van Helden, M.J.G.

    2011-01-01

    When a respiratory virus successfully infects the lungs, cascades of immune responses are initiated aimed to remove the pathogen. Immediate non-specific protection is provided by the innate immune system and this reduces the viral load during the first days of infection. The adaptive immune response

  7. Adaptation of the black yeast Wangiella dermatitidis to ionizing radiation: molecular and cellular mechanisms.

    Directory of Open Access Journals (Sweden)

    Kelly L Robertson

    Full Text Available Observations of enhanced growth of melanized fungi under low-dose ionizing radiation in the laboratory and in the damaged Chernobyl nuclear reactor suggest they have adapted the ability to survive or even benefit from exposure to ionizing radiation. However, the cellular and molecular mechanism of fungal responses to such radiation remains poorly understood. Using the black yeast Wangiella dermatitidis as a model, we confirmed that ionizing radiation enhanced cell growth by increasing cell division and cell size. Using RNA-seq technology, we compared the transcriptomic profiles of the wild type and the melanin-deficient wdpks1 mutant under irradiation and non-irradiation conditions. It was found that more than 3000 genes were differentially expressed when these two strains were constantly exposed to a low dose of ionizing radiation and that half were regulated at least two fold in either direction. Functional analysis indicated that many genes for amino acid and carbohydrate metabolism and cell cycle progression were down-regulated and that a number of antioxidant genes and genes affecting membrane fluidity were up-regulated in both irradiated strains. However, the expression of ribosomal biogenesis genes was significantly up-regulated in the irradiated wild-type strain but not in the irradiated wdpks1 mutant, implying that melanin might help to contribute radiation energy for protein translation. Furthermore, we demonstrated that long-term exposure to low doses of radiation significantly increased survivability of both the wild-type and the wdpks1 mutant, which was correlated with reduced levels of reactive oxygen species (ROS, increased production of carotenoid and induced expression of genes encoding translesion DNA synthesis. Our results represent the first functional genomic study of how melanized fungal cells respond to low dose ionizing radiation and provide clues for the identification of biological processes, molecular pathways and

  8. Endothelial Cellular Responses to Biodegradable Metal Zinc.

    Science.gov (United States)

    Ma, Jun; Zhao, Nan; Zhu, Donghui

    Biodegradable zinc (Zn) metals, a new generation of biomaterials, have attracted much attention due to their excellent biodegradability, bioabsorbability, and adaptability to tissue regeneration. Compared with magnesium (Mg) and iron (Fe), Zn exhibits better corrosion and mechanical behaviors in orthopedic and stent applications. After implantation, Zn containing material will slowly degrade, and Zn ions (Zn(2+)) will be released to the surrounding tissue. For stent applications, the local Zn(2+)concentration near endothelial tissue/cells could be high. However, it is unclear how endothelia will respond to such high concentrations of Zn(2+), which is pivotal to vascular remodeling and regeneration. Here, we evaluated the short-term cellular behaviors of primary human coronary artery endothelial cells (HCECs) exposed to a concentration gradient (0-140 μM) of extracellular Zn(2+). Zn(2+) had an interesting biphasic effect on cell viability, proliferation, spreading, and migration. Generally, low concentrations of Zn(2+) promoted viability, proliferation, adhesion, and migration, while high concentrations of Zn(2+) had opposite effects. For gene expression profiles, the most affected functional genes were related to cell adhesion, cell injury, cell growth, angiogenesis, inflammation, vessel tone, and coagulation. These results provide helpful information and guidance for Zn-based alloy design as well as the controlled release of Zn(2+)in stent and other related medical applications.

  9. Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Hazawa, Masaharu; Tomiyama, Kenichi; Saotome-Nakamura, Ai; Obara, Chizuka; Yasuda, Takeshi; Gotoh, Takaya; Tanaka, Izumi; Yakumaru, Haruko; Ishihara, Hiroshi; Tajima, Katsushi, E-mail: tajima@nirs.go.jp

    2014-04-18

    Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation.

  10. Effects of anesthesia-induced modest hypothermia on cellular radiation sensitivity

    Institute of Scientific and Technical Information of China (English)

    XIANG; Yingsong(项莺松); TANG; Gusheng(唐古生); XU; Xiongfei(许熊飞); YANG; Rujun(杨如俊); CAI; Jianming(蔡建明); ZHANG; Minghui(张明辉); CAO; Xuetao(曹雪涛)

    2002-01-01

    To assess the mechanisms of modest hypothermia(MH) and its effects on cellular radiation response, a model of anesthesia-induced modest hypothermia(AIMH) in the adult mice and a model of pure MH in the newborn mice were established. The survival rate of lethally irradiated mice was increased to 72% through AIMH before irradiation. Both apoptosis and necrosis of human fetal bone marrow CD34+ hematopoietic stem cells cultured under MH were significantly decreased as detected by MTT and flow cytometry, with three-color labeled by PE-CD34+/ FITC-AnnexinV /7AAD. The survival and proliferation of mouse bone marrow MNC treated with MH after irradiation were also increased. The MH exerted similar protective effects on the leukemia cell lines A20, HL60, K562 to the normal bone marrow cells, but it enhanced the radiation sensitivity of leukemia cell line FBL3 and mouse melanoma B16F10. No effects have been found on the radiation sensitivity of those cells treated with MH before irradiation. The results also showed that MH mediated the effects on radiation sensitivity, in addition to increasing the oxygen tension. These results show different effects of MH on different cells:(i) AIMH exerts a protective effect on the normal hematopoietic stem cells, some leukemia cell lines A20, HL60, K562, and some neoplasma 3LL, LOVO. And MH exhibits a synthetic effect with anesthetic.(ii) MH enhances the radiation sensitivity of another leukemia and neoplasma cell lines FBL3, B16F10 and CT26. Therefore, AIMH has a potential to enhance the effects of radiation-therapy and decrease side effects on some tumors.

  11. Cognitive effects of cellular phones: a possible role of non-radiofrequency radiation factors.

    Science.gov (United States)

    Hareuveny, Ronen; Eliyahu, Ilan; Luria, Roy; Meiran, Nachshon; Margaliot, Menachem

    2011-10-01

    Some studies found that cognitive functions of human beings may be altered while exposed to radiofrequency radiation (RFR) emitted by cellular phones. In two recent studies, we have found that experiment duration and exposure side (i.e., phone's location--right or left) may have a major influence on the detection of such effects. In this brief follow-up experiment, 29 right-handed male subjects were divided into two groups. Each subject had two standard cellular phones attached to both sides of his head. The subjects performed a spatial working memory task that required either a left-hand or a right-hand response under one of the two exposure conditions: left side of the head or right side. Contrary to our previous studies, in this work external antennas located far away from the subjects were connected to the cellular phones. This setup prevents any emission of RFR from the internal antenna, thus drastically reducing RFR exposure. Despite that, the results remain similar to those obtained in our previous work. These results indicate that some of the effects previously attributed to RFR can be the result of some confounders.

  12. Prevention of γ-radiation induced cellular genotoxicity by tempol: protection of hematopoietic system.

    Science.gov (United States)

    Ramachandran, Lakshmy; Nair, Cherupally Krishnan Krishnan

    2012-09-01

    Tempol (TPL) under in vitro conditions reduced the extent of gamma radiation induced membrane lipid peroxidation and disappearance of covalently closed circular form of plasmid pBR322. TPL protected cellular DNA from radiation-induced damage in various tissues under ex vivo and in vivo conditions as evidenced by comet assay. TPL also prevented radiation induced micronuclei formation (in peripheral blood leucocytes) and chromosomal aberrations (in bone marrow cells) in whole body irradiated mice. TPL enhanced the rate of repair of cellular DNA (blood leucocytes and bone marrow cells) damage when administered immediately after radiation exposure as revealed from the increased Cellular DNA Repair Index (CRI). The studies thus provided compelling evidence to reveal the effectiveness of TPL to protect hematopoietic system from radiation injury.

  13. Ionizing Radiation Induces Cellular Senescence of Articular Chondrocytes via Negative Regulation of SIRT1 by p38 Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Eun Hee; Hwang, Sang Gu [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-05-15

    Senescent cells exhibit irreversible growth arrest, large flat morphology, and up-regulated senescence-associated {beta}-galactosidase activity at pH 6.0. Several conditions, including oncogenic stress, oxidative stress, and DNA damage are associated with cellular senescence. Massive acute DNA double-strand breaks occurring as a result of mechanical and chemical stress can be repaired, but some DNA damage persists, eventually triggering premature senescence. Since ionizing radiation directly induces DBS, it is possible that cellular senescence is activated under these conditions. The biological events in chondrocytes following irradiation are poorly understood, and limited information is available on the molecular signal transduction mechanisms of cellular senescence at present. In this study, we identify SIRT1 as a target molecule of p38 kinase and demonstrate that the interactions between p38 kinase and SIRT1 protein play an important role in the regulation of cellular senescence in response to IR.

  14. Modeling In Vitro Cellular Responses to Silver Nanoparticles

    Directory of Open Access Journals (Sweden)

    Dwaipayan Mukherjee

    2014-01-01

    Full Text Available Engineered nanoparticles (NPs have been widely demonstrated to induce toxic effects to various cell types. In vitro cell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systems in vitro, to develop a mechanistic mathematical model that can support analysis and prediction of in vivo effects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized using in vitro measurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includes in vitro cellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based on in vitro measurements, and provides a “stepping stone” for the development of more advanced in vivo models that will incorporate additional cellular and NP interactions.

  15. Cellular response of Campylobacter jejuni to trisodium phosphate

    DEFF Research Database (Denmark)

    Riedel, Charlotte Tandrup; Cohn, M. T.; Stabler, R. A.

    2012-01-01

    The highly alkaline compound trisodium phosphate (TSP) is used as an intervention to reduce the load of Campylobacter on poultry meat in U.S. poultry slaughter plants. The aim of the present study was to investigate the cellular responses of Campylobacter jejuni NCTC11168 when exposed to sublethal...

  16. Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles

    Science.gov (United States)

    With increasing knowledge about the potential mechanisms underlying cellular functions, it is becoming feasible to predict the response of biological systems to genetic and environmental perturbations. Due to the lack of homogeneity in living tissues it is difficult to estimate t...

  17. Neuroendocrine system response modulates oxidative cellular damage in burn patients.

    Science.gov (United States)

    Xie, Xiao-Qi; Shinozawa, Yotaro; Sasaki, Junichi; Takuma, Kiyotsugu; Akaishi, Satoshi; Yamanouchi, Satoshi; Endo, Tomoyuki; Nomura, Ryosuke; Kobayashi, Michio; Kudo, Daisuke; Hojo, Nobuko

    2007-02-01

    Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.

  18. Dynamical theory of active cellular response to external stress.

    Science.gov (United States)

    De, Rumi; Safran, Samuel A

    2008-09-01

    We present a comprehensive, theoretical treatment of the orientational response to external stress of active, contractile cells embedded in a gel-like elastic medium. The theory includes both the forces that arise from the deformation of the matrix as well as forces due to the internal regulation of the stress fibers and focal adhesions of the cell. We calculate the time-dependent response of both the magnitude and the direction of the elastic dipole that characterizes the active forces exerted by the cell, for various situations. For static or quasistatic external stress, cells orient parallel to the stress while for high frequency dynamic external stress, cells orient nearly perpendicular. Both numerical and analytical calculations of these effects are presented. In addition we predict the relaxation time for the cellular response for both slowly and rapidly varying external stresses; several characteristic scaling regimes for the relaxation time as a function of applied frequency are predicted. We also treat the case of cells for which the regulation of the stress fibers and focal adhesions is controlled by strain (instead of stress) and show that the predicted dependence of the cellular orientation on the Poisson ratio of the matrix can differentiate strain vs stress regulation of cellular response.

  19. Dynamical theory of active cellular response to external stress

    Science.gov (United States)

    de, Rumi; Safran, Samuel A.

    2008-09-01

    We present a comprehensive, theoretical treatment of the orientational response to external stress of active, contractile cells embedded in a gel-like elastic medium. The theory includes both the forces that arise from the deformation of the matrix as well as forces due to the internal regulation of the stress fibers and focal adhesions of the cell. We calculate the time-dependent response of both the magnitude and the direction of the elastic dipole that characterizes the active forces exerted by the cell, for various situations. For static or quasistatic external stress, cells orient parallel to the stress while for high frequency dynamic external stress, cells orient nearly perpendicular. Both numerical and analytical calculations of these effects are presented. In addition we predict the relaxation time for the cellular response for both slowly and rapidly varying external stresses; several characteristic scaling regimes for the relaxation time as a function of applied frequency are predicted. We also treat the case of cells for which the regulation of the stress fibers and focal adhesions is controlled by strain (instead of stress) and show that the predicted dependence of the cellular orientation on the Poisson ratio of the matrix can differentiate strain vs stress regulation of cellular response.

  20. Electromagnetic Radiation Measurements and Safety Issues of some Cellular

    Directory of Open Access Journals (Sweden)

    A. Mousa

    2011-01-01

    Full Text Available As the mobile telecommunication systems are tremendously growing allover the world then the numbers of handheld andbase stations are also rapidly growing and it became very popular to see these base stations distributed everywhere in theneighborhood and on roof tops which has caused a considerable amount of panic to the public in Palestine concerning witherthe radiated electromagnetic field from these base stations may cause any health effect or hazard. This paper focuses on theradiated electromagnetic energy from some typical mobile base stations around the city of Nablus. The exposure levels dueto these stations were measured and compared to some international standard guidelines like ICNIRP and FCC to see if itmeets these standards, this is in order to answer some of the public fear and concern. The results are presented and somecomments are made on the other sources of electromagnetic radiation in the 200 kHz to 3 GHz range.

  1. Cell-cycle radiation response: Role of intracellular factors

    Science.gov (United States)

    Blakely, E.; Chang, P.; Lommel, L.; Bjornstad, K.; Dixon, M.; Tobias, C.; Kumar, K.; Blakely, W. F.

    We have been studying variations of radiosensitivity and endogenous cellular factors during the course of progression through the human and hamster cell cycle. After exposure to low-LET radiations, the most radiosensitive cell stages are mitosis and the G1/S interface. The increased activity of a specific antioxidant enzyme such as superoxide dismutase in G1-phase, and the variations of endogenous thiols during cell division are thought to be intracellular factors of importance to the radiation survival response. These factors may contribute to modifying the age-dependent yield of lesions or more likely, to the efficiency of the repair processes. These molecular factors have been implicated in our cellular measurements of the larger values for the radiobiological oxygen effect late in the cycle compared to earlier cell ages. Low-LET radiation also delays progression through S phase which may allow more time for repair and hence contribute to radioresistance in late-S-phase. The cytoplasmic and intranuclear milieu of the cell appears to have less significant effects on lesions produced by high-LET radiation compared to those made by low-LET radiation. High-LET radiation fails to slow progression through S phase, and there is much less repair of lesions evident at all cell ages; however, high-LET particles cause a more profound block in G2 phase than that observed after low-LET radiation. Hazards posed by the interaction of damage from sequential doses of radiations of different qualities have been evaluated and are shown to lead to a cell-cycle-dependent enhancement of radiobiological effects. A summary comparison of various cell-cycle-dependent endpoints measured with low-or high-LET radiations is given and includes a discussion of the possible additional effects introduced by microgravity.

  2. [Cellular and molecular mechanisms of radiation-induced brain injury: can peripheral markers be detected?].

    Science.gov (United States)

    Piskunov, A K; Nikitin, K V; Potapov, A A

    2015-01-01

    Investigation of the mechanisms of radiation-induced brain injury is a relevant fundamental objective of radiobiology and neuroradiology. Damage to the healthy brain tissue is the key factor limiting the application of radiation therapy in patients with nervous systems neoplasms. Furthermore, postradiation brain injury can be clinically indiscernible from continued tumor growth and requires differential diagnosis. Thus, there exists high demand for biomarkers of radiation effects on the brain in neurosurgery and radiobiology. These markers could be used for better understanding and quantifying the effects of ionizing radiation on brain tissues, as well as for elaborating personalized therapy. Despite the high demand, biomarkers of radiation-induced brain injury have not been identified thus far. The cellular and molecular mechanisms of the effect of ionizing radiation on the brain were analyzed in this review in order to identify potential biomarkers of radiation-induced injury to nervous tissue.

  3. The influence of microwave radiation from cellular phone on fetal rat brain.

    Science.gov (United States)

    Jing, Ji; Yuhua, Zhang; Xiao-qian, Yang; Rongping, Jiang; Dong-mei, Guo; Xi, Cui

    2012-03-01

    The increasing use of cellular phones in our society has brought focus on the potential detrimental effects to human health by microwave radiation. The aim of our study was to evaluate the intensity of oxidative stress and the level of neurotransmitters in the brains of fetal rats chronically exposed to cellular phones. The experiment was performed on pregnant rats exposed to different intensities of microwave radiation from cellular phones. Thirty-two pregnant rats were randomly divided into four groups: CG, GL, GM, and GH. CG accepted no microwave radiation, GL group radiated 10 min each time, GM group radiated 30 min, and GH group radiated 60 min. The 3 experimental groups were radiated 3 times a day from the first pregnant day for consecutively 20 days, and on the 21st day, the fetal rats were taken and then the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), noradrenaline (NE), dopamine (DA), and 5-hydroxyindole acetic acid (5-HT) in the brain were assayed. Compared with CG, there were significant differences (Pcellular phones during pregnancy has certain harm on fetal rat brains.

  4. Mammalian stem cells reprogramming in response to terahertz radiation.

    Directory of Open Access Journals (Sweden)

    Jonathan Bock

    Full Text Available We report that extended exposure to broad-spectrum terahertz radiation results in specific changes in cellular functions that are closely related to DNA-directed gene transcription. Our gene chip survey of gene expression shows that whereas 89% of the protein coding genes in mouse stem cells do not respond to the applied terahertz radiation, certain genes are activated, while other are repressed. RT-PCR experiments with selected gene probes corresponding to transcripts in the three groups of genes detail the gene specific effect. The response was not only gene specific but also irradiation conditions dependent. Our findings suggest that the applied terahertz irradiation accelerates cell differentiation toward adipose phenotype by activating the transcription factor peroxisome proliferator-activated receptor gamma (PPARG. Finally, our molecular dynamics computer simulations indicate that the local breathing dynamics of the PPARG promoter DNA coincides with the gene specific response to the THz radiation. We propose that THz radiation is a potential tool for cellular reprogramming.

  5. SIRT1 promotes DNA repair activity in response to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae-Min; Lee, Kee-Ho [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2006-07-01

    Human SIRT1 controls various physiological responses including cell fate, stress, and aging, through deacetylation of its specific substrate protein. In processing DNA damage signaling, SIRT1 attenuates a cellular apoptotic response by deacetylation of p53 tumor suppressor. Ectopically over-expressed SIRT1 resulted in the increase of repair of DNA strand breakages produced by radiation. On the other hand, repression of endogenous SIRT1 expression by SIRT1 siRNA led to the decrease of this repair activity, indicating that SIRT1 can regulate DNA repair capacity of cells with DNA strand breaks.

  6. Enhancement of radiation response with bevacizumab

    Directory of Open Access Journals (Sweden)

    Hoang Tien

    2012-04-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF plays a critical role in tumor angiogenesis. Bevacizumab is a humanized monoclonal antibody that neutralizes VEGF. We examined the impact on radiation response by blocking VEGF signaling with bevacizumab. Methods Human umbilical vein endothelial cell (HUVEC growth inhibition and apoptosis were examined by crystal violet assay and flow cytometry, respectively. In vitro HUVEC tube formation and in vivo Matrigel assays were performed to assess the anti-angiogenic effect. Finally, a series of experiments of growth inhibition on head and neck (H&N SCC1 and lung H226 tumor xenograft models were conducted to evaluate the impact of bevacizumab on radiation response in concurrent as well as sequential therapy. Results The anti-angiogenic effect of bevacizumab appeared to derive not only from inhibition of endothelial cell growth (40% but also by interfering with endothelial cell function including mobility, cell-to-cell interaction and the ability to form capillaries as reflected by tube formation. In cell culture, bevacizumab induced a 2 ~ 3 fold increase in endothelial cell apoptosis following radiation. In both SCC1 and H226 xenograft models, the concurrent administration of bevacizumab and radiation reduced tumor blood vessel formation and inhibited tumor growth compared to either modality alone. We observed a siginificant tumor reduction in mice receiving the combination of bevacizumab and radiation in comparison to mice treated with bevacizumab or radiation alone. We investigated the impact of bevacizumab and radiation treatment sequence on tumor response. In the SCC1 model, tumor response was strongest with radiation followed by bevacizumab with less sequence impact observed in the H226 model. Conclusions Overall, these data demonstrate enhanced tumor response when bevacizumab is combined with radiation, supporting the emerging clinical investigations that are combining anti

  7. Innate Cellular Immune Responses in Aedes caspius (Diptera: Culicidae) Mosquitoes.

    Science.gov (United States)

    Soliman, D E; Farid, H A; Hammad, R E; Gad, A M; Bartholomay, L C

    2016-03-01

    Mosquitoes transmit a variety of pathogens that have devastating consequences for global public and veterinary health. Despite their capacity to serve as vectors, these insects have a robust capacity to respond to invading organisms with strong cellular and humoral immune responses. In Egypt, Aedes caspius (Pallas, 1771) has been suspected to act as a bridge vector of Rift Valley Fever virus between animals and humans. Microscopic analysis of Ae. caspius hemolymph revealed the presence of phagocytic cells called granulocytes. We further evaluated cellular immune responses produced by Ae. caspius as a result of exposure to a Gram-negative, and Gram-positive bacterium, and to latex beads. After challenge, a rapid and strong phagocytic response against either a natural or synthetic invader was evident. Hemocyte integrity in bacteria-inoculated mosquitoes was not morphologically affected. The number of circulating granulocytes decreased with age, reducing the overall phagocytic capacity of mosquitoes over time. The magnitude and speed of the phagocytic response suggested that granulocytes act as an important force in the battle against foreign invaders, as has been characterized in other important mosquito vector species.

  8. Antioxidant responses and cellular adjustments to oxidative stress.

    Science.gov (United States)

    Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

    2015-12-01

    Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases.

  9. Antioxidant responses and cellular adjustments to oxidative stress

    Science.gov (United States)

    Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

    2015-01-01

    Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. PMID:26233704

  10. The Effect of Radiation on the Immune Response to Cancers

    Directory of Open Access Journals (Sweden)

    Bonggoo Park

    2014-01-01

    Full Text Available In cancer patients undergoing radiation therapy, the beneficial effects of radiation can extend beyond direct cytotoxicity to tumor cells. Delivery of localized radiation to tumors often leads to systemic responses at distant sites, a phenomenon known as the abscopal effect which has been attributed to the induction and enhancement of the endogenous anti-tumor innate and adaptive immune response. The mechanisms surrounding the abscopal effect are diverse and include trafficking of lymphocytes into the tumor microenvironment, enhanced tumor recognition and killing via up-regulation of tumor antigens and antigen presenting machinery and, induction of positive immunomodulatory pathways. Here, we discuss potential mechanisms of radiation-induced enhancement of the anti-tumor response through its effect on the host immune system and explore potential combinational immune-based strategies such as adoptive cellular therapy using ex vivo expanded NK and T cells as a means of delivering a potent effector population in the context of radiation-enhanced anti-tumor immune environment.

  11. A Bioinformatics Filtering Strategy for Identifying Radiation Response Biomarker Candidates

    Science.gov (United States)

    Oh, Jung Hun; Wong, Harry P.; Wang, Xiaowei; Deasy, Joseph O.

    2012-01-01

    The number of biomarker candidates is often much larger than the number of clinical patient data points available, which motivates the use of a rational candidate variable filtering methodology. The goal of this paper is to apply such a bioinformatics filtering process to isolate a modest number (<10) of key interacting genes and their associated single nucleotide polymorphisms involved in radiation response, and to ultimately serve as a basis for using clinical datasets to identify new biomarkers. In step 1, we surveyed the literature on genetic and protein correlates to radiation response, in vivo or in vitro, across cellular, animal, and human studies. In step 2, we analyzed two publicly available microarray datasets and identified genes in which mRNA expression changed in response to radiation. Combining results from Step 1 and Step 2, we identified 20 genes that were common to all three sources. As a final step, a curated database of protein interactions was used to generate the most statistically reliable protein interaction network among any subset of the 20 genes resulting from Steps 1 and 2, resulting in identification of a small, tightly interacting network with 7 out of 20 input genes. We further ranked the genes in terms of likely importance, based on their location within the network using a graph-based scoring function. The resulting core interacting network provides an attractive set of genes likely to be important to radiation response. PMID:22768051

  12. A bioinformatics filtering strategy for identifying radiation response biomarker candidates.

    Directory of Open Access Journals (Sweden)

    Jung Hun Oh

    Full Text Available The number of biomarker candidates is often much larger than the number of clinical patient data points available, which motivates the use of a rational candidate variable filtering methodology. The goal of this paper is to apply such a bioinformatics filtering process to isolate a modest number (<10 of key interacting genes and their associated single nucleotide polymorphisms involved in radiation response, and to ultimately serve as a basis for using clinical datasets to identify new biomarkers. In step 1, we surveyed the literature on genetic and protein correlates to radiation response, in vivo or in vitro, across cellular, animal, and human studies. In step 2, we analyzed two publicly available microarray datasets and identified genes in which mRNA expression changed in response to radiation. Combining results from Step 1 and Step 2, we identified 20 genes that were common to all three sources. As a final step, a curated database of protein interactions was used to generate the most statistically reliable protein interaction network among any subset of the 20 genes resulting from Steps 1 and 2, resulting in identification of a small, tightly interacting network with 7 out of 20 input genes. We further ranked the genes in terms of likely importance, based on their location within the network using a graph-based scoring function. The resulting core interacting network provides an attractive set of genes likely to be important to radiation response.

  13. Fluorescence studies on radiation oxidative damage to membranes with implications to cellular radiosensitivity

    Indian Academy of Sciences (India)

    K P Mishra

    2002-12-01

    Radiation oxidative damage to plasma membrane and its consequences to cellular radiosensitivity have received increasing attention in the past few years. This review gives a brief account of radiation oxidative damage in model and cellular membranes with particular emphasis on results from our laboratory. Fluorescence and ESR spin probes have been employed to investigate the structural and functional alterations in membranes after g-irradiation. Changes in the lipid bilayer in irradiated unilamellar liposomes prepared from egg yolk lecithin (EYL) were measured by using diphenylhexatriene (DPH) as a probe. The observed increase in DPH polarization and decrease in fluorescence intensity after g-irradiation of liposomes imply radiationinduced decrease in bilayer fluidity. Inclusion of cholesterol in liposome was found to protect lipids against radiation damage, possibly by modulation of bilayer organization e.g. lipid packing. Measurements on dipalmitoyl phosphatidylcholine (DPPC) liposomes loaded with 6-carboxyfluorescein (CF) showed radiation dose-dependent release of the probe indicating radiation-induced increased permeability. Changes in plasma membrane permeability of thymocytes were monitored by fluorescein diacetate (FDA) and induced intracellular reactive oxygen species (ROS) were determined by 2,7-dichlorodihydro fluorescein diacetate (DCH-FDA). Results suggest a correlation between ROS generation and membrane permeability changes induced by radiation within therapeutic doses (0-10 Gy). It is concluded that increase in membrane permeability was the result of ROS-mediated oxidative reactions, which might trigger processes leading to apoptotic cell death after radiation exposure.

  14. Responsive copolymer films obtained by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Burillo, G.; Bucio, E. [Departamento de Quimica de Radiaciones y Radioquimica, Instituto de Ciencias Nucleares, UNAM, Circuito Exterior, Ciudad Universitaria, Mexico 04510, D. F. (Mexico)], e-mail: burillo@nucleares.unam.mx

    2009-07-01

    The graft copolymerization of ph and/or thermo sensitive monomers onto polymeric films can be achieved by different radiation methods which have great advantages compared to conventional methods. Their ph and thermal sensitivity properties, as well as LCST and critical ph point, have been studied by DSC, UV, FTIR, water contact angle and swelling. Graft copolymerization can be carried out by pre-irradiation oxidative and direct methods, using {sup 6}0Co gamma radiation or a Van de Graaff electron beam accelerator. The influence of synthesis conditions, such as pre-irradiation or radiation doses, dose rate, reaction time, monomer concentration, and reaction temperature are being studied. Advances in the field of responsive polymeric systems synthesized by ionizing radiation, their applications and promising future research on radiation graft polymerization and crosslinking will be discussed. (Author)

  15. Radiation response of the canine cardiovascular system

    Energy Technology Data Exchange (ETDEWEB)

    Gavin, P.R. (Washington State Univ., Pullman); Gillette, E.L.

    1982-06-01

    The hearts of dogs were irradiated with /sup 60/Co ..gamma.. rays. The dose required to produce pericardial effusion in 50% of the dogs by 180 days (PED/sub 50///sub 180/) was 1220 rad. For cardiac tamponade, the CTD /sub 50///sub 180/ was 1500 rad. Morphometric analyses of the hearts showed decreased capillary volume and increased fibrosis as radiation dose increased. The pericardial thickness increased with increased radiation dose. The slopes of the dose response for these parameters were similar as determined by linear regression of the parameter versus radiation dose.

  16. Cell damage from radiation-induced bystander effects for different cell densities simulated by a mathematical model via cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Meireles, Sincler P. de; Santos, Adriano M.; Grynberg, Suely Epsztein, E-mail: spm@cdtn.b, E-mail: amsantos@cdtn.b, E-mail: seg@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Nunes, Maria Eugenia S., E-mail: mariaeugenia@iceb.ufop.b [Universidade Federal de Ouro Preto (UFOP), MG (Brazil)

    2011-07-01

    During recent years, there has been a shift from an approach focused entirely on DNA as the main target of ionizing radiation to a vision that considers complex signaling pathways in cells and among cells within tissues. Several newly recognized responses were classified as the so-called non-target responses in which the biological effects are not directly related to the amount of energy deposited in the DNA of cells that were traversed by radiation. In 1992 the bystander effect was described referring to a series of responses such as death, chromosomal instability or other abnormalities that occur in non-irradiated cells that came into contact with irradiated cells or medium from irradiated cells. In this work, we have developed a mathematical model via cellular automata, to quantify cell death induced by the bystander effect. The model is based on experiments with irradiated cells conditioned medium which suggests that irradiated cells secrete molecules in the medium that are capable of damaging other cells. The computational model consists of two-dimensional cellular automata which is able to simulate the transmission of bystander signals via extrinsic route and via Gap junctions. The model has been validated by experimental results in the literature. The time evolution of the effect and the dose-response curves were obtained in good accordance to them. Simulations were conducted for different values of bystander and irradiated cell densities with constant dose. From this work, we have obtained a relationship between cell density and effect. (author)

  17. Radiation-induced gene responses

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Paunesku, T.; Shearin-Jones, P.; Oryhon, J.

    1996-12-31

    In the process of identifying genes that are differentially regulated in cells exposed to ultraviolet radiation (UV), we identified a transcript that was repressed following the exposure of cells to a combination of UV and salicylate, a known inhibitor of NF-kappaB. Sequencing this band determined that it has identify to lactate dehydrogenase, and Northern blots confirmed the initial expression pattern. Analysis of the sequence of the LDH 5` region established the presence of NF-kappaB, Sp1, and two Ap-2 elements; two partial AP- 1; one partial RE, and two halves of E-UV elements were also found. Electromobility shift assays were then performed for the AP-1, NF- kappaB, and E-UV elements. These experiments revealed that binding to NF-kappaB was induced by UV but repressed with salicylic acid; UV did not affect AP-1 binding, but salicylic acid inhibited it alone or following UV exposure; and E-UV binding was repressed by UV, and salicylic acid had little effect. Since the binding of no single element correlated with the expression pattern of LDH, it is likely that multiple elements govern UV/salicylate-mediated expression.

  18. WORKSHOP REPORT: MOLECULAR & CELLULAR BIOLOGY OF MODERATE DOSE (1-10 GY) RADIATION & POTENTIAL MECHANISMS OF RADIATION PROTECTION

    Science.gov (United States)

    EXECUTIVE SUMMARYNormal tissue response and injury after exposure to ionizing radiation are of great importance to patients with cancer, populations potentially subjected to military, accidental or intentional exposure including bioterrorism, and workers in the nuclear po...

  19. Radiation triggering immune response and inflammation.

    Science.gov (United States)

    Hekim, Nezih; Cetin, Zafer; Nikitaki, Zacharenia; Cort, Aysegul; Saygili, Eyup Ilker

    2015-11-28

    Radiation therapy (RT) is a well-established but still under optimization branch of Cancer Therapy (CT). RT uses electromagnetic waves or charged particles in order to kill malignant cells, by accumulating the energy onto these cells. The issue at stake for RT, as well as for any other Cancer Therapy technique, is always to kill only cancer cells, without affecting the surrounding healthy ones. This perspective of CT is usually described under the terms "specificity" and "selectivity". Specificity and selectivity are the ideal goal, but the ideal is never entirely achieved. Thus, in addition to killing healthy cells, changes and effects are observed in the immune system after irradiation. In this review, we mainly focus on the effects of ionizing radiation on the immune system and its components like bone marrow. Additionally, we are interested in the effects and benefits of low-dose ionizing radiation on the hematopoiesis and immune response. Low dose radiation has been shown to induce biological responses like inflammatory responses, innate immune system activation and DNA repair (adaptive response). This review reveals the fact that there are many unanswered questions regarding the role of radiation as either an immune-activating (low dose) or immunosuppressive (high dose) agent.

  20. The cellular bases of antibody responses during dengue virus infection

    Directory of Open Access Journals (Sweden)

    Juan Carlos Yam-Puc

    2016-06-01

    Full Text Available Dengue virus (DENV is one of the most significant human viral pathogens transmitted by mosquitoes and can cause from an asymptomatic disease to mild undifferentiated fever, classical dengue, and severe dengue. Neutralizing memory antibody (Ab responses are one of the most important mechanisms that counteract reinfections and are therefore the main aim of vaccination. However, it has also been proposed that in dengue, some of these class-switched (IgG memory Abs might worsen the disease. Although these memory Abs derive from B cells by T-cell dependent processes, we know rather little about the (acute, chronic or memory B cell responses and the complex cellular mechanisms generating these Abs during DENV infections.This review aims to provide an updated and comprehensive perspective of the B cell responses during DENV infection, starting since the very early events like the cutaneous DENV entrance and the arrival into draining lymph nodes, to the putative B cell activation, proliferation and germinal centers (GCs formation (the source of affinity-matured class-switched memory Abs, till the outcome of GC reactions such as the generation of plasmablasts, Ab-secreting plasma cells and memory B cells. We discuss topics very poorly explored such as the possibility of B cell infection by DENV or even activation-induced B cell death. The current information about the nature of the Ab responses to DENV is also illustrated.

  1. Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles

    Directory of Open Access Journals (Sweden)

    Shah Imran

    2011-07-01

    Full Text Available Abstract Background With increasing knowledge about the potential mechanisms underlying cellular functions, it is becoming feasible to predict the response of biological systems to genetic and environmental perturbations. Due to the lack of homogeneity in living tissues it is difficult to estimate the physiological effect of chemicals, including potential toxicity. Here we investigate a biologically motivated model for estimating tissue level responses by aggregating the behavior of a cell population. We assume that the molecular state of individual cells is independently governed by discrete non-deterministic signaling mechanisms. This results in noisy but highly reproducible aggregate level responses that are consistent with experimental data. Results We developed an asynchronous threshold Boolean network simulation algorithm to model signal transduction in a single cell, and then used an ensemble of these models to estimate the aggregate response across a cell population. Using published data, we derived a putative crosstalk network involving growth factors and cytokines - i.e., Epidermal Growth Factor, Insulin, Insulin like Growth Factor Type 1, and Tumor Necrosis Factor α - to describe early signaling events in cell proliferation signal transduction. Reproducibility of the modeling technique across ensembles of Boolean networks representing cell populations is investigated. Furthermore, we compare our simulation results to experimental observations of hepatocytes reported in the literature. Conclusion A systematic analysis of the results following differential stimulation of this model by growth factors and cytokines suggests that: (a using Boolean network ensembles with asynchronous updating provides biologically plausible noisy individual cellular responses with reproducible mean behavior for large cell populations, and (b with sufficient data our model can estimate the response to different concentrations of extracellular ligands. Our

  2. The DNA damage response in viral-induced cellular transformation.

    Science.gov (United States)

    Nikitin, P A; Luftig, M A

    2012-01-31

    The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress downstream of aberrant oncogene over-expression. Recent studies have now implicated the DDR as a sensor of oncogenic virus infection. In this review, we discuss the mechanisms by which tumour viruses activate and also suppress the host DDR. The mechanism of tumour virus induction of the DDR is intrinsically linked to the need for these viruses to promote an S-phase environment to replicate their nucleic acid during infection. However, inappropriate expression of viral oncoproteins can also activate the DDR through various mechanisms including replicative stress, direct interaction with DDR components and induction of reactive oxygen species. Given the growth-suppressive consequences of activating the DDR, tumour viruses have also evolved mechanisms to attenuate these pathways. Aberrant expression of viral oncoproteins may therefore promote tumourigenesis through increased somatic mutation and aneuploidy due to DDR inactivation. This review will focus on the interplay between oncogenic viruses and the DDR with respect to cellular checkpoint control and transformation.

  3. Humoral and Cellular Immune Response in Canine Hypothyroidism.

    Science.gov (United States)

    Miller, J; Popiel, J; Chełmońska-Soyta, A

    2015-07-01

    Hypothyroidism is one of the most common endocrine diseases in dogs and is generally considered to be autoimmune in nature. In human hypothyroidism, the thyroid gland is destroyed by both cellular (i.e. autoreactive helper and cytotoxic T lymphocytes) and humoral (i.e. autoantibodies specific for thyroglobulin, thyroxine and triiodothyronine) effector mechanisms. Other suggested factors include impaired peripheral immune suppression (i.e. the malfunction of regulatory T cells) or an additional pro-inflammatory effect of T helper 17 lymphocytes. The aim of this study was to evaluate immunological changes in canine hypothyroidism. Twenty-eight clinically healthy dogs, 25 hypothyroid dogs without thyroglobulin antibodies and eight hypothyroid dogs with these autoantibodies were enrolled into the study. There were alterations in serum proteins in hypothyroid dogs compared with healthy controls (i.e. raised concentrations of α-globulins, β2- and γ-globulins) as well as higher concentration of acute phase proteins and circulating immune complexes. Hypothyroid animals had a lower CD4:CD8 ratio in peripheral blood compared with control dogs and diseased dogs also had higher expression of interferon γ (gene and protein expression) and CD28 (gene expression). Similar findings were found in both groups of hypothyroid dogs. Canine hypothyroidism is therefore characterized by systemic inflammation with dominance of a cellular immune response.

  4. UV radiation in marine ectotherms: Molecular effects and responses

    Energy Technology Data Exchange (ETDEWEB)

    Dahms, Hans-U. [National Research Lab of Marine Molecular and Environmental Bioscience, Department of Chemistry and the Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Green Life Science, College of Natural Science, Sangmyung University, Seoul 110-743 (Korea, Republic of); Lee, Jae-Seong, E-mail: jslee2@hanyang.ac.kr [National Research Lab of Marine Molecular and Environmental Bioscience, Department of Chemistry and the Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2010-04-01

    This review summarizes current knowledge on ultraviolet radiation (UVR)-induced cellular and molecular damage in marine ectotherms (invertebrates and fish). UVR impairs sperm motility, reduces fertilization, and causes embryo malformation that in turn affects recruitment and therefore the sustainability of natural populations. The direct molecular effects of UVR are mediated by absorption of certain wavelengths by specific macromolecules and the dissipation of the absorbed energy via photochemical reactions. Most organisms have defense mechanisms that either prevent UVR-induced damage, or mechanisms that repair the damage. Photoprotective pigments, antioxidant defense compounds, and cell cycle development genes are some of the molecules involved in UVR defense. Photoenzymatic repair and nucleotide excision repair are the two primary DNA repair systems in marine ectotherms. We anticipate that toxicogenomic studies will gain importance in UVR research because they can elucidate the primary processes involved in UVR damage and the cellular response to this damage.

  5. Combined Effect of Low-Intensity Helium-Neon Laser and X-Ray Radiation on in Vivo Cellular Response of the Whole Blood and Lymphoid Organs in Mice.

    Science.gov (United States)

    Zaichkina, S I; Dyukina, A R; Rozanova, O M; Romanchenko, S P; Sirota, N P; Kuznetsova, E A; Simonova, N B; Sorokina, S S; Zakrzhevskaya, D T; Yusupov, V I; Bagratishvili, V N

    2016-09-01

    We studied the effect of exposure to helium-neon laser (dose range 0.16-50 mJ/cm(2)) on activation of natural protection reserve in mice using the adaptive response test. DNA comets method revealed a protective response manifested in DNA damage level in whole blood leukocytes of mice and in lymphoid organs by the thymus and spleen weight index; preexposure to laser did not induce the adaptive response. ROS level in the whole blood was assessed by the level of zymosan-induced luminol chemiluminescence. In mice subjected to adaptive laser irradiation in doses of 0.16-5 mJ/cm(2) followed by X-ray irradiation in a dose of 1.5 Gy, the activation index calculated as the ratio of induced to spontaneous area of luminescence was by 1.4 times lower than that in non-irradiated animals, which attested to reduced ROSgeneration reserve capacity of neutrophils.

  6. MOF maintains transcriptional programs regulating cellular stress response.

    Science.gov (United States)

    Sheikh, B N; Bechtel-Walz, W; Lucci, J; Karpiuk, O; Hild, I; Hartleben, B; Vornweg, J; Helmstädter, M; Sahyoun, A H; Bhardwaj, V; Stehle, T; Diehl, S; Kretz, O; Voss, A K; Thomas, T; Manke, T; Huber, T B; Akhtar, A

    2016-05-01

    MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions. However, in response to injury, MOF is absolutely critical for podocyte maintenance in vivo. Consistently, we detect defective nuclear, endoplasmic reticulum and Golgi structures, as well as presence of multivesicular bodies in vivo in podocytes lacking Mof following injury. Undertaking genome-wide expression analysis of podocytes, we uncover several MOF-regulated pathways required for stress response. We find that MOF, along with the members of the non-specific lethal but not the male-specific lethal complex, directly binds to genes encoding the lysosome, endocytosis and vacuole pathways, which are known regulators of podocyte maintenance. Thus, our work identifies MOF as a key regulator of cellular stress response in glomerular podocytes.

  7. Mechano-biological Coupling of Cellular Responses to Microgravity

    Science.gov (United States)

    Long, Mian; Wang, Yuren; Zheng, Huiqiong; Shang, Peng; Duan, Enkui; Lü, Dongyuan

    2015-11-01

    Cellular response to microgravity is a basic issue in space biological sciences as well as space physiology and medicine. It is crucial to elucidate the mechano-biological coupling mechanisms of various biological organisms, since, from the principle of adaptability, all species evolved on the earth must possess the structure and function that adapts their living environment. As a basic element of an organism, a cell usually undergoes mechanical and chemical remodeling to sense, transmit, transduce, and respond to the alteration of gravitational signals. In the past decades, new computational platforms and experimental methods/techniques/devices are developed to mimic the biological effects of microgravity environment from the viewpoint of biomechanical approaches. Mechanobiology of plant gravisensing in the responses of statolith movements along the gravity vector and the relevant signal transduction and molecular regulatory mechanisms are investigated at gene, transcription, and protein levels. Mechanotransduction of bone or immune cell responses and stem cell development and tissue histogenesis are elucidated under microgravity. In this review, several important issues are briefly discussed. Future issues on gravisensing and mechanotransducing mechanisms are also proposed for ground-based studies as well as space missions.

  8. Biophysical responses upon the interaction of nanomaterials with cellular interfaces.

    Science.gov (United States)

    Wu, Yun-Long; Putcha, Nirupama; Ng, Kee Woei; Leong, David Tai; Lim, Chwee Teck; Loo, Say Chye Joachim; Chen, Xiaodong

    2013-03-19

    The explosion of study of nanomaterials in biological applications (the nano-bio interface) can be ascribed to nanomaterials' growing importance in diagnostics, therapeutics, theranostics (therapeutic diagnostics), and targeted modulation of cellular processes. However, a growing number of critics have raised concerns over the potential risks of nanomaterials to human health and safety. It is essential to understand nanomaterials' potential toxicity before they are tested in humans. These risks are complicated to unravel, however, because of the complexity of cells and their nanoscale macromolecular components, which enable cells to sense and respond to environmental cues, including nanomaterials. In this Account, we explore these risks from the perspective of the biophysical interactions between nanomaterials and cells. Biophysical responses to the uptake of nanomaterials can include conformational changes in biomolecules like DNA and proteins, and changes to the cellular membrane and the cytoskeleton. Changes to the latter two, in particular, can induce changes in cell elasticity, morphology, motility, adhesion, and invasion. This Account reviews what is known about cells' biophysical responses to the uptake of the most widely studied and used nanoparticles, such as carbon-based, metal, metal-oxide, and semiconductor nanomaterials. We postulate that the biophysical structure impairment induced by nanomaterials is one of the key causes of nanotoxicity. The disruption of cellular structures is affected by the size, shape, and chemical composition of nanomaterials, which are also determining factors of nanotoxicity. Currently, popular nanotoxicity characterizations, such as the MTT and lactate dehydrogenase (LDH) assays, only provide end-point results through chemical reactions. Focusing on biophysical structural changes induced by nanomaterials, possibly in real-time, could deepen our understanding of the normal and altered states of subcellular structures and

  9. Robust network topologies for generating switch-like cellular responses.

    Directory of Open Access Journals (Sweden)

    Najaf A Shah

    2011-06-01

    Full Text Available Signaling networks that convert graded stimuli into binary, all-or-none cellular responses are critical in processes ranging from cell-cycle control to lineage commitment. To exhaustively enumerate topologies that exhibit this switch-like behavior, we simulated all possible two- and three-component networks on random parameter sets, and assessed the resulting response profiles for both steepness (ultrasensitivity and extent of memory (bistability. Simulations were used to study purely enzymatic networks, purely transcriptional networks, and hybrid enzymatic/transcriptional networks, and the topologies in each class were rank ordered by parametric robustness (i.e., the percentage of applied parameter sets exhibiting ultrasensitivity or bistability. Results reveal that the distribution of network robustness is highly skewed, with the most robust topologies clustering into a small number of motifs. Hybrid networks are the most robust in generating ultrasensitivity (up to 28% and bistability (up to 18%; strikingly, a purely transcriptional framework is the most fragile in generating either ultrasensitive (up to 3% or bistable (up to 1% responses. The disparity in robustness among the network classes is due in part to zero-order ultrasensitivity, an enzyme-specific phenomenon, which repeatedly emerges as a particularly robust mechanism for generating nonlinearity and can act as a building block for switch-like responses. We also highlight experimentally studied examples of topologies enabling switching behavior, in both native and synthetic systems, that rank highly in our simulations. This unbiased approach for identifying topologies capable of a given response may be useful in discovering new natural motifs and in designing robust synthetic gene networks.

  10. Ethanol cellular defense induce unfolded protein response in yeast

    Directory of Open Access Journals (Sweden)

    Elisabet eNavarro-Tapia

    2016-02-01

    Full Text Available Ethanol is a valuable industrial product and a common metabolite used by many cell types. However, this molecule produces high levels of cytotoxicity affecting cellular performance at several levels. In the presence of ethanol, cells must adjust some of their components, such as the membrane lipids to maintain homeostasis. In the case of microorganism as Saccharomyces cerevisiae, ethanol is one of the principal products of their metabolism and is the main stress factor during fermentation. Although many efforts have been made, mechanisms of ethanol tolerance are not fully understood and very little evidence is available to date for specific signaling by ethanol in the cell. This work studied two Saccharomyces cerevisiae strains, CECT10094 and Temohaya-MI26, isolated from flor wine and agave fermentation (a traditional fermentation from Mexico respectively, which differ in ethanol tolerance, in order to understand the molecular mechanisms underlying the ethanol stress response and the reasons for different ethanol tolerance. The transcriptome was analyzed after ethanol stress and, among others, an increased activation of genes related with the unfolded protein response (UPR and its transcription factor, Hac1p, was observed in the tolerant strain CECT10094. We observed that this strain also resist more UPR agents than Temohaya-MI26 and the UPR-ethanol stress correlation was corroborated observing growth of 15 more strains and discarding UPR correlation with other stresses as thermal or oxidative stress. Furthermore, higher activation of UPR pathway in the tolerant strain CECT10094 was observed using a UPR mCherry reporter. Finally, we observed UPR activation in response to ethanol stress in other S. cerevisiae ethanol tolerant strains as the wine strains T73 and EC1118. This work demonstrates that the UPR pathway is activated under ethanol stress occurring in a standard fermentation and links this response to an enhanced ethanol tolerance. Thus

  11. Review of photokeratitis: Corneal response to ultraviolet radiation (UVR exposure*

    Directory of Open Access Journals (Sweden)

    L A. Moore

    2010-12-01

    Full Text Available The development of photokeratitis in response to natural solar ultraviolet radiation (UVR is prevalent in individuals participating in outdoor recreational activities in environments with high reflective surfaces, such as beach activities, water sports and snow skiing. Eye care practitioners (ECPs are frequently encouraged by manufacturers and researchers to recommend UVR-blocking eyewear in the form of sunglasses and contact lenses. However, little is known about the precise nature of the corneal tissue response in the development of photokeratitis. This paper reviews the mechanisms responsible for the development of photokeratitis. Clinical signs and symptoms of photokeratitis, UVR corneal threshold and action spectra, corneal cellular changes and ocular protection from corneal UVR exposure are discussed. The content of this article will be useful to ECPs in making appropriate recommendations when prescribing UVR-protec-tive eyewear. (S Afr Optom 2010 69(3 123-131

  12. Semantic annotation of biological concepts interplaying microbial cellular responses

    Directory of Open Access Journals (Sweden)

    Carreira Rafael

    2011-11-01

    Full Text Available Abstract Background Automated extraction systems have become a time saving necessity in Systems Biology. Considerable human effort is needed to model, analyse and simulate biological networks. Thus, one of the challenges posed to Biomedical Text Mining tools is that of learning to recognise a wide variety of biological concepts with different functional roles to assist in these processes. Results Here, we present a novel corpus concerning the integrated cellular responses to nutrient starvation in the model-organism Escherichia coli. Our corpus is a unique resource in that it annotates biomedical concepts that play a functional role in expression, regulation and metabolism. Namely, it includes annotations for genetic information carriers (genes and DNA, RNA molecules, proteins (transcription factors, enzymes and transporters, small metabolites, physiological states and laboratory techniques. The corpus consists of 130 full-text papers with a total of 59043 annotations for 3649 different biomedical concepts; the two dominant classes are genes (highest number of unique concepts and compounds (most frequently annotated concepts, whereas other important cellular concepts such as proteins account for no more than 10% of the annotated concepts. Conclusions To the best of our knowledge, a corpus that details such a wide range of biological concepts has never been presented to the text mining community. The inter-annotator agreement statistics provide evidence of the importance of a consolidated background when dealing with such complex descriptions, the ambiguities naturally arising from the terminology and their impact for modelling purposes. Availability is granted for the full-text corpora of 130 freely accessible documents, the annotation scheme and the annotation guidelines. Also, we include a corpus of 340 abstracts.

  13. Cellular basis for the olfactory response to nicotine.

    Science.gov (United States)

    Bryant, Bruce; Xu, Jiang; Audige, Valery; Lischka, Fritz W; Rawson, Nancy E

    2010-03-17

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (Rose J. E., et al. (1993) Pharmacol., Biochem. Behav.44 (4), 891-900). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (Mombaerts P. (1999) Annu. Rev. Neurosci.22, 487-509), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (Gomez G., et al. (2000) J. Neurosci. Res.62 (5), 737-749), and rat olfactory neurons. Rat and human OSNs responded to S(-)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation.

  14. Alterations in phosphate metabolism during cellular recovery of radiation damage in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Holahan, P.K.; Knizner, S.A.; Gabriel, C.M.; Swenberg, C.E.

    1988-01-01

    Alterations were examined in phosphate pools during cellular recovery from radiation damage in intact, wild-type diploid yeast cells using phosphorus 31 nuclear magnetic resonance (NMR) spectroscopy. Concurrent cell survival analysis was determined following exposure to cobalt 60 gamma radiation. Cells held in citrate-buffered saline (CBS) showed increased survival with increasing time after irradiation (liquid holding recovery, LHR) with no further recovery beyond 48 h. Addition of 100 mmol/cu. dm glucose to the recovery medium resulted in greater recovery. In the presence of 5 mmol/cu. dm 2-deoxyglucose (2-DG), LHR was completely inhibited. ATP was observable by NMR only when glucose was present in the recovery medium. In control cells, ATP concentrations increased and plateaued with increasing recovery time. With increasing radiation dose, the increase in ATP was of lesser magnitude, and after 2000 Gy no increase was observed. The observations suggest that either the production of ATP in irradiated cells is suppressed, or there is enhanced ATP utilization for repair of radiation damage. In CBS with 100 mmol/cu. dm glucose, a dose-dependent decrease in polyphosphate (polyP) was detectable with no concurrent increase in inorganic phosphate (p sub i). When 2-DG was present in the recovery medium, polyP decreased, but there was a simultaneous increase in p sub i with increasing radiation dose and recovery time. This suggests that the polyP are hydrolyzed as a source of phosphates for repair of radiation damage.

  15. Microtubule modification influences cellular response to amyloid-β exposure

    Directory of Open Access Journals (Sweden)

    Nicole Shamitko-Klingensmith

    2016-05-01

    Full Text Available During the normal aging process, cytoskeletal changes such as a reduction in density or disruption of cytoskeletal components occur that can affect neuronal function. As aging is the biggest risk factor for Alzheimer's disease (AD, this study sought to determine how microtubule (MT modification influences cellular response upon exposure to β-amyloid1-42 (Aβ1-42, which is implicated in AD. The MT networks of hypothalamic GT1-7 neurons were modified by common disrupting or stabilizing drugs, and then the physical and mechanical properties of the modified neurons were determined. The MT modified neurons were then exposed to Aβ1-42 and the ability of the neurons to cope with this exposure was determined by a variety of biochemical assays. Flow cytometry studies indicated that MT disruption reduced the binding of Aβ1-42 to the plasma membrane by 45% per cell compared to neurons with stabilized or unaltered MTs. Although the cells with disrupted MTs experienced less peptide-membrane binding, they experienced similar or increased levels of cytotoxicity caused by the Aβ1-42 exposure. In contrast, MT stabilization delayed toxicity caused by Aβ1-42. These results demonstrate that MT modification significantly influences the ability of neurons to cope with toxicity induced by Aβ1-42.

  16. Epidermal Homeostasis and Radiation Responses in a Multiscale Tissue Modeling Framework

    Science.gov (United States)

    Hu, Shaowen; Cucinotta, Francis A.

    2013-01-01

    The surface of skin is lined with several thin layers of epithelial cells that are maintained throughout life time by a small population of stem cells. High dose radiation exposures could injure and deplete the underlying proliferative cells and induce cutaneous radiation syndrome. In this work we propose a multiscale computational model for skin epidermal dynamics that links phenomena occurring at the subcellular, cellular, and tissue levels of organization, to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis. Incorporating experimentally measured histological and cell kinetic parameters, we obtain results of population kinetics and proliferation indexes comparable to observations in unirradiated and acutely irradiated swine experiments. At the sub-cellular level, several recently published Wnt signaling controlled cell-cycle models are applied and the roles of key components and parameters are analyzed. Based on our simulation results, we demonstrate that a moderate increase of proliferation rate for the survival proliferative cells is sufficient to fully repopulate the area denuded by high dose radiation, as long as the integrity of underlying basement membrane is maintained. Our work highlights the importance of considering proliferation kinetics as well as the spatial organization of tissues when conducting in vivo investigations of radiation responses. This integrated model allow us to test the validity of several basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and enhance our understanding of the pathophysiological effects of ionizing radiation on skin.

  17. Cellular characterization of ultrasound-stimulated microbubble radiation enhancement in a prostate cancer xenograft model

    Directory of Open Access Journals (Sweden)

    Azza A. Al-Mahrouki

    2014-03-01

    Full Text Available Tumor radiation resistance poses a major obstacle in achieving an optimal outcome in radiation therapy. In the current study, we characterize a novel therapeutic approach that combines ultrasound-driven microbubbles with radiation to increase treatment responses in a prostate cancer xenograft model in mice. Tumor response to ultrasound-driven microbubbles and radiation was assessed 24 hours after treatment, which consisted of radiation treatments alone (2 Gy or 8 Gy or ultrasound-stimulated microbubbles only, or a combination of radiation and ultrasound-stimulated microbubbles. Immunohistochemical analysis using in situ end labeling (ISEL and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL revealed increased cell death within tumors exposed to combined treatments compared with untreated tumors or tumors exposed to radiation alone. Several biomarkers were investigated to evaluate cell proliferation (Ki67, blood leakage (factor VIII, angiogenesis (cluster of differentiation molecule CD31, ceramide-formation, angiogenesis signaling [vascular endothelial growth factor (VEGF], oxygen limitation (prolyl hydroxylase PHD2 and DNA damage/repair (γH2AX. Results demonstrated reduced vascularity due to vascular disruption by ultrasound-stimulated microbubbles, increased ceramide production and increased DNA damage of tumor cells, despite decreased tumor oxygenation with significantly less proliferating cells in the combined treatments. This combined approach could be a feasible option as a novel enhancing approach in radiation therapy.

  18. Sacramento Regional Response Guide to Radiation Emergencies

    Science.gov (United States)

    2006-09-01

    53 3. Case History, Goiania , Federative Republic of Brazil....................54 4. Emergency Response Personnel...families.”61 The staffing of these centers will be a challenge to any municipality. For example, in Goiania , Brazil, approximately 112,000 people were...What is.”138 3. Case History, Goiania , Federative Republic of Brazil “Because of the extreme fears of radiation, it is anticipated that the number of

  19. Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation.

    Directory of Open Access Journals (Sweden)

    Xurui Zhang

    Full Text Available Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92-1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research.

  20. Chromatin modifications and the DNA damage response to ionizing radiation

    Science.gov (United States)

    Kumar, Rakesh; Horikoshi, Nobuo; Singh, Mayank; Gupta, Arun; Misra, Hari S.; Albuquerque, Kevin; Hunt, Clayton R.; Pandita, Tej K.

    2013-01-01

    In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double-strand breaks (DSBs), that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: (1) non-homologous end joining, which re-ligates the broken ends of the DNA and (2) homologous recombination, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but post-translational modification of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modifications by the respective chromatin modifying factors that occur during the DNA damage response. PMID:23346550

  1. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees.

  2. Potential role of DNA-dependent protein kinase in cellular resistance to ionizing radiation

    Institute of Scientific and Technical Information of China (English)

    LI Ning; ZHANG Hong; WANG Yanling; WANG Xiaohu; HAO Jifang

    2009-01-01

    In this paper, we study the ability of DNA-PK-deficient (M059J) and -proficient (M059K) cells to undergo the rate of cellular proliferation, cell cycle distribution and apoptosis after 10 Gy X-ray irradiation, and the role of DNA-PK in radiosensitivity. The results showed that M059J cells exhibited hyper-radiosensitivity compared with M059K cells. A strong G2 phase arrest was observed in M059J cells post irradiation. Significant accumulation in the G2 phase in M059J cells was accompanied by apoptosis at 12 h. Altogether, the data suggested that DNA-PK may have two roles in mammalian cells after DNA damage, a role in DNA DSB repair and a second role in DNA-damaged cells to traverse a G2 checkpoint, by which DNA-PK may affect cellular sensitivity to ionizing radiation.

  3. Cellular parameters for track structure modelling of radiation hazard in space

    Science.gov (United States)

    Hollmark, M.; Lind, B.; Gudowska, I.; Waligorski, M.

    Based on irradiation with 45 MeV/u N and B ions and with Co-60 gamma rays, track structure cellular parameters have been fitted for V 79-379A Chinese hamster lung fibroblasts and for human melanoma cells (AA wtp53). These sets of parameters will be used to develop a calculation of radiation hazard in deep space, based on the system for evaluating, summing and reporting occupational exposures proposed in 1967 by subcommittee of the NCRP, but never issued as an NCRP report. The key concepts of this system were: i) expression of the risk from all radiation exposures relative to that from a whole-body exposure to Co-60 radiation; ii) relating the risk from any exposure to that of the standard (Co-60) radiation through an "effectiveness factor" (ef), a product of sub-factors representing radiation quality, body region irradiated, and depth of penetration of radiation; the product of absorbed dose by ef being termed the "exposure record unit" (eru); iii) development of ef values and a cumulative eru record for external and internal emitters. Application of this concept should provide a better description of the Gy -equivalent presently in use by NASA for evaluating risk in deep space than the equivalent dose, following ICRP-60 recommendations. Dose and charged particle fluence levels encountered in space, particularly after Solar Particle Events, require that deterministic rather than stochastic effects be considered. Also, synergistic effects due to simultaneous multiple charged particle transfers, may have to be considered. Thus, models applicable in radiotherapy, where the Gy -equivalent is also applied, in conjunction with transport calculations performed using, e.g. the ADAM and EVA phantoms, along the concepts of the 1967 NCRP system, may be more appropriate for evaluating the radiation hazard from external fields with a large flux and a major high-LET component.

  4. Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance

    DEFF Research Database (Denmark)

    D’Andrea, Filippo P.; Safwat, Akmal; Kassem, Moustapha;

    2011-01-01

    BackgroundCancer stem cells are thought to be a radioresistant population and may be the seeds for recurrence after radiotherapy. Using tumorigenic clones of retroviral immortalized human mesenchymal stem cell with small differences in their phenotype, we investigated possible genetic expression...... that could explain cancer stem cell radiation resistance. MethodsTumorigenic mesenchymal cancer stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for clonogenic surviving fraction. Altered gene expression before and after 2Gy was assessed by Affymetric exon chip analysis and further...... found the genes involved in cancer, proliferation, DNA repair and cell death. ConclusionsThe higher radiation resistance in clone CE8 is likely due to NNMT overexpression. The higher levels of NNMT could affect the cellular damage resistance through depletion of the accessible amounts of nicotinamide...

  5. Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Yasuda, Takeshi [Radiation Emergency Medicine Research Program, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Fujita, Mayumi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Asada, Masahiro [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Meineke, Viktor [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany); Imamura, Toru [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan)

    2014-02-01

    Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation with γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the

  6. Responses to low doses of ionizing radiation in biological systems.

    Science.gov (United States)

    Feinendegen, Ludwig E; Pollycove, Myron; Sondhaus, Charles A

    2004-07-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.To examine tissue effects specific for low-dose radiation, (1) absorbed dose in tissue is replaced by the sum of the energies deposited by each track event, or hit, in a cell-equivalent tissue micromass (1 ng) in all micromasses exposed, that is, by the mean energy delivered by all microdose hits in the exposed micromasses, with cell dose expressing the total energy per micromass from multiple microdoses; and (2) tissue effects are related to cell damage and protective cellular responses per average microdose hit from a given radiation quality for all such hits in the exposed micromasses.The probability of immediate DNA damage per low-linear-energy-transfer (LET) average micro-dose hit is extremely small, increasing over a certain dose range in proportion to the number of hits. Delayed temporary adaptive protection (AP) involves (a) induced detoxification of reactive oxygen species, (b) enhanced rate of DNA repair, (c) induced removal of damaged cells by apoptosis followed by normal cell replacement and by cell differentiation, and (d) stimulated immune response, all with corresponding changes in gene expression. These AP categories may last from less than a day to weeks and be tested by cell responses against renewed irradiation. They operate physiologically against nonradiogenic, largely endogenous DNA damage, which occurs abundantly and continually. Background radiation damage caused by rare microdose hits per micromass is many orders of magnitude less frequent. Except for apoptosis, AP increasingly fails above about 200 mGy of low-LET radiation, corresponding to about 200 microdose hits per exposed micromass. This ratio appears to exceed approximately

  7. Actinic reticuloid idiopathic photodermatosis with cellular sensitivity to near ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Botcherby, P.K.; Marimo, B.; Giannelli, F. (Guy' s Hospital Medical School, London (UK)); Magnus, I.A. (Institute of Dermatology, London (UK))

    1984-05-01

    Long wavelength UV radiations (320-400 nm) cause persistent inhibition of RNA synthesis and marked cytopathic changes in fibroblasts from patients with actinic reticuloid (AR) but not in those from patients with Bloom syndrome or xeroderma pigmentosum. Furthermore, the AR cells show abnormal DNA fragmentation when they are irradiated at temperatures compatible with enzyme activity. Germicidal UVR (ca. 95% 254 nm) stimulates DNA repair synthesis and inhibits DNA replication to a normal extent in the AR cells. Thus, actinic reticuloid, a severe photodermatosis, characterised by skin sensitivity to UV-B, UV-A and part of the visible spectrum and infiltrates reminiscent of mycosis fungoides, is a human disease with in vitro cellular sensitivity to UV-A and is also the first to be reported. A hypothesis is advanced that inefficient cellular neutralisation of free radicals may explain the cellular phenotype of actinic reticuloid and contribute to the establishment of a vicious circle that would favour the chronic clinical course and persistent lympho-histiocytic skin infiltrates characteristic of the disease.

  8. Radiation emergency response in Illinois, Alabama, and Texas

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, D.K.; Chester, R.O.

    1978-03-01

    The objective of this study was to examine state radiation emergency response and to locate any areas of emergency planning in need of improvement. This report briefly presents a summary of laws and defining documents governing radiation emergency response, describes the existing and projected need for such response, and presents the authors' analyses of the evolution of state response plans and their application to radiation incidents. Three states' programs are discussed in detail: Illinois, Alabama, and Texas. These states were selected because they have quite different emergency-response programs. Therefore, these state programs provide a wide variety of approaches to state radiation emergency response.

  9. Cellular and molecular alterations in human epithelial cells transformed by high let radiation

    Science.gov (United States)

    Hei, T. K.; Piao, C. Q.; Sutter, T.; Willey, J. C.; Suzuki, K.

    An understanding of the radiobiological effects of high LET radiation is essential for human risk estimation and radiation protection. In the present study, we show that a single, 30 cGy dose of 150 keV/mum ^4He ions can malignantly transform human papillomavirus immortalized human bronchial epithelial [BEP2D] cells. Transformed cells produce progressively growing tumors in nude mice. The transformation frequency by the single dose of alpha particles is estimated to be approximately 4 x 10^-7. Based on the average cross-sectional area of BEP2D cells, it can be calculated that a mean traversal of 1.4 particles per cell is sufficient to induce tumorigenic conversion of these cells 3 to 4 months post-irradiation. Tumorigenic BEP2D cells overexpress mutated p53 tumor suppressor oncoproteins in addition to the cell cycle control gene cyclin D1 and D2. This model provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells.

  10. Effect of Gold Nanorod Surface Chemistry on Cellular Response

    Science.gov (United States)

    2011-03-15

    Recombi - nation DNA Repair Network for Targeted Cancer Therapy. World J. Clin. Oncol. 2011, 2, 73–79. 36. Higashi, H.; Vallb€ohmer, D.; Warnecke-Eberz, U...cellular morphology, mitochondrial function, mitochondrial membrane potential (MMP), intracellular calcium levels, DNA damage-related gene expression, and of...observed in the MMP and Ca++ levels, up or down regulation of DNA damage related gene expression suggested a differential cell death mechanism based on

  11. Contrasting Responses of Marine and Freshwater Photosynthetic Organisms to UVB Radiation: A Meta-Analysis

    KAUST Repository

    Jin, Peng

    2017-03-14

    Ultraviolet-B (UVB) radiation is a global stressor that has profound impacts on freshwater and marine ecosystems. However, an analysis of the patterns of sensitivity to UVB radiation across aquatic photosynthetic organisms has not yet been published. Here, we performed a meta-analysis on results reported in 214 studies compiled from the published literature to quantify and compare the magnitude of responses of aquatic photosynthetic organisms to changes in UVB radiation. The meta-analysis was conducted on observations of marine (n = 893) and freshwater macroalgae (n = 126) and of marine (n = 1,087) and freshwater (n = 2,889) microalgae (total n = 4,995). Most of these studies (85%) analyzed the performance of organisms exposed to natural solar radiation when UVB was partially or totally reduced compared with the organismal performance under the full solar radiation spectrum, whereas the remaining 15% of the studies examined the responses of organisms to elevated UVB radiation mostly using artificial lamps. We found that marine photosynthetic organisms tend to be more sensitive than freshwater photosynthetic organisms to UVB radiation; responses to either decreased or increased UVB radiation vary among taxa; the mortality rate is the most sensitive of the trait responses to elevated UVB radiation, followed by changes in cellular and molecular traits; the sensitivity of microalgae to UVB radiation is dependent on size, with small-celled microalgae more sensitive than large-celled microalgae to UVB radiation. Thick macroalgae morphotypes were the less sensitive to UVB, but this effect could not be separated from phylogenetic differences. The high sensitivity of marine species, particularly the smallest photosynthetic organisms, to increased UVB radiation suggests that the oligotrophic ocean, a habitat comprising 70% of the world\\'s oceans with high UVB penetration and dominated by picoautotrophs, is extremely vulnerable to changes in UVB radiation.

  12. Medical response to effects of ionising radiation. [Nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Crosbie, W.A.; Gittus, J.H. (UKAEA Headquarters, London (UK))

    1989-01-01

    The proceedings of a conference on 'Medical Response to Effects of Ionising Radiation' in 1989 in the form of nineteen papers published as a book. Topics discussed include radiation accidents at nuclear facilities, the medical management of radiation casualties, the responsibilities, plans and resources for coping with a nuclear accident and finally the long term effects of radiation, including leukaemia epidemiology studies. All papers were selected and indexed separately. (UK).

  13. Radiation Induces Cathepsin S through ROS-IFN-{gamma} Pathways: Involvement of Cellular Radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Haeng Ran; Lee, Yun-Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Joon [Korea University, Seoul (Korea, Republic of)

    2008-05-15

    Ionizing radiation can elicit an activated phenotype that promotes rapid and persistent remodeling of the extracellular matrix (ECM) through the induction of proteases and growth factors, as well as in response to chronic production of reactive oxygen species (ROS). In addition, the results of previously conducted cDNA microarrays and real-time RT-PCR analysis (unpublished) suggest that radiation-induced mammary tumors were specifically induced by cathepsin S (CTSS), but that dimethylbenz(a)anthracene (DMBA)-induced mammary tumors were not. CTSS is a lysosomal cystein protease that is synthesized as an inactive precursor (36kDa) and activated in the acidic environment of lysosomes by proteolytic cleavage of its propeptide. In this study, we further investigate the mechanism by which CTSS is induced by radiation as well as its function.

  14. Marine molluscs in environmental monitoring. I. Cellular and molecular responses

    Science.gov (United States)

    Bresler, Vladimir; Abelson, Avigdor; Fishelson, Lev; Feldstein, Tamar; Rosenfeld, Michael; Mokady, Ofer

    2003-10-01

    The study reported here is part of an ongoing effort to establish sensitive and reliable biomonitoring markers for probing the coastal marine environment. Here, we report comparative measurements of a range of histological, cellular and sub-cellular parameters in molluscs sampled in polluted and reference sites along the Mediterranean coast of Israel and in the northern tip of the Gulf of Aqaba, Red Sea. Available species enabled an examination of conditions in two environmental 'compartments': benthic (Donax trunculus) and intertidal (Brachidontes pharaonis, Patella caerulea) in the Mediterranean; pelagic (Pteria aegyptia) and intertidal (Cellana rota) in the Red Sea. The methodology used provides rapid results by combining specialized fluorescent probes and contact microscopy, by which all parameters are measured in unprocessed animal tissue. The research focused on three interconnected levels. First, antixenobiotic defence mechanisms aimed at keeping hazardous agents outside the cell. Paracellular permeability was 70-100% higher in polluted sites, and membrane pumps (MXRtr and SATOA) activity was up to 65% higher in polluted compared to reference sites. Second, intracellular defence mechanisms that act to minimize potential damage by agents having penetrated the first line of defence. Metallothionein expression and EROD activity were 160-520% higher in polluted sites, and lysosomal functional activity (as measured by neutral red accumulation) was 25-50% lower. Third, damage caused by agents not sufficiently eliminated by the above mechanisms (e.g. single-stranded DNA breaks, chromosome damage and other pathological alterations). At this level, the most striking differences were observed in the rate of micronuclei formation and DNA breaks (up to 150% and 400% higher in polluted sites, respectively). The different mollusc species used feature very similar trends between polluted and reference sites in all measured parameters. Concentrating on relatively basic

  15. p53-Mediated Cellular Response to DNA Damage in Cells with Replicative Hepatitis B Virus

    Science.gov (United States)

    Puisieux, Alain; Ji, Jingwei; Guillot, Celine; Legros, Yann; Soussi, Thierry; Isselbacher, Kurt; Ozturk, Mehmet

    1995-02-01

    Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G_1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studied the p53-mediated cellular response to DNA damage in 2215 hepatoma cells with replicative hepatitis B virus. We demonstrate that hepatitis B virus replication does not interfere with known cellular functions of p53 protein.

  16. In vivo optical imaging of tumor and microvascular response to ionizing radiation.

    Directory of Open Access Journals (Sweden)

    Azusa Maeda

    Full Text Available Radiotherapy is a widely used cancer treatment. However, understanding how ionizing radiation affects tumor cells and their vasculature, particularly at cellular, subcellular, genetic, and protein levels, has been limited by an inability to visualize the response of these interdependent components within solid tumors over time and in vivo. Here we describe a new preclinical experimental platform combining intravital multimodal optical microscopy for cellular-level longitudinal imaging, a small animal x-ray microirradiator for reproducible spatially-localized millimeter-scale irradiations, and laser-capture microdissection of ex vivo tissues for transcriptomic profiling. Using this platform, we have developed new methods that exploit the power of optically-enabled microscopic imaging techniques to reveal the important role of the tumor microvasculature in radiation response of tumors. Furthermore, we demonstrate the potential of this preclinical platform to study quantitatively--with cellular and sub-cellular details--the spatio-temporal dynamics of the biological response of solid tumors to ionizing radiation in vivo.

  17. In vivo optical imaging of tumor and microvascular response to ionizing radiation.

    Science.gov (United States)

    Maeda, Azusa; Leung, Michael K K; Conroy, Leigh; Chen, Yonghong; Bu, Jiachuan; Lindsay, Patricia E; Mintzberg, Shani; Virtanen, Carl; Tsao, Julissa; Winegarden, Neil A; Wang, Yanchun; Morikawa, Lily; Vitkin, I Alex; Jaffray, David A; Hill, Richard P; DaCosta, Ralph S

    2012-01-01

    Radiotherapy is a widely used cancer treatment. However, understanding how ionizing radiation affects tumor cells and their vasculature, particularly at cellular, subcellular, genetic, and protein levels, has been limited by an inability to visualize the response of these interdependent components within solid tumors over time and in vivo. Here we describe a new preclinical experimental platform combining intravital multimodal optical microscopy for cellular-level longitudinal imaging, a small animal x-ray microirradiator for reproducible spatially-localized millimeter-scale irradiations, and laser-capture microdissection of ex vivo tissues for transcriptomic profiling. Using this platform, we have developed new methods that exploit the power of optically-enabled microscopic imaging techniques to reveal the important role of the tumor microvasculature in radiation response of tumors. Furthermore, we demonstrate the potential of this preclinical platform to study quantitatively--with cellular and sub-cellular details--the spatio-temporal dynamics of the biological response of solid tumors to ionizing radiation in vivo.

  18. Atypical radiation response of SCID cells

    Science.gov (United States)

    Chawapun, Nisa

    Murine SCID (severe combined immune deficiency) cells are well known for their defect in DNA double-strand break repair and in variable(diversity)joining [V(D)J] recombination due to a mutation in a catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). As a consequence, scid cells are hypersensitive to ionizing radiation. The present study showed that asynchronous populations of scid cells were about two-fold more sensitive than Balb/c with respect to cell killing and the defect in scid cells was corrected by complementation with human chromosome 8. Analysis of the survival of synchronized populations as a function of the cell cycle revealed that while scid cells were hypersensitive in all cell cycle phases compared to wild-type cells, this hypersensitivity is even more pronounced in G1 phase. The hypersensitivity reduced as the cells progressed into S phase suggested that homologous recombination repair plays a role. The results imply that there are at least two pathways for the repair of DSB DNA, consistent with a model previously proposed by others. The scid cells were also more sensitive to UVC light (254 nm) killing as compared to wild type cells by clonogenic survival. Using a host cell reactivation (HCR) assay to study the nucleotide excision repair (NER) which is the major repair pathway for UV-photoproducts, the results showed that NER in scid cells was not as efficient as CB- 17. This suggests that DNA-PK is involved in NER as well as non-homologous end-joining (NHEJ) DSB repair which is responsible for ionizing radiation sensitivity in scid cells. Repair in scid cells was not totally absent as shown by low dose rate sparing of cell killing after exposure to 137Cs γ-rays at dose rate of 0.6 cGy/h, 1.36 cGy/h, 6 cGy/h as compared to high dose rate at 171 cGy/min, although this phenomenon could be explained partly by proliferation. However, for radiation induced transformation, no significant dose rate effect was seen. A plot of transformation

  19. Evolutionary principles underlying structure and response dynamics of cellular networks.

    Science.gov (United States)

    Steinacher, Arno; Soyer, Orkun S

    2012-01-01

    The network view in systems biology, in conjunction with the continuing development of experimental technologies, is providing us with the key structural and dynamical features of both cell-wide and pathway-level regulatory, signaling and metabolic systems. These include for example modularity and presence of hub proteins at the structural level and ultrasensitivity and feedback control at the level of dynamics. The uncovering of such features, and the seeming commonality of some of them, makes many systems biologists believe that these could represent design principles that underpin cellular systems across organisms. Here, we argue that such claims on any observed feature requires an understanding of how it has emerged in evolution and how it can shape subsequent evolution. We review recent and past studies that aim to achieve such evolutionary understanding for observed features of cellular networks. We argue that this evolutionary framework could lead to deciphering evolutionary origin and relevance of proposed design principles, thereby allowing to predict their presence or absence in an organism based on its environment and biochemistry and their effect on its future evolution.

  20. Cellular Responses to the Metal-Binding Properties of Metformin

    Science.gov (United States)

    Logie, Lisa; Harthill, Jean; Patel, Kashyap; Bacon, Sandra; Hamilton, D. Lee; Macrae, Katherine; McDougall, Gordon; Wang, Huan-Huan; Xue, Lin; Jiang, Hua; Sakamoto, Kei; Prescott, Alan R.; Rena, Graham

    2012-01-01

    In recent decades, the antihyperglycemic biguanide metformin has been used extensively in the treatment of type 2 diabetes, despite continuing uncertainty over its direct target. In this article, using two independent approaches, we demonstrate that cellular actions of metformin are disrupted by interference with its metal-binding properties, which have been known for over a century but little studied by biologists. We demonstrate that copper sequestration opposes known actions of metformin not only on AMP-activated protein kinase (AMPK)-dependent signaling, but also on S6 protein phosphorylation. Biguanide/metal interactions are stabilized by extensive π-electron delocalization and by investigating analogs of metformin; we provide evidence that this intrinsic property enables biguanides to regulate AMPK, glucose production, gluconeogenic gene expression, mitochondrial respiration, and mitochondrial copper binding. In contrast, regulation of S6 phosphorylation is prevented only by direct modification of the metal-liganding groups of the biguanide structure, supporting recent data that AMPK and S6 phosphorylation are regulated independently by biguanides. Additional studies with pioglitazone suggest that mitochondrial copper is targeted by both of these clinically important drugs. Together, these results suggest that cellular effects of biguanides depend on their metal-binding properties. This link may illuminate a better understanding of the molecular mechanisms enabling antihyperglycemic drug action. PMID:22492524

  1. The molecular and cellular response of normal and progressed human bronchial epithelial cells to HZE particles

    Science.gov (United States)

    Story, Michael; Ding, Liang-Hao; Minna, John; Park, Seong-mi; Larsen, Jill

    We have used a model of non-oncogenically immortalized normal human bronchial epithelial cells to determine the response of such cells to particles found outside the protection of the earth’s electromagnetic field. We have identified an enhanced frequency of cellular transformation, as measured by growth in soft agar, for both 56Fe and 28Si (1 GeV/n) that is maximal (4-6 fold) at 0.25 Gy and 0.40 Gy, respectively. At 4 months post-irradiation 38 individual soft agar clones were isolated. These clones were characterized extensively for cellular and molecular changes. Gene expression analysis suggested that these clones had down-regulated several genes associated with anti-oxidant pathways including GLS2, GPX1 and 4, SOD2, PIG3, and NQO1 amongst others. As a result, many of these transformed clones were exposed to high levels of intracellular radical oxygen species (ROS), although there appeared not to be any enhanced mitochondrial ROS. DNA repair pathways associated with ATM/ATR signaling were also upregulated. However, these transformants do not develop into tumors when injected into immune-compromised mice, suggesting that they have not progressed sufficiently to become oncogenic. Therefore we chose 6 soft agar clones for continuous culture for an additional 14 months. Amongst the 6 clones, only one clone showed any significant change in phenotype. Clone 3kt-ff.2a, propagated for 18 months, were 2-fold more radioresistant, had a shortened doubling time and the background rate of transformation more than doubled. Furthermore, the morphology of transformed clones changed. Clones from this culture are being compared to the original clone as well as the parental HBEC3KT and will be injected into immune-compromised mice for oncogenic potential. Oncogenically progressed HBECs, HBEC3KT cells that overexpress a mutant RAS gene and where p53 has been knocked down, designated HBEC3KTR53, responded quite differently to HZE particle exposure. First, these cells are more

  2. Alterations in phosphate metabolism during cellular recovery of radiation damage in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Holahan, P.K.; Knizner, S.A.; Gabriel, C.M.; Swenberg, C.E.

    1988-10-01

    The authors examined alterations in phosphate pools during cellular recovery from radiation damage in intact, wild-type diploid yeast cells using /sup 31/P nuclear magnetic resonance (NMR) spectroscopy. Concurrent cell survival analysis was determined following exposure to /sup 60/Co ..gamma..-irradiation. Cells held in citrate-buffered saline (CBS) showed increased survival with increasing time after irradiation (liquid holding recovery, LHR) with no further recovery beyond 48 h. Addition of 100 mmol dm/sup -3/ glucose to the recovery medium resulted in greater recovery. In the presence of 5 mmol dm/sup /-/sup 3/ 2-deoxyglucose (2-DG), LHR was completely inhibited. NMR analyses were done on cells perfused in agarose threads and maintained under conditions similar to those in the survival studies. ATP was observable by NMR only when glucose was present in the recovery medium. In control cells, ATP concentrations increased and plateaued with increasing recovery time. With increasing radiation dose the increase in ATP was of lesser magnitude, and after 2000 Gy no increase was observed.

  3. Development of second generation peptides modulating cellular adiponectin receptor responses

    Science.gov (United States)

    Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

    2014-10-01

    The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

  4. Development of second generation peptides modulating cellular adiponectin receptor responses

    Directory of Open Access Journals (Sweden)

    Laszlo eOtvos

    2014-10-01

    Full Text Available The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC. In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399. The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400 was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400 at similar concentrations will be an important target validation tool to study adiponectin functions.

  5. Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy

    OpenAIRE

    Harting, Matthew T.; jimenez, fernando; Adams, Sasha D.; Mercer, David W.; Cox, Charles S.

    2008-01-01

    While cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.

  6. Gene Expression Profile Changes and Cellular Responses to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Kidane, Yared; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Rohde, Larry; Wu, Honglu

    2016-01-01

    Living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. In addition, DNA in space can be damaged by toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage affects the accuracy of the radiation risk assessment for astronauts and the mutation rate in microorganisms. Although possible synergistic effects of space radiation and microgravity have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate the effects of spaceflight on cellular responses to DNA damage, confluent human fibroblast cells (AG1522) flown on the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB). Damages in the DNA were quantified by immunofluorescence staining for ?-H2AX, which showed similar percentages of different types of stained cells between flight and ground. However, there was a slight shift in the distribution of the ?-H2AX foci number in the flown cells with countable foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. A microarray analysis of gene expressions in response to bleomycin treatment was also performed. Comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. Similar responses at the RNA level between different gravity conditions were also observed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly

  7. Response of hematopoietic stem cells to ionizing radiation; Reponse des cellules souches hematopoitiques aux radiations ionisantes

    Energy Technology Data Exchange (ETDEWEB)

    Simonnet, A

    2008-12-15

    Hematopoietic stem cells (HSCs) maintain blood and immune system throughout life and restore them after hematological injuries. Exposure of an organism to ionizing radiation (IR) causes rapid and acute myelosuppression and challenges the replenishment capacity of HSCs. Yet, the precise damages that are generated remain largely unexplored. To better understand these effects, phenotypic and functional changes in the stem/progenitor compartments of sublethally irradiated mice were monitored over a ten week period after radiation exposure. We report that shortly after sublethal IR-exposure, HSCs, defined by their repopulating ability, still segregate in the Hoechst dye excluding side population (SP); yet, their Sca-1 (S) and c-Kit (K) expression levels are increased and severely reduced, respectively, with a concurrent increase in the proportion of SP{sup SK} cells positive for established indicators of HSC presence: CD150{sup +} and CD105{sup +}. A great proportion of HSCs quickly but transiently enter the cell cycle to replenish the bone marrow of myelo-ablated mice. Ten weeks after, whereas bone marrow cellularity has recovered and hematopoietic homeostasis is restored, major phenotypic modifications can be observed within the Lin{sup -/low} Sca-1{sup +} c-Kit{sup +} (LSK) stem/progenitor compartment: CD150{sup +}/Flk2{sup -} and CD150{sup -}/Flk2{sup +} LSK cell frequencies are increased and dramatically reduced, respectively. CD150{sup +} LSK cells also show impaired reconstitution capacity, accrued number of {gamma}-H2AX foci and increased tendency to apoptosis. This demonstrates that the LSK compartment is not properly restored 10 weeks after sublethal exposure, and that long-term IR-induced injury to the bone marrow proceeds, at least partially, through direct damage to the stem cell pool. Thrombopoietin (TPO) has been shown to promote the survival of lethally irradiated mice when administrated quickly after exposure. We investigated the mechanisms underlying

  8. Relief of delayed oxidative stress by ascorbic acid can suppress radiation-induced cellular senescence in mammalian fibroblast cells.

    Science.gov (United States)

    Kobashigawa, Shinko; Kashino, Genro; Mori, Hiromu; Watanabe, Masami

    2015-03-01

    Ionizing radiation-induced cellular senescence is thought to be caused by nuclear DNA damage that cannot be repaired. However, here we found that radiation induces delayed increase of intracellular oxidative stress after irradiation. We investigated whether the relief of delayed oxidative stress by ascorbic acid would suppress the radiation-induced cellular senescence in Syrian golden hamster embryo (SHE) cells. We observed that the level of oxidative stress was drastically increased soon after irradiation, then declined to the level in non-irradiated cells, and increased again with a peak on day 3 after irradiation. We found that the inductions of cellular senescence after X-irradiation were reduced along with suppression of the delayed induction of oxidative stress by treatment with ascorbic acid, but not when oxidative stress occurred immediately after irradiation. Moreover, treatment of ascorbic acid inhibited p53 accumulation at 3 days after irradiation. Our data suggested a delayed increase of intracellular oxidative stress levels plays an important role in the process of radiation-induced cellular senescence by p53 accumulation.

  9. The relationship between cellular adhesion and surface roughness for polyurethane modified by microwave plasma radiation

    Directory of Open Access Journals (Sweden)

    Heidari S

    2011-04-01

    Full Text Available Saeed Heidari Keshel1, S Neda Kh Azhdadi2, Azadeh Asefnezhad2, Mohammad Sadraeian3, Mohamad Montazeri4, Esmaeil Biazar51Stem Cell Preparation Unit, Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences; 2Department of Biomaterial Engineering, Faculty of Biomedical Engineering, Science and Research Branch - Islamic Azad University; 3Young Researchers Club, Islamic Azad University, North Tehran Branch, Tehran; 4Faculty of Medical Sciences, Babol University of Medical Sciences, Babol; 5Department of Chemistry, Islamic Azad University, Tonekabon, IranAbstract: Surface modification of medical polymers is carried out to improve biocompatibility. In this study, conventional polyurethane was exposed to microwave plasma treatment with oxygen and argon gases for 30 seconds and 60 seconds. Attenuated total reflection Fourier transform infrared spectra investigations of irradiated samples indicated the presence of functional groups. Atomic force microscope images of samples irradiated with inert and active gases indicated the nanometric topography of the sample surfaces. Samples irradiated by oxygen plasma indicated high roughness compared with those irradiated by inert plasma for the different lengths of time. In addition, surface roughness increased with time, which can be due to a reduction of contact angle of samples irradiated by oxygen plasma. Contact angle analysis indicated a reduction in samples irradiated with both types of plasma. However, samples irradiated with oxygen plasma indicated lower contact angle compared with those irradiated by argon plasma. Cellular investigations with unrestricted somatic stem cells showed better adhesion, cell growth, and proliferation among samples radiated by oxygen plasma for longer than for normal samples.Keywords: surface topography, polyurethane, plasma treatment, cellular investigation

  10. Modification of the cellular heat sensitivity of cucumber by growth under supplemental ultraviolet-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, C.R. [Department of Agriculture, Beltsville, MD (United States)

    1994-02-01

    The effect of ultraviolet B (UV-B) radiation on the thermal sensitivity of cucumber (Cucumis sativus L.) was studied using UV-B-sensitive cv Poinsett 76 and UV-B-resistant cv Ashley grown under control and elevated (300 mW m{sup -2}) UV-B radiation levels. Using both cotyledon and leaf discs, the ability of the tissue to reduce triphenyl tetrazolium chloride (TTC) was determined after treatment at 50{degrees}C for various times. Semilogarithmic plots of TTC reduction as a function of time at 50{degrees}were curvilinear. They were monophasic for the control cucumber and biphasic for cucumber grown in the presence of elevated UV-B. Treatment of cucumber plants at 37{degrees}C for 24 h or of tissue discs at acute UV-B levels for 1 h further modified their response to elevated temperature. These results suggest that growth of cucumber under enhanced UV-B radiation levels increased its ability to withstand elevated temperatures. 19 refs., 2 figs., 2 tabs.

  11. Effects of Spaceflight on Molecular and Cellular Responses to Bleomycin-Induced DNA Damages in Confluent Human Fibroblasts

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

    2016-01-01

    Spaceflights expose human beings to various risk factors. Among them are microgravity related physiological stresses in immune, cytoskeletal, and cardiovascular systems, and space radiation related elevation of cancer risk. Cosmic radiation consists of energetic protons and other heavier charged particles that induce DNA damages. Effective DNA damage response and repair mechanism is important to maintain genomic integrity and reduce cancer risk. There were studies on effects of spaceflight and microgravity on DNA damage response in cell and animal models, but the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on molecular and cellular responses to DNA damages, bleomycin, an anti-cancer drug and radiomimetic reagent, was used to induce DNA damages in confluent human fibroblasts flown to the International Space Station (ISS) and on ground. After exposure to 1.0 µg/ml bleomycin for 3 hours, cells were fixed for immunofluorescence assays and for RNA preparation. Extents of DNA damages were quantified by foci and pattern counting of phosphorylated histone protein H2AX (?-H2AX). The cells on the ISS showed modestly increased average foci counts per nucleus while the distribution of patterns was similar to that on the ground. PCR array analysis showed that expressions of several genes, including CDKN1A and PCNA, were significantly changed in response to DNA damages induced by bleomycin in both flight and ground control cells. However, there were no significant differences in the overall expression profile of DNA damage response genes between the flight and ground samples. Analysis of cellular proliferation status with Ki-67 staining showed a slightly higher proliferating population in cells on the ISS than those on ground. Our results suggested that the difference in ?-H2AX focus counts between flight and ground was due to the higher percentage of proliferating cells in space, but spaceflight did not significantly affect

  12. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  13. The cellular response to curvature-induced stress

    Science.gov (United States)

    Biton, Y. Y.; Safran, S. A.

    2009-12-01

    We present a theoretical model to explain recent observations of the orientational response of cells to unidirectional curvature. Experiments show that some cell types when plated on a rigid cylindrical surface tend to reorient their shape and stress fibers along the axis of the cylinder, while others align their stress fibers perpendicular to that axis. Our model focuses on the competition of the shear stress—that results from cell adhesion and active contractility—and the anisotropic bending stiffness of the stress fibers. We predict the cell orientation angle that results from the balance of these two forces in a mechanical equilibrium. The conditions under which the different experimental observations can be obtained are discussed in terms of the theory.

  14. Radiation-induced p53 protein response in the A549 cell line is culture growth-phase dependent

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, N.F.; Gurule, D.M.; Carpenter, T.R.

    1995-12-01

    One role of the p53 tumor suppressor protein has been recently revealed. Kastan, M.B. reported that p53 protein accumulates in cells exposed to ionizing radiation. The accumulation of p53 protein is in response to DNA damage, most importantly double-strand breaks, that results from exposure to ionizing radiation. The rise in cellular p53 levels is necessary for an arrest in the G{sub 1} phase of the cell cycle to provide additional time for DNA repair. The p53 response has also been demonstrated to enhance PCNA-dependent repair. p53 is thus an important regulator of the cellular response to DNA-damaging radiation. From this data, it can be concluded that the magnitude of the p53 response is not dependent on the phase of culture growth.

  15. The relationship between cellular adhesion and surface roughness in polystyrene modified by microwave plasma radiation

    Directory of Open Access Journals (Sweden)

    Biazar E

    2011-03-01

    Full Text Available Esmaeil Biazar1, Majid Heidari2, Azadeh Asefnezhad2, Naser Montazeri11Department of Chemistry, Islamic Azad University, Tonekabon Branch, Mazandaran; 2Department of Biomaterial Engineering, Faculty of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, IranBackground: Surface modification of medical polymers can improve biocompatibility. Pure polystyrene is hydrophobic and cannot provide a suitable environment for cell cultures. The conventional method for surface modification of polystyrene is treatment with plasma. In this study, conventional polystyrene was exposed to microwave plasma treatment with oxygen and argon gases for 30, 60, and 180 seconds.Methods and results: Attenuated total reflection Fourier transform infrared spectra investigations of irradiated samples indicated clearly the presence of functional groups. Atomic force microscopic images of samples irradiated with inert and active gases indicated nanometric surface topography. Samples irradiated with oxygen plasma showed more roughness (31 nm compared with those irradiated with inert plasma (16 nm at 180 seconds. Surface roughness increased with increasing duration of exposure, which could be due to reduction of the contact angle of samples irradiated with oxygen plasma. Contact angle analysis showed reduction in samples irradiated with inert plasma. Samples irradiated with oxygen plasma showed a lower contact angle compared with those irradiated by argon plasma.Conclusion: Cellular investigations with unrestricted somatic stem cells showed better adhesion, cell growth, and proliferation for samples radiated by oxygen plasma with increasing duration of exposure than those of normal samples.Keywords: surface topography, polystyrene, plasma treatment, argon, oxygen

  16. The Impact of the Myeloid Response to Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Michael J. Gough

    2013-01-01

    Full Text Available Radiation therapy is showing potential as a partner for immunotherapies in preclinical cancer models and early clinical studies. As has been discussed elsewhere, radiation provides debulking, antigen and adjuvant release, and inflammatory targeting of effector cells to the treatment site, thereby assisting multiple critical checkpoints in antitumor adaptive immunity. Adaptive immunity is terminated by inflammatory resolution, an active process which ensures that inflammatory damage is repaired and tissue function is restored. We discuss how radiation therapy similarly triggers inflammation followed by repair, the consequences to adaptive immune responses in the treatment site, and how the myeloid response to radiation may impact immunotherapies designed to improve control of residual cancer cells.

  17. Initial Human Response to Nuclear Radiation

    Science.gov (United States)

    1982-04-01

    symptoms and course of the illness. Herbert Fanger and Clarence C. Lushbaugh, "Radiation Death from Cardiovascular Shock Following a Criticality...irradiated victim died on day 32. The least-irradiated victim recovered more slowly than the others. Herbert Fanger and Clarence C. Lushbaugh, "Radiation...Sources Accident (A) Fanger and Lushbaugh, 1967 Hubner and Fry (eds.), 1980 Karas and Stanbury, 1965 International Atomic Energy Agency and World Health

  18. Tissue radiation response with maximum Tsallis entropy.

    Science.gov (United States)

    Sotolongo-Grau, O; Rodríguez-Pérez, D; Antoranz, J C; Sotolongo-Costa, Oscar

    2010-10-08

    The expression of survival factors for radiation damaged cells is currently based on probabilistic assumptions and experimentally fitted for each tumor, radiation, and conditions. Here, we show how the simplest of these radiobiological models can be derived from the maximum entropy principle of the classical Boltzmann-Gibbs expression. We extend this derivation using the Tsallis entropy and a cutoff hypothesis, motivated by clinical observations. The obtained expression shows a remarkable agreement with the experimental data found in the literature.

  19. Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Audette-Stuart, M., E-mail: stuartm@aecl.ca [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada); Kim, S.B.; McMullin, D.; Festarini, A.; Yankovich, T.L.; Carr, J.; Mulpuru, S. [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada)

    2011-06-15

    Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms. - Highlights: > Frogs were collected from background and higher tritium level habitats. > The micronucleus assay was conducted on liver cells obtained from the frogs. > No detrimental effects were noted in frogs exposed to elevated tritium. > Adaptive responses were observed in frogs exposed to elevated tritium.

  20. In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents

    OpenAIRE

    Hilliard, Massimo A.; Apicella, Alfonso J.; Kerr, Rex; Suzuki, Hiroshi; Bazzicalupo, Paolo; Schafer, William R

    2004-01-01

    ASH sensory neurons are required in Caenorhabditis elegans for a wide range of avoidance behaviors in response to chemical repellents, high osmotic solutions and nose touch. The ASH neurons are therefore hypothesized to be polymodal nociceptive neurons. To understand the nature of polymodal sensory response and adaptation at the cellular level, we expressed the calcium indicator protein cameleon in ASH and analyzed intracellular Ca2+ responses following stimulation with chemical repellents, o...

  1. Biological Bases for Radiation Adaptive Responses in the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby R. [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Lin, Yong [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Wilder, Julie [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Belinsky, Steven [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States)

    2015-03-01

    Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis which now is known to be unsupported by a large volume of data.

  2. Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress.

    Science.gov (United States)

    Naudi, Alba; Jove, Mariona; Ayala, Victoria; Cassanye, Anna; Serrano, Jose; Gonzalo, Hugo; Boada, Jordi; Prat, Joan; Portero-Otin, Manuel; Pamplona, Reinald

    2012-01-01

    Oxidative stress has been implicated in diabetes long-term complications. In this paper, we summarize the growing evidence suggesting that hyperglycemia-induced overproduction of superoxide by mitochondrial electron transport chain triggers a maladaptive response by affecting several metabolic and signaling pathways involved in the pathophysiology of cellular dysfunction and diabetic complications. In particular, it is our goal to describe physiological mechanisms underlying the mitochondrial free radical production and regulation to explain the oxidative stress derived from a high intracellular glucose concentration and the resulting maladaptive response that leads to a cellular dysfunction and pathological state. Finally, we outline potential therapies for diabetes focused to the prevention of mitochondrial oxidative damage.

  3. The Yin-Yang of DNA Damage Response: Roles in Tumorigenesis and Cellular Senescence

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    2013-01-01

    Full Text Available Senescent cells are relatively stable, lacking proliferation capacity yet retaining metabolic activity. In contrast, cancer cells are rather invasive and devastating, with uncontrolled proliferative capacity and resistance to cell death signals. Although tumorigenesis and cellular senescence are seemingly opposite pathological events, they are actually driven by a unified mechanism: DNA damage. Integrity of the DNA damage response (DDR network can impose a tumorigenesis barrier by navigating abnormal cells to cellular senescence. Compromise of DDR, possibly due to the inactivation of DDR components, may prevent cellular senescence but at the expense of tumor formation. Here we provide an overview of the fundamental role of DDR in tumorigenesis and cellular senescence, under the light of the Yin-Yang concept of Chinese philosophy. Emphasis is placed on discussing DDR outcome in the light of in vivo models. This information is critical as it can help make better decisions for clinical treatments of cancer patients.

  4. Effects of helio-neon laser radiation upon cellular cycle in a plant model

    Energy Technology Data Exchange (ETDEWEB)

    de Barioglio, S.R.; Fiol de Cuneo, M.; Lacuara, J.L.; Juri, H.

    1989-01-01

    The scope of this study was to investigate possible relationships between He-Neon laser radiation and mitotic and phase indices in meristematic cells of Allium cepa L. bulbs. Our results indicate that mitotic index increased after irradiation depending this modification on the time exposure and the potency of the He-Neon beam. Phase indices were also modified: frequency of prophase increased, while inter- meta- and anaphase decreased: telophases remain unchanged. These variations were significative only when the preparations were irradiated (a) with 5 mW for 10 min. or more, (b) with 10 mW or (c) when the preparations were processed 60 min. after irradiation. These findings could not be attributed to thermal changes. Modifications in RNA or protein synthesis could be responsible.

  5. Dynamics of cellular immune responses in the acute phase of dengue virus infection.

    Science.gov (United States)

    Yoshida, Tomoyuki; Omatsu, Tsutomu; Saito, Akatsuki; Katakai, Yuko; Iwasaki, Yuki; Kurosawa, Terue; Hamano, Masataka; Higashino, Atsunori; Nakamura, Shinichiro; Takasaki, Tomohiko; Yasutomi, Yasuhiro; Kurane, Ichiro; Akari, Hirofumi

    2013-06-01

    In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection.

  6. The cellular response of Saccharomyces cerevisiae to multi-walled carbon nanotubes (MWCNTs

    Directory of Open Access Journals (Sweden)

    Chantelle L. Phillips

    2015-03-01

    Full Text Available Nanoparticles (NPs especially those of carbon nanotubes (CNTs have remarkable properties that are very desirable in various biological and biomedical applications. This has necessitated the rapid study of CNT toxicities, to augment their safe use, particularly, in yeast cells. The yeast cell; Saccharomyces cerevisiae is a widely used industrial and biological organism with very limited data regarding their cellular behaviour in NPs. The current study examines the cellular response of S. cerevisiae to MWCNTs. The CNTs were produced by the swirled floating catalytic chemical vapour deposition (SFCCVD method and covalently functionalised using 1,3-dipolar cycloaddition. The CNT properties such as size, surface area, quality and surface vibrations were characterized using TEM, SEM, BET, TGA and Raman spectroscopy, respectively. The cellular uptake was confirmed with a FITC functionalised MWCNTs using 1H NMR, SEM and TEM. The CNT concentrations of 2–40 μg/ml were used to determine the cellular response through cell growth phases and cell viability characteristics. The TEM and SEM analyses showed the production of MWCNTs with an average diameter of 53 ± 12 nm and a length of 2.5 ± 0.5 μm. The cellular uptake of FITC-MWCNTs showed 100% internalisation in the yeast cells. The growth curve responses to the MWCNT doses showed no significant differences at P > 0.05 on the growth rate and viability of the S. cerevisiae cells.

  7. A mathematical model representing cellular immune development and response to Salmonella of chicken intestinal tissue

    NARCIS (Netherlands)

    Schokker, D.; Bannink, A.; Smits, M.A.; Rebel, J.M.J.

    2013-01-01

    The aim of this study was to create a dynamic mathematical model of the development of the cellular branch of the intestinal immune system of poultry during the first 42 days of life and of its response towards an oral infection with Salmonella enterica serovar Enteritidis. The system elements were

  8. Cellular response of mucociliary differentiated primary bronchial epithelial cells to diesel exhaust

    NARCIS (Netherlands)

    Zarcone, M.C.; Duistermaat, E.; Schadewijk, A. van; Jedynksa, A.D.; Hiemstra, P.S.; Kooter, I.M.

    2016-01-01

    Cellular response of mucociliary differentiated primary bronchial epithelial cells to diesel exhaust. Am J Physiol Lung Cell Mol Physiol 311: L111–L123, 2016. First published May 17, 2016; doi:10.1152/ajplung.00064.2016.—Diesel emissions are the main source of air pollution in urban areas, and diese

  9. Role of p53 in the cellular response following oleic acid accumulation in Chang liver cells.

    Science.gov (United States)

    Park, Eun-Jung; Lee, Ah Young; Chang, Seung-Hee; Yu, Kyeong-Nam; Kim, Jae-Ho; Cho, Myung-Haing

    2014-01-03

    Abnormal accumulation of fatty acids triggers the harmful cellular response called lipotoxicity. In this study, we investigated the cellular response following accumulation of oleic acid (OA), a monounsaturated fatty acid, in human Chang liver cells. OA droplets were distributed freely in the cytoplasm and/or degraded within lysosomes. OA exposure increased ATP production and concomitantly dilated mitochondria. At 24h after OA exposure, cell viability decreased slightly and was coupled with a reduction in mitochondrial Ca(2+) concentration, the alteration in cell viability was also associated with the generation of reactive oxygen species and changes in the cell cycle. Moreover, OA treatment increased the expression of autophagy- and apoptotic cell death-related proteins in a dose-dependent manner. Furthermore, we investigated the role of p53, a tumor suppressor protein, in the cellular response elicited by OA accumulation. OA-induced changes in cell viability and ATP production were rescued to control levels when cells were pretreated with pifithrin-alpha (PTA), a p53 inhibitor. By contrast, the expressions of LC3-II and perilipin, proteins required for lipophagy, were down-regulated by PTA pretreatment. Taken together, our results suggest that p53 plays a key role in the cellular response elicited by OA accumulation in Chang liver cells.

  10. Cellular and humoral local immune responses in sheep experimentally infected with Oestrus ovis (Diptera: Oestridae).

    Science.gov (United States)

    Tabouret, Guillaume; Lacroux, Caroline; Andreoletti, Olivier; Bergeaud, Jean Paul; Hailu-Tolosa, Yacob; Hoste, Hervé; Prevot, Françoise; Grisez, Christelle; Dorchies, Philippe; Jacquiet, Philippe

    2003-01-01

    Cellular and humoral local responses were investigated following repetitive artificial Oestrus ovis infections in lambs. The presence of larvae induced a huge local recruitment of either leucocytes (T and B lymphocytes, macrophages) or granulocytes (eosinophils, mast cells and globule leucocytes). This cellular response was more pronounced in the ethmoid and sinus (development sites of second and third instar larvae) than in the septum or turbinates where first instar larvae migrate. Infected lambs produced Oestrus ovis specific IgG and IgA antibodies in their mucus. This local humoral response was mainly directed against larval salivary gland antigens and not against larval digestive tract antigens. Compared to the control animals, the sinusal mucosa of infected animals was extremely thickened and the epithelium exhibited hyperplasia, metaplasia and eosinophilic exocytosis. The possible roles of these local immune responses in the regulation of O. ovis larvae populations in sheep are discussed.

  11. Surface energy budget responses to radiative forcing at Summit, Greenland

    Science.gov (United States)

    Miller, Nathaniel B.; Shupe, Matthew D.; Cox, Christopher J.; Noone, David; Persson, P. Ola G.; Steffen, Konrad

    2017-02-01

    Greenland Ice Sheet surface temperatures are controlled by an exchange of energy at the surface, which includes radiative, turbulent, and ground heat fluxes. Data collected by multiple projects are leveraged to calculate all surface energy budget (SEB) terms at Summit, Greenland, for the full annual cycle from July 2013 to June 2014 and extend to longer periods for the radiative and turbulent SEB terms. Radiative fluxes are measured directly by a suite of broadband radiometers. Turbulent sensible heat flux is estimated via the bulk aerodynamic and eddy correlation methods, and the turbulent latent heat flux is calculated via a two-level approach using measurements at 10 and 2 m. The subsurface heat flux is calculated using a string of thermistors buried in the snow pack. Extensive quality-control data processing produced a data set in which all terms of the SEB are present 75 % of the full annual cycle, despite the harsh conditions. By including a storage term for a near-surface layer, the SEB is balanced in this data set to within the aggregated uncertainties for the individual terms. November and August case studies illustrate that surface radiative forcing is driven by synoptically forced cloud characteristics, especially by low-level, liquid-bearing clouds. The annual cycle and seasonal diurnal cycles of all SEB components indicate that the non-radiative terms are anticorrelated to changes in the total radiative flux and are hence responding to cloud radiative forcing. Generally, the non-radiative SEB terms and the upwelling longwave radiation component compensate for changes in downwelling radiation, although exact partitioning of energy in the response terms varies with season and near-surface characteristics such as stability and moisture availability. Substantial surface warming from low-level clouds typically leads to a change from a very stable to a weakly stable near-surface regime with no solar radiation or from a weakly stable to neutral

  12. GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, F.; Molina, M.; Berthier-Vergnes, O.; Lamartine, J. [Universite de Lyon, Lyon, F-69003 (France); Universite Lyon 1, Lyon, F-69003 (France); CNRS, UMR5534, Centre de Genetique Moleculaire et Cellulaire, Villeurbanne, F-69622 (France); Malet, C.; Ginestet, C. [Centre Leon Berard, Service de Radiotherapie, Lyon F-69008 (France); Martin, M.T. [Laboratoire de Genomique et Radiobiologie de la Keratinopoiese, CEA, IRCM, Evry F-91000 (France)

    2009-07-01

    Background: The general population is constantly exposed to low levels of radiation through natural, occupational or medical irradiation. Even if the biological effects of low-level radiation have been intensely debated and investigated, the molecular mechanisms underlying the cellular response to low doses remain largely unknown. Results: The present study investigated the role of GATA3 protein in the control of the cellular and molecular response of human keratinocytes exposed to a 1 cGy dose of X-rays. Chromatin immunoprecipitation showed GATA3 to be able to bind the promoter of 4 genes responding to a 1 cGy exposure. To go further into the role of GATA3 after ionizing radiation exposure, we studied the cellular and molecular consequences of radiation in GATA3 knock-down cells. Knockdown was obtained by lentiviral-mediated expression of an shRNA targeting the GATA3 transcript in differentiated keratinocytes. First, radiosensitivity was assessed: the toxicity, in terms of immediate survival (with XTT test), associated with 1 cGy radiation was found to be increased in GATA3 knock-down cells. The impact of GATA3 knock-down on the transcriptome of X-ray irradiated cells was also investigated, using oligonucleotide micro-arrays to assess changes between 3 h and 72 h post-irradiation in normal vs GATA3 knock-down backgrounds; transcriptome response was found to be completely altered in GATA3 knock-down cells, with a strong induction/repression peak 48 h after irradiation. Functional annotation revealed enrichment in genes known to be involved in chaperone activity, TGF{beta} signalling and stress response. Conclusion: Taken together, these data indicate that GATA3 is an important regulator of the cellular and molecular response of epidermal cells to very low doses of radiation. (authors)

  13. Vanguards of Paradigm Shift in Radiation Biology: Radiation-Induced Adaptive and Bystander Responses

    OpenAIRE

    MATSUMOTO, Hideki; Hamada, Nobuyuki; Takahashi, Akihisa; Kobayashi, Yasuhiko; Ohnishi, Takeo

    2007-01-01

    The risks of exposure to low dose ionizing radiation (below 100 mSv) are estimated by extrapolating from data obtained after exposure to high dose radiation, using a linear no-threshold model (LNT model). However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose/low dose-rate radiation than they do to high dose/high dose-rate radiation. In oth...

  14. Involvement of Noxa in mediating cellular ER stress responses to lytic virus infection

    OpenAIRE

    2011-01-01

    Noxa is a Bcl-2 homology domain-containing pro-apoptotic mitochondrial protein. Noxa mRNA and protein expression are upregulated by dsRNA or virus, and ectopic Noxa expression enhances cellular sensitivity to virus or dsRNA-induced apoptosis. Here we demonstrate that Noxa null baby mouse kidney (BMK) cells are deficient in normal cytopathic response to lytic viruses, and that reconstitution of the knockout cells with wild type Noxa restored normal cytopathic responses. Noxa regulation by viru...

  15. Global functional analyses of cellular responses to pore-forming toxins.

    Directory of Open Access Journals (Sweden)

    Cheng-Yuan Kao

    2011-03-01

    Full Text Available Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs. PFTs are uniquely important bacterial virulence factors, comprising the single largest class of bacterial protein toxins and being important for the pathogenesis in humans of many Gram positive and Gram negative bacteria. Their mode of action is deceptively simple, poking holes in the plasma membrane of cells. The scattered studies to date of PFT-host cell interactions indicate a handful of genes are involved in cellular defenses to PFTs. How many genes are involved in cellular defenses against PFTs and how cellular defenses are coordinated are unknown. To address these questions, we performed the first genome-wide RNA interference (RNAi screen for genes that, when knocked down, result in hypersensitivity to a PFT. This screen identifies 106 genes (∼0.5% of genome in seven functional groups that protect Caenorhabditis elegans from PFT attack. Interactome analyses of these 106 genes suggest that two previously identified mitogen-activated protein kinase (MAPK pathways, one (p38 studied in detail and the other (JNK not, form a core PFT defense network. Additional microarray, real-time PCR, and functional studies reveal that the JNK MAPK pathway, but not the p38 MAPK pathway, is a key central regulator of PFT-induced transcriptional and functional responses. We find C. elegans activator protein 1 (AP-1; c-jun, c-fos is a downstream target of the JNK-mediated PFT protection pathway, protects C. elegans against both small-pore and large-pore PFTs and protects human cells against a large-pore PFT. This in vivo RNAi genomic study of PFT responses proves that cellular commitment to PFT defenses is enormous, demonstrates the JNK MAPK pathway as a key regulator of transcriptionally-induced PFT defenses, and identifies AP-1 as the first cellular component broadly important for defense against large- and small-pore PFTs.

  16. Radiation sterilized bone response to dynamic loading

    Energy Technology Data Exchange (ETDEWEB)

    Mardas, Marcin, E-mail: marcin.mardas@skpp.edu.pl [Department of Oncology, Poznan University of Medical Sciences, ul. Szamarzewskiego 82/84, 60-569 Poznan (Poland); Kubisz, Leszek [Department of Biophysics, Poznan University of Medical Sciences, ul. Fredry 10, 61-701 Poznan (Poland); Biskupski, Piotr; Mielcarek, Slawomir [Department of Physics, Adam Mickiewicz University, ul. Umultowska 85, 61-614 Poznan (Poland); Stelmach-Mardas, Marta [Department of Bromatology, Poznan University of Medical Sciences, ul. Marcelinska 420, 60-354 Poznan (Poland); Kaluska, Iwona [Centre for Radiation Research and Technology, Institute of Nuclear Chemistry and Technology, ul. Dorodna 16, 03-195 Warsaw (Poland)

    2012-08-01

    Allogeneic bone grafts are used on a large scale in surgeries. To avoid the risk of infectious diseases, allografts should be radiation-sterilized. So far, no international consensus has been achieved regarding the optimal radiation dose. Many authors suggest that bone sterilization deteriorates bone mechanical properties. However, no data on the influence of ionizing radiation on bone dynamic mechanical properties are available. Bovine femurs from 2-year old animal were machine cut and irradiated with the doses 10, 15, 25, 35, 45 and 50 kGy. Dynamic mechanical analysis was performed at 1-10 Hz at the temperature range of 0-350 Degree-Sign C in 3-point bending configuration. No statistically significant differences in storage modulus were observed. However, there were significant decreased values of loss modulus between the samples irradiated with doses of 10 ({down_arrow}14.3%), 15, 45 and 50 kGy ({down_arrow}33.2%) and controls. It was stated that increased irradiation dose decreases the temperature where collagen denaturation process starts and increases the temperature where the collagen denaturation process finishes. It was shown that activation energy of denaturation process is significantly higher for the samples irradiated with the dose of 50 kGy (615 kJ/mol) in comparison with control samples and irradiation with other doses (100-135 kJ/mol). - Highlights: Black-Right-Pointing-Pointer We examine changes in the storage modulus and loss modulus of samples irradiated with doses of 10-50 kGy. Black-Right-Pointing-Pointer We examine changes in the denaturation temperature of samples irradiated with doses of 10-50 kGy. Black-Right-Pointing-Pointer We examine changes in the activation energy of denaturation process of samples irradiated with doses of 10-50 kGy.

  17. Cellular and molecular research to reduce uncertainties in estimates of health effects from low-level radiation

    Energy Technology Data Exchange (ETDEWEB)

    Elkind, M.M.; Bedford, J.; Benjamin, S.A.; Waldren, C.A. (Colorado State Univ., Fort Collins, CO (USA)); Gotchy, R.L. (Science Applications International Corp., McLean, VA (USA))

    1990-10-01

    A study was undertaken by five radiation scientists to examine the feasibility of reducing the uncertainties in the estimation of risk due to protracted low doses of ionizing radiation. In addressing the question of feasibility, a review was made by the study group: of the cellular, molecular, and mammalian radiation data that are available; of the way in which altered oncogene properties could be involved in the loss of growth control that culminates in tumorigenesis; and of the progress that had been made in the genetic characterizations of several human and animal neoplasms. On the basis of this analysis, the study group concluded that, at the present time, it is feasible to mount a program of radiation research directed at the mechanism(s) of radiation-induced cancer with special reference to risk of neoplasia due to protracted, low doses of sparsely ionizing radiation. To implement a program of research, a review was made of the methods, techniques, and instruments that would be needed. This review was followed by a survey of the laboratories and institutions where scientific personnel and facilities are known to be available. A research agenda of the principal and broad objectives of the program is also discussed. 489 refs., 21 figs., 14 tabs.

  18. Study of effects of radio-wave frequency radiation emitted from cellular telephones on embryonic development of danio rerio

    Science.gov (United States)

    Vagula, Mary; Harkless, Ryan

    2013-05-01

    Radio wave frequency (RF) radiation emitted from cellular telephones has become increasingly ubiquitous as a result of the popularity of these phones. With the increasing and unavoidable exposure to RF radiation a reality, it is imperative that the effects of such radiation on living tissue be well understood. In particular, it is critical to understand any effects that RF radiation may have as a carcinogen and on embryonic development, as pregnant women are not exempt from such exposure. As a model organism, zebrafish (Danio rerio) have been studied extensively, and their value in studies of gene expression cannot be overstated. This study observed the effects of RF radiation on the embryonic development of zebrafish. The expression of two genes, shha and hoxb9a, that are key to the early development of the fish was examined. Both genes have homologs in humans as well as in other model organisms. Preliminary results suggest that exposure to cell phone radiation might have an effect on the expression of shha in zebrafish embryos, causing under expression. More trials are necessary to validate these results.

  19. Immune Modulation and Stereotactic Radiation: Improving Local and Abscopal Responses

    Directory of Open Access Journals (Sweden)

    Jing Zeng

    2013-01-01

    Full Text Available New and innovative treatment strategies for cancer patients in the fields of immunotherapy and radiotherapy are rapidly developing in parallel. Among the most promising preclinical treatment approaches is combining immunotherapy with radiotherapy where early data suggest synergistic effects in several tumor model systems. These studies demonstrate that radiation combined with immunotherapy can result in superior efficacy for local tumor control. More alluring is the emergence of data suggesting an equally profound systemic response also known as “abscopal” effects with the combination of radiation and certain immunotherapies. Studies addressing optimal radiation dose, fractionation, and modality to be used in combination with immunotherapy still require further exploration. However, recent anecdotal clinical reports combining stereotactic or hypofractionated radiation regimens with immunotherapy have resulted in dramatic sustained clinical responses, both local and abscopal. Technologic advances in clinical radiation therapy has made it possible to deliver hypofractionated regimens anywhere in the body using stereotactic radiation techniques, facilitating further clinical investigations. Thus, stereotactic radiation in combination with immunotherapy agents represents an exciting and potentially fruitful new space for improving cancer therapeutic responses.

  20. Low-Dose UVA Radiation-Induced Adaptive Response in Cultured Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Zhongrong Liu

    2012-01-01

    Full Text Available Objective. To investigate the mechanism of the adaptive response induced by low-dose ultraviolet A (UVA radiation. Methods. Cultured dermal fibroblasts were irradiated by a lethal dose of UVA (86.4 J/cm2 with preirradiation of single or repetitive low dose of UVA (7.2 J/cm2. Alterations of cellular morphology were observed by light microscope and electron microscope. Cell cycle and cellular apoptosis were assayed by flow cytometer. The extent of DNA damage was determined by single-cell gel electrophoresis (SCGE. Results. The cultured dermal fibroblasts, with pretreatment of single or repetitive irradiation of 7.2 J/cm2 UVA relieved toxic reaction of cellular morphology and arrest of cell cycle, decreased apoptosis ratio, reduced DNA chain breakage, and accelerated DNA repair caused by subsequent 86.4 J/cm2 UVA irradiation. Compared with nonpretreatment groups, all those differences were significant (P<0.01 or P<0.05. Conclusions. The adaptation reaction might depend on the accumulated dose of low-dose UVA irradiation. Low-dose UVA radiation might induce adaptive response that may protect cultured dermal fibroblasts from the subsequent challenged dose of UVA damage. The duration and protective capability of the adaptive reaction might be related to the accumulated dose of low-dose UVA Irradiation.

  1. Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-09-01

    Full Text Available Silver nanoparticles (AgNPs have attracted increased interest and are currently used in various industries including medicine, cosmetics, textiles, electronics, and pharmaceuticals, owing to their unique physical and chemical properties, particularly as antimicrobial and anticancer agents. Recently, several studies have reported both beneficial and toxic effects of AgNPs on various prokaryotic and eukaryotic systems. To develop nanoparticles for mediated therapy, several laboratories have used a variety of cell lines under in vitro conditions to evaluate the properties, mode of action, differential responses, and mechanisms of action of AgNPs. In vitro models are simple, cost-effective, rapid, and can be used to easily assess efficacy and performance. The cytotoxicity, genotoxicity, and biocompatibility of AgNPs depend on many factors such as size, shape, surface charge, surface coating, solubility, concentration, surface functionalization, distribution of particles, mode of entry, mode of action, growth media, exposure time, and cell type. Cellular responses to AgNPs are different in each cell type and depend on the physical and chemical nature of AgNPs. This review evaluates significant contributions to the literature on biological applications of AgNPs. It begins with an introduction to AgNPs, with particular attention to their overall impact on cellular effects. The main objective of this review is to elucidate the reasons for different cell types exhibiting differential responses to nanoparticles even when they possess similar size, shape, and other parameters. Firstly, we discuss the cellular effects of AgNPs on a variety of cell lines; Secondly, we discuss the mechanisms of action of AgNPs in various cellular systems, and try to elucidate how AgNPs interact with different mammalian cell lines and produce significant effects; Finally, we discuss the cellular activation of various signaling molecules in response to AgNPs, and conclude with

  2. Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

    Science.gov (United States)

    Zhang, Xi-Feng; Shen, Wei; Gurunathan, Sangiliyandi

    2016-01-01

    Silver nanoparticles (AgNPs) have attracted increased interest and are currently used in various industries including medicine, cosmetics, textiles, electronics, and pharmaceuticals, owing to their unique physical and chemical properties, particularly as antimicrobial and anticancer agents. Recently, several studies have reported both beneficial and toxic effects of AgNPs on various prokaryotic and eukaryotic systems. To develop nanoparticles for mediated therapy, several laboratories have used a variety of cell lines under in vitro conditions to evaluate the properties, mode of action, differential responses, and mechanisms of action of AgNPs. In vitro models are simple, cost-effective, rapid, and can be used to easily assess efficacy and performance. The cytotoxicity, genotoxicity, and biocompatibility of AgNPs depend on many factors such as size, shape, surface charge, surface coating, solubility, concentration, surface functionalization, distribution of particles, mode of entry, mode of action, growth media, exposure time, and cell type. Cellular responses to AgNPs are different in each cell type and depend on the physical and chemical nature of AgNPs. This review evaluates significant contributions to the literature on biological applications of AgNPs. It begins with an introduction to AgNPs, with particular attention to their overall impact on cellular effects. The main objective of this review is to elucidate the reasons for different cell types exhibiting differential responses to nanoparticles even when they possess similar size, shape, and other parameters. Firstly, we discuss the cellular effects of AgNPs on a variety of cell lines; Secondly, we discuss the mechanisms of action of AgNPs in various cellular systems, and try to elucidate how AgNPs interact with different mammalian cell lines and produce significant effects; Finally, we discuss the cellular activation of various signaling molecules in response to AgNPs, and conclude with future perspectives

  3. Intraspecific variation in cellular and biochemical heat response strategies of Mediterranean Xeropicta derbentina [Pulmonata, Hygromiidae].

    Directory of Open Access Journals (Sweden)

    Sandra Troschinski

    Full Text Available Dry and hot environments challenge the survival of terrestrial snails. To minimize overheating and desiccation, physiological and biochemical adaptations are of high importance for these animals. In the present study, seven populations of the Mediterranean land snail species Xeropicta derbentina were sampled from their natural habitat in order to investigate the intraspecific variation of cellular and biochemical mechanisms, which are assigned to contribute to heat resistance. Furthermore, we tested whether genetic parameters are correlated with these physiological heat stress response patterns. Specimens of each population were individually exposed to elevated temperatures (25 to 52°C for 8 h in the laboratory. After exposure, the health condition of the snails' hepatopancreas was examined by means of qualitative description and semi-quantitative assessment of histopathological effects. In addition, the heat-shock protein 70 level (Hsp70 was determined. Generally, calcium cells of the hepatopancreas were more heat resistant than digestive cells - this phenomenon was associated with elevated Hsp70 levels at 40°C.We observed considerable variation in the snails' heat response strategy: Individuals from three populations invested much energy in producing a highly elevated Hsp70 level, whereas three other populations invested energy in moderate stress protein levels - both strategies were in association with cellular functionality. Furthermore, one population kept cellular condition stable despite a low Hsp70 level until 40°C exposure, whereas prominent cellular reactions were observed above this thermal limit. Genetic diversity (mitochondrial cytochrome c oxidase subunit I gene within populations was low. Nevertheless, when using genetic indices as explanatory variables in a multivariate regression tree (MRT analysis, population structure explained mean differences in cellular and biochemical heat stress responses, especially in the group

  4. Immunologic Monitoring of Cellular Responses by Dendritic/Tumor Cell Fusion Vaccines

    Directory of Open Access Journals (Sweden)

    Shigeo Koido

    2011-01-01

    Full Text Available Although dendritic cell (DC- based cancer vaccines induce effective antitumor activities in murine models, only limited therapeutic results have been obtained in clinical trials. As cancer vaccines induce antitumor activities by eliciting or modifying immune responses in patients with cancer, the Response Evaluation Criteria in Solid Tumors (RECIST and WHO criteria, designed to detect early effects of cytotoxic chemotherapy in solid tumors, may not provide a complete assessment of cancer vaccines. The problem may, in part, be resolved by carrying out immunologic cellular monitoring, which is one prerequisite for rational development of cancer vaccines. In this review, we will discuss immunologic monitoring of cellular responses for the evaluation of cancer vaccines including fusions of DC and whole tumor cell.

  5. The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Cattaneo, Paola; Berezin, Vladimir

    2009-01-01

    different from that elicited by FGF-2. In contrast to FGF-induced degradation of endocytic FGFR1, NCAM promotes the stabilization of the receptor, which is recycled to the cell surface in a Rab11- and Src-dependent manner. In turn, FGFR1 recycling is required for NCAM-induced sustained activation of various...... effectors. Furthermore, NCAM, but not FGF-2, promotes cell migration, and this response depends on FGFR1 recycling and sustained Src activation. Our results implicate NCAM as a nonconventional ligand for FGFR1 that exerts a peculiar control on the intracellular trafficking of the receptor, resulting...... in a specific cellular response. Besides introducing a further level of complexity in the regulation of FGFR1 function, our findings highlight the link of FGFR recycling with sustained signaling and cell migration and the critical role of these events in dictating the cellular response evoked by receptor...

  6. Modeling Clinical Radiation Responses in the IMRT Era

    Science.gov (United States)

    Schwartz, J. L.; Murray, D.; Stewart, R. D.; Phillips, M. H.

    2014-03-01

    The purpose of this review is to highlight the critical issues of radiobiological models, particularly as they apply to clinical radiation therapy. Developing models of radiation responses has a long history that continues to the present time. Many different models have been proposed, but in the field of radiation oncology, the linear-quadratic (LQ) model has had the most impact on the design of treatment protocols. Questions have been raised as to the value of the LQ model given that the biological assumption underlying it has been challenged by molecular analyses of cell and tissue responses to radiation. There are also questions as to use of the LQ model for hypofractionation, especially for high dose treatments using a single fraction. While the LQ model might over-estimate the effects of large radiation dose fractions, there is insufficient information to fully justify the adoption of alternative models. However, there is increasing evidence in the literature that non-targeted and other indirect effects of radiation sometimes produce substantial deviations from LQ-like dose-response curves. As preclinical and clinical hypofractionation studies accumulate, new or refined dose-response models that incorporate high-dose/fraction non-targeted and indirect effects may be required, but for now the LQ model remains a simple, useful tool to guide the design of treatment protocols.

  7. Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response

    Directory of Open Access Journals (Sweden)

    Tadanobu Takahashi

    2011-01-01

    Full Text Available Membrane rafts are small (10–200 nm sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts play an important role in viral infection cycles and viral virulence. Viruses are divided into four main classes, enveloped DNA virus, enveloped RNA virus, nonenveloped DNA virus, and nonenveloped RNA virus. General virus infection cycle is also classified into two sections, the early stage (entry process and the late stage (assembly, budding, and release processes of virus particles. In the viral cycle, membrane rafts act as a scaffold of many cellular signal transductions, which are associated with symptoms caused by viral infections. In this paper, we describe the functions of membrane rafts in viral lifecycles and host cellular response according to each virus classification, each stage of the virus lifecycle, and each virus-induced signal transduction.

  8. Elucidation of changes in molecular signalling leading to increased cellular transformation in oncogenically progressed human bronchial epithelial cells exposed to radiations of increasing LET.

    Science.gov (United States)

    Ding, Liang-Hao; Park, Seongmi; Xie, Yang; Girard, Luc; Minna, John D; Story, Michael D

    2015-09-01

    The early transcriptional response and subsequent induction of anchorage-independent growth after exposure to particles of high Z and energy (HZE) as well as γ-rays were examined in human bronchial epithelial cells (HBEC3KT) immortalised without viral oncogenes and an isogenic variant cell line whose p53 expression was suppressed but that expressed an active mutant K-RAS(V12) (HBEC3KT-P53KRAS). Cell survival following irradiation showed that HBEC3KT-P53KRAS cells were more radioresistant than HBEC3KT cells irrespective of the radiation species. In addition, radiation enhanced the ability of the surviving HBEC3KT-P53RAS cells but not the surviving HBEC3KT cells to grow in anchorage-independent fashion (soft agar colony formation). HZE particle irradiation was far more efficient than γ-rays at rendering HBEC3KT-P53RAS cells permissive for soft agar growth. Gene expression profiles after radiation showed that the molecular response to radiation for HBEC3KT-P53RAS, similar to that for HBEC3KT cells, varies with radiation quality. Several pathways associated with anchorage independent growth, including the HIF-1α, mTOR, IGF-1, RhoA and ERK/MAPK pathways, were over-represented in the irradiated HBEC3KT-P53RAS cells compared to parental HBEC3KT cells. These results suggest that oncogenically progressed human lung epithelial cells are at greater risk for cellular transformation and carcinogenic risk after ionising radiation, but particularly so after HZE radiations. These results have implication for: (i) terrestrial radiation and suggests the possibility of enhanced carcinogenic risk from diagnostic CT screens used for early lung cancer detection; (ii) enhanced carcinogenic risk from heavy particles used in radiotherapy; and (iii) for space radiation, raising the possibility that astronauts harbouring epithelial regions of dysplasia or hyperplasia within the lung that contain oncogenic changes, may have a greater risk for lung cancers based upon their exposure to heavy

  9. Oxidative Stress and Autophagy Responses of Osteocytes Exposed to Spaceflight-like Radiation.

    Science.gov (United States)

    Tahimic, Candice; Rael, Victoria E.; Globus, Ruth K.

    2015-01-01

    Weightlessness and radiation, two of the unique elements of the space environment, causes a profound decrement in bone mass that mimics aging. This bone loss is thought to result from increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our current understanding of the signaling factors and mechanisms underlying bone loss is incomplete. However, it is known that oxidative stress, characterized by the excess production of free radicals, is elevated during radiation exposure. The goals of this study is to examine the response of osteocytes to spaceflight-like radiation and to identify signaling processes that may be targeted to mitigate bone loss in scenarios of space exploration, earth-based radiotherapy and accidental radiation exposure. We hypothesize that (1) oxidative stress, as induced by radiation, decreases osteocyte survival and increases pro-osteoclastogenic signals and that (2) autophagy is one of the key cellular defenses against oxidative stress. Autophagy is the process by which cellular components including organelles and proteins are broken down and recycled. To test our hypothesis, we exposed the osteocyte-like cell line, MLO-Y4, to 0.5, 1, and 2 Gy of simulated space radiation (Iron-56 radiation at 600 MeV/n) and assessed cell numbers, cell growth-associated molecules as well as markers of autophagy and oxidative stress at various time points post-irradiation. We observed a reduction in cell numbers in the groups exposed to 1 and 2 Gy of Iron-56 radiation. Collectively, flow cytometry and gene expression analysis revealed that radiation caused a shift in cell cycle distribution consistent with growth arrest. Compared to sham-treatment, 2 Gy of Iron-56 increased FoxO3, SOD1, and RANKL gene expression yet unexpectedly decreased LC3B-II protein levels at 4 and 24 hours post-IR. Taken together, these findings suggest that simulated space radiation invoke

  10. Anomalous response of superconducting titanium nitride resonators to terahertz radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bueno, J., E-mail: j.bueno@sron.nl; Baselmans, J. J. A [SRON, Netherlands Institute of Space Research, Utrecht (Netherlands); Coumou, P. C. J. J.; Zheng, G. [Kavli Institute of Nanoscience, Delft University of Technology, Delft (Netherlands); Visser, P. J. de [SRON, Netherlands Institute of Space Research, Utrecht (Netherlands); Kavli Institute of Nanoscience, Delft University of Technology, Delft (Netherlands); Klapwijk, T. M. [Kavli Institute of Nanoscience, Delft University of Technology, Delft (Netherlands); Physics Department, Moscow State Pedagogical University, 119991 Moscow (Russian Federation); Driessen, E. F. C. [Université Grenoble Alpes, INAC-SPSMS, F-38000 Grenoble (France); CEA, INAC-SPSMS, F-38000 Grenoble (France); Doyle, S. [Cardiff University, School of Physics and Astronomy, Queens Buildings, Cardiff CF24 3AA (United Kingdom)

    2014-11-10

    We present an experimental study of kinetic inductance detectors (KIDs) fabricated of atomic layer deposited TiN films and characterized at radiation frequencies of 350 GHz. The responsivity to radiation is measured and found to increase with the increase in radiation powers, opposite to what is expected from theory and observed for hybrid niobium titanium nitride/aluminium (NbTiN/Al) and all-aluminium (all-Al) KIDs. The noise is found to be independent of the level of the radiation power. The noise equivalent power improves with higher radiation powers, also opposite to what is observed and well understood for hybrid NbTiN/Al and all-Al KIDs. We suggest that an inhomogeneous state of these disordered superconductors should be used to explain these observations.

  11. The dielectric response to the magnetic field of electromagnetic radiation

    Science.gov (United States)

    Mukherjee, Shouvik; Mukhopadhyay, Sourabh; Datta, Prasanta Kumar

    2017-04-01

    Light–matter interaction in transparent dielectrics is revisited, including the magnetic force on bound charges in the Lorentz oscillator model. The parameter ranges of incident radiation and the medium on which the magnetic field of the electromagnetic radiation will have a significant effect are traced using Floquet theory. The analysis reveals that the threshold intensity for a significant response of the magnetic field of the radiation at the second harmonic of the incident radiation can be reduced to {10}12 {{W}}{{cm}}-2 for off resonant and even lower for resonant interaction. This phenomenon has already been observed indirectly in experiments [1, 2]. Induced magnetizing current due to the magnetic force is shown to originate from a modified dielectric response, which may be useful in future magneto-optic devices, solar energy harvesting, and studying the ultrafast dynamics in doped dielectrics.

  12. Chromosome damage and micronucleus formation in human blood lymphocytes exposed in vitro to radiofrequency radiation at a cellular telephone frequency (847.74 MHz, CDMA).

    Science.gov (United States)

    Vijayalaxmi; Bisht, K S; Pickard, W F; Meltz, M L; Roti Roti, J L; Moros, E G

    2001-10-01

    Peripheral blood samples collected from four healthy nonsmoking human volunteers were diluted with tissue culture medium and exposed in vitro for 24 h to 847.74 MHz radiofrequency (RF) radiation (continuous wave), a frequency employed for cellular telephone communications. A code division multiple access (CDMA) technology was used with a nominal net forward power of 75 W and a nominal power density of 950 W/m(2) (95 mW/cm(2)). The mean specific absorption rate (SAR) was 4.9 or 5.5 W/kg. Blood aliquots that were sham-exposed or exposed in vitro to an acute dose of 1.5 Gy of gamma radiation were included in the study as controls. The temperatures of the medium during RF-radiation and sham exposures in the Radial Transmission Line facility were controlled at 37 +/- 0.3 degrees C. Immediately after the exposures, lymphocytes were cultured at 37 +/- 1 degrees C for 48 or 72 h. The extent of genetic damage was assessed from the incidence of chromosome aberrations and micronuclei. The kinetics of cell proliferation was determined from the mitotic indices in 48-h cultures and from the incidence of binucleate cells in 72-h cultures. The data indicated no significant differences between RF-radiation-exposed and sham-exposed lymphocytes with respect to mitotic indices, frequencies of exchange aberrations, excess fragments, binucleate cells, and micronuclei. The response of gamma-irradiated lymphocytes was significantly different from that of both RF-radiation-exposed and sham-exposed cells for all of these indices. Thus there was no evidence for induction of chromosome aberrations and micronuclei in human blood lymphocytes exposed in vitro for 24 h to 847.74 MHz RF radiation (CDMA) at SARs of 4.9 or 5.5 W/kg.

  13. Effects of Spaceflight on Molecular and Cellular Responses to Bleomycin-induced DNA Damages in Confluent Human Fibroblasts

    Science.gov (United States)

    Lu, Tao; Wu, Honglu; Karouia, Fathi; Stodieck, Louis; Zhang, Ye; Wong, Michael

    2016-07-01

    Spaceflights expose human beings to various risk factors. Among them are microgravity related physiological stresses in immune, cytoskeletal, and cardiovascular systems, and space radiation related elevation of cancer risk. Cosmic radiation consists of energetic protons and other heavier charged particles that induce DNA damages. Effective DNA damage response and repair mechanism is important to maintain genomic integrity and reduce cancer risk. There were studies on effects of spaceflight and microgravity on DNA damage response in cell and animal models, but the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on molecular and cellular responses to DNA damages, bleomycin, an anti-cancer drug and radiomimetic reagent, was used to induce DNA damages in confluent human fibroblasts flown to the International Space Station (ISS) and on ground. After exposure to 1.0 mg/ml bleomycin for 3 hours, cells were fixed for immunofluorescence assays and for RNA preparation. Extents of DNA damages were quantified by focus pattern and focus number counting of phosphorylated histone protein H2AX (γg-H2AX). The cells on the ISS showed modestly increased average focus counts per nucleus while the distribution of patterns was similar to that on the ground. PCR array analysis showed that expressions of several genes, including CDKN1A and PCNA, were significantly changed in response to DNA damages induced by bleomycin in both flight and ground control cells. However, there were no significant differences in the overall expression profiles of DNA damage response genes between the flight and ground samples. Analysis of cellular proliferation status with Ki-67 staining showed a slightly higher proliferating population in cells on the ISS than those on ground. Our results suggested that the difference in γg-H2AX focus counts between flight and ground was due to the higher percentage of proliferating cells in space, but spaceflight did not

  14. The involvement of XPC protein in the cisplatin DNA damaging treatment-mediated cellular response

    Institute of Scientific and Technical Information of China (English)

    Gan WANG; Alan DOMBKOWSKI; Lynn CHUANG; Xiao Xin S XU

    2004-01-01

    Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. XPC is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the XPC protein in cisplatin DNA damaging treatment-mediated cellular response. Comparison of the microarray data from both normal and XPCdefective human fibroblasts identified 861 XPC-responsive genes in the cisplatin treatment (with minimum fold change≥1.5).The cell cycle and cell proliferation-related genes are the most affected genes by the XPC defect in the treatment. Many other cellular function genes, especially the DNA repair and signal transduction-related genes, were also affected by the XPC defect in the treatment. To validate the microarray data, the transcription levels of some microarray-identified genes were also determined by an RT-PCR based real time PCR assay. The real time PCR results are consistent with the microarray data for most of the tested genes, indicating the reliability of the microarray data. To further validate the microarray data, the cisplatin treatment-mediated caspase-3 activation was also determined. The Western blot hybridization results indicate that the XPC defect greatly attenuates the cisplatin treatment-mediated Caspase-3 activation. We elucidated the role of p53 protein in the XPC protein DNA damage recognition-mediated signaling process. The XPC defect reduces the cisplatin treatment-mediated p53 response. These results suggest that the XPC protein plays an important role in the cisplatin treatment-mediated cellular response. It may also suggest a possible mechanism of cancer cell drug resistance.

  15. Mitigation of radiation-induced hematopoietic injury via regulation of cellular MAPK/phosphatase levels and increasing hematopoietic stem cells.

    Science.gov (United States)

    Patwardhan, R S; Sharma, Deepak; Checker, Rahul; Sandur, Santosh K

    2014-03-01

    Here we describe a novel strategy for mitigation of ionizing radiation-induced hematopoietic syndrome by suppressing the activity of MKP3, resulting in ERK activation and enhanced abundance of hematopoietic stem cells, using the antioxidant flavonoid baicalein (5,6,7-trihydroxyflavone). It offered complete protection to mouse splenic lymphocytes against radiation-induced cell death. Inhibitors of ERK and Nrf-2 could significantly abrogate baicalein-mediated radioprotection in lymphocytes. Baicalein inhibited phosphatase MKP3 and thereby enhanced phosphorylation of ERK and its downstream proteins such as Elk and Nrf-2. It also increased the nuclear levels of Nrf-2 and the mRNA levels of its dependent genes. Importantly, baicalein administration to mice before radiation exposure led to significant recovery of loss of bone marrow cellularity and also inhibited cell death. Administration of baicalein increased the hematopoietic stem cell frequency as measured by side-population assay and also by antibody staining. Further, baicalein offered significant protection against whole-body irradiation (WBI; 7.5Gy)-induced mortality in mice. Interestingly, we found that baicalein works by activating the same target molecules ERK and Nrf-2 both in vitro and in vivo. Finally, administration of all-trans-retinoic acid (inhibitor of Nrf-2) significantly abrogated baicalein-mediated protection against WBI-induced mortality in mice. Thus, in contrast to the generalized conception of antioxidants acting as radioprotectors, we provide a rationale that antioxidants exhibit pleiotropic effects through the activation of multiple cellular signaling pathways.

  16. Mechanisms of radiation-induced gene responses

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Paunesku, T.

    1996-10-01

    In the process of identifying genes differentially expressed in cells exposed ultraviolet radiation, we have identified a transcript having a 26-bp region that is highly conserved in a variety of species including Bacillus circulans, yeast, pumpkin, Drosophila, mouse, and man. When the 5` region (flanking region or UTR) of a gene, the sequence is predominantly in +/+ orientation with respect to the coding DNA strand; while in the coding region and the 3` region (UTR), the sequence is most frequently in the +/-orientation with respect to the coding DNA strand. In two genes, the element is split into two parts; however, in most cases, it is found only once but with a minimum of 11 consecutive nucleotides precisely depicting the original sequence. The element is found in a large number of different genes with diverse functions (from human ras p21 to B. circulans chitonase). Gel shift assays demonstrated the presence of a protein in HeLa cell extracts that binds to the sense and antisense single-stranded consensus oligomers, as well as to the double- stranded oligonucleotide. When double-stranded oligomer was used, the size shift demonstrated as additional protein-oligomer complex larger than the one bound to either sense or antisense single-stranded consensus oligomers alone. It is speculated either that this element binds to protein(s) important in maintaining DNA is a single-stranded orientation for transcription or, alternatively that this element is important in the transcription-coupled DNA repair process.

  17. JAK/STAT signaling in Drosophila muscles controls the cellular immune response against parasitoid infection.

    Science.gov (United States)

    Yang, Hairu; Kronhamn, Jesper; Ekström, Jens-Ola; Korkut, Gül Gizem; Hultmark, Dan

    2015-12-01

    The role of JAK/STAT signaling in the cellular immune response of Drosophila is not well understood. Here, we show that parasitoid wasp infection activates JAK/STAT signaling in somatic muscles of the Drosophila larva, triggered by secretion of the cytokines Upd2 and Upd3 from circulating hemocytes. Deletion of upd2 or upd3, but not the related os (upd1) gene, reduced the cellular immune response, and suppression of the JAK/STAT pathway in muscle cells reduced the encapsulation of wasp eggs and the number of circulating lamellocyte effector cells. These results suggest that JAK/STAT signaling in muscles participates in a systemic immune defense against wasp infection.

  18. Review on Impedance Detection of Cellular Responses in Micro/Nano Environment

    Directory of Open Access Journals (Sweden)

    Kin Fong Lei

    2014-01-01

    Full Text Available In general, cell culture-based assays, investigations of cell number, viability, and metabolic activities during culture periods, are commonly performed to study the cellular responses under various culture conditions explored. Quantification of cell numbers can provide the information of cell proliferation. Cell viability study can understand the percentage of cell death under a specific tested substance. Monitoring of the metabolic activities is an important index for the study of cell physiology. Based on the development of microfluidic technology, microfluidic systems incorporated with impedance measurement technique, have been reported as a new analytical approach for cell culture-based assays. The aim of this article is to review recent developments on the impedance detection of cellular responses in micro/nano environment. These techniques provide an effective and efficient technique for cell culture-based assays.

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

    Directory of Open Access Journals (Sweden)

    Lingling Zhang

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

  20. Cytokine, antibody and proliferative cellular responses elicited by Taenia solium calreticulin upon experimental infection in hamsters.

    Science.gov (United States)

    Mendlovic, Fela; Cruz-Rivera, Mayra; Ávila, Guillermina; Vaughan, Gilberto; Flisser, Ana

    2015-01-01

    Taenia solium causes two diseases in humans, cysticercosis and taeniosis. Tapeworm carriers are the main risk factor for neurocysticercosis. Limited information is available about the immune response elicited by the adult parasite, particularly the induction of Th2 responses, frequently associated to helminth infections. Calreticulin is a ubiquitous, multifunctional protein involved in cellular calcium homeostasis, which has been suggested to play a role in the regulation of immune responses. In this work, we assessed the effect of recombinant T. solium calreticulin (rTsCRT) on the cytokine, humoral and cellular responses upon experimental infection in Syrian Golden hamsters (Mesocricetus auratus). Animals were infected with T. solium cysticerci and euthanized at different times after infection. Specific serum antibodies, proliferative responses in mesenteric lymph nodes and spleen cells, as well as cytokines messenger RNA (mRNA) were analyzed. The results showed that one third of the infected animals elicited anti-rTsCRT IgG antibodies. Interestingly, mesenteric lymph node (MLN) cells from either infected or non-infected animals did not proliferate upon in vitro stimulation with rTsCRT. Additionally, stimulation with a tapeworm crude extract resulted in increased expression of IL-4 and IL-5 mRNA. Upon stimulation, rTsCRT increased the expression levels of IL-10 in spleen and MLN cells from uninfected and infected hamsters. The results showed that rTsCRT favors a Th2-biased immune response characterized by the induction of IL-10 in mucosal and systemic lymphoid organs. Here we provide the first data on the cytokine, antibody and cellular responses to rTsCRT upon in vitro stimulation during taeniasis.

  1. Cytokine, antibody and proliferative cellular responses elicited by Taenia solium calreticulin upon experimental infection in hamsters.

    Directory of Open Access Journals (Sweden)

    Fela Mendlovic

    Full Text Available Taenia solium causes two diseases in humans, cysticercosis and taeniosis. Tapeworm carriers are the main risk factor for neurocysticercosis. Limited information is available about the immune response elicited by the adult parasite, particularly the induction of Th2 responses, frequently associated to helminth infections. Calreticulin is a ubiquitous, multifunctional protein involved in cellular calcium homeostasis, which has been suggested to play a role in the regulation of immune responses. In this work, we assessed the effect of recombinant T. solium calreticulin (rTsCRT on the cytokine, humoral and cellular responses upon experimental infection in Syrian Golden hamsters (Mesocricetus auratus. Animals were infected with T. solium cysticerci and euthanized at different times after infection. Specific serum antibodies, proliferative responses in mesenteric lymph nodes and spleen cells, as well as cytokines messenger RNA (mRNA were analyzed. The results showed that one third of the infected animals elicited anti-rTsCRT IgG antibodies. Interestingly, mesenteric lymph node (MLN cells from either infected or non-infected animals did not proliferate upon in vitro stimulation with rTsCRT. Additionally, stimulation with a tapeworm crude extract resulted in increased expression of IL-4 and IL-5 mRNA. Upon stimulation, rTsCRT increased the expression levels of IL-10 in spleen and MLN cells from uninfected and infected hamsters. The results showed that rTsCRT favors a Th2-biased immune response characterized by the induction of IL-10 in mucosal and systemic lymphoid organs. Here we provide the first data on the cytokine, antibody and cellular responses to rTsCRT upon in vitro stimulation during taeniasis.

  2. Radiating Fröhlich system as a model of cellular electromagnetism.

    Science.gov (United States)

    Šrobár, Fedor

    2015-01-01

    Oscillating polar entities inside the biological cells, most notably microtubules, are bound to emit electromagnetic radiation. This phenomenon is described by Fröhlich kinetic equations expressing, in terms of quantum occupancy numbers of each discrete collective oscillatory mode, the balance between incoming metabolic energy flow and losses due to linear and non-linear interactions with the thermal environs of the oscillators. Hitherto, radiation losses have not been introduced as part of the balance; it was assumed that they were proportional to the modal occupation numbers. It is demonstrated that this formulation is incorrect and the radiation losses must be taken into account in the kinetic equations explicitly. Results of a numerical study of kinetic equations, enlarged in this sense, are presented for the case of three coupled oscillators which was shown to evince the essential attributes of the Fröhlich systems. Oscillator eigenfrequencies were chosen, alternatively, to fall into the MHz and the THz frequency domains. It was found that large radiation levels destroy the main hallmark of the Fröhlich systems, the energy condensation in the lowest frequency mode. The system then functions as a convertor of metabolic energy into radiation. At more moderate radiation levels, both energy condensation and significant radiation can coexist. Possible consequences for the cell physiology are suggested.

  3. Metal oxide nanoparticles interact with immune cells and activate different cellular responses

    OpenAIRE

    Simón-Vázquez R; Lozano-Fernández T; Dávila-Grana A; González-Fernández A

    2016-01-01

    Rosana Simón-Vázquez, Tamara Lozano-Fernández, Angela Dávila-Grana, Africa González-Fernández Immunology Laboratory, Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo, Campus Lagoas Marcosende, Vigo, Pontevedra, Spain Abstract: Besides cell death, nanoparticles (Nps) can induce other cellular responses such as inflammation. The potential immune respon...

  4. Cellular Response of the Amoeba Acanthamoeba castellanii to Chlorine, Chlorine Dioxide, and Monochloramine Treatments ▿

    OpenAIRE

    Mogoa, Emerancienne; Bodet, Charles; Morel, Franck; Rodier, Marie-Hélène; Legube, Bernard; Héchard, Yann

    2011-01-01

    Acanthamoeba castellanii is a free-living amoebae commonly found in water systems. Free-living amoebae might be pathogenic but are also known to bear phagocytosis-resistant bacteria, protecting these bacteria from water treatments. The mode of action of these treatments is poorly understood, particularly on amoebae. It is important to examine the action of these treatments on amoebae in order to improve them. The cellular response to chlorine, chlorine dioxide, and monochloramine was tested o...

  5. Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain

    OpenAIRE

    Martin, David A.; Nichols, Charles D.

    2016-01-01

    There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT2A-expres...

  6. A nonstandard finite difference scheme for a basic model of cellular immune response to viral infection

    Science.gov (United States)

    Korpusik, Adam

    2017-02-01

    We present a nonstandard finite difference scheme for a basic model of cellular immune response to viral infection. The main advantage of this approach is that it preserves the essential qualitative features of the original continuous model (non-negativity and boundedness of the solution, equilibria and their stability conditions), while being easy to implement. All of the qualitative features are preserved independently of the chosen step-size. Numerical simulations of our approach and comparison with other conventional simulation methods are presented.

  7. A priming dose of protons alters the early cardiac cellular and molecular response to 56Fe irradiation

    Science.gov (United States)

    Ramadan, Samy S.; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R.; Hauer-Jensen, Martin; Nelson, Gregory A.; Boerma, Marjan

    2016-02-01

    Purpose: Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of 56Fe in a mouse model. Methods: Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of 56Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of 56Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Results: Exposure to 56Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before 56Fe prevented all of the responses to 56Fe. Conclusions: This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.

  8. Cellular responses and cytokine profiles in Ascaris lumbricoides and Trichuris trichiura infected patients.

    Science.gov (United States)

    Geiger, Stefan M; Massara, Cristiano L; Bethony, Jeffrey; Soboslay, Peter T; Carvalho, Omar S; Corrêa-Oliveira, Rodrigo

    2002-01-01

    The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and interferon (IFN)-gamma secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-alpha, IL-12 and IFN-gamma was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-alpha, IFN-gamma and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage.

  9. In vivo and in vitro cellular response to PEG-based hydrogels for wound repair

    Science.gov (United States)

    Waldeck, Heather

    Biomaterials are continuously being explored as a means to support, improve, or influence wound healing processes. Understanding the determining factors controlling the host response to biomaterials is crucial in developing strategies to employ materials for biomedical uses. In order to evaluate the host response to poly(ethylene glycol) (PEG)-based hydrogels, both in vivo and in vitro studies were performed to determine its efficacy as a dermal wound treatment and to investigate the mechanisms controlling cell-material interaction, respectively. The results of an in vivo study using a full thickness wound in a rat model demonstrated that both soluble and immobilized bioactive factors could be incorporated into a PEG-based semi-interpenetrating network (sIPN) to enhance the rate and the quality of dermal wound healing. To gain a better understanding of the results observed in vivo, in vitro studies were then conducted to examine the dynamics and mechanisms of the cell-material interaction. Degradation of the sIPN was explored as an influential factor in both mediating cellular response and controlling solute transport from the material. As degradation through gelatin dissolution could be influenced by simple alterations to the material formulation, these results provide facile guidelines to control the delivery of high molecular weight compounds. Further investigation of the cellular response to PEG-based biomaterials focused on key factors influencing cell-material interaction. Specifically, the role of the beta1 integrin subunit and several serum proteins (TGF-aalpha, IL-1beta and PDGF-BB) in mediating cellular response was explored. As cell-material interactions are based on commonly occurring interfaces between cells and molecules of the native extracellular environment, these studies provided insight into the mechanisms controlling the observed cellular response. Finally, the inflammatory response of primary monocytes to biomaterials was examined. Monocytes

  10. Various eicosanoids modulate the cellular and humoral immune responses of the beet armyworm, Spodoptera exigua.

    Science.gov (United States)

    Shrestha, Sony; Kim, Yonggyun

    2009-09-01

    Cyclooxygenase (COX) and lipoxygenase (LOX) can catalyze the oxidation of C20 fatty acids to produce certain eicosanoids, which play roles in mediating immune responses in insects. Despite their critical role in insect immunity, there have been few studies of the unique effects of different eicosanoids on immune responses. This study analyzed cellular and humoral immune responses of the beet armyworm, Spodoptera exigua, using seven eicosanoids selected from two major eicosanoid subgroups: prostaglandin (PG) and leukotriene (LT), derived from catalytic activities of COX and LOX respectively. Upon bacterial challenge, all seven eicosanoids (PGA(1), PGB(2), PGD(2), PGE(1), PGE(2), PGF(1alpha), and LTB(4)) significantly induced hemocyte nodulation and phagocytosis in the presence of dexamethasone, an eicosanoid biosynthesis inhibitor. However, only PGs induced cell lysis of oenocytoids to release prophenoloxidase, which resulted in an increase in phenoloxidase activity. These seven eicosanoids also induced expression of humoral immune-associated genes, including prophenoloxidase, serpin, dopa decarboxylase, cecropin, and lysozyme, in which PGB(2) and PGE(1) did not induce gene expression of prophenoloxidase. To understand the interactions between different eicosanoids, mixture effects of these eicosanoids were compared with their individual eicosanoid effects on mediating nodule formation in response to bacterial challenge. All six single PGs showed increases in nodule formation in a dose-dependent manner without significant difference among the different types. LTB(4) was more potent than the tested PGs in mediating the cellular immune response. At low doses, all combinations of two eicosanoids showed significant additive effects on nodule formation. These results indicate that immune target cells, such as hemocyte and fat body, of S. exigua can respond to different COX and LOX products to express cellular and humoral immune responses, and their overlapping, additive

  11. Gamma radiation induced micronuclei and erythrocyte cellular abnormalities in the fish Catla catla

    Energy Technology Data Exchange (ETDEWEB)

    Anbumani, S. [Biodosimetry Laboratory, Radiological Safety Division, Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam, Tamilnadu 603102 (India); Mohankumar, Mary N., E-mail: marynmk@rediffmail.com [Biodosimetry Laboratory, Radiological Safety Division, Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam, Tamilnadu 603102 (India)

    2012-10-15

    Ionizing radiation induced DNA damage in fishes is a scarcely studied topic and very few studies are available in fishes exposed to ionizing radiation using the erythrocyte micronucleus assay under laboratory conditions. Since radionuclides released accidentally or during a nuclear disaster can contaminate inland water bodies, biomonitoring methods are required for assessing the impacts of high and low levels of radiation that may ultimately result in ionizing radiation exposure to both humans and non-human biota. Fresh water fish, Catla catla were subjected to protracted (0.002 Gy/min) and acute (3.2 Gy/min) gamma radiation to a total dose of 5 Gy. Peripheral blood samples were collected at different intervals (days 3, 6, 12, 18, 30, 45, 90, 135, 202) and analyzed by the erythrocyte micronucleus assay. Nuclear anomalies observed were micronuclei (MN), deformed nuclei (DN), nuclear bud (NBu), nuclear bridge (NBr), vacuolated nucleus (VN), binucleated cell (BNC), apoptotic cells (AC) while cytoplasmic abnormalities detected were vacuolated cytoplasm (VC), anisochromasia (AN), echinocytes (EC) and enucleus (EN). Both exposures caused a statistically significant increase in nuclear and cytoplasmic abnormalities that correlated with micronucleus and other nuclear anomalies. However, the extent of damage is higher after an acute exposure lasting for a longer period leading to apoptosis. Nuclear and cytoplasmic abnormalities are the resultants of gamma radiation induced genotoxicity and cytotoxicity.

  12. Radiation response of the mouse tongue epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Moses, R.; Kummermehr, J.

    1986-01-01

    Mouse tongue mucosa has been used as a model to study dose responses to local irradiation. Although the irradiation procedures is less feasible and more time-consuming than e.g. snout irradiation, the tongue is the only location where a reasonable area of intraoral, multilayered epithelium in the mouse can be locally treated and scored, and a relatively small burden is imposed on the animal. In pilot experiments with external 300 kV x-irradiation just tolerated by the lip, the authors did not see critical damage to the tongue. In the present model, the onset of denudation was not correctly predicted by the normal turnover time of the tissue.

  13. The CK1 family: contribution to cellular stress response and its role in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Uwe eKnippschild

    2014-05-01

    Full Text Available Members of the highly conserved and ubiquitously expressed pleiotropic CK1 family play major regulatory roles in many cellular processes including DNA-processing and repair, proliferation, cytoskeleton dynamics, vesicular trafficking, apoptosis, and cell differentiation. As a consequence of cellular stress conditions, interaction of CK1 with the mitotic spindle is manifold increased pointing to regulatory functions at the mitotic checkpoint. Furthermore, CK1 is able to alter the activity of key regulatory proteins and signal integration molecules and is tightly connected to the regulation of β-catenin, p53- and MDM2-specific functions and degradation. Considering the importance of CK1 for accurate cell division and regulation of tumor suppressor functions it is not surprising that mutations and alterations in the expression and/or activity of CK1 isoforms are often detected in various tumor entities including cancer of the kidney, choriocarcinomas, breast carcinomas, oral cancer, adenocarcinomas of the pancreas, and ovarian cancer. Therefore, effort has enormously increased (i to understand the regulation of CK1 and its involvement in tumorigenesis- and tumor progression-related signal transduction pathways and (ii to develop CK1-specific inhibitors for the use in personalized therapy concepts. In this review we summarize the current knowledge regarding the regulation, functions, and interactions of CK1 family members with cellular proteins playing central roles in cellular stress-responses and carcinogenesis.

  14. The Nuclear Factor kappaB Pathway: A Link to the Immune System in the Radiation Response

    Science.gov (United States)

    Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther; Chishti, Arif Ali; Koch, Kristina; Manchanda, Kashish

    Understanding the cellular radiation response is an essential prerequisite for the risk assessment of astronauts’ space radiation exposure during long-term space missions and for effective countermeasure development. In addition to the space radiation effects, other environmental factors during space missions such as microgravity have profound effects on the body, e.g. suppression of the innate and acquired immune response. Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor kB (NF-kappaB). In this work, the role of NF-kappaB in the cellular response to space relevant radiation qualities was analyzed. It was shown with a recombinant human NF-kappaB reporter cell line that heavy ions with a linear energy transfer (LET) of 100-300 keV/µm have a nine times higher potential to activate the NF-kappaB pathway compared to X-rays (150 kV). ATM was essential for NF-kappaB activation in response to X-rays and heavy ions. Knockdown of the NF-kappaB subunit RelA (p65) resulted in higher sensitivity towards X-rays. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) experiments showed that after exposure to radiation, NF-kappaB predominantly upregulates genes involved in intercellular communication processes, especially genes coding for chemokines, suggesting an important contribution of NF-kappaB in the molecular profile of the reaction to radiation, which can comprise features of inflammation and wound healing processes. This is process is strictly NF-kappaB dependent as this response is completely absent in RelA knockdown cells. These results show that the role of NF-kappaB in

  15. Chromatin Modifications and the DNA Damage Response to Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Tej K Pandita

    2013-01-01

    Full Text Available In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double strand breaks (DSBs, that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: 1 non-homologous end-joining (NHEJ, which re-ligates the broken ends of the DNA and 2 homologous recombination (HR, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but posttranslational modification (PTMs of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modification by t

  16. Interactions between glucocorticoid treatment and cis-regulatory polymorphisms contribute to cellular response phenotypes.

    Directory of Open Access Journals (Sweden)

    Joseph C Maranville

    2011-07-01

    Full Text Available Glucocorticoids (GCs mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor. Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1 and that influence the secretion of IL6.

  17. A Review on Hemeoxygenase-2: Focus on Cellular Protection and Oxygen Response

    Directory of Open Access Journals (Sweden)

    Jorge Muñoz-Sánchez

    2014-01-01

    Full Text Available Hemeoxygenase (HO system is responsible for cellular heme degradation to biliverdin, iron, and carbon monoxide. Two isoforms have been reported to date. Homologous HO-1 and HO-2 are microsomal proteins with more than 45% residue identity, share a similar fold and catalyze the same reaction. However, important differences between isoforms also exist. HO-1 isoform has been extensively studied mainly by its ability to respond to cellular stresses such as hemin, nitric oxide donors, oxidative damage, hypoxia, hyperthermia, and heavy metals, between others. On the contrary, due to its apparently constitutive nature, HO-2 has been less studied. Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function. HO-2 presents particular characteristics that made it a unique protein in the HO system. Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform. We summarize information on gene description, protein structure, and catalytic activity of HO-2 and particular facts such as its cellular impact and activity regulation. Finally, we call attention on the role of HO-2 in oxygen sensing, discussing proposed hypothesis on heme binding motifs and redox/thiol switches that participate in oxygen sensing as well as evidences of HO-2 response to hypoxia.

  18. [Regulatory role of mechanical stress response in cellular function: development of new drugs and tissue engineering].

    Science.gov (United States)

    Momose, Kazutaka; Matsuda, Takehisa; Oike, Masahiro; Obara, Kazuo; Laher, Ismail; Sugiura, Seiryo; Ohata, Hisayuki; Nakayama, Koichi

    2003-02-01

    The investigation of mechanotransduction in the cardiovascular system is essentially important for elucidating the cellular and molecular mechanisms involved in not only the maintenance of hemodynamic homeostasis but also etiology of cardiovascular diseases including arteriosclerosis. The present review summarizes the latest research performed by six academic groups, and presented at the 75th Annual Meeting of the Japanese Pharmacological Society. Technology of cellular biomechanics is also required for research and clinical application of a vascular hybrid tissue responding to pulsatile stress. 1) Vascular tissue engineering: Design of pulsatile stress-responsive scaffold and in vivo vascular wall reconstruction (T. Matsuda); 2) Cellular mechanisms of mechanosensitive calcium transients in vascular endothelium (M. Oike et al.); 3) Cross-talk of stimulation with fluid flow and lysophosphatidic acid in vascular endothelial cells (K. Momose et al.); 4) Mechanotransduction of vascular smooth muscles: Rate-dependent stretch-induced protein phosphorylations and contractile activation (K. Obara et al.); 5) Lipid mediators in vascular myogenic tone (I. Laher et al.); and 6) Caldiomyocyte regulates its mechanical output in response to mechanical load (S. Sugiura et al.).

  19. The cellular magnetic response and biocompatibility of biogenic zinc- and cobalt-doped magnetite nanoparticles

    Science.gov (United States)

    Moise, Sandhya; Céspedes, Eva; Soukup, Dalibor; Byrne, James M.; El Haj, Alicia J.; Telling, Neil D.

    2017-01-01

    The magnetic moment and anisotropy of magnetite nanoparticles can be optimised by doping with transition metal cations, enabling their properties to be tuned for different biomedical applications. In this study, we assessed the suitability of bacterially synthesized zinc- and cobalt-doped magnetite nanoparticles for biomedical applications. To do this we measured cellular viability and activity in primary human bone marrow-derived mesenchymal stem cells and human osteosarcoma-derived cells. Using AC susceptibility we studied doping induced changes in the magnetic response of the nanoparticles both as stable aqueous suspensions and when associated with cells. Our findings show that the magnetic response of the particles was altered after cellular interaction with a reduction in their mobility. In particular, the strongest AC susceptibility signal measured in vitro was from cells containing high-moment zinc-doped particles, whilst no signal was observed in cells containing the high-anisotropy cobalt-doped particles. For both particle types we found that the moderate dopant levels required for optimum magnetic properties did not alter their cytotoxicity or affect osteogenic differentiation of the stem cells. Thus, despite the known cytotoxicity of cobalt and zinc ions, these results suggest that iron oxide nanoparticles can be doped to sufficiently tailor their magnetic properties without compromising cellular biocompatibility.

  20. Cell-permeable intrinsic cellular inhibitors of apoptosis protect and rescue intestinal epithelial cells from radiation-induced cell death.

    Science.gov (United States)

    Matsuzaki-Horibuchi, Shiori; Yasuda, Takeshi; Sakaguchi, Nagako; Yamaguchi, Yoshihiro; Akashi, Makoto

    2015-01-01

    One of the important mechanisms for gastrointestinal (GI) injury following high-dose radiation exposure is apoptosis of epithelial cells. X-linked inhibitor of apoptosis (XIAP) and cellular IAP2 (cIAP2) are intrinsic cellular inhibitors of apoptosis. In order to study the effects of exogenously added IAPs on apoptosis in intestinal epithelial cells, we constructed bacterial expression plasmids containing genes of XIAP (full-length, BIR2 domain and BIR3-RING domain with and without mutations of auto-ubiquitylation sites) and cIAP2 proteins fused to a protein-transduction domain (PTD) derived from HIV-1 Tat protein (TAT) and purified these cell-permeable recombinant proteins. When the TAT-conjugated IAPs were added to rat intestinal epithelial cells IEC6, these proteins were effectively delivered into the cells and inhibited apoptosis, even when added after irradiation. Our results suggest that PTD-mediated delivery of IAPs may have clinical potential, not only for radioprotection but also for rescuing the GI system from radiation injuries.

  1. On the effects of geometry, defects, and material asymmetry on the mechanical response of shape memory alloy cellular lattice structures

    Science.gov (United States)

    Karamooz Ravari, M. R.; Nasr Esfahani, S.; Taheri Andani, M.; Kadkhodaei, M.; Ghaei, A.; Karaca, H.; Elahinia, M.

    2016-02-01

    Shape memory alloy (such as NiTi) cellular lattice structures are a new class of advanced materials with many potential applications. The cost of fabrication of these structures however is high. It is therefore necessary to develop modeling methods to predict the functional behavior of these alloys before fabrication. The main aim of the present study is to assess the effects of geometry, microstructural imperfections and material asymmetric response of dense shape memory alloys on the mechanical response of cellular structures. To this end, several cellular and dense NiTi samples are fabricated using a selective laser melting process. Both cellular and dense specimens were tested in compression in order to obtain their stress-strain response. For modeling purposes, a three -dimensional (3D) constitutive model based on microplane theory which is able to describe the material asymmetry was employed. Five finite element models based on unit cell and multi-cell methods were generated to predict the mechanical response of cellular lattices. The results show the considerable effects of the microstructural imperfections on the mechanical response of the cellular lattice structures. The asymmetric material response of the bulk material also affects the mechanical response of the corresponding cellular structure.

  2. Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens.

    Science.gov (United States)

    Piessens, W F; McGreevy, P B; Piessens, P W; McGreevy, M; Koiman, I; Saroso, J S; Dennis, D T

    1980-01-01

    We evaluated the cellular immune competence of 101 subjects living in an area of South Kalimantan (Borneo) where Malayan filariasis is endemic. All patients with elephantiasis but none with other clinical stages of filariasis reacted with adult worm antigens. The majority of subjects without clinical or parasitological evidence of filariasis and approximately one-half of those with amicrofilaremic filariasis reacted with microfilarial antigens. In contrast, most patients with patent microfilaremia did not respond to microfilarial antigens. The in vitro reactivity of all patient categories to nonparasite antigens was similar to that of the distant control group. These results indicate that patent microfilaremia is associated with a state of specific cellular immune unresponsiveness and are consistent with the current hypothesis that the various clinical manifestations of filariasis result from different types of immune responses to distinct antigens associated with different developmental stages of filarial worms. PMID:7350196

  3. Enhanced radiation response in radioresistant MCF-7 cells by targeting peroxiredoxin II

    Directory of Open Access Journals (Sweden)

    Diaz AJG

    2013-10-01

    Full Text Available Anthony Joseph Gomez Diaz,1 Daniel Tamae,2 Yun Yen,3 JianJian Li,4 Tieli Wang1 1Department of Chemistry and Biochemistry, California State University at Dominguez Hills, Carson, CA, 2Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 3Department of Clinical and Molecular Pharmacology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA, 4Department of Radiation Oncology, University of California Davis, Sacramento, CA, USA Abstract: In our previous study, we identified that a protein target, peroxiredoxin II (PrxII, is overexpressed in radioresistant MCF+FIR3 breast-cancer cells and found that its expression and function is associated with breast-cancer radiation sensitivity or resistance. Small interference RNA (siRNA targeting PrxII gene expression was able to sensitize MCF+FIR3 radioresistant breast-cancer cells to ionizing radiation. The major focus of this work was to investigate how the radiation response of MCF+FIR3 radioresistant cells was affected by the siRNA that inhibits PrxII gene expression. Our results, presented here, show that silencing PrxII gene expression increased cellular toxicity by altering cellular thiol status, inhibiting Ca2+ efflux from the cells, and perturbing the intracellular Ca2+ homeostasis. By combining radiotherapy and siRNA technology, we hope to develop new therapeutic strategies that may have potential to enhance the efficacy of chemotherapeutic agents due to this technology's property of targeting to specific cancer-related genes. Keywords: siRNA, PrxII, radiation resistance, Ca2+, MCF+FIR3

  4. Fructose-1,6-bisphosphatase mediates cellular responses to DNA damage and aging in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Kitanovic, Ana [Institut fuer Pharmazie und Molekulare Biotechnologie, Ruprecht-Karls-Universitaet Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg (Germany); Woelfl, Stefan [Institut fuer Pharmazie und Molekulare Biotechnologie, Ruprecht-Karls-Universitaet Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg (Germany)]. E-mail: wolfl@uni-hd.de

    2006-02-22

    Response to DNA damage, lack of nutrients and other stress conditions is an essential property of living systems. The coordinate response includes DNA damage repair, activation of alternate biochemical pathways, adjustment of cellular proliferation and cell cycle progression as well as drastic measures like cellular suicide which prevents proliferation of severely damaged cells. Investigating the transcriptional response of Saccharomyces cerevisiae to low doses of the alkylating agent methylmethane sulfonate (MMS) we observed induction of genes involved in glucose metabolism. RT-PCR analysis showed that the expression of the key enzyme in gluconeogenesis fructose-1,6-bisphosphatase (FBP1) was clearly up-regulated by MMS in glucose-rich medium. Interestingly, deletion of FBP1 led to reduced sensitivity to MMS, but not to other DNA-damaging agents, such as 4-NQO or phleomycin. Reintroduction of FBP1 in the knockout restored the wild-type phenotype while overexpression increased MMS sensitivity of wild-type, shortened life span and increased induction of RNR2 after treatment with MMS. Deletion of FBP1 reduced production of reactive oxygen species (ROS) in response to MMS treatment and in untreated aged cells, and increased the amount of cells able to propagate and to form colonies, but had no influence on the genotoxic effect of MMS. Our results indicate that FBP1 influences the connection between DNA damage, aging and oxidative stress through either direct signalling or an intricate adaptation in energy metabolism.0.

  5. Signaling pathways implicated in the cellular innate immune responses of Drosophila

    Directory of Open Access Journals (Sweden)

    AJ Nappi

    2004-06-01

    Full Text Available The phylogenetically conserved innate immune systems of insects and other invertebrates employblood cells (hemocytes that are functionally reminiscent of vertebrate macrophages, attesting to theimportance of phagocytosis and other cell-mediated responses in eliminating various pathogens. Receptorligandbinding activates signaling cascades that promote collaborative cellular interactions and theproduction of pathogen-specific cytotoxic responses. Numerous comparative genetic and molecularstudies have shown the cytotoxic effector responses made by cells of the innate immune system to beevolutionarily conserved. Comparative analyses of genomic sequences provide convincing evidence thatmany of the biochemical processes manifested by immune-activated hemocytes are similar to thosemade by activated vertebrate macrophages. Included in this genomic repertoire are enzymes associatedwith reactive intermediates of oxygen and nitrogen, cellular redox homeostasis, and apoptosis, thesynthesis of extracellular matrix, cell adhesion and pattern recognition molecules. Surprisingly, little isknown of the types of cytotoxic molecules produced by invertebrate hemocytes, and the signaling andtranscriptional events associated with their collaborative interactions when engaging pathogens andparasites. This review examines certain aspects of the blood cell-mediated defense responses ofDrosophila, and some of the signaling pathways that have been implicated in hemocyte activation,differentiation, and the regulation of hematopoiesis.

  6. Transition between immune and disease states in a cellular automaton model of clonal immune response

    CERN Document Server

    Bezzi, M; Ruffo, S; Seiden, P E; Bezzi, Michele; Celada, Franco; Ruffo, Stefano; Seiden, Philip E.

    1997-01-01

    In this paper we extend the Celada-Seiden (CS) model of the humoral immune response to include infectious virus and cytotoxic T lymphocytes (cellular response). The response of the system to virus involves a competition between the ability of the virus to kill the host cells and the host's ability to eliminate the virus. We find two basins of attraction in the dynamics of this system, one is identified with disease and the other with the immune state. There is also an oscillating state that exists on the border of these two stable states. Fluctuations in the population of virus or antibody can end the oscillation and drive the system into one of the stable states. The introduction of mechanisms of cross-regulation between the two responses can bias the system towards one of them. We also study a mean field model, based on coupled maps, to investigate virus-like infections. This simple model reproduces the attractors for average populations observed in the cellular automaton. All the dynamical behavior connect...

  7. Distinctive behavioral and cellular responses to fluoxetine in the mouse model for Fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Marko eUutela

    2014-05-01

    Full Text Available Fluoxetine is used as a therapeutic agent for autism spectrum disorder (ASD, including Fragile X syndrome (FXS. The treatment often associates with disruptive behaviors such as agitation and disinhibited behaviors in FXS. To identify mechanisms that increase the risk to poor treatment outcome, we investigated the behavioral and cellular effects of fluoxetine on adult Fmr1 knockout (KO mice, a mouse model for FXS. We found that fluoxetine reduced anxiety-like behavior of both wild type and Fmr1 KO mice seen as shortened latency to enter the center area in the open field test. In Fmr1 KO mice, fluoxetine normalized locomotor hyperactivity but abnormally increased exploratory activity. Reduced Brain-derived neurotrophic factor (BDNF and increased TrkB receptor expression levels in the hippocampus of Fmr1 KO mice associated with inappropriate coping responses under stressful condition and abolished antidepressant activity of fluoxetine. Fluoxetine response in the cell proliferation was also missing in the hippocampus of Fmr1 KO mice when compared with wild type controls. The postnatal expression of serotonin transporter was reduced in the thalamic nuclei of Fmr1 KO mice during the time of transient innervation of somatosensory neurons suggesting that developmental changes of serotonin transporter (SERT expression were involved in the differential cellular and behavioral responses to fluoxetine in wild type and Fmr1 mice. The results indicate that changes of BDNF/TrkB signaling contribute to differential behavioral responses to fluoxetine among individuals with ASD.

  8. Electrolyte effects on the surface chemistry and cellular response of anodized titanium

    Energy Technology Data Exchange (ETDEWEB)

    Ohtsu, Naofumi, E-mail: nohtsu@mail.kitami-it.ac.jp [Instrumental Analysis Center, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido 090-8507 (Japan); Kozuka, Taro; Hirano, Mitsuhiro [Instrumental Analysis Center, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido 090-8507 (Japan); Arai, Hirofumi [Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, Kitami, Hokkaido 090-8507 (Japan)

    2015-09-15

    Highlights: • Ti samples were anodized using various electrolytes. • Anodization decreased carbon adsorption, improving hydrophilicity. • Improved hydrophilicity led to improved cellular attachment. • Only one electrolyte showed any heteroatom incorporation into the TiO{sub 2} layer. • Choice of electrolyte played no role on the effects of anodization. - Abstract: Anodic oxidation of titanium (Ti) material is used to enhance biocompatibility, yet the effects of various electrolytes on surface characteristics and cellular behavior have not been completely elucidated. To investigate this topic, oxide layers were produced on Ti substrates by anodizing them in aqueous electrolytes of (NH{sub 4}){sub 2}O·5B{sub 2}O{sub 3}, (NH{sub 4}){sub 2}SO{sub 4}, or (NH{sub 4}){sub 3}PO{sub 4}, after which their surface characteristics and cellular responses were examined. Overall, no surface differences between the electrolytes were visually observed. X-ray photoelectron spectroscopy (XPS) revealed that the anodized surfaces are composed of titanium dioxide (TiO{sub 2}), while incorporation from electrolyte was only observed for (NH{sub 4}){sub 3}PO{sub 4}. Surface adsorption of carbon contaminants during sterilization was suppressed by anodization, leading to lower water contact angles. The attachment of MC3T3-E1 osteoblast-like cells was also improved by anodization, as evidenced by visibly enlarged pseudopods. This improved attachment performance is likely due to TiO{sub 2} formation. Overall, electrolyte selection showed no effect on either surface chemistry or cellular response of Ti materials.

  9. A candidate DNA vaccine elicits HCV specific humoral and cellular immune responses

    Institute of Scientific and Technical Information of China (English)

    Li-Xin Zhu; Jing Liu; Ye Ye; You-Hua Xie; Yu-Ying Kong; Guang-Di Li; Yuan Wang

    2004-01-01

    AIM: To investigate the immunogenicity of candidate DNA vaccine against hepatitis C virus (HCV) delivered by two plasmids expressing HCV envelope protein 1 (E1) and envelope protein 2 (E2) antigens respectively and to study the effect of CpG adjuvant on this candidate vaccine.METHODS: Recombinant plasmids expressing HCV E1 and E2 antigens respectively were used to simultaneously inoculate mice with or without CpG adjuvant. Antisera were then collected and titers of anti-HCV antibodies were analyzed by ELISA. One month after the last injection, animals were sacrificed to prepare single-cell suspension of splenocytes.These cells were subjected to HCVantigen specific proliferation assays and cytokine secretion assays to evaluate the cellular immune responses of the vaccinated animals.RESULTS: Antibody responses to HCV E1 and E2 antigens were detected in vaccinated animals. Animals receiving CpG adjuvant had slightly lower titers of anti-HCV antibodies in the sera, while the splenocytes from these animals showed higher HCV-antigen specific proliferation. Analysis of cytokine secretion from the splenocytes was consistent with the above results. While no antigen-specific IL-4 secretion was detected for all vaccinated animals, HCV antigen-specific INF-γ secretion was detected for the splenocytes of vaccinated animals. CpG adjuvant enhanced the secretion of INF-γ but did not change the profile of IL-4 secretion.CONCLUSION: Vaccination of mice with plasmids encoding HCV E1 and E2 antigens induces humoral and cellular immune responses. CpG adjuvant significantly enhances the cellular immune response.

  10. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

    Directory of Open Access Journals (Sweden)

    Renata eToth

    2015-10-01

    Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

  11. Model of cell response to {\\alpha}-particle radiation

    CERN Document Server

    Liu, Longjian

    2012-01-01

    Starting from a general equation for organism (or cell system) growth and attributing additional cell death rate (besides the natural rate) to therapy, we derive an equation for cell response to {\\alpha} radiation. Different from previous models that are based on statistical theory, the present model connects the consequence of radiation with the growth process of a biosystem and each variable or parameter has meaning regarding the cell evolving process. We apply this equation to model the dose response for {\\alpha}-particle radiation. It interprets the results of both high and low linear energy transfer (LET) radiations. When LET is high, the additional death rate is a constant, which implies that the localized cells are damaged immediately and the additional death rate is proportional to the number of cells present. While at low LET, the additional death rate includes a constant term and a linear term of radiation dose, implying that the damage to some cell nuclei has a time accumulating effect. This model ...

  12. DNA repair pathways in radiation induced cellular damage: a molecular approach

    NARCIS (Netherlands)

    L.R. van Veelen (Lieneke)

    2005-01-01

    markdownabstract__Abstract__ DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations, translocat

  13. Cellular proliferation and regeneration following tissue damage. Progress report. [X radiation; rabbit lenses

    Energy Technology Data Exchange (ETDEWEB)

    Harding, C.V.

    1977-01-01

    Studies were conducted on the following research projects: effects of x radiation on rabbit lenses; DNA synthesis and mitosis in cultured lenses; serum dependency and actinomycin D sensitivity; changes in ultrastructure; injury-induced growth of vascular endothelium; corneal neovascularization following injury; and human cataractous lenses. (HLW)

  14. Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2017-01-01

    Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative

  15. The p53 Codon 72 Polymorphism Modifies the Cellular Response to Inflammatory Challenge in the Liver.

    Science.gov (United States)

    Leu, Julia I-Ju; Murphy, Maureen E; George, Donna L

    2013-01-01

    The p53 protein is a critical stress-response mediator and signal coordinator in cellular metabolism and environmental exposure to deleterious agents. In human populations, the p53 gene contains a common single nucleotide polymorphism (SNP) affecting codon 72 that determines whether a proline (P72) or an arginine (R72) is present at this amino acid position of the polypeptide. Previous studies carried out using human populations, mouse models, and cell culture analyses have provided evidence that this amino acid difference can alter p53 functional activities, and potentially also can affect clinical presentation of disease. The clinical presentation associated with many forms of liver disease is variable, but few of the responsible underlying genetic factors or molecular pathways have been identified. The aim of the present study was to investigate whether the p53 codon 72 polymorphism influences the cellular response to hepatic stresses. A humanized p53 knock-in (Hupki) mouse model was used to address this issue. Mice expressing either the P72 or R72 normal variation of p53 were given an acute-, intermittent- or a chronic challenge, associated with exposure to lipopolysaccharide, D-galactosamine, or a high-fat diet. The results reveal that the livers of the P72 and R72 mice exhibit notable differences in inflammatory and apoptotic response to these distinct forms of stress. Interestingly the influence of this polymorphism on the response to stress is context dependent, with P72 showing increased response to liver toxins (lipopolysaccharide and D-galactosamine), but R72 showing increased response to metabolic stress (high fat diet). When taken together, these data point to the p53 codon 72 polymorphism as an important molecular mediator of events contributing to hepatic inflammation and metabolic homeostasis.

  16. Transcriptome analysis reveals the contribution of thermal and the specific effects in cellular response to millimeter wave exposure.

    Science.gov (United States)

    Habauzit, Denis; Le Quément, Catherine; Zhadobov, Maxim; Martin, Catherine; Aubry, Marc; Sauleau, Ronan; Le Dréan, Yves

    2014-01-01

    Radiofrequency radiations constitute a new form of environmental pollution. Among them, millimeter waves (MMW) will be widely used in the near future for high speed communication systems. This study aimed therefore to evaluate the biocompatibility of MMW at 60 GHz. For this purpose, we used a whole gene expression approach to assess the effect of acute 60 GHz exposure on primary cultures of human keratinocytes. Controls were performed to dissociate the electromagnetic from the thermal effect of MMW. Microarray data were validated by RT-PCR, in order to ensure the reproducibility of the results. MMW exposure at 20 mW/cm2, corresponding to the maximum incident power density authorized for public use (local exposure averaged over 1 cm2), led to an increase of temperature and to a strong modification of keratinocyte gene expression (665 genes differentially expressed). Nevertheless, when temperature is artificially maintained constant, no modification in gene expression was observed after MMW exposure. However, a heat shock control did not mimic exactly the MMW effect, suggesting a slight but specific electromagnetic effect under hyperthermia conditions (34 genes differentially expressed). By RT-PCR, we analyzed the time course of the transcriptomic response and 7 genes have been validated as differentially expressed: ADAMTS6, NOG, IL7R, FADD, JUNB, SNAI2 and HIST1H1A. Our data evidenced a specific electromagnetic effect of MMW, which is associated to the cellular response to hyperthermia. This study raises the question of co-exposures associating radiofrequencies and other environmental sources of cellular stress.

  17. Transcriptome analysis reveals the contribution of thermal and the specific effects in cellular response to millimeter wave exposure.

    Directory of Open Access Journals (Sweden)

    Denis Habauzit

    Full Text Available Radiofrequency radiations constitute a new form of environmental pollution. Among them, millimeter waves (MMW will be widely used in the near future for high speed communication systems. This study aimed therefore to evaluate the biocompatibility of MMW at 60 GHz. For this purpose, we used a whole gene expression approach to assess the effect of acute 60 GHz exposure on primary cultures of human keratinocytes. Controls were performed to dissociate the electromagnetic from the thermal effect of MMW. Microarray data were validated by RT-PCR, in order to ensure the reproducibility of the results. MMW exposure at 20 mW/cm2, corresponding to the maximum incident power density authorized for public use (local exposure averaged over 1 cm2, led to an increase of temperature and to a strong modification of keratinocyte gene expression (665 genes differentially expressed. Nevertheless, when temperature is artificially maintained constant, no modification in gene expression was observed after MMW exposure. However, a heat shock control did not mimic exactly the MMW effect, suggesting a slight but specific electromagnetic effect under hyperthermia conditions (34 genes differentially expressed. By RT-PCR, we analyzed the time course of the transcriptomic response and 7 genes have been validated as differentially expressed: ADAMTS6, NOG, IL7R, FADD, JUNB, SNAI2 and HIST1H1A. Our data evidenced a specific electromagnetic effect of MMW, which is associated to the cellular response to hyperthermia. This study raises the question of co-exposures associating radiofrequencies and other environmental sources of cellular stress.

  18. Expression patterns and action analysis of genes associated with physiological responses during rat liver regeneration: Cellular immune response

    Institute of Scientific and Technical Information of China (English)

    Lian-Xing Zhang; Li-Feng Zhao; An-Shi Zhang; Xiao-Guang Chen; Cun-Shuan Xu

    2006-01-01

    AIM: To study the cellular immune response during rat liver regeneration (LR) at a transcriptional level.METHODS: Genes associated with the cellular immune response were obtained by collecting the data from databases and retrieving articles. Gene expression changes during LR were detected by rat genome 230 2.0 array.RESULTS: A total of 127 genes were found to be associated with LR. The number of initially and totally expressing genes in the initial phase of LR [0.5-4 h after partial hepatectomy (PH)], transition from G0-G1(4-6 h after PH), cell proliferation (6-66 h after PH),cell differentiation and structure-function reconstruction (66-168 h after PH) was 54, 11, 34, 3 and 54, 49, 70, 49 respectively, illustrating that the associated genes were mainly triggered at the initiation of LR, and worked at different phases. According to their expression similarity,these genes were classified into 41 up-regulated, 21 predominantly up-regulated, 41 down-regulated, 14 predominantly down-regulated, 10 similarly up-regulated and down-regulated genes, respectively. The total upand down-regulated expression times were 419 and 274,respectively, demonstrating that the expression of most genes was increased while the expression of a small number of genes was decreased. Their time relevance was classified into 14 groups, showing that the cellular physiological and biochemical activities were staggered during LR. According to the gene expression patterns,they were classified into 21 types, showing the activities were diverse and complicated during LR.CONCLUSION: Antigen processing and presentation are enhanced mainly in the forepart, prophase and anaphase of LR. T-cell activation and antigen elimination are enhanced mainly in the forepart and prophase of LR. A total of 127 genes associated with LR play an important role in cellular immunity.

  19. Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response

    Directory of Open Access Journals (Sweden)

    Killeen S. Kirkconnell

    2016-06-01

    Full Text Available Dynamic regulation of gene expression via signal transduction pathways is of fundamental importance during many biological processes such as cell state transitioning, cell cycle progression and stress responses. In this study we used serum stimulation as a cell response paradigm to apply the nascent RNA Bru-seq technique in order to capture early dynamic changes in the nascent transcriptome. Our data provides an unprecedented view of the dynamics of genome-wide transcription during the first two hours of serum stimulation in human fibroblasts. While some genes showed sustained induction or repression, other genes showed transient or delayed responses. Surprisingly, the dynamic patterns of induction and suppression of response genes showed a high degree of similarity, suggesting that these opposite outcomes are triggered by a common set of signals. As expected, early response genes such as those encoding components of the AP-1 transcription factor and those involved in the circadian clock were immediately but transiently induced. Surprisingly, transcription of important DNA damage response genes and histone genes were rapidly repressed. We also show that RNA polymerase II accelerates as it transcribes large genes and this was independent of whether the gene was induced or not. These results provide a unique genome-wide depiction of dynamic patterns of transcription of serum response genes and demonstrate the utility of Bru-seq to comprehensively capture rapid and dynamic changes of the nascent transcriptome.

  20. Unraveling the global microRNAome responses to ionizing radiation in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Mykyta V Sokolov

    Full Text Available MicroRNAs (miRNA comprise a group of short ribonucleic acid molecules implicated in regulation of key biological processes and functions at the post-transcriptional level. Ionizing radiation (IR causes DNA damage and generally triggers cellular stress response. However, the role of miRNAs in IR-induced response in human embryonic stem cells (hESC has not been defined yet. Here, by using system biology approaches, we show for the first time, that miRNAome undergoes global alterations in hESC (H1 and H9 lines after IR. Interrogation of expression levels of 1,090 miRNA species in irradiated hESC showed statistically significant changes in 54 genes following 1 Gy of X-ray exposures; global miRNAome alterations were found to be highly temporally and cell line--dependent in hESC. Time-course studies showed that the 16 hr miRNAome radiation response of hESC is much more robust compared to 2 hr-response signature (only eight genes, and may be involved in regulating the cell cycle. Quantitative real-time PCR performed on some miRNA species confirms the robustness of our miRNA microarray platform. Positive regulation of differentiation-, cell cycle-, ion transport- and endomembrane system-related processes were predicted to be negatively affected by miRNAome changes in irradiated hESC. Our findings reveal a fundamental role of miRNAome in modulating the radiation response, and identify novel molecular targets of radiation in hESC.

  1. The cellular and genetic basis of olfactory responses in Caenorhabditis elegans.

    Science.gov (United States)

    Sengupta, P; Colbert, H A; Kimmel, B E; Dwyer, N; Bargmann, C I

    1993-01-01

    The small soil nematode Caenorhabditis elegans has only 302 neurons in its entire nervous system, so it is possible to analyse the functions of individual neurons in the animal's behaviour. We are using behavioural, cellular and genetic analyses of chemotactic responses to find out how olfactory behaviour patterns are generated and regulated. Single chemosensory neurons in C. elegans can recognize several different attractive odorants that are distinguished by the animal. Distinct sets of chemosensory neurons detect high and low concentrations of a single odorant. Odorant responses adapt after prolonged exposure to an odorant; this adaptation is odorant specific and reversible. Mutants with defects in odorant responses have been identified. Some genes appear to be necessary for the development or function of particular kinds of sensory neurons. Other genes have effects that suggest that they participate in odorant reception or signal transduction.

  2. Cellular immune response of humans to the circumsporozoite protein of Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    Mauricio M. Rodrigues

    1991-06-01

    Full Text Available The cellular immune response to the circumsporozoite (CS protein of plasmodium vivax of individuals from malaria-endemic areas of Brazil was studied. We examined the in vitro proliferative response of the peripheral blood mononuclear cells (PBMC of 22 individuals when stimulated with a CS recombinant protein (rPvCS-2 and two other synthetic peptides based on the sequenceof the P. vivax CS protein. Seven of the individuals from malaria-endemic area displayed an antigen specific in vitro proliferative responseto the recombinant protein PvCS-2 and one out of 6, proliferative response to the peptide 308-320. In contrast, none of the individuals displayed a proliferative reponse when stimulated with the D/A peptide which represent some of the repeated units present in this CS protein. Our study, therefore, provides evidence for the presence, withinthe major surface antigen of P. vivax sporozoites, of epitopes capble to induce proliferation of human PBMC.

  3. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low

    Energy Technology Data Exchange (ETDEWEB)

    Kadhim, Munira A

    2012-08-22

    The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program. To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e. less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these "non-targeted responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate non-targeted effects of ionizing radiation with a focus on the induction of genomic instability (GI) in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/CaH and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition in these models on genomic instability. We will specifically focus on the effects of low doses of low LET radiation, down to the dose of 10mGy (0.01Gy) X-rays. Using conventional X-ray and we will be able to assess the role of genetic variation under various conditions at a range of doses down to the very low dose of 0.01Gy. Irradiations will be carried out using facilities in routine operation for such studies. Mechanistic studies of instability in different cell

  4. Cellular and biomolecular responses of human ovarian cancer cells to cytostatic dinuclear platinum(II) complexes.

    Science.gov (United States)

    Lin, Miaoxin; Wang, Xiaoyong; Zhu, Jianhui; Fan, Damin; Zhang, Yangmiao; Zhang, Junfeng; Guo, Zijian

    2011-03-01

    Polynuclear platinum(II) complexes represent a class of potential anticancer agents that have shown promising pharmacological properties in preclinical studies. The nature of cellular responses induced by these complexes, however, is poorly understood. In this research, the cellular responses of human ovarian cancer COC1 cells to dinuclear platinum(II) complexes {[cis-Pt(NH₃)₂Cl]₂L¹}(NO₃)₂ (1) and {[cis-Pt(NH₃)₂Cl]₂L²}(NO₃)₂ (2) (L¹ = α,α'-diamino-p-xylene, L² = 4,4'-methylenedianiline) has been studied using cisplatin as a reference. The effect of platinum complexes on the proliferation, death mode, mitochondrial membrane potential, and cell cycle progression has been examined by MTT assay and flow cytometry. The activation of cell cycle checkpoint kinases (CHK1/2), extracellular signal-regulated kinases (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) of the cells by the complexes has also been analyzed using phospho-specific flow cytometry. Complex 1 is more cytotoxic than complex 2 and cisplatin at most concentrations; complex 2 and cisplatin are comparably cytotoxic. These complexes kill the cells through an apoptotic or apoptosis-like pathway characterized by exposure of phosphatidylserine and dissipation of mitochondrial membrane potential. Complex 1 shows the strongest inductive effect on the morphological changes of the cells, followed by cisplatin and complex 2. Complexes 1 and 2 arrest the cell cycle in G2 or M phase, while cisplatin arrests the cell cycle in S phase. The influence of these complexes on CHK1/2, ERK1/2, and p38 MAPK varies with the dose of the drugs or reaction time. Activation of phospho-ERK1/2 and phospho-p38 MAPK by these complexes is closely related to the cytostatic activity. The results demonstrate that dinuclear platinum(II) complexes can induce some cellular responses different from those caused by cisplatin.

  5. Separate and combined responses to water deficit and UV-B radiation.

    Science.gov (United States)

    Bandurska, Hanna; Niedziela, Justyna; Chadzinikolau, Tamara

    2013-12-01

    Crops and other plants in natural conditions are routinely affected by several stresses acting simultaneously or in sequence. In areas affected by drought, plants may also be exposed to enhanced UV-B radiation (280-315nm). Each of these stress factors differently affects cellular metabolism. A common consequence of plant exposure to the separate action of water deficit and UV-B radiation is the enhanced generation of reactive oxygen species (ROS) causing damage to proteins, lipids, carbohydrates and DNA. Despite this destructive activity, ROS also act as signalling molecules in cellular processes responsible for defence responses. Plants have evolved many physiological and biochemical mechanisms that avoid or tolerate the effects of stress factors. Water deficit avoidance leads to stomatal closure, stimulation of root growth, and accumulation of free proline and other osmolytes. Secondary metabolites (flavonols, flavones and anthocyanins) that accumulate in epidermal cells effectively screen UV-B irradiation and reduce its penetration to mesophyll tissue. The coordinated increased activity of the enzymatic antioxidant defence system such as up-regulation of superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase and glutathione reductase is an important mechanism of tolerance to water deficit and UV-B radiation. The accumulation of low molecular antioxidants (proline, glycine betaine, ascorbate and glutathione) can also contribute to tolerance to water deficit. Polyamines, tocopherol, carotenoids, alkaloids, flavonoids and other secondary metabolites participate in the removal of ROS under conditions of increased UV-B radiation. The combination of water deficit and UV-B radiation induces responses that can be antagonistic, additive or synergistic in comparison with the action of single stresses. UV-B radiation may enhance resistance to water deficit and vice versa. Hydrogen peroxide, nitric oxide (NO), abscisic acid (ABA), jasmonic acid, ethylene

  6. Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

    Directory of Open Access Journals (Sweden)

    Clemens Kiecker

    2016-12-01

    Full Text Available A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in competence for Hedgehog (HH signalling, a signalling pathway that is reiteratively employed in embryos and adult organisms. We discuss the upstream signals and mechanisms that may establish differential competence for HHs in a range of different tissues. We argue that the changing competence for HH signalling provides a four-dimensional framework for the interpretation of the signal that is essential for the emergence of functional anatomy. A number of diseases—including several types of cancer—are caused by malfunctions of the HH pathway. A better understanding of what provides differential competence for this signal may reveal HH-related disease mechanisms and equip us with more specific tools to manipulate HH signalling in the clinic.

  7. Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain.

    Science.gov (United States)

    Martin, David A; Nichols, Charles D

    2016-09-01

    There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT2A-expressing excitatory neurons is directly activated by psychedelics and subsequently recruits other select cell types including subpopulations of inhibitory somatostatin and parvalbumin GABAergic interneurons, as well as astrocytes, to produce distinct and regional responses. To gather data regarding the response of specific neuronal populations, we developed methodology for fluorescence-activated cell sorting (FACS) to segregate and enrich specific cellular subtypes in the brain. These methods allow for robust neuronal sorting based on cytoplasmic epitopes followed by downstream nucleic acid analysis, expanding the utility of FACS in neuroscience research.

  8. Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain

    Directory of Open Access Journals (Sweden)

    David A. Martin

    2016-09-01

    Full Text Available There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT2A-expressing excitatory neurons is directly activated by psychedelics and subsequently recruits other select cell types including subpopulations of inhibitory somatostatin and parvalbumin GABAergic interneurons, as well as astrocytes, to produce distinct and regional responses. To gather data regarding the response of specific neuronal populations, we developed methodology for fluorescence-activated cell sorting (FACS to segregate and enrich specific cellular subtypes in the brain. These methods allow for robust neuronal sorting based on cytoplasmic epitopes followed by downstream nucleic acid analysis, expanding the utility of FACS in neuroscience research.

  9. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors.

    Science.gov (United States)

    Vilgelm, Anna E; Washington, Mary K; Wei, Jinxiong; Chen, Heidi; Prassolov, Vladimir S; Zaika, Alexander I

    2010-03-01

    p53, p63, and p73 are members of the p53 protein family involved in regulation of cell cycle, apoptosis, differentiation, and other critical cellular processes. Here, we investigated the contribution of the entire p53 family in chemotherapeutic drug response in gastrointestinal tumors. Real-time PCR and immunohistochemistry revealed complexity and variability of expression profiles of the p53 protein family. Using colon and esophageal cancer cells, we found that the integral transcription activity of the entire p53 family, as measured by the reporter analysis, associated with response to drug treatment in studied cells. We also found that p53 and p73, as well as p63 and p73, bind simultaneously to the promoters of p53 target genes. Taken together, our results support the view that the p53 protein family functions as an interacting network of proteins and show that cellular responses to chemotherapeutic drug treatment are determined by the total activity of the entire p53 family rather than p53 alone.

  10. Cellular and molecular aspects of the anti-inflammatory effects of low-dose radiation therapy

    OpenAIRE

    Large, Martin

    2015-01-01

    For decades an anti-inflammatory and analgesic effect of low-dose X-irradiation (LD-RT) has clinically been well established in the treatment of a plethora of benign diseases and chronic degenerative disorders with empirically identified single doses < 1 Gy to be most effective. Although considerable progress has been achieved in the understanding of immune modulatory effects of ionising radiation, especially in the low-dose range, the underlying molecular mechanisms are currently not fully r...

  11. Functional recognition imaging using artificial neural networks: applications to rapid cellular identification via broadband electromechanical response

    Energy Technology Data Exchange (ETDEWEB)

    Nikiforov, M P; Guo, S; Kalinin, S V; Jesse, S [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN 37831 (United States); Reukov, V V; Thompson, G L; Vertegel, A A, E-mail: sergei2@ornl.go [Department of Bioengineering, Clemson University, Clemson, SC 29634 (United States)

    2009-10-07

    Functional recognition imaging in scanning probe microscopy (SPM) using artificial neural network identification is demonstrated. This approach utilizes statistical analysis of complex SPM responses at a single spatial location to identify the target behavior, which is reminiscent of associative thinking in the human brain, obviating the need for analytical models. We demonstrate, as an example of recognition imaging, rapid identification of cellular organisms using the difference in electromechanical activity over a broad frequency range. Single-pixel identification of model Micrococcus lysodeikticus and Pseudomonas fluorescens bacteria is achieved, demonstrating the viability of the method.

  12. Radioadaptive response for protection against radiation-induced teratogenesis.

    Science.gov (United States)

    Okazaki, Ryuji; Ootsuyama, Akira; Norimura, Toshiyuki

    2005-03-01

    To clarify the characteristics of the radioadaptive response in mice, we compared the incidence of radiation-induced malformations in ICR mice. Pregnant ICR mice were exposed to a priming dose of 2 cGy (667 muGy/min) on day 9.5 of gestation and to a challenging dose of 2 Gy (1.04 Gy/min) 4 h later and were killed on day 18.5 of gestation. The incidence of malformations and prenatal death and fetal body weights were studied. The incidence of external malformations was significantly lower (by approximately 10%) in the primed (2 cGy + 2 Gy) mice compared to the unprimed (2 Gy alone) mice. However, there were no differences in the incidence of prenatal death or the skeletal malformations or the body weights between primed and unprimed mice. These results suggest that primary conditioning with low doses of radiation suppresses radiation-induced teratogenesis.

  13. Cellular and humoral immune responses to Borrelia burgdorferi antigens in patients with culture-positive early Lyme disease.

    Science.gov (United States)

    Vaz, A; Glickstein, L; Field, J A; McHugh, G; Sikand, V K; Damle, N; Steere, A C

    2001-12-01

    We determined cellular and humoral immune responses to Borrelia burgdorferi lysate and to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 culture-positive patients with erythema migrans and in 20 healthy control subjects. During the acute illness, a median of 4 days after the onset of erythema migrans, 51% of the patients had proliferative cellular responses and 72% had antibody responses to at least one of the borrelial antigens tested. During convalescence, at the conclusion of antibiotic therapy, 64% of the patients had proliferative cellular reactivity and 95% had antibody reactivity with at least one of the spirochetal antigens tested. In both acute- and convalescent-phase samples, cellular immune responses were found as frequently to OspA as to OspC and FlaB. Although antibody responses were also frequently seen to OspC and FlaB, only a few patients had marginal antibody reactivity with OspA. The percentage of patients with proliferative responses was similar in those with clinical evidence of localized or disseminated infection, whereas humoral reactivity was found more often in those with disseminated disease. We conclude that cellular and humoral responses to B. burgdorferi antigens are often found among patients with early Lyme disease. In contrast with the other antigens tested, cellular but not humoral reactivity was often found with OspA.

  14. Low-dose ionizing radiation induces direct activation of natural killer cells and provides a novel approach for adoptive cellular immunotherapy.

    Science.gov (United States)

    Yang, Guozi; Kong, Qingyu; Wang, Guanjun; Jin, Haofan; Zhou, Lei; Yu, Dehai; Niu, Chao; Han, Wei; Li, Wei; Cui, Jiuwei

    2014-12-01

    Recent evidence indicates that limited availability and cytotoxicity have restricted the development of natural killer (NK) cells in adoptive cellular immunotherapy (ACI). While it has been reported that low-dose ionizing radiation (LDIR) could enhance the immune response in animal studies, the influence of LDIR at the cellular level has been less well defined. In this study, the authors aim to investigate the direct effects of LDIR on NK cells and the potential mechanism, and explore the application of activation and expansion of NK cells by LDIR in ACI. The authors found that expansion and cytotoxicity of NK cells were markedly augmented by LDIR. The levels of IFN-γ and TNF-α in the supernatants of cultured NK cells were significantly increased after LDIR. Additionally, the effect of the P38 inhibitor (SB203580) significantly decreased the expanded NK cell cytotoxicity, cytokine levels, and expression levels of FasL and perforin. These findings indicate that LDIR induces a direct expansion and activation of NK cells through possibly the P38-MAPK pathway, which provides a potential mechanism for stimulation of NK cells by LDIR and a novel but simplified approach for ACI.

  15. Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Maryam Yazdanian

    2015-01-01

    Conclusion: Fusion of HBsAg to HCVcp in the context of a DNA vaccine modality could augment Th1-oriented cellular and CTL responses toward a protective epitope, comparable to that of HCVcp (subunit HCV vaccine immunization.

  16. Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Cuzzocrea, Salvatore; Iavicoli, Ivo; Rizzarelli, Enrico; Calabrese, Edward J

    2011-08-01

    Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR). CR appears to prolong life by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways. By sensing the intracellular nutrient and energy status, the functional state of mitochondria, and the concentration of ROS produced in mitochondria, the longevity network regulates life span across species by co-ordinating information flow along its convergent, divergent and multiply branched signaling pathways, including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, such as carnosine, carnitines or polyphenols, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose-response, challenges long-standing beliefs about the nature of the dose-response in a lowdose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. In this review we discuss the most current and up to date

  17. DNA-encapsulated magnesium phosphate nanoparticles elicit both humoral and cellular immune responses in mice

    Directory of Open Access Journals (Sweden)

    Gajadhar Bhakta

    2014-01-01

    Full Text Available The efficacy of pEGFP (plasmid expressing enhanced green fluorescent protein-encapsulated PEGylated (meaning polyethylene glycol coated magnesium phosphate nanoparticles (referred to as MgPi-pEGFP nanoparticles for the induction of immune responses was investigated in a mouse model. MgPi-pEGFP nanoparticles induced enhanced serum antibody and antigen-specific T-lymphocyte responses, as well as increased IFN-γ and IL-12 levels compared to naked pEGFP when administered via intravenous, intraperitoneal or intramuscular routes. A significant macrophage response, both in size and activity, was also observed when mice were immunized with the nanoparticle formulation. The response was highly specific for the antigen, as the increase in interaction between macrophages and lymphocytes as well as lymphocyte proliferation took place only when they were re-stimulated with recombinant green fluorescence protein (rGFP. Thus the nanoparticle formulation elicited both humoral as well as cellular responses. Cytokine profiling revealed the induction of Th-1 type responses. The results suggest DNA-encapsulated magnesium phosphate (MgPi nanoparticles may constitute a safer, more stable and cost-efficient DNA vaccine formulation.

  18. Microbial Degradation of Cellular Kinases Impairs Innate Immune Signaling and Paracrine TNFα Responses.

    Science.gov (United States)

    Barth, Kenneth; Genco, Caroline Attardo

    2016-10-04

    The NFκB and MAPK signaling pathways are critical components of innate immunity that orchestrate appropriate immune responses to control and eradicate pathogens. Their activation results in the induction of proinflammatory mediators, such as TNFα a potent bioactive molecule commonly secreted by recruited inflammatory cells, allowing for paracrine signaling at the site of an infection. In this study we identified a novel mechanism by which the opportunistic pathogen Porphyromonas gingivalis dampens innate immune responses by disruption of kinase signaling and degradation of inflammatory mediators. The intracellular immune kinases RIPK1, TAK1, and AKT were selectively degraded by the P. gingivalis lysine-specific gingipain (Kgp) in human endothelial cells, which correlated with dysregulated innate immune signaling. Kgp was also observed to attenuate endothelial responsiveness to TNFα, resulting in a reduction in signal flux through AKT, ERK and NFκB pathways, as well as a decrease in downstream proinflammatory mRNA induction of cytokines, chemokines and adhesion molecules. A deficiency in Kgp activity negated decreases to host cell kinase protein levels and responsiveness to TNFα. Given the essential role of kinase signaling in immune responses, these findings highlight a unique mechanism of pathogen-induced immune dysregulation through inhibition of cell activation, paracrine signaling, and dampened cellular proinflammatory responses.

  19. Expression and cellular distribution of ubiquitin in response to injury in the developing spinal cord of Monodelphis domestica

    DEFF Research Database (Denmark)

    Noor, Natassya M; Møllgård, Kjeld; Wheaton, Benjamin J;

    2013-01-01

    Ubiquitin, an 8.5 kDa protein associated with the proteasome degradation pathway has been recently identified as differentially expressed in segment of cord caudal to site of injury in developing spinal cord. Here we describe ubiquitin expression and cellular distribution in spinal cord up to pos...... changes in ubiquitin expression and cellular distribution in development and response to spinal injury suggest an intricate regulatory system that modulates these responses which, when better understood, may lead to potential therapeutic targets....

  20. Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation.

    Science.gov (United States)

    Beltrán-Pardo, Eliana; Jönsson, K Ingemar; Harms-Ringdahl, Mats; Haghdoost, Siamak; Wojcik, Andrzej

    2015-01-01

    Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at ~ 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation.

  1. Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation.

    Directory of Open Access Journals (Sweden)

    Eliana Beltrán-Pardo

    Full Text Available Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at ~ 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely, and dividing cells are known to be more sensitive to radiation.

  2. Characterization through a data display of the different cellular responses in X-irradiated small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Carr, K.E.; McCullough, J.S. (Queen' s Univ., Belfast, Northern Ireland (United Kingdom). Medical Biology Centre); Nelson, A.C.; Hume, S.P.

    1992-06-01

    Previous work on small intestinal radiation injury has reported changes in epithelial and non-epithelial tissues, but with few quantitative comparisons of different responses by individual cell types. The approach used here quantifies the responses of mouse duodenum to X-irradiation with 6 Gy, 10 Gy and 20 Gy, sampled three days after treatment, and 10 Gy sampled 6 hours, 1 day and 3 days after treatment. Tissue area measurements and counts per circumference for 13 different structural elements are subjected to statistical tests. New data reported here for X-irradiation include the fact that cryptal cells do not respond uniformly, indicating that the crypt/microcolony cannot always be used as a standard unit in assessing radiation injury. Non-epithelial structures, such as submucosal arterioles, are also affected. The data display also includes control-referenced ratios, from which are calculated Tissue Indices and a final Morphological Index, which estimates total structural damage. The Indices are useful in drawing attention to unexpected changes in extent or range of data sets. In addition, the Epithelial Index appears to be a sensitive indicator of radiation damage, even at low doses and early time points. The data display includes a graph of the total Indices and summary tables of data, and encourages close study of the constituent data points. (author).

  3. Biosorption and biodegradation of pyrene by Brevibacillus brevis and cellular responses to pyrene treatment.

    Science.gov (United States)

    Liao, Liping; Chen, Shuona; Peng, Hui; Yin, Hua; Ye, Jinshao; Liu, Zehua; Dang, Zhi; Liu, Zhichen

    2015-05-01

    Biodegradation has been proposed as an effective approach to remove pyrene, however, the information regarding cellular responses to pyrene treatment is limited thus far. In this study, the biodegradation and biosorption of pyrene by Brevibacillus brevis, along with cellular responses caused by pollutant were investigated by means of flow cytometry assay and scanning electron microscopy. The experimental results showed that pyrene was initially adsorbed by B. brevis and subsequently transported and intracellularly degraded. During this process, pyrene removal was primarily dependent on biodegradation. Cell invagination and cell surface corrugation occurred due to pyrene exposure. Nevertheless, cell regrowth after 96h treatment was observed, and the proportion of necrotic cell was only 2.8% after pyrene exposure for 120h, confirming that B. brevis could utilize pyrene as a sole carbon source for growth. The removal and biodegradation amount of pyrene (1mg/L) at 168h were 0.75 and 0.69mg/L, respectively, and the biosorption amount by inactivated cells was 0.41mg/L at this time.

  4. Hormesis, cellular stress response and neuroinflammation in schizophrenia: Early onset versus late onset state.

    Science.gov (United States)

    Calabrese, Vittorio; Giordano, James; Crupi, Rosalia; Di Paola, Rosanna; Ruggieri, Martino; Bianchini, Rio; Ontario, Maria Laura; Cuzzocrea, Salvatore; Calabrese, Edward J

    2017-05-01

    Abnormal redox homeostasis and oxidative stress have been proposed to play a role in the etiology of several neuropsychiatric spectrum disorders. Emerging interest has recently focused on markers of oxidative stress and neuroinflammation in schizophrenic spectrum disorders, at least in particular subgroups of patients. Altered expression of genes related to oxidative stress, oxidative damage to DNA, protein and lipids, as well as reduced glutathione levels in central and peripheral tissues could act synergistically, and contribute to the course of the disease.  Herein, we discuss cellular mechanisms that may be operative in neuroinflammation and contributory to schizophrenia. We address modulation of endogenous cellular defense mechanisms as a potentially innovative approach to therapeutics for schizophrenia, and other neuropsychiatric conditions that are associated with neuroinflammation. Specifically, we discuss the emerging role of heme oxygenase as prominent member of neuroprotective network in redox stress responsive mechanisms, as well as the importance of glutathione relevant in schizophrenia pathophysiology. Finally we introduce the hormetic dose response concept as relevant and important to neuroprotection, and review hormetic mechanisms as possible approaches to manipulation of neuroinflammatory targets that may be viable for treating schizophrenia spectrum disorders. © 2016 Wiley Periodicals, Inc.

  5. More Than a Pore: The Cellular Response to Cholesterol-Dependent Cytolysins

    Directory of Open Access Journals (Sweden)

    Sara K. B. Cassidy

    2013-04-01

    Full Text Available Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and immunity, beyond their role in intoxication. In this review, we discuss the cellular response to CDC intoxication with emphasis on the effects of pore formation on the host cell plasma membrane and subcellular organelles and whether subsequent cellular responses contribute to the survival of the affected cell.

  6. Glioblastoma stem cells: radiobiological response to ionising radiations of different qualities.

    Science.gov (United States)

    Pecchia, I; Dini, V; Ricci-Vitiani, L; Biffoni, M; Balduzzi, M; Fratini, E; Belli, M; Campa, A; Esposito, G; Cirrone, G; Romano, F; Stancampiano, C; Pelacchi, F; Pallini, R; Tabocchini, M A

    2015-09-01

    Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour, with very poor prognosis. The high recurrence rate and failure of conventional treatments are expected to be related to the presence of radio-resistant cancer stem cells (CSCs) inside the tumour mass. CSCs can both self-renew and differentiate into the heterogeneous lineages of cancer cells. Recent evidence showed a higher effectiveness of C-ions and protons in inactivating CSCs, suggesting a potential advantage of Hadrontherapy compared with conventional radiotherapy for GBM treatment. To investigate the mechanisms involved in the molecular and cellular responses of CSCs to ionising radiations, two GBM stem cell (GSC) lines, named lines 1 and 83, which were derived from patients with different clinical outcomes and having different metabolic profiles (as shown by NMR spectroscopy), were irradiated with (137)Cs photons and with protons or C-ions of 62 MeV u(-1) in the dose range of 5-40 Gy. The biological effects investigated were: cell death, cell cycle progression, and DNA damage induction and repair. Preliminary results show a different response to ionising radiation between the two GSC lines for the different end points investigated. Further experiments are in progress to consolidate the data and to get more insights on the influence of radiation quality.

  7. Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise.

    Science.gov (United States)

    Hyldahl, Robert D; Hubal, Monica J

    2014-02-01

    The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders.

  8. Unraveling the cellular response to oxidative stress in the endoplasmic reticulum

    DEFF Research Database (Denmark)

    Hansen, Henning Gram

    , disulfide bonds are predominantly generated by the two isoforms of the ER oxidoreductin-1 (Ero1) family: Ero1α and Ero1β. Both enzymes oxidize the active-site cysteines in protein disulfide isomerases (PDIs), which in turn introduce disulfide bonds into newly synthesized proteins. Ero1 is re......-oxidized by molecular oxygen and this step generates hydrogen peroxide: a reactive oxygen species. Intramolecular disulfide bonds tightly regulate the oxidase activity of Ero1α. Whereas the regulatory mechanisms that regulate Ero1α activity are well understood, the overall cellular response to oxidative stress...... generated by Ero1α in the lumen of the mammalian ER is poorly characterized. The work presented here shows that overexpression of a hyperactive mutant (C104A/C131A) of Ero1α leads to hyperoxidation of the ER oxidoreductase ERp57 and induces the unfolded protein response (UPR). These effects are likely...

  9. Impaired cellular immune response to tetanus toxoid but not to cytomegalovirus in effectively HAART-treated HIV-infected children.

    Science.gov (United States)

    Alsina, Laia; Noguera-Julian, Antoni; Fortuny, Clàudia

    2013-05-07

    Despite of highly active antiretroviral therapy, the response to vaccines in HIV-infected children is poor and short-lived, probably due to a defect in cellular immune responses. We compared the cellular immune response (assessed in terms of IFN-γ production) to tetanus toxoid and to cytomegalovirus in a series of 13 HIV-perinatally-infected children and adolescents with optimal immunovirological response to first line antiretroviral therapy, implemented during chronic infection. A stronger cellular response to cytomegalovirus (11 out of 13 patients) was observed, as compared to tetanus toxoid (1 out of 13; p=0.003). These results suggest that the repeated exposition to CMV, as opposed to the past exposition to TT, is able to maintain an effective antigen-specific immune response in stable HIV-infected pediatric patients and strengthen current recommendations on immunization practices in these children.

  10. Radiative Forcing and Climate Response: From Paleoclimate to Future Climate

    Science.gov (United States)

    Caldeira, K.; Cao, L.

    2011-12-01

    The concept of radiative forcing was introduced to allow comparison of climate effects of different greenhouse gases. In the classic view, radiative forcing is applied to the climate system and the climate responds to this forcing, approaching some equilibrium temperature change that is the product of the radiative forcing times the 'climate sensitivity' to radiative forcing. However, this classic view is oversimplified in several respects. Climate forcing and response often cannot be clearly separated. When carbon dioxide is added to the atmosphere, within days, the increased absorption of longwave radiation begins to warm the interior of the troposphere, affecting various tropospheric properties. Especially in the case of aerosols, it has been found that considering rapid tropospheric adjustment gives a better predictor of "equilibrium" climate change than does the classic definition of radiative forcing. Biogeochemistry also provides additional feedbacks on the climate system. It is generally thought that biogeochemistry helps diminish climate sensitivity to a carbon dioxide emission, since carbon dioxide tends to stimulate carbon dioxide uptake by land plants and the ocean. However, there is potential to destabilize carbon locked up in permafrost and at least some possibility to destabilize methane in continental shelf sediments. Furthermore, wetlands may provide a significant methane feedback. These and other possible biogeochemical feedbacks have the potential to greatly increase the sensitivity of the climate system to carbon dioxide emissions. As time scales extend out to millennia, the large ice sheets can begin to play an important role. In addition to affecting atmospheric flows by their sheer bulk, ice sheets tend to reflect a lot of energy to space. If carbon dioxide remains in the atmosphere long enough, there is potential to melt back the large ice sheets, which would add additional warming to the climate system. It is likely that these millennial

  11. Investigating the Cellular and Metabolic Responses of World-Class Canoeists Training: A Sportomics Approach

    Directory of Open Access Journals (Sweden)

    Wagner Santos Coelho

    2016-11-01

    Full Text Available (1 Background: We have been using the Sportomics approach to evaluate biochemical and hematological changes in response to exercise. The aim of this study was to evaluate the metabolic and hematologic responses of world-class canoeists during a training session; (2 Methods: Blood samples were taken at different points and analyzed for their hematological properties, activities of selected enzymes, hormones, and metabolites; (3 Results: Muscle stress biomarkers were elevated in response to exercise which correlated with modifications in the profile of white blood cells, where a leukocyte rise was observed after the canoe session. These results were accompanied by an increase in other exercise intensity parameters such as lactatemia and ammonemia. Adrenocorticotropic hormone and cortisol increased during the exercise sessions. The acute rise in both erythrocytes and white blood profile were probably due to muscle cell damage, rather than hepatocyte integrity impairment; (4 Conclusion: The cellular and metabolic responses found here, together with effective nutrition support, are crucial to understanding the effects of exercise in order to assist in the creation of new training and recovery planning. Also we show that Sportomics is a primal tool for training management and performance improvement, as well as to the understanding of metabolic response to exercise.

  12. Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients

    Science.gov (United States)

    Ortiz-Sánchez, Juan P.; Cabrera-Chávez, Francisco; Calderón de la Barca, Ana M.

    2013-01-01

    Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet. PMID:24152750

  13. Investigating the Cellular and Metabolic Responses of World-Class Canoeists Training: A Sportomics Approach

    Science.gov (United States)

    Coelho, Wagner Santos; Viveiros de Castro, Luis; Deane, Elizabeth; Magno-França, Alexandre; Bassini, Adriana; Cameron, Luiz-Claudio

    2016-01-01

    (1) Background: We have been using the Sportomics approach to evaluate biochemical and hematological changes in response to exercise. The aim of this study was to evaluate the metabolic and hematologic responses of world-class canoeists during a training session; (2) Methods: Blood samples were taken at different points and analyzed for their hematological properties, activities of selected enzymes, hormones, and metabolites; (3) Results: Muscle stress biomarkers were elevated in response to exercise which correlated with modifications in the profile of white blood cells, where a leukocyte rise was observed after the canoe session. These results were accompanied by an increase in other exercise intensity parameters such as lactatemia and ammonemia. Adrenocorticotropic hormone and cortisol increased during the exercise sessions. The acute rise in both erythrocytes and white blood profile were probably due to muscle cell damage, rather than hepatocyte integrity impairment; (4) Conclusion: The cellular and metabolic responses found here, together with effective nutrition support, are crucial to understanding the effects of exercise in order to assist in the creation of new training and recovery planning. Also we show that Sportomics is a primal tool for training management and performance improvement, as well as to the understanding of metabolic response to exercise. PMID:27845704

  14. Investigation of cellular and molecular responses to pulsed focused ultrasound in a mouse model.

    Directory of Open Access Journals (Sweden)

    Scott R Burks

    Full Text Available Continuous focused ultrasound (cFUS has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation. pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules. We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e.g., IL-1α, IL-1β, TNFα, INFγ, MIP-1α, MCP-1, and GMCSF creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1α and cell adhesion molecules (e.g., ICAM-1 and VCAM-1 on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology.

  15. Low-Radiation Cellular Inductive Powering of Rodent Wireless Brain Interfaces: Methodology and Design Guide.

    Science.gov (United States)

    Soltani, Nima; Aliroteh, Miaad S; Salam, M Tariqus; Perez Velazquez, Jose Luis; Genov, Roman

    2016-08-01

    This paper presents a general methodology of inductive power delivery in wireless chronic rodent electrophysiology applications. The focus is on such systems design considerations under the following key constraints: maximum power delivery under the allowable specific absorption rate (SAR), low cost and spatial scalability. The methodology includes inductive coil design considerations within a low-frequency ferrite-core-free power transfer link which includes a scalable coil-array power transmitter floor and a single-coil implanted or worn power receiver. A specific design example is presented that includes the concept of low-SAR cellular single-transmitter-coil powering through dynamic tracking of a magnet-less receiver spatial location. The transmitter coil instantaneous supply current is monitored using a small number of low-cost electronic components. A drop in its value indicates the proximity of the receiver due to the reflected impedance of the latter. Only the transmitter coil nearest to the receiver is activated. Operating at the low frequency of 1.5 MHz, the inductive powering floor delivers a maximum of 15.9 W below the IEEE C95 SAR limit, which is over three times greater than that in other recently reported designs. The power transfer efficiency of 39% and 13% at the nominal and maximum distances of 8 cm and 11 cm, respectively, is maintained.

  16. Elemental mapping by synchrotron radiation X-Ray microfluorescence in cellular spheroid of prostate tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Leitao, R.G.; Anjos, M.J.; Lopes, R.T., E-mail: roberta@lin.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Lab. de Instrumentacao Nuclear; Santos, C.A.N. [Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO), Duque de Caxias, RJ (Brazil). Lab. de Biotecnologia; Palumbo Junior, A.; Souza, P.A.V.R.; Nasciutti, L.E. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Ciencias Biomedicas; Pereira, G.R. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Lab. de Ensaios Nao Destrutivos, Corrosao e Soldagem

    2013-08-15

    Prostate cancer is the sixth most common type of cancer and the third most common in males in Western industrialized countries. Cellular spheroid serves as excellent physiologic tumor models as they mimic avascular tumors and micrometastases. Trace elements play a significant role in biological processes. They are capable of affecting human health by competing with essential elements for available binding sites and by the activation or inhibition of reactions between metabolic enzymes. It is well known that zinc levels in the peripheral zone of dorsal and lateral lobes of the prostate are almost 10 times higher than in other soft tissues. Prostate tumor cells were isolated of the prostate tissue samples that were collected from patients submitted to surgery. The measurements were performed in XRF beam line at the Synchrotron Light National Laboratory (LNLS) in Campinas, Brazil. The results showed that all elements were heterogeneously distributed in different areas of the spheroids analyzed. P, S and Cl showed similar elemental distribution in all the samples analyzed while K, Ca, Fe, and Cu showed different elemental distribution. In all spheroids analyzed, Zn presented more intense distributions in the central region of the spheroid. The relationship between the function of Zn in the secretory epithelial cells and the carcinogenic process suggests that more studies on elemental mapping in spheroids are necessary. (author)

  17. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  18. Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients.

    Science.gov (United States)

    Roque-Cuéllar, M C; Sánchez, B; García-Lozano, J R; Praena-Fernández, J M; Núñez-Roldán, A; Aguilar-Reina, J

    2011-10-01

    It is unknown whether hepatitis C virus (HCV)-specific cellular immune responses can develop in seronegative sexual partners of chronically HCV-infected patients and whether they have occult infection. Thirty-one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks. Ten healthy individuals and 17 anti-HCV seropositive patients, without viremia, were used as controls. Virus-specific CD4+ and CD8+ T-cell responses were measured by flow cytometry against six HCV peptides, situated within the nonstructural (NS) proteins NS3, NS4 and NS5, through intracellular detection of gamma interferon (IFN-γ) or interleukin 4 (IL-4) production and CD69 expression. Sexual partners had a higher production of IFN-γ and IL-4 by CD4+ cells against NS3-p124 (P = 0.003), NS5b-p257 (P = 0.005) and NS5b-p294 (P = 0.012), and CD8+ cells against NS3-p124 (P = 0.002), NS4b-p177 (P = 0.001) and NS3-p294 (P = 0.004) as compared with healthy controls. We observed elevated IFN-γ production by CD4+ T cells against NS5b-p257 (P = 0.042) and NS5b-p294 (P = 0.009) in the sexual partners with HCV transmission risks (sexual, professional and familial altogether) than in those without risks. RNA was extracted from peripheral blood mononuclear cells (PBMC), and detection of HCV-RNA positive and replicative (negative) strands was performed by strand-specific real-time PCR. In four sexual partners, the presence of positive and negative HCV- RNA strands in PBMC was confirmed. Hence, we found an HCV-specific cellular immune response as well as occult HCV infection in seronegative and aviremic sexual partners of chronically HCV-infected patients.

  19. Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

    Directory of Open Access Journals (Sweden)

    Zhang Quanfu

    2011-06-01

    Full Text Available Abstract Background The incidence of dengue, an infectious disease caused by dengue virus (DENV, has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated. Results By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses. Conclusions Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.

  20. SAR Simulation with Magneto Chiral Effects for Human Head Radiated from Cellular Phones

    Science.gov (United States)

    Torres-Silva, H.

    2008-09-01

    A numerical method for a microwave signal emitted by a cellular phone, propagating in a magneto-chiral media, characterized by an extended Born-Fedorov formalism, is presented. It is shown that the use of a cell model, combined with a real model of the human head, derived from the magnetic resonance of images allows a good determination of the near fields induced in the head when the brain chirality and the battery magnetic field are considered together. The results on a 2-Dim human head model show the evolution of the specific absorption rate, (SAR coefficient) and the spatial peak specific absorption rate which are sensitives to the magneto-chiral factor, which is important in the brain layer. For GSM/PCN phones, extremely low frequency real pulsed magnetic fields (in the order of 10 to 60 milligauss) are added to the model through the whole of the user's head. The more important conclusion of our work is that the head absorption is bigger than the results for a classical model without the magneto chiral effect. Hot spots are produced due to the combination of microwave and the magnetic field produced by the phone's operation. The FDTD method was used to compute the SARs inside the MRI based head models consisting of various tissues for 1.8 GHz. As a result, we found that in the head model having more than four kinds of tissue, the localized peak SAR reaches maximum inside the head for over five tissues including skin, bone, blood and brain cells.

  1. Effect of UV-B radiation on the fatty acid composition of the marine phytoplankter Tetraselmis sp.: Relationahip to cellular pigments

    Digital Repository Service at National Institute of Oceanography (India)

    Goes, J.I.; Handa, N.; Taguchi, S.; Hama, T.

    : 259-274,1994 MARINE ECOLOGY PROGRESS SERIES Mar. Ecol. Prog. Ser. I Published November 17 l Effect of UV-B radiation on the fatty acid composition of the marine phytoplankter Tetraselmis sp.: relationship to cellular pigments Joaquim I. ~oesl... and pig- ment composition of Tetraselmis sp. resulting from exposure to UV-B radiation. Although fatty acids con- stitute a small proportion of the total organic matter synthesized by marine phytoplankton (Hama & Handa 1987, Hama 1991...

  2. Lysophosphatidic acid receptor-5 negatively regulates cellular responses in mouse fibroblast 3T3 cells

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yan; Hirane, Miku; Araki, Mutsumi [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Tsujiuchi, Toshifumi, E-mail: ttujiuch@life.kindai.ac.jp [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

    2014-04-04

    Highlights: • LPA{sub 5} inhibits the cell growth and motile activities of 3T3 cells. • LPA{sub 5} suppresses the cell motile activities stimulated by hydrogen peroxide in 3T3 cells. • Enhancement of LPA{sub 5} on the cell motile activities inhibited by LPA{sub 1} in 3T3 cells. • The expression and activation of Mmp-9 were inhibited by LPA{sub 5} in 3T3 cells. • LPA signaling via LPA{sub 5} acts as a negative regulator of cellular responses in 3T3 cells. - Abstract: Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors (LPA{sub 1}–LPA{sub 6}) mediates a variety of biological functions, including cell migration. Recently, we have reported that LPA{sub 1} inhibited the cell motile activities of mouse fibroblast 3T3 cells. In the present study, to evaluate a role of LPA{sub 5} in cellular responses, Lpar5 knockdown (3T3-L5) cells were generated from 3T3 cells. In cell proliferation assays, LPA markedly stimulated the cell proliferation activities of 3T3-L5 cells, compared with control cells. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3-L5 cells were significantly higher than those of control cells. The activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. 3T3-L5 cells stimulated the activation of Mmp-2, correlating with the expression levels of Mmp-2 gene. Moreover, to assess the co-effects of LPA{sub 1} and LPA{sub 5} on cell motile activities, Lpar5 knockdown (3T3a1-L5) cells were also established from Lpar1 over-expressing (3T3a1) cells. 3T3a1-L5 cells increased the cell motile activities of 3T3a1 cells, while the cell motile activities of 3T3a1 cells were significantly lower than those of control cells. These results suggest that LPA{sub 5} may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA{sub 1}.

  3. Comparison of cellular responses induced by low level light in different cell types

    Science.gov (United States)

    Huang, Ying-Ying; Chen, Aaron C.-H.; Sharma, Sulbha K.; Wu, Qiuhe; Hamblin, Michael R.

    2010-02-01

    Discoveries are rapidly being made in multiple laboratories that shed "light" on the fundamental molecular and cellular mechanisms underlying the use of low level light therapy (LLLT) in vitro, in animal models and in clinical practice. Increases in cellular levels of respiration, in cytochrome c oxidase activity, in ATP levels and in cyclic AMP have been found. Increased expression of reactive oxygen species and release of nitric oxide have also been shown. In order for these molecular changes to have a major effect on cell behavior, it is likely that various transcription factors will be activated, possibly via different signal transduction pathways. In this report we compare and contrast the effects of LLLT in vitro on murine embryonic fibroblasts, primary cortical neurons, cardiomyocytes and bone-marrow derived dendritic cells. We also examined two human cell lines, HeLa cancer cells and HaCaT keratinocytes. The effects of 810-nm near-infra-red light delivered at low and high fluences were addressed. Reactive oxygen species generation, transcription factor activation and ATP increases are reported. The data has led to the hypothesis that cells with a high level of mitochondrial activity (mitochondrial membrane potential) have a higher response to light than cells with low mitochondrial activity.

  4. Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer

    Directory of Open Access Journals (Sweden)

    John Wikswo

    2009-03-01

    Full Text Available Harnessing the potential of cells as complex biosensors promises the potential to create sensitive and selective detectors for discrimination of biodefense agents. Here we present toxin detection and suggest discrimination using cells in a multianalyte microphysiometer (MMP that is capable of simultaneously measuring flux changes in four extracellular analytes (acidification rate, glucose uptake, oxygen uptake, and lactate production in real-time. Differential short-term cellular responses were observed between botulinum neurotoxin A and ricin toxin with neuroblastoma cells, alamethicin and anthrax protective antigen with RAW macrophages, and cholera toxin, muscarine, 2,4-dinitro-phenol, and NaF with CHO cells. These results and the post exposure dynamics and metabolic recovery observed in each case suggest the usefulness of cell-based detectors to discriminate between specific analytes and classes of compounds in a complex matrix, and furthermore to make metabolic inferences on the cellular effects of the agents. This may be particularly valuable for classifying unknown toxins.

  5. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  6. Cellular heredity in haploid cultures of somatic cells. Comprehensive report, April 1975--June 1977. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Freed, J.J.

    1977-07-01

    This report reviews genetic studies carried out since 1975 on a haploid cultured cell line from frog embryos (ICR 2A). Although a single chromosome set would be expected to facilitate recovery of recessive mutants, experiments suggested that cell culture variants might arise through processes more complex than the selection of simple mutational changes. Therefore, the objectives of the work reported here have been to throw light on just how cell culture variants arise in this system. First, we have continued to characterize the ICR 2A line, with emphasis on stability of karyotype and DNA content. Second, we have studied in detail the origin of two classes of drug-resistant variants. Bromodeoxyuridine resistance of the thymidine deficiency type has been shown to arise through sequential loss of two forms of thymidine-phosphorylating enzyme; loss of the second form of enzyme is complex, suggesting that changes more complex than simple recessive mutations may be involved. Another form of resistance, in which tolerance of high levels of bromodeoxyuridine is found in cells that continue to express thymidine kinase, remains under study. Variants resistant to microtubule inhibitors were isolated. It was found that these haploid strains have properties distinguishing them from analogous resistant strains isolated from diploid mammalian cell cultures in other laboratories. In order to understand better how mutagens are involved in the origin of cell culture variants, we have examined the effect of different forms of DNA repair on the frequency of drug-resistant colonies induced by ultraviolet radiation. Preliminary experiments suggest that the frequency of such colonies is greater when repair takes place through (presumably error-prone) dark repair than when (error-free) photoreversal is allowed to occur. Such experiments can determine whether new phenotypes arise from alterations in DNA, and thus whether, in a broad sense, they are likely to be mutational in nature.

  7. Cellular Responses Evoked by Different Surface Characteristics of Intraosseous Titanium Implants

    Directory of Open Access Journals (Sweden)

    Liviu Feller

    2015-01-01

    Full Text Available The properties of biomaterials, including their surface microstructural topography and their surface chemistry or surface energy/wettability, affect cellular responses such as cell adhesion, proliferation, and migration. The nanotopography of moderately rough implant surfaces enhances the production of biological mediators in the peri-implant microenvironment with consequent recruitment of differentiating osteogenic cells to the implant surface and stimulates osteogenic maturation. Implant surfaces with moderately rough topography and with high surface energy promote osteogenesis, increase the ratio of bone-to-implant contact, and increase the bonding strength of the bone to the implant at the interface. Certain features of implant surface chemistry are also important in enhancing peri-implant bone wound healing. It is the purpose of this paper to review some of the more important features of titanium implant surfaces which have an impact on osseointegration.

  8. Cellular Responses of Resistant and Susceptible Soybean Genotypes Infected with Meloidogyne arenaria Races 1 and 2.

    Science.gov (United States)

    Pedrosa, E M; Hussey, R S; Boerma, H R

    1996-06-01

    The cellular responses induced by Meloidogyne arenaria races 1 and 2 in three soybean genotypes, susceptible CNS, resistant Jackson, and resistant PI 200538, were examined by light microscopy 20 days after inoculation. Differences in giant-cell development were greater between races than among the soybean genotypes. M. arenaria race 1 stimulated small, poorly formed giant-cells in contrast with M. arenaria race 2, which induced well-developed, thick-walled, multinucleate giant-cells. The number of nuclei per giant-celt was variable, but fewer nuclei were usually present in giant-cells induced by race 1 (mean 16 nuclei) than in giant-cells induced by race 2 (mean 41 nuclei). Differences observed in giant-cell development were related to differences in growth and maturation of M. arenaria races 1 and 2 and host suitability of the soybean genotypes.

  9. Thioredoxin-dependent Redox Regulation of Cellular Signaling and Stress Response through Reversible Oxidation of Methionines

    Energy Technology Data Exchange (ETDEWEB)

    Bigelow, Diana J.; Squier, Thomas C.

    2011-06-01

    Generation of reactive oxygen species (ROS) is a common feature of many forms of stress to which plants are exposed. Successful adaptation to changing environmental conditions requires sensitive sensors of ROS such as protein-bound methionines that are converted to their corresponding methionine sulfoxides, which in turn can influence cellular signaling pathways. Such a signaling protein is calmodulin, which represents an early and central point in calcium signaling pathways important to stress response in plants. We describe recent work elucidating fundamental mechanisms of reversible methionine oxidation within calmodulin, including the sensitivity of individual methionines within plant and animal calmodulin to ROS, the structural and functional consequences of their oxidation, and the interactions of oxidized calmodulin with methionine sulfoxide reductase enzymes.

  10. Human papillomavirus (HPV upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response.

    Directory of Open Access Journals (Sweden)

    Rezaul Karim

    Full Text Available Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV may cause cancer. Keratinocytes are equipped with different pattern recognition receptors (PRRs but hrHPV has developed ways to dampen their signals resulting in minimal inflammation and evasion of host immunity for sustained periods of time. To understand the mechanisms underlying hrHPV's capacity to evade immunity, we studied PRR signaling in non, newly, and persistently hrHPV-infected keratinocytes. We found that active infection with hrHPV hampered the relay of signals downstream of the PRRs to the nucleus, thereby affecting the production of type-I interferon and pro-inflammatory cytokines and chemokines. This suppression was shown to depend on hrHPV-induced expression of the cellular protein ubiquitin carboxyl-terminal hydrolase L1 (UCHL1 in keratinocytes. UCHL1 accomplished this by inhibiting tumor necrosis factor receptor-associated factor 3 (TRAF3 K63 poly-ubiquitination which lead to lower levels of TRAF3 bound to TANK-binding kinase 1 and a reduced phosphorylation of interferon regulatory factor 3. Furthermore, UCHL1 mediated the degradation of the NF-kappa-B essential modulator with as result the suppression of p65 phosphorylation and canonical NF-κB signaling. We conclude that hrHPV exploits the cellular protein UCHL1 to evade host innate immunity by suppressing PRR-induced keratinocyte-mediated production of interferons, cytokines and chemokines, which normally results in the attraction and activation of an adaptive immune response. This identifies UCHL1 as a negative regulator of PRR-induced immune responses and consequently its virus-increased expression as a strategy for hrHPV to persist.

  11. Monitoring cellular stress responses to nanoparticles using a lab-on-a-chip.

    Science.gov (United States)

    Richter, Lukas; Charwat, Verena; Jungreuthmayer, Christian; Bellutti, Florian; Brueckl, Hubert; Ertl, Peter

    2011-08-07

    As nanotechnology moves towards widespread commercialization, new technologies are needed to adequately address the potential health impact of nanoparticles (NPs). Assessing the safety of over 30,000 NPs through animal testing would not only be expensive, but it would also raise a number of ethical considerations. Furthermore, existing in vitro cell-based assays are not sufficient in scope to adequately address the complexity of cell-nanoparticle interactions including NP translocation, accumulation and co-transport of e.g. allergens. In particular, classical optical/fluorescent endpoint detection methods are known to provide irreproducible, inaccurate and unreliable results since these labels can directly react with the highly catalytic surfaces of NP. To bridge this technological gap we have developed a lab-on-a-chip capable of continuously and non-invasively monitoring the collagen production of primary human fibroblast cells (NHDF) using contactless dielectric microsensors. Human dermal fibroblast cells are responsible for the maintenance of soft tissue integrity, are found throughout the human body and their primary function is collagen expression. We show that cellular collagen production can be readily detected and used to assess cellular stress responses to a variety of external stimuli, including exposure to nanoparticles. Results of the study showed a 20% and 95% reduction of collagen production following 4 hour exposure to 10 μg mL(-1) gold and silver nanoparticles (dia.10 nm), respectively. Furthermore a prolonged perfusion of sub-toxic concentrations (0.1 μg mL(-1)) of silver NP reduced NHDF collagen production by 40% after 10 h indicating increased NP take up and accumulation. We demonstrate that the application of microfluidics for the tailored administration of different NP treatments constitutes a powerful new tool to study cell-nanoparticle interactions and nanoparticle accumulation effects in small cell populations.

  12. Cellular and molecular responses of E. fetida coelomocytes exposed to TiO{sub 2} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Bigorgne, Emilie, E-mail: emilie.bigorgne@univ-lorraine.fr; Foucaud, Laurent [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Caillet, Celine [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Giamberini, Laure; Nahmani, Johanne [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Thomas, Fabien [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Rodius, Francois [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France)

    2012-07-15

    An in vitro approach using coelomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO{sub 2} nanoparticles. Coelomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO{sub 2} nanoparticles (1-25 {mu}g/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO{sub 2} nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 {mu}g/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO{sub 2} in our experimental conditions. This in vitro approach showed that TiO{sub 2} nanoparticles were taken up by coelomocytes and they could modify the molecular response of immune and detoxification system.

  13. Development of cross-protective influenza A vaccines based on cellular responses

    Directory of Open Access Journals (Sweden)

    Peter Christiaan Soema

    2015-05-01

    Full Text Available Seasonal influenza vaccines provide protection against matching influenza A virus (IAV strains mainly through the induction of neutralizing serum IgG antibodies. However, these antibodies fail to confer a protective effect against mismatched IAV. This lack of efficacy against heterologous influenza strains has spurred the vaccine development community to look for other influenza vaccine concepts, which have the ability to elicit cross-protective immune responses.One of the concepts that is currently been worked on are influenza vaccines inducing influenza-specific T cell responses. T cells are able to lyse infected host cells, thereby clearing the virus. More interestingly, these T cells can recognize highly conserved epitopes of internal influenza proteins, making cellular responses less vulnerable to antigenic variability. T cells are therefore cross-reactive against many influenza strains, and thus are a promising concept for future influenza vaccines. Despite their potential, there are currently no T cell based IAV vaccines on the market. Selection of the proper antigen, appropriate vaccine formulation and evaluation of the efficacy of T cell vaccines remains challenging, both in preclinical and clinical settings.In this review, we will discuss the current developments in influenza T cell vaccines, focusing on existing protein-based and novel peptide-based vaccine formulations. Furthermore, we will discuss the feasibility of influenza T cell vaccines and their possible use in the future.

  14. Cellular, physiological, and molecular adaptive responses of Erwinia amylovora to starvation.

    Science.gov (United States)

    Santander, Ricardo D; Oliver, James D; Biosca, Elena G

    2014-05-01

    Erwinia amylovora causes fire blight, a destructive disease of rosaceous plants distributed worldwide. This bacterium is a nonobligate pathogen able to survive outside the host under starvation conditions, allowing its spread by various means such as rainwater. We studied E. amylovora responses to starvation using water microcosms to mimic natural oligotrophy. Initially, survivability under optimal (28 °C) and suboptimal (20 °C) growth temperatures was compared. Starvation induced a loss of culturability much more pronounced at 28 °C than at 20 °C. Natural water microcosms at 20 °C were then used to characterize cellular, physiological, and molecular starvation responses of E. amylovora. Challenged cells developed starvation-survival and viable but nonculturable responses, reduced their size, acquired rounded shapes and developed surface vesicles. Starved cells lost motility in a few days, but a fraction retained flagella. The expression of genes related to starvation, oxidative stress, motility, pathogenicity, and virulence was detected during the entire experimental period with different regulation patterns observed during the first 24 h. Further, starved cells remained as virulent as nonstressed cells. Overall, these results provide new knowledge on the biology of E. amylovora under conditions prevailing in nature, which could contribute to a better understanding of the life cycle of this pathogen.

  15. Time-lapse analysis of potential cellular responsiveness to Johrei, a Japanese healing technique

    Directory of Open Access Journals (Sweden)

    Moore Dan

    2005-01-01

    Full Text Available Abstract Background Johrei is an alternative healing practice which involves the channeling of a purported universal healing energy to influence the health of another person. Despite little evidence to support the efficacy of such practices the use of such treatments is on the rise. Methods We assessed cultured human cancer cells for potential responsiveness to Johrei treatment from a short distance. Johrei treatment was delivered by practitioners who participated in teams of two, alternating every half hour for a total of four hours of treatment. The practitioners followed a defined set of mental procedures to minimize variability in mental states between experiments. An environmental chamber maintained optimal growth conditions for cells throughout the experiments. Computerized time-lapse microscopy allowed documentation of cancer cell proliferation and cell death before, during and after Johrei treatments. Results Comparing eight control experiments with eight Johrei intervention experiments, we found no evidence of a reproducible cellular response to Johrei treatment. Conclusion Cell death and proliferation rates of cultured human cancer cells do not appear responsive to Johrei treatment from a short distance.

  16. Involvement of Noxa in mediating cellular ER stress responses to lytic virus infection.

    Science.gov (United States)

    Rosebeck, Shaun; Sudini, Kuladeep; Chen, Tiannan; Leaman, Douglas W

    2011-09-01

    Noxa is a Bcl-2 homology domain-containing pro-apoptotic mitochondrial protein. Noxa mRNA and protein expression are upregulated by dsRNA or virus, and ectopic Noxa expression enhances cellular sensitivity to virus or dsRNA-induced apoptosis. Here we demonstrate that Noxa null baby mouse kidney (BMK) cells are deficient in normal cytopathic response to lytic viruses, and that reconstitution of the knockout cells with wild-type Noxa restored normal cytopathic responses. Noxa regulation by virus mirrored its regulation by proteasome inhibitors or ER stress inducers and the ER stress response inhibitor salubrinal protected cells against viral cytopathic effects. Noxa mRNA and protein were synergistically upregulated by IFN or dsRNA when combined with ER stress inducers, leading to Noxa/Mcl-1 interaction, activation of Bax and pro-apoptotic caspases, degradation of Mcl-1, loss of mitochondrial membrane potential and initiation of apoptosis. These data highlight the importance of ER stress in augmenting the expression of Noxa following viral infection.

  17. Potential role of Hedgehog pathway in liver response to radiation.

    Directory of Open Access Journals (Sweden)

    Sihyung Wang

    Full Text Available Radiation-induced fibrosis constitutes a major problem that is commonly observed in the patients undergoing radiotherapy; therefore, understanding its pathophysiological mechanism is important. The Hedgehog (Hh pathway induces the proliferation of progenitors and myofibroblastic hepatic stellate cells (MF-HSCs and promotes the epithelial-to-mesenchymal transition (EMT, thereby regulating the repair response in the damaged liver. We examined the response of normal liver to radiation injury. Male mice were sacrificed at 6 weeks and 10 weeks after exposure to a single dose of 6 Gy and the livers were collected for biochemical analysis. Irradiated (IR and control mice were compared for progenitors, fibrosis, Hh pathway, and EMT at 6 and 10 weeks post irradiation. Fatty hepatocytes were observed and the expressions of Hh ligand, Indian Hh. were greater in the livers at 6 weeks, whereas expression of another Hh ligand, Sonic Hh, increased at 10 weeks post irradiation. Both Smoothened, Hh receptor, and Gli2, Hh-target gene, were up-regulated at 6 and 10 weeks after irradiation. Accumulation of progenitors (CD44, Pan-cytokeratin, and Sox9 was significant in IR livers at 6 and 10 weeks. RNA analysis showed enhanced expression of the EMT-stimulating factor, tgf-β, in the IR livers at 6 weeks and the upregulation of mesenchymal markers (α-SMA, collagen, N-cadherin, and s100a4, but down-regulation of EMT inhibitors, in IR mouse livers at 6 and 10 weeks. Increased fibrosis was observed in IR mouse livers at 10 weeks. Treatment of mice with Hh inhibitor, GDC-0449, suppressed Hh activity and block the proliferation of hepatic progenitor and expression of EMT-stimulating genes in irradiated mice. Therefore, those results demonstrated that the Hh pathway increased in response to liver injury by radiation and promoted a compensatory proliferation of MF-HSCs and progenitors, thereby regulating liver remodeling.

  18. Role of toll-like receptors 3, 4 and 7 in cellular uptake and response to titanium dioxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Peng Chen, Koki Kanehira and Akiyoshi Taniguchi

    2013-01-01

    Full Text Available Innate immune response is believed to be among the earliest provisional cellular responses, and mediates the interactions between microbes and cells. Toll-like receptors (TLRs are critical to these interactions. We hypothesize that TLRs also play an important role in interactions between nanoparticles (NPs and cells, although little information has been reported concerning such an interaction. In this study, we investigated the role of TLR3, TLR4 and TLR7 in cellular uptake of titanium dioxide NP (TiO2 NP agglomerates and the resulting inflammatory responses to these NPs. Our data indicate that TLR4 is involved in the uptake of TiO2 NPs and promotes the associated inflammatory responses. The data also suggest that TLR3, which has a subcellular location distinct from that of TLR4, inhibits the denaturation of cellular protein caused by TiO2 NPs. In contrast, the unique cellular localization of TLR7 has middle-ground functional roles in cellular response after TiO2 NP exposure. These findings are important for understanding the molecular interaction mechanisms between NPs and cells.

  19. Telomeres and Telomerase in the Radiation Response: implications for instability, reprogramming, and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Brock James Sishc

    2015-11-01

    Full Text Available Telomeres are nucleoprotein complexes comprised of tandem arrays of repetitive DNA sequence that serve to protect chromosomal termini from inappropriate degradation, as well as to prevent these natural DNA ends from being recognized as broken DNA (double-strand breaks; DSBs and triggering of inappropriate DNA damage responses. Preservation of telomere length requires telomerase, the specialized reverse transcriptase capable of maintaining telomere length via template-mediated addition of telomeric repeats onto the ends of newly synthesized chromosomes. Loss of either end-capping function or telomere length maintenance has been associated with genomic instability or senescence in a variety of settings; therefore telomeres and telomerase have well-established connections to cancer and aging. It has long been recognized that oxidative stress promotes shortening of telomeres, and that telomerase activity is a radiation-inducible function. However, the effects of ionizing radiation (IR exposure on telomeres per se are much less well understood and appreciated. To gain a deeper understanding of the roles telomeres and telomerase play in the response of human cells to ionizing radiations of different qualities, we tracked changes in telomeric end-capping function, telomere length, and telomerase activity in panels of mammary epithelial and hematopoietic cell lines exposed to low linear energy transfer (LET gamma(γ-rays or high LET high charge, high energy (HZE particles, delivered either acutely or at low dose rates (LDR. In addition to demonstrating that dysfunctional telomeres contribute to IR-induced mutation frequencies and genome instability, we reveal non-canonical roles for telomerase, in that telomerase activity was required for IR-induced enrichment of mammary epithelial putative stem/progenitor cell populations, a finding also suggestive of cellular reprogramming. Taken together, the results reported here establish the critical importance of

  20. Observed ozone response to variations in solar ultraviolet radiation

    Science.gov (United States)

    Gille, J. C.; Smythe, C. M.; Heath, D. F.

    1984-01-01

    During the winter of 1979, the solar ultraviolet irradiance varied with a period of 13.5 days and an amplitude of 1 percent. The zonal mean ozone values in the tropics varied with the solar irradiance, with an amplitude of 0.25 to 0.60 percent. This observation agrees with earlier calculations, although the response may be overestimated. These results imply changes in ozone at an altitude of 48 kilometers of up to 12 percent over an 11-year solar cycle. Interpretation of ozone changes in the upper stratosphere will require measurements of solar ultraviolet radiation at wavelengths near 200 nanometers.

  1. Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation.

    Science.gov (United States)

    Zhao, Yuchao; Ricci, Paolo F

    2010-03-18

    For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health.

  2. SU-C-303-02: Correlating Metabolic Response to Radiation Therapy with HIF-1alpha Expression

    Energy Technology Data Exchange (ETDEWEB)

    Campos, D [University of Wisconsin Madison, Madison, WI (United States); Peeters, W [Radboud University Medical Center, Nijmegen, GA (United States); Nickel, K [University of Wisconsin, Madison, WI (United States); Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M [University of Wisconsin, Madison, Wisconsin (United States)

    2015-06-15

    Purpose: To understand radiation induced alterations in cellular metabolism which could be used to assess treatment or normal tissue response to aid in patient-specific adaptive radiotherapy. This work aims to compare the metabolic response of two head and neck cell lines, one malignant (UM-SCC-22B) and one benign (Normal Oral Keratinocyte), to ionizing radiation. Responses are compared to alterations in HIF-1alpha expression. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Measurements of metabolism and HIF-1alpha expression were taken before and X minutes after a 10 Gy dose of radiation delivered via an orthovoltage x-ray source. In vitro changes in metabolic activity were measured via fluorescence lifetime imaging (FLIM) to assess the mean lifetime of NADH autofluorescence following a dose of 10 Gy. HIF-1alpha expression was measured via immunohistochemical staining of in vitro treated cells and expression was quantified using the FIJI software package. Results: FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways for malignant cells; whereas this benign cell line showed little change in metabolic signature. Immunohistochemical analysis showed significant changes in HIF-1alpha expression in response to 10 Gy of radiation that correlate to metabolic profiles. Conclusion: Radiation induces significant changes in metabolic activity and HIF-1alpha expression. These alterations occur on time scales approximating the duration of common radiation treatments (approximately tens of minutes). Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response.

  3. Modeling detector response in solid-state systems for radiation therapy and radiobiology

    Energy Technology Data Exchange (ETDEWEB)

    Hugtenburg, R.P. [School of Physics and Astronomy, University of Birmingham, B15 2TT, UK (United Kingdom); Bradley, D.A. [Department of Physics, University of Surrey, Guildford, GU2 7XH, UK (United Kingdom)

    2006-07-01

    In order for the many advantageous properties of solid-state dosimeters to be realised in clinic, strategies must be evolved for the calibration of detector systems for an ever expanding range of radiation sources including spectrally complex and mixed radiation fields. Monte Carlo models of the source and detector systems provide a means to account in a precise way for energy absorbed in the detector allowing for primary and secondary radiation processes including multiple scattering. Solid- state dosimeters including Si diodes, MOSFET, diamond detectors and doped optical fibres have been calibrated for dose in monoenergetic synchrotron X-rays in the range 5-50 keV, for quasi monoenergetic X-rays sources from 20-200 keV and for megavoltage X-ray and proton sources, such as are used in radical radiation therapy. With careful consideration of the elemental composition of the detector it is possible to achieve high quality agreement (2-3%) between measurement and Monte Carlo models of the variation of the detector response over a wide energy range. This information is needed in radiation therapy dosimetry where, for large external X-ray beams, detectors see a mixture of high energy primary photons and low energy (e.g. Compton scattered and pair-production-annihilation) photons. Typically, for solid-state detectors, different cavity theories are required for the two energy groups. In addition, high-Z constituents in detectors lead to an enhanced photoelectric absorption, which in the case of pure silicon detectors is up to 8 times greater than the tissue equivalent response. Information from maps of the elemental composition in the detectors, obtained via XRF and PIXE, is used in the models. Monte Carlo models are also being developed for contributions to the response from electron transport, including the microdosimetric response of detectors. Current Monte Carlo codes are able to handle large variations in density that typify tissue equivalent gas

  4. Cellular responses in sea fan corals: granular amoebocytes react to pathogen and climate stressors.

    Directory of Open Access Journals (Sweden)

    Laura D Mydlarz

    Full Text Available BACKGROUND: Climate warming is causing environmental change making both marine and terrestrial organisms, and even humans, more susceptible to emerging diseases. Coral reefs are among the most impacted ecosystems by climate stress, and immunity of corals, the most ancient of metazoans, is poorly known. Although coral mortality due to infectious diseases and temperature-related stress is on the rise, the immune effector mechanisms that contribute to the resistance of corals to such events remain elusive. In the Caribbean sea fan corals (Anthozoa, Alcyonacea: Gorgoniidae, the cell-based immune defenses are granular acidophilic amoebocytes, which are known to be involved in wound repair and histocompatibility. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate for the first time in corals that these cells are involved in the organismal response to pathogenic and temperature stress. In sea fans with both naturally occurring infections and experimental inoculations with the fungal pathogen Aspergillus sydowii, an inflammatory response, characterized by a massive increase of amoebocytes, was evident near infections. Melanosomes were detected in amoebocytes adjacent to protective melanin bands in infected sea fans; neither was present in uninfected fans. In naturally infected sea fans a concurrent increase in prophenoloxidase activity was detected in infected tissues with dense amoebocytes. Sea fans sampled in the field during the 2005 Caribbean Bleaching Event (a once-in-hundred-year climate event responded to heat stress with a systemic increase in amoebocytes and amoebocyte densities were also increased by elevated temperature stress in lab experiments. CONCLUSIONS/SIGNIFICANCE: The observed amoebocyte responses indicate that sea fan corals use cellular defenses to combat fungal infection and temperature stress. The ability to mount an inflammatory response may be a contributing factor that allowed the survival of even infected sea fan corals during a

  5. Identification of feedback loops embedded in cellular circuits by investigating non-causal impulse response components.

    Science.gov (United States)

    Dong, Chao-Yi; Yoon, Tae-Woong; Bates, Declan G; Cho, Kwang-Hyun

    2010-02-01

    Feedback circuits are crucial dynamic motifs which occur in many biomolecular regulatory networks. They play a pivotal role in the regulation and control of many important cellular processes such as gene transcription, signal transduction, and metabolism. In this study, we develop a novel computationally efficient method to identify feedback loops embedded in intracellular networks, which uses only time-series experimental data and requires no knowledge of the network structure. In the proposed approach, a non-parametric system identification technique, as well as a spectral factor analysis, is applied to derive a graphical criterion based on non-causal components of the system's impulse response. The appearance of non-causal components in the impulse response sequences arising from stochastic output perturbations is shown to imply the presence of underlying feedback connections within a linear network. In order to extend the approach to nonlinear networks, we linearize the intracellular networks about an equilibrium point, and then choose the magnitude of the output perturbations sufficiently small so that the resulting time-series responses remain close to the chosen equilibrium point. In this way, the impulse response sequences of the linearized system can be used to determine the presence or absence of feedback loops in the corresponding nonlinear network. The proposed method utilizes the time profile data from intracellular perturbation experiments and only requires the perturbability of output nodes. Most importantly, the method does not require any a priori knowledge of the system structure. For these reasons, the proposed approach is very well suited to identifying feedback loops in large-scale biomolecular networks. The effectiveness of the proposed method is illustrated via two examples: a synthetic network model with a negative feedback loop and a nonlinear caspase function model of apoptosis with a positive feedback loop.

  6. DNA-damage response network at the crossroads of cell-cycle checkpoints,cellular senescence and apoptosis

    Institute of Scientific and Technical Information of China (English)

    SCHMITT Estelle; PAQUET Claudie; BEAUCHEMIN Myriam; BERTRAND Richard

    2007-01-01

    Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation,cellular senescence and cell death.Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities.Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms.Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death.The intimate link between the cell cycle,cellular senescence,apoptosis regulation,cancer development and tumor responses to cancer treatment has become eminently apparent.Extensive research on tumor suppressor genes,oncogenes,the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways,referred to as the DNA-damage response network,are tied to cell proliferation,cell-cycle arrest,cellular senescence and apoptosis.DNA-damage responses are complex,involving "sensor" proteins that sense the damage,and transmit signals to "transducer" proteins,which,in turn,convey the signals to numerous "effector" proteins implicated in specific cellular pathways,including DNA repair mechanisms,cell-cycle checkpoints,cellular senescence and apoptosis.The Bcl-2 family of proteins stands among the most crucial regulators of apoptosis and performs vital functions in deciding whether a cell will live or die after cancer chemotherapy and irradiation.In addition,several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle,DNA repair/recombination and cellular senescence,effects that are generally distinct from their function in apoptosis.In this review,we report progress in understanding the molecular networks that regulate cell-cycle checkpoints,cellular senescence and apoptosis after DNA damage,and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation.

  7. Gene expression in response to ionizing radiation and family history of gastric cancer.

    Science.gov (United States)

    Marcon, Francesca; Silvestrini, Francesco; Siniscalchi, Ester; Palli, Domenico; Saieva, Calogero; Crebelli, Riccardo

    2011-03-01

    Genes and molecular pathways involved in familial clustering of gastric cancer have not yet been identified. The purpose of the present study was to investigate gene expression changes in response to a cellular stress, and its link with a positive family history for this neoplasia. To this aim leukocytes of healthy first-degree relatives of gastric cancer patients and controls were challenged in vitro with ionizing radiation and gene expression evaluated 4 h later on microarrays with 1,800 cancer-related genes. Eight genes, mainly involved in signal transduction and cell cycle regulation, were differentially expressed in healthy relatives of gastric cancer cases. Functional class scoring by Gene Ontology classification highlighted two G-protein related pathways, implicated in the proliferation of neoplastic tissue, which were differentially expressed in healthy subjects with positive family history of gastric cancer. The relative expression of 84 genes related to these pathways was examined using the SYBR green-based quantitative real-time PCR. The results confirmed the indication of an involvement of G-protein coupled receptor pathways in GC familiarity provided by microarray analysis. This study indicates a possible association between familiarity for gastric cancer and altered transcriptional response to ionizing radiation.

  8. Activation of the cellular unfolded protein response by recombinant adeno-associated virus vectors.

    Directory of Open Access Journals (Sweden)

    Balaji Balakrishnan

    Full Text Available The unfolded protein response (UPR is a stress-induced cyto-protective mechanism elicited towards an influx of large amount of proteins in the endoplasmic reticulum (ER. In the present study, we evaluated if AAV manipulates the UPR pathways during its infection. We first examined the role of the three major UPR axes, namely, endoribonuclease inositol-requiring enzyme-1 (IRE1α, activating transcription factor 6 (ATF6 and PKR-like ER kinase (PERK in AAV infected cells. Total RNA from mock or AAV infected HeLa cells were used to determine the levels of 8 different ER-stress responsive transcripts from these pathways. We observed a significant up-regulation of IRE1α (up to 11 fold and PERK (up to 8 fold genes 12-48 hours after infection with self-complementary (scAAV2 but less prominent with single-stranded (ssAAV2 vectors. Further studies demonstrated that scAAV1 and scAAV6 also induce cellular UPR in vitro, with AAV1 vectors activating the PERK pathway (3 fold while AAV6 vectors induced a significant increase on all the three major UPR pathways [6-16 fold]. These data suggest that the type and strength of UPR activation is dependent on the viral capsid. We then examined if transient inhibition of UPR pathways by RNA interference has an effect on AAV transduction. siRNA mediated silencing of PERK and IRE1α had a modest effect on AAV2 and AAV6 mediated gene expression (∼1.5-2 fold in vitro. Furthermore, hepatic gene transfer of scAAV2 vectors in vivo, strongly elevated IRE1α and PERK pathways (2 and 3.5 fold, respectively. However, when animals were pre-treated with a pharmacological UPR inhibitor (metformin during scAAV2 gene transfer, the UPR signalling and its subsequent inflammatory response was attenuated concomitant to a modest 2.8 fold increase in transgene expression. Collectively, these data suggest that AAV vectors activate the cellular UPR pathways and their selective inhibition may be beneficial during AAV mediated gene transfer.

  9. Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

    Science.gov (United States)

    Sokolov, Mykyta; Neumann, Ronald

    2015-01-01

    Exposure to ionizing radiation (IR) is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD) rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR) compared to those observed after a short-term high-dose IR exposure (HDIR). With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes. PMID:26729107

  10. Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Mykyta Sokolov

    2015-12-01

    Full Text Available Exposure to ionizing radiation (IR is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR compared to those observed after a short-term high-dose IR exposure (HDIR. With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes.

  11. Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Song, You, E-mail: you.song@niva.no [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway); Salbu, Brit; Teien, Hans-Christian; Heier, Lene Sørlie [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Rosseland, Bjørn Olav [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management, P.O. Box 5003, N-1432 Ås (Norway); Tollefsen, Knut Erik [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway)

    2014-11-15

    affected DEGs associated with cellular signaling and immune response; 70 mGy radiation affected cell cycle regulation and DNA damage repair, cellular energy production; and 280 mGy radiation affected pathways related to cell cycle regulation and DNA repair, mitochondrial dysfunction and immune functions. Twelve genes representative of key pathways found in this study were verified by qPCR. Potential common MoAs of low-dose gamma radiation may include induction of oxidative stress, DNA damage and disturbance of oxidative phosphorylation (OXPHOS). Although common MoAs were proposed, a number of DEGs and pathways were still found to be dose-specific, potentially indicating multiple mechanisms of action (MOAs) of low-dose gamma radiation in fish. In addition, plasma glucose displayed an apparent increase with increasing radiation doses, although the results were not significantly different from the control. These findings suggested that sublethal doses of gamma radiation may cause dose-dependent transcriptional changes in the liver of Atlantic salmon after short-term exposure. The current study predicted multiple MoA for gamma radiation and may aid future impact assessment of environmental radioactivity in fish.

  12. Cellular responses during morphological transformation in Azospirillum brasilense and Its flcA knockout mutant.

    Directory of Open Access Journals (Sweden)

    Xingsheng Hou

    Full Text Available FlcA is a response regulator controlling flocculation and the morphological transformation of Azospirillum cells from vegetative to cyst-like forms. To understand the cellular responses of Azospirillum to conditions that cause morphological transformation, proteins differentially expressed under flocculation conditions in A. brasilense Sp7 and its flcA knockout mutant were investigated. Comparison of 2-DE protein profiles of wild-type (Sp7 and a flcA deletion mutant (Sp7-flcAΔ revealed a total of 33 differentially expressed 2-DE gel spots, with 22 of these spots confidently separated to allow protein identification. Analysis of these spots by liquid chromatography-tandem mass spectrometry (LC-MS/MS and MASCOT database searching identified 48 proteins (≥10% emPAI in each spot. The functional characteristics of these proteins included carbon metabolism (beta-ketothiolase and citrate synthase, nitrogen metabolism (Glutamine synthetase and nitric oxide synthase, stress tolerance (superoxide dismutase, Alkyl hydroperoxidase and ATP-dependent Clp protease proteolytic subunit and morphological transformation (transducer coupling protein. The observed differences between Sp7 wild-type and flcA- strains enhance our understanding of the morphological transformation process and help to explain previous phenotypical observations. This work is a step forward in connecting the Azospirillum phenome and genome.

  13. Signaling beyond Punching Holes: Modulation of Cellular Responses by Vibrio cholerae Cytolysin

    Directory of Open Access Journals (Sweden)

    Barkha Khilwani

    2015-08-01

    Full Text Available Pore-forming toxins (PFTs are a distinct class of membrane-damaging cytolytic proteins that contribute significantly towards the virulence processes employed by various pathogenic bacteria. Vibrio cholerae cytolysin (VCC is a prominent member of the beta-barrel PFT (beta-PFT family. It is secreted by most of the pathogenic strains of the intestinal pathogen V. cholerae. Owing to its potent membrane-damaging cell-killing activity, VCC is believed to play critical roles in V. cholerae pathogenesis, particularly in those strains that lack the cholera toxin. Large numbers of studies have explored the mechanistic basis of the cell-killing activity of VCC. Consistent with the beta-PFT mode of action, VCC has been shown to act on the target cells by forming transmembrane oligomeric beta-barrel pores, thereby leading to permeabilization of the target cell membranes. Apart from the pore-formation-induced direct cell-killing action, VCC exhibits the potential to initiate a plethora of signal transduction pathways that may lead to apoptosis, or may act to enhance the cell survival/activation responses, depending on the type of target cells. In this review, we will present a concise view of our current understanding regarding the multiple aspects of these cellular responses, and their underlying signaling mechanisms, evoked by VCC.

  14. The adaptor protein FHL2 enhances the cellular innate immune response to influenza A virus infection.

    Science.gov (United States)

    Nordhoff, Carolin; Hillesheim, Andrea; Walter, Beate M; Haasbach, Emanuel; Planz, Oliver; Ehrhardt, Christina; Ludwig, Stephan; Wixler, Viktor

    2012-07-01

    The innate immune response of influenza A virus-infected cells is predominantly mediated by type I interferon-induced proteins. Expression of the interferon β (IFNβ) itself is initiated by accumulating viral RNA and is transmitted by different signalling cascades that feed into activation of the three transcriptional elements located in the IFNβ promoter, AP-1, IRF-3 and NF-κB. FHL2 (four-and-a-half LIM domain protein 2) is an adaptor molecule that shuttles between membrane and nucleus regulating signalling cascades and gene transcription. Here we describe FHL2 as a novel regulator of influenza A virus propagation. Using mouse FHL2 wild-type, knockout and rescued cells and human epithelial cells with different expression levels of FHL2 we showed that FHL2 decreases influenza A virus propagation by regulating the intrinsic cellular antiviral immune response. On virus infection FHL2 translocates into the nucleus, potentiating the IRF-3-dependent transcription of the IFNβ gene.

  15. Cellular and humoral antibody responses of normal pastel and sapphire mink to goat erythrocytes.

    Science.gov (United States)

    Lodmell, D L; Bergman, R K; Hadlow, W J; Munoz, J J

    1971-02-01

    This study was undertaken to determine whether normal sapphire and royal pastel mink differ immunologically at the cellular and humoral levels. Two days after primary intraperitoneal (ip) inoculation of goat erythrocytes (GE), essentially no 19 or 7S plaque-forming cells (PFC) per 10(6) cells were detected in spleen or in abdominal and peripheral lymph nodes of either color phase. On the 4th day, more 19S PFC were detected in pastel than in sapphire tissues; pastel tissues also contained 7S PFC, whereas essentially none was present in sapphires until the 6th day. After an ip booster inoculation, the number of PFC was markedly different between the two color phases. These differences were most apparent in spleen and peripheral lymph nodes. In parallel with differences observed in PFC responses between the color phases, total hemolysin and 2-mercaptoethanol-resistant hemolysin titers of pastels exceeded those of sapphires in all but one interval after the primary, and at every interval after the booster, inoculation. These data indicate that sapphire mink are not immunological cripples, nor are they immunologically hyperactive, but that differences do exist between sapphire and royal pastel mink, especially in the response to booster injections of GE.

  16. Metal oxide nanoparticles interact with immune cells and activate different cellular responses

    Directory of Open Access Journals (Sweden)

    Simón-Vázquez R

    2016-09-01

    Full Text Available Rosana Simón-Vázquez, Tamara Lozano-Fernández, Angela Dávila-Grana, Africa González-Fernández Immunology Laboratory, Biomedical Research Center (CINBIO and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI, University of Vigo, Campus Lagoas Marcosende, Vigo, Pontevedra, Spain Abstract: Besides cell death, nanoparticles (Nps can induce other cellular responses such as inflammation. The potential immune response mediated by the exposure of human lymphoid cells to metal oxide Nps (moNps was characterized using four different moNps (CeO2, TiO2, Al2O3, and ZnO to study the three most relevant mitogen-activated protein kinase subfamilies and the nuclear factor kappa-light-chain-enhancer of the activated B-cell inhibitor, IκBα, as well as the expression of several genes by immune cells incubated with these Nps. The moNps activated different signaling pathways and altered the gene expression in human lymphocyte cells. The ZnO Nps were the most active and the release of Zn2+ ions was the main mechanism of toxicity. CeO2 Nps induced the smallest changes in gene expression and in the IκBα protein. The effects of the particles were strongly dependent on the type and concentration of the Nps and on the cell activation status prior to Np exposure. Keywords: Jurkat, MAPK, NFκB, qPCR, inflammation, metabolism

  17. Microfluidic chips for in vivo imaging of cellular responses to neural injury in Drosophila larvae.

    Directory of Open Access Journals (Sweden)

    Mostafa Ghannad-Rezaie

    Full Text Available With powerful genetics and a translucent cuticle, the Drosophila larva is an ideal model system for live imaging studies of neuronal cell biology and function. Here, we present an easy-to-use approach for high resolution live imaging in Drosophila using microfluidic chips. Two different designs allow for non-invasive and chemical-free immobilization of 3(rd instar larvae over short (up to 1 hour and long (up to 10 hours time periods. We utilized these 'larva chips' to characterize several sub-cellular responses to axotomy which occur over a range of time scales in intact, unanaesthetized animals. These include waves of calcium which are induced within seconds of axotomy, and the intracellular transport of vesicles whose rate and flux within axons changes dramatically within 3 hours of axotomy. Axonal transport halts throughout the entire distal stump, but increases in the proximal stump. These responses precede the degeneration of the distal stump and regenerative sprouting of the proximal stump, which is initiated after a 7 hour period of dormancy and is associated with a dramatic increase in F-actin dynamics. In addition to allowing for the study of axonal regeneration in vivo, the larva chips can be utilized for a wide variety of in vivo imaging applications in Drosophila.

  18. Toxicity of silver nanoparticles in human macrophages: uptake, intracellular distribution and cellular responses

    Energy Technology Data Exchange (ETDEWEB)

    Haase, A; Tentschert, J; Jungnickel, H; Goetz, M E; Luch, A [BfR - Federal Institute for Risk Assessment, Department of Product Safety, Thielallee 88-92, 14195 Berlin (Germany); Graf, P [University of Basel, Department of Chemistry, Klingelbergstrasse 80, 4056 Basel (Switzerland); Mantion, A; Thuenemann, A F [BAM - Federal Institute for Materials Research and Testing, Richard-Willstaetter-Strasse 11, 12489 Berlin (Germany); Draude, F; Galla, S; Arlinghaus, H F [University of Muenster, Institute of Physics, Wilhelm Klemm Strasse 10, 48149 Muenster (Germany); Plendl, J [Free University of Berlin, Department of Veterinary Medicine, Institute of Veterinary Anatomy, Koserstrasse 20, 14195 Berlin (Germany); Masic, A; Taubert, A, E-mail: andrea.haase@bfr.bund.de, E-mail: alexandre.mantion@bam.de [University of Potsdam, Institute of Chemistry, Karl- Liebknecht- Strasse 24-25, 14476 Potsdam-Golm (Germany)

    2011-07-06

    Silver nanoparticles (SNP) are among the most commercialized nanoparticles worldwide. They can be found in many diverse products, mostly because of their antibacterial properties. Despite its widespread use only little data on possible adverse health effects exist. It is difficult to compare biological data from different studies due to the great variety in sizes, coatings or shapes of the particles. Here, we applied a novel synthesis approach to obtain SNP, which are covalently stabilized by a small peptide. This enables a tight control of both size and shape. We applied these SNP in two different sizes of 20 or 40 nm (Ag20Pep and Ag40Pep) and analyzed responses of THP-1-derived human macrophages. Similar gold nanoparticles with the same coating (Au20Pep) were used for comparison and found to be non-toxic. We assessed the cytotoxicity of particles and confirmed their cellular uptake via transmission electron microscopy and confocal Raman microscopy. Importantly a majority of the SNP could be detected as individual particles spread throughout the cells. Furthermore we studied several types of oxidative stress related responses such as induction of heme oxygenase I or formation of protein carbonyls. In summary, our data demonstrate that even low doses of SNP exerted adverse effects in human macrophages.

  19. Cellular responses during morphological transformation in Azospirillum brasilense and Its flcA knockout mutant.

    Science.gov (United States)

    Hou, Xingsheng; McMillan, Mary; Coumans, Joëlle V F; Poljak, Anne; Raftery, Mark J; Pereg, Lily

    2014-01-01

    FlcA is a response regulator controlling flocculation and the morphological transformation of Azospirillum cells from vegetative to cyst-like forms. To understand the cellular responses of Azospirillum to conditions that cause morphological transformation, proteins differentially expressed under flocculation conditions in A. brasilense Sp7 and its flcA knockout mutant were investigated. Comparison of 2-DE protein profiles of wild-type (Sp7) and a flcA deletion mutant (Sp7-flcAΔ) revealed a total of 33 differentially expressed 2-DE gel spots, with 22 of these spots confidently separated to allow protein identification. Analysis of these spots by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and MASCOT database searching identified 48 proteins (≥10% emPAI in each spot). The functional characteristics of these proteins included carbon metabolism (beta-ketothiolase and citrate synthase), nitrogen metabolism (Glutamine synthetase and nitric oxide synthase), stress tolerance (superoxide dismutase, Alkyl hydroperoxidase and ATP-dependent Clp protease proteolytic subunit) and morphological transformation (transducer coupling protein). The observed differences between Sp7 wild-type and flcA- strains enhance our understanding of the morphological transformation process and help to explain previous phenotypical observations. This work is a step forward in connecting the Azospirillum phenome and genome.

  20. Cyclophilin 20-3 relays a 12-oxo-phytodienoic acid signal during stress responsive regulation of cellular redox homeostasis.

    Science.gov (United States)

    Park, Sang-Wook; Li, Wei; Viehhauser, Andrea; He, Bin; Kim, Soonok; Nilsson, Anders K; Andersson, Mats X; Kittle, Joshua D; Ambavaram, Madana M R; Luan, Sheng; Esker, Alan R; Tholl, Dorothea; Cimini, Daniela; Ellerström, Mats; Coaker, Gitta; Mitchell, Thomas K; Pereira, Andy; Dietz, Karl-Josef; Lawrence, Christopher B

    2013-06-04

    The jasmonate family of phytohormones plays central roles in plant development and stress acclimation. However, the architecture of their signaling circuits remains largely unknown. Here we describe a jasmonate family binding protein, cyclophilin 20-3 (CYP20-3), which regulates stress-responsive cellular redox homeostasis. (+)-12-Oxo-phytodienoic acid (OPDA) binding promotes CYP20-3 to form a complex with serine acetyltransferase 1, which triggers the formation of a hetero-oligomeric cysteine synthase complex with O-acetylserine(thiol)lyase B in chloroplasts. The cysteine synthase complex formation then activates sulfur assimilation that leads to increased levels of thiol metabolites and the buildup of cellular reduction potential. The enhanced redox capacity in turn coordinates the expression of a subset of OPDA-responsive genes. Thus, we conclude that CYP20-3 is a key effector protein that links OPDA signaling to amino acid biosynthesis and cellular redox homeostasis in stress responses.

  1. Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket.

    Science.gov (United States)

    Nishida, Erika; Miyaji, Hirofumi; Kato, Akihito; Takita, Hiroko; Iwanaga, Toshihiko; Momose, Takehito; Ogawa, Kosuke; Murakami, Shusuke; Sugaya, Tsutomu; Kawanami, Masamitsu

    2016-01-01

    Graphene oxide (GO) consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 µg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM), physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 µg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1 µg/mL GO scaffold were, respectively, approximately 2.5-fold and 1.4-fold greater than those of the control. Particularly, the infiltration of ED2-positive (M2) macrophages and blood vessels were prominent in the GO scaffold. Dog bone-formation tests showed that 1 µg/mL GO scaffold implantation enhanced bone formation. New bone formation following GO scaffold implantation was enhanced fivefold compared to that in control subjects. These results suggest that GO was biocompatible and had high bone-formation capability for the scaffold

  2. Cellular stress response in Eca-109 cells inhibits apoptosis during early exposure to isorhamnetin.

    Science.gov (United States)

    Shi, C; Fan, L Y; Cai, Z; Liu, Y Y; Yang, C L

    2012-01-01

    The flavonol aglycone isorhamnetin shows anti-proliferative activity in a variety of cancer cells. Previous work, from our laboratory showed that isorhamnetin inhibits the proliferation of human esophageal squamous carcinoma Eca-109 cells in vitro, but only after 72 h of exposure. This led us to propose that isorhamnetin exposure induces a cellular stress response that inhibits the antiproliferative and apoptotic effects of the compound during early exposure. To test this hypothesis, the present study examined the effects of isorhamnetin on Eca-109 cells during the first 72 h of exposure. Cell growth was assessed using the trypan blue exclusion assay, and expression of IκBα, NF-κB/p65, NF-κB/p50, phospho-Akt, Bcl-2, COX-2, Mcl-1, Bax, p53 and Id-1 were analyzed by Western blot. During the first 72 h of exposure, NF-κB/p65 and NF-κB/p50 accumulated in nuclei and expression of COX-2, Bcl-2 and Mcl-1 increased. In contrast, expression of IκBα and Bax fell initially but later increased. Expression of phospho-Akt and p53 showed no detectable change during the first 48 h. Pretreatment with the NF-κB inhibitor MG132 before exposure to isorhamnetin blocked the nuclear accumulation of p50 and p65, thereby inhibiting cell proliferation. These results show that during early exposure of Eca-109 cells to isorhamnetin, the NF-κB signaling pathway is activated and COX-2 expression increases, and this increase in expression partially inhibits isorhamnetin-induced apoptosis. Beyond 72 h of exposure, however, the apoptotic effect of isorhamnetin dominates, leading to inhibition of the NF-κB pathway and of cellular proliferation. These results will need to be taken into account when exploring the use of isorhamnetin against cancer in vivo.

  3. Expression of cellular components in granulomatous inflammatory response in Piaractus mesopotamicus model.

    Directory of Open Access Journals (Sweden)

    Wilson Gómez Manrique

    Full Text Available The present study aimed to describe and characterize the cellular components during the evolution of chronic granulomatous inflammation in the teleost fish pacus (P. mesopotamicus induced by Bacillus Calmette-Guerin (BCG, using S-100, iNOS and cytokeratin antibodies. 50 fish (120±5.0 g were anesthetized and 45 inoculated with 20 μL (40 mg/mL (2.0 x 10(6 CFU/mg and five inoculated with saline (0,65% into muscle tissue in the laterodorsal region. To evaluate the inflammatory process, nine fish inoculated with BCG and one control were sampled in five periods: 3rd, 7th, 14th, 21st and 33rd days post-inoculation (DPI. Immunohistochemical examination showed that the marking with anti-S-100 protein and anti-iNOS antibodies was weak, with a diffuse pattern, between the third and seventh DPI. From the 14th to the 33rd day, the marking became stronger and marked the cytoplasm of the macrophages. Positivity for cytokeratin was initially observed in the 14th DPI, and the stronger immunostaining in the 33rd day, period in which the epithelioid cells were more evident and the granuloma was fully formed. Also after the 14th day, a certain degree of cellular organization was observed, due to the arrangement of the macrophages around the inoculated material, with little evidence of edema. The arrangement of the macrophages around the inoculum, the fibroblasts, the lymphocytes and, in most cases, the presence of melanomacrophages formed the granuloma and kept the inoculum isolated in the 33rd DPI. The present study suggested that the granulomatous experimental model using teleost fish P. mesopotamicus presented a similar response to those observed in mammals, confirming its importance for studies of chronic inflammatory reaction.

  4. Neuronal cellular responses to extremely low frequency electromagnetic field exposure: implications regarding oxidative stress and neurodegeneration.

    Science.gov (United States)

    Reale, Marcella; Kamal, Mohammad A; Patruno, Antonia; Costantini, Erica; D'Angelo, Chiara; Pesce, Miko; Greig, Nigel H

    2014-01-01

    Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs) on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD), have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF)-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1 mT; frequency, 50-Hz) on a well-characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2(-), which were countered by compensatory changes in antioxidant catylase (CAT) activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a decline in CAT

  5. Solar ultraviolet radiation response of EBT2 Gafchromic, radiochromic film.

    Science.gov (United States)

    Butson, Ethan T; Yu, Peter K N; Butson, Martin J

    2013-11-07

    Measurement of solar ultraviolet (UV) radiation is an important aspect of dosimetry for the improved knowledge of UV exposure and its associated health related issues. EBT2 Gafchromic film has been designed by its manufacturers as an improved tool for ionizing radiation dosimetry. The film is stated as exhibiting a significant reduction in UV response. However, results have shown that when exposed to UV from the 'bottom side' i.e. from the thick laminate side, the film exhibits a sensitivity to solar UV radiation which is both measurable and accurate for UV dosimetry. Films were irradiated in this position to known solar UV exposures and results are quantified showing a reproducibility of measurement to within ±7% (1 SD) when compared to calibrated UV meters. With an exposure of 20 J cm(-2) broad spectrum solar UV, the films net OD change was found to be 0.248 OD ± 0.021 OD when analysing the results using the red channel region of an Epson V700 desktop scanner. This was compared to 0.0294 OD ± 0.0053 OD change with exposure to the same UV exposure from the top side. This means that solar UV dosimetry can be performed using EBT2 Gafchromic film utilizing the underside of the film for dosimetry. The main advantages of this film type for measurement of UV exposure is the visible colour change and thus easy analysis using a desktop scanner as well as its uniformity in response and its robust physical strength for use in outside exposure situations.

  6. A method to adjust radiation dose-response relationships for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane Lindegaard; Vogelius, Ivan R

    2012-01-01

    Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

  7. NR4A2 is regulated by gastrin and influences cellular responses of gastric adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kristine Misund

    Full Text Available The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2 expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1, suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells.

  8. Response of ionization chamber based pocket dosimeter to beta radiation.

    Science.gov (United States)

    Kumar, Munish; Gupta, Anil; Pradhan, S M; Bakshi, A K; Chougaonkar, M P; Babu, D A R

    2013-12-01

    Quantitative estimate of the response of ionization chamber based pocket dosimeters (DRDs) to various beta sources was performed. It has been established that the ionization chamber based pocket dosimeters do not respond to beta particles having energy (Emax)1 MeV, the DRDs exhibit measureable response and the values are ~8%, ~14% and ~27% per mSv for natural uranium, (90)Sr/(90)Y and (106)Ru/(106)Rh beta sources respectively. As the energy of the beta particles increases, the response also increases. The response of DRDs to beta particles having energy>1 MeV arises due to the fact that the thickness of the chamber walls is less than the maximum range of beta particles. This may also be one of the reasons for disparity between doses measured with passive/legal dosimeters (TLDs) and DRDs in those situations in which radiation workers are exposed to mixed field of gamma photons and beta particles especially at uranium processing plants, nuclear (power and research) reactors, waste management facilities and fuel reprocessing plants etc. The paper provides the reason (technical) for disparity between the doses recorded by TLDs and DRDs in mixed field of photons and beta particles.

  9. Genetic screening of new genes responsible for cellular adaptation to hypoxia using a genome-wide shRNA library.

    Science.gov (United States)

    Yoshino, Seiko; Hara, Toshiro; Weng, Jane S; Takahashi, Yuka; Seiki, Motoharu; Sakamoto, Takeharu

    2012-01-01

    Oxygen is a vital requirement for multi-cellular organisms to generate energy and cells have developed multiple compensatory mechanisms to adapt to stressful hypoxic conditions. Such adaptive mechanisms are intricately interconnected with other signaling pathways that regulate cellular functions such as cell growth. However, our understanding of the overall system governing the cellular response to the availability of oxygen remains limited. To identify new genes involved in the response to hypoxic stress, we have performed a genome-wide gene knockdown analysis in human lung carcinoma PC8 cells using an shRNA library carried by a lentiviral vector. The knockdown analysis was performed under both normoxic and hypoxic conditions to identify shRNA sequences enriched or lost in the resulting selected cell populations. Consequently, we identified 56 candidate genes that might contribute to the cellular response to hypoxia. Subsequent individual knockdown of each gene demonstrated that 13 of these have a significant effect upon oxygen-sensitive cell growth. The identification of BCL2L1, which encodes a Bcl-2 family protein that plays a role in cell survival by preventing apoptosis, validates the successful design of our screen. The other selected genes have not previously been directly implicated in the cellular response to hypoxia. Interestingly, hypoxia did not directly enhance the expression of any of the identified genes, suggesting that we have identified a new class of genes that have been missed by conventional gene expression analyses to identify hypoxia response genes. Thus, our genetic screening method using a genome-wide shRNA library and the newly-identified genes represent useful tools to analyze the cellular systems that respond to hypoxic stress.

  10. Plasmid DNA Vaccine Co-Immunisation Modulates Cellular and Humoral Immune Responses Induced by Intranasal Inoculation in Mice.

    Directory of Open Access Journals (Sweden)

    Deborah F L King

    Full Text Available An effective HIV vaccine will likely require induction of both mucosal and systemic cellular and humoral immune responses. We investigated whether intramuscular (IM delivery of electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal (IN and IM routes could be combined to induce mucosal and systemic cellular and humoral immune responses to a model HIV-1 CN54 gp140 antigen in mice.Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic or mucosal IgA responses. Cellular IFNγ responses were preserved in co-immunisation protocols compared to protein-only vaccination groups. The addition of DNA to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein induced expression of cytokines that promote B-cell function, generation of TFH cells and CCR5 ligands that can reduce HIV infectivity.These data suggest that while IN inoculation alone elicits both cellular and humoral responses, co-administration with homologous DNA vaccination can tailor these towards a more balanced Th1/Th2 phenotype modulating the cellular cytokine profile while eliciting high-levels of antigen-specific antibody. This work provides insights on how to generate differential immune responses within the same vaccination visit, and supports co-immunisation with DNA and protein by a mucosal route as a potential delivery strategy for HIV vaccines.

  11. Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure.

    Science.gov (United States)

    Fliedner, T M; Graessle, D; Paulsen, C; Reimers, K

    2002-08-01

    It is the purpose of this presentation to review the unique structure and function of bone marrow anchored hematopoiesis in their significance for its response mechanisms to an exposure to ionizing radiation. The ultimate objective of bone marrow hematopoiesis is to maintain in the peripheral blood a constant level of the different blood cell types (erythrocytes, granulocytes, platelets, lymphocytes, etc.). All of them have their particular turnover kinetics (such as granulocytes 120 x 10(9)/d, erythrocytes 200 x 10(9)/d or thrombocytes 150 x 10(9)/d), are semi-autonomous in their steady state regulatory mechanisms and dependent on a life-long supply of mature cells from a stem cell pool with unlimited replicative and pluripotent differentiative potential. The present knowledge of hematopoietic cellular renewal is the result of years of basic experimental and clinical studies using radionuclides in various metabolic forms including (59)Fe, (32)P (DF (32)P), (51)Cr, (131)I, (60)Co, (3)H ((3)HTdR) and (14)C ((14)CTdR). To understand the physiology but in particular the radiation-pathophysiology, it is essential to recognize in detail the infrastructure of the bone marrow as a distinct unit. Indispensable for a life-long cell production is the capsule of the marrow - the bone cortex -, the arterial supply of blood connected to the sinusoidal microvascular architecture with its sinusoids contorti and recti as well as the central (cell collecting) sinusoids. It is further of importance to recognize the significance of nerval regulation of blood flow, characterized by myelinated and unmyelinated nerve fibers. The type of unique lining cells of the sinusoids is the prerequisite for the cell traffic between the hemopoietic parenchyma and the blood. This in turn cannot be achieved without an alternative opening and closing of the sinusoidal segments which - in turn - requires a rigid long capsule to assure an - in toto - constant volume of each bone marrow unit. If a bone

  12. Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Ying; Zhang, Ningzhe; Ellerby, Lisa M.; Davalos, Albert R.; Zeng, Xianmin; Campisi, Judith [Buck Institute for Research on Aging, Novato, CA 94945 (United States); Desprez, Pierre-Yves, E-mail: pydesprez@cpmcri.org [Buck Institute for Research on Aging, Novato, CA 94945 (United States); California Pacific Medical Center, Research Institute, San Francisco, CA 94107 (United States)

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer hESCs and their progeny, NSCs and neurons, were exposed to ionizing radiation. Black-Right-Pointing-Pointer Upon irradiation, most hESCs died within 5-7 h. Black-Right-Pointing-Pointer Surviving NSCs underwent senescence and displayed features of astrocytes. Black-Right-Pointing-Pointer Surviving NSCs did not display the secretory phenotype expressed by pure astrocytes. Black-Right-Pointing-Pointer This study is to better understand the stress-responses of hESCs and their progeny. -- Abstract: Human embryonic stem cells (hESCs) hold promise for the treatment of many human pathologies. For example, hESCs and the neuronal stem cells (NSCs) and neurons derived from them have significant potential as transplantation therapies for a variety of neurodegenerative diseases. Two concerns about the use of hESCs and their differentiated derivatives are their ability to function and their ability to resist neoplastic transformation in response to stresses that inevitably arise during their preparation for transplantation. To begin to understand how these cells handle genotoxic stress, we examined the responses of hESCs and derived NSCs and neurons to ionizing radiation (IR). Undifferentiated hESCs were extremely sensitive to IR, with nearly all the cells undergoing cell death within 5-7 h. NSCs and neurons were substantially more resistant to IR, with neurons showing the most resistant. Of interest, NSCs that survived IR underwent cellular senescence and acquired astrocytic characteristics. Unlike IR-treated astrocytes, however, the NSC-derived astrocytic cells that survived IR did not display the typical pro-inflammatory, pro-carcinogenic senescence-associated secretory phenotype. These findings suggest distinct genotoxic stress-responses of hESCs and derived NSC and neuronal populations, and suggest that damaged NSCs, while failing to function, may not cause local inflammation.

  13. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun [Division of heavy ion clinical research, Korea University, Seoul (Korea, Republic of); Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2012-11-15

    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy.

  14. Climate Response of Direct Radiative Forcing of Anthropogenic Black Carbon

    Science.gov (United States)

    Chung, Serena H.; Seinfeld,John H.

    2008-01-01

    The equilibrium climate effect of direct radiative forcing of anthropogenic black carbon (BC) is examined by 100-year simulations in the Goddard Institute for Space Studies General Circulation Model II-prime coupled to a mixed-layer ocean model. Anthropogenic BC is predicted to raise globally and annually averaged equilibrium surface air temperature by 0.20 K if BC is assumed to be externally mixed. The predicted increase is significantly greater in the Northern Hemisphere (0.29 K) than in the Southern Hemisphere (0.11 K). If BC is assumed to be internally mixed with the present day level of sulfate aerosol, the predicted annual mean surface temperature increase rises to 0.37 K globally, 0.54 K for the Northern Hemisphere, and 0.20 K for the Southern Hemisphere. The climate sensitivity of BC direct radiative forcing is calculated to be 0.6 K W (sup -1) square meters, which is about 70% of that of CO2, independent of the assumption of BC mixing state. The largest surface temperature response occurs over the northern high latitudes during winter and early spring. In the tropics and midlatitudes, the largest temperature increase is predicted to occur in the upper troposphere. Direct radiative forcing of anthropogenic BC is also predicted to lead to a change of precipitation patterns in the tropics; precipitation is predicted to increase between 0 and 20 N and decrease between 0 and 20 S, shifting the intertropical convergence zone northward. If BC is assumed to be internally mixed with sulfate instead of externally mixed, the change in precipitation pattern is enhanced. The change in precipitation pattern is not predicted to alter the global burden of BC significantly because the change occurs predominantly in regions removed from BC sources.

  15. CELLULAR RESPONSES TO DNA DAMAGE AND ONCOGENESIS BY THE p53 AND pRb/E2F PATHWAYS

    Directory of Open Access Journals (Sweden)

    Elza Ibrahim Auerkari

    2015-07-01

    Full Text Available Cellular responses to stress including DNA damage, show multiple options involving the mechanisms of growth arrest. DNA repair and programmed cell death or apoptosis. Failures in these mechanisms can result in oncogenesis or accelerated senescence. Much of the response is coordinated by p53, a nuclear phosphoprotein with a central role in the defences against physical, chemical and pathogenic agents which challenge the DNA integrity. The p53 pathways for mobilising the cellular defences are linked to the pRB/E2D pathways regulating the cell cycle progression. This paper aims to review the current understanding on the networks and main molecular machinery of these processes. In addition, the implications on cellular decision making for the defences as well as revolutionary aspects of these mechanisms are discussed in brief.

  16. Radiation response and electrical properties of polymer energy storage capacitors: PVF2, Polysulfone, and Mylar

    Science.gov (United States)

    Edwards, L. R.

    1981-01-01

    Efforts were made to develop a polymer film capacitor that is tolerant to radiation. The capacitors are to be utilized in a high voltage pulse discharge application. Radiation response data at high dose/dose rate levels are presented for polyvinylidene fluoride (PVF2), polysulfone, and Mylar. The results show that PVF2 is the most radiation tolerant while Mylar is the least tolerant. The data also show that the radiation response is quite dependent on operating electric stress.

  17. Bacterial formyl peptides affect the innate cellular antimicrobial responses of larval Galleria mellonella (Insecta: Lepidoptera).

    Science.gov (United States)

    Alavo, Thiery B C; Dunphy, Gary B

    2004-04-01

    The non-self cellular (hemocytic) responses of Galleria mellonella larvae, including the attachment to slides and the removal of the bacteria Xenorhabdus nematophila and Bacillus subtilis from the hemolymph, were affected by N-formyl peptides. Both N-formyl methionyl-leucyl-phenylalanine (fMLF) and the ester derivative decreased hemocyte adhesion in vitro, and both elevated hemocyte counts and suppressed the removal of both X. nematophila and B. subtilis from the hemolymph in vivo. The amide derivative and the antagonist tertiary-butoxy-carbonyl-methionyl-leucyl-phenylalanine (tBOC) increased hemocyte attachment to glass. The fMLF suppressed protein discharge from monolayers of granular cells with and without bacterial stimulation, while tBOC stimulated protein discharge. The peptide tBOC offset the effects of fMLF in vitro and in vivo. This is the first report implying the existence of formyl peptide receptors on insect hemocytes in which the compounds fMLF and tBOC inhibited and activated hemocyte activity, respectively.

  18. Temporal regulation of cerebellar EGL migration through a switch in cellular responsiveness to the meninges.

    Science.gov (United States)

    Zhu, Yan; Yu, Tao; Rao, Yi

    2004-03-01

    We have studied the temporal and spatial control of cell migration from the external germinal layer (EGL) in the mammalian cerebellum as a model for cortical migration. Our results have demonstrated that embryonic EGL cells do not migrate into internal layers because they respond to a diffusible attractant in the meninges, the nonneural tissues covering the nervous system, and to a repellent in the neuroepithelium. Two developmental changes are important for postnatal EGL migration: the disappearance of the repellent in the inner layers and a switch in cellular responsiveness of EGL cells so that the postnatal EGL cells respond to the repellent, but not the attractant in the meninges. Besides revealing the signaling role of meninges in cortical development, our study suggests that an active mechanism is required to prevent cell migration, and that mechanisms of cell migration should be studied even in the absence of apparent changes in cell positions. We propose a model for the developmental control of neuronal migration in the cerebellar cortex.

  19. Evidence for a regulatory role of diatom silicon transporters in cellular silicon responses.

    Science.gov (United States)

    Shrestha, Roshan P; Hildebrand, Mark

    2015-01-01

    The utilization of silicon by diatoms has both global and small-scale implications, from oceanic primary productivity to nanotechnological applications of their silica cell walls. The sensing and transport of silicic acid are key aspects of understanding diatom silicon utilization. At low silicic acid concentrations (silicon starvation. SIT1 and SIT2 were localized in the plasma membrane, and protein levels were generally inversely correlated with cellular silicon needs, with a distinct response being found when the two SITs were compared. We developed highly effective approaches for RNA interference and antisense knockdowns, the first such approaches developed for a centric diatom. SIT knockdown differentially affected the uptake of silicon and the incorporation of silicic acid and resulted in the induction of lipid accumulation under silicon starvation conditions far earlier than in the wild-type cells, suggesting that the cells were artificially sensing silicon limitation. The data suggest that the transport role of the SITs is relatively minor under conditions with sufficient silicic acid. Their primary role is to sense silicic acid levels to evaluate whether the cell can proceed with its cell wall formation and division processes.

  20. Cellular Response of the Amoeba Acanthamoeba castellanii to Chlorine, Chlorine Dioxide, and Monochloramine Treatments ▿

    Science.gov (United States)

    Mogoa, Emerancienne; Bodet, Charles; Morel, Franck; Rodier, Marie-Hélène; Legube, Bernard; Héchard, Yann

    2011-01-01

    Acanthamoeba castellanii is a free-living amoebae commonly found in water systems. Free-living amoebae might be pathogenic but are also known to bear phagocytosis-resistant bacteria, protecting these bacteria from water treatments. The mode of action of these treatments is poorly understood, particularly on amoebae. It is important to examine the action of these treatments on amoebae in order to improve them. The cellular response to chlorine, chlorine dioxide, and monochloramine was tested on A. castellanii trophozoites. Doses of disinfectants leading to up to a 3-log reduction were compared by flow cytometry and electron microscopy. Chlorine treatment led to size reduction, permeabilization, and retraction of pseudopods. In addition, treatment with chlorine dioxide led to a vacuolization of the cytoplasm. Monochloramine had a dose-dependent effect. At the highest doses monochloramine treatment resulted in almost no changes in cell size and permeability, as shown by flow cytometry, but the cell surface became smooth and dense, as seen by electron microscopy. We show that these disinfectants globally induced size reduction, membrane permeabilization, and morphological modifications but that they have a different mode of action on A. castellanii. PMID:21602398

  1. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

    Energy Technology Data Exchange (ETDEWEB)

    Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S; Neve, Richard M; Das, Debopriya; Gray, Joe W; Groves, Jay T

    2009-09-09

    Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

  2. Cellular Stress Response Gene Expression During Upper and Lower Body High Intensity Exercises

    Science.gov (United States)

    Kochanowicz, Andrzej; Sawczyn, Stanisław; Niespodziński, Bartłomiej; Mieszkowski, Jan; Kochanowicz, Kazimierz

    2017-01-01

    Objectives The aim was to compare the effect of upper and lower body high-intensity exercise on chosen genes expression in athletes and non-athletes. Method Fourteen elite male artistic gymnasts (EAG) aged 20.6 ± 3.3 years and 14 physically active men (PAM) aged 19.9 ± 1.0 years performed lower and upper body 30 s Wingate Tests. Blood samples were collected before, 5 and 30 minutes after each effort to assess gene expression via PCR. Results Significantly higher mechanical parameters after lower body exercise was observed in both groups, for relative power (8.7 ± 1.2 W/kg in gymnasts, 7.2 ± 1.2 W/kg in controls, p = 0.01) and mean power (6.7 ± 0.7 W/kg in gymnasts, 5.4 ± 0.8 W/kg in controls, p = 0.01). No differences in lower versus upper body gene expression were detected for all tested genes as well as between gymnasts and physical active man. For IL-6 m-RNA time-dependent effect was observed. Conclusions Because of no significant differences in expression of genes associated with cellular stress response the similar adaptive effect to exercise may be obtained so by lower and upper body exercise. PMID:28141870

  3. Effect of MWCNT surface and chemical modification on in vitro cellular response

    Energy Technology Data Exchange (ETDEWEB)

    Fraczek-Szczypta, Aneta; Menaszek, Elzbieta [AGH-University of Science and Technology, Department of Biomaterials, Faculty of Materials Science and Ceramics (Poland); Syeda, Tahmina Bahar; Misra, Anil; Alavijeh, Mohammad [Pharmidex Pharmaceutical Services (United Kingdom); Adu, Jimi [University of Brighton, School of Pharmacy and Biomolecular Sciences (United Kingdom); Blazewicz, Stanislaw, E-mail: blazew@agh.edu.pl [AGH-University of Science and Technology, Department of Biomaterials, Faculty of Materials Science and Ceramics (Poland)

    2012-10-15

    The aim of this study was to evaluate the impact of multi-walled carbon nanotubes (MWCNTs with diameter in the range of 10-30 nm) before and after chemical surface functionalisation on macrophages response. The study has shown that the detailed analysis of the physicochemical properties of this particular form of carbon nanomaterial is a crucial issue to interpret properly its impact on the cellular response. Effects of carbon nanotubes (CNTs) characteristics, including purity, dispersity, chemistry and dimension upon the nature of the cell environment-material interaction were investigated. Various techniques involving electron microscopy (SEM, TEM), infrared spectroscopy (FTIR), inductively coupled plasma optical emission spectrometry, X-ray photoelectron spectroscopy have been employed to evaluate the physicochemical properties of the materials. The results demonstrate that the way of CNT preparation prior to biological tests has a fundamental impact on their behavior, cell viability and the nature of cell-nanotube interaction. Chemical functionalisation of CNTs in an acidic ambient (MWCNT-Fs) facilitates interaction with cells by two possible mechanisms, namely, endocytosis/phagocytosis and by energy-independent passive process. The results indicate that MWCNT-F in macrophages may decrease the cell proliferation process by interfering with the mitotic apparatus without negative consequences on cell viability. On the contrary, the as-prepared MWCNTs, without any surface treatment produce the least reduction in cell proliferation with reference to control, and the viability of cells exposed to this sample was substantially reduced with respect to control. A possible explanation of such a phenomenon is the presence of MWCNT's agglomerates surrounded by numerous cells releasing toxic substances.

  4. A new in vitro model to study cellular responses after thermomechanical damage in monolayer cultures.

    Directory of Open Access Journals (Sweden)

    Alice Hettler

    Full Text Available Although electrosurgical instruments are widely used in surgery to cut tissue layers or to achieve hemostasis by coagulation (electrocautery, only little information is available concerning the inflammatory or immune response towards the debris generated. Given the elevated local temperatures required for successful electrocautery, the remaining debris is likely to contain a plethora of compounds entirely novel to the intracorporal setting. A very common in vitro method to study cell migration after mechanical damage is the scratch assay, however, there is no established model for thermomechanical damage to characterise cellular reactions. In this study, we established a new in vitro model to investigate exposure to high temperature in a carefully controlled cell culture system. Heatable thermostat-controlled aluminium stamps were developed to induce local damage in primary human umbilical vein endothelial cells (HUVEC. The thermomechanical damage invoked is reproducibly locally confined, therefore allowing studies, under the same experimental conditions, of cells affected to various degrees as well as of unaffected cells. We show that the unaffected cells surrounding the thermomechanical damage zone are able to migrate into the damaged area, resulting in a complete closure of the 'wound' within 48 h. Initial studies have shown that there are significant morphological and biological differences in endothelial cells after thermomechanical damage compared to the mechanical damage inflicted by using the unheated stamp as a control. Accordingly, after thermomechanical damage, cell death as well as cell protection programs were activated. Mononuclear cells adhered in the area adjacent to thermomechanical damage, but not to the zone of mechanical damage. Therefore, our model can help to understand the differences in wound healing during the early phase of regeneration after thermomechanical vs. mechanical damage. Furthermore, this model lends itself

  5. Knowledge-based matrix factorization temporally resolves the cellular responses to IL-6 stimulation

    Directory of Open Access Journals (Sweden)

    Gretz Norbert

    2010-11-01

    Full Text Available Abstract Background External stimulations of cells by hormones, cytokines or growth factors activate signal transduction pathways that subsequently induce a re-arrangement of cellular gene expression. The analysis of such changes is complicated, as they consist of multi-layered temporal responses. While classical analyses based on clustering or gene set enrichment only partly reveal this information, matrix factorization techniques are well suited for a detailed temporal analysis. In signal processing, factorization techniques incorporating data properties like spatial and temporal correlation structure have shown to be robust and computationally efficient. However, such correlation-based methods have so far not be applied in bioinformatics, because large scale biological data rarely imply a natural order that allows the definition of a delayed correlation function. Results We therefore develop the concept of graph-decorrelation. We encode prior knowledge like transcriptional regulation, protein interactions or metabolic pathways in a weighted directed graph. By linking features along this underlying graph, we introduce a partial ordering of the features (e.g. genes and are thus able to define a graph-delayed correlation function. Using this framework as constraint to the matrix factorization task allows us to set up the fast and robust graph-decorrelation algorithm (GraDe. To analyze alterations in the gene response in IL-6 stimulated primary mouse hepatocytes, we performed a time-course microarray experiment and applied GraDe. In contrast to standard techniques, the extracted time-resolved gene expression profiles showed that IL-6 activates genes involved in cell cycle progression and cell division. Genes linked to metabolic and apoptotic processes are down-regulated indicating that IL-6 mediated priming renders hepatocytes more responsive towards cell proliferation and reduces expenditures for the energy metabolism. Conclusions GraDe provides

  6. Palliative radiation treatment of cutaneous mycosis fungoides - a dose response

    Energy Technology Data Exchange (ETDEWEB)

    Cotter, G.W.; Baglan, R.J.; Wasserman, T.H.; Mill, W.

    1983-10-01

    Between 1966 and 1981, 20 patients (191 lesions) underwent palliative radiation therapy for control of biopsy-proven cutaneous mycosis fungoides. Six patients (47 lesions) and an additional 34 lesions from the remaining 14 patients with complete response to treatment were excluded from the study because of follow-up of less than one year. Included in the remaining 110 lesions were all recurrences and all partial responses. The modalities for treatment included superficial X rays, Cobalt-60 or electron beam irradiation. The total tumor doses employed ranged from 600-4000 cGy. The 110 lesions (14 patients) were retrospectively analyzed to determine the dose required for local control of the lesions. Fifty-three percent of the lesions were classified as plaques, 20% as tumors less than or equal to 3 cm in diameter, and 27% as tumors > 3 cm in diameter. Complete response to treatment was observed in 95% of the plaque lesions, 95% of the tumors less than or equal to 3 cm in diameter and 93% of tumor > 3 cm in diameter. A complete response to treatment was noted in all lesions receiving greater than 2000 cGy. In the total population of lesions having a complete response, a local infield recurrence rate of 42% was noted in the group receiving less than or equal to 1000 cGy, 32% in those receiving 1001-2000 cGy, 21% in those receiving 2001-3000 cGy, and 0% in the group receiving > 3000 cGy. The data from this study indicate that tumor doses equivalent to at least 3000 cGy at 200 cGy per fraction, five fractions per week (TDF greater than or equal to) are needed for adquate local control of cutaneous mycosis fungoides lesions.

  7. Rapid enzymatic response to compensate UV radiation in copepods.

    Directory of Open Access Journals (Sweden)

    María Sol Souza

    Full Text Available Ultraviolet radiation (UVR causes physical damage to DNA, carboxylation of proteins and peroxidation of lipids in copepod crustaceans, ubiquitous and abundant secondary producers in most aquatic ecosystems. Copepod adaptations for long duration exposures include changes in behaviour, changes in pigmentation and ultimately changes in morphology. Adaptations to short-term exposures are little studied. Here we show that short-duration exposure to UVR causes the freshwater calanoid copepod, Eudiaptomus gracilis, to rapidly activate production of enzymes that prevent widespread collateral peroxidation (glutathione S-transferase, GST, that regulate apoptosis cell death (Caspase-3, Casp-3, and that facilitate neurotransmissions (cholinesterase-ChE. None of these enzyme systems is alone sufficient, but they act in concert to reduce the stress level of the organism. The interplay among enzymatic responses provides useful information on how organisms respond to environmental stressors acting on short time scales.

  8. Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket

    Directory of Open Access Journals (Sweden)

    Nishida E

    2016-05-01

    Full Text Available Erika Nishida,1 Hirofumi Miyaji,1 Akihito Kato,1 Hiroko Takita,2 Toshihiko Iwanaga,3 Takehito Momose,1 Kosuke Ogawa,1 Shusuke Murakami,1 Tsutomu Sugaya,1 Masamitsu Kawanami11Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan; 2Support Section for Education and Research, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan; 3Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Sapporo, JapanAbstract: Graphene oxide (GO consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 µg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM, physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 µg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1

  9. Neuronal cellular responses to extremely low frequency electromagnetic field exposure: implications regarding oxidative stress and neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Marcella Reale

    Full Text Available Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD, have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1 mT; frequency, 50-Hz on a well-characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2(-, which were countered by compensatory changes in antioxidant catylase (CAT activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a

  10. The jejunal cellular responses in chickens infected with a single dose of Ascaridia galli eggs

    DEFF Research Database (Denmark)

    Luna Olivares, Luz Adilia; Kyvsgaard, Niels Christian; Ferdushy, Tania;

    2015-01-01

    This histopathological study was carried out in order to investigate the cellular response in the jejunum to Ascaridia galli during the first 7 weeks of infection. Fourty-two ISA Brown chickens (7 weeks old) were infected orally with 500 embryonated A. galli eggs each while 28 chickens were left ...

  11. Cellular and humoral immune responses in a population from the Baringo District, Kenya to Leishmania promastigote lipophosphoglycan

    DEFF Research Database (Denmark)

    Kurtzhals, J A; Hey, A S; Theander, T G

    1992-01-01

    In a cross-sectional house-to-house study in a leishmaniasis-endemic area in Kenya, the cellular and humoral immune response to Leishmania lipophosphoglycan (LPG) was determined. Clinical data, peripheral blood mononuclear cells, and plasma were obtained from 50 individuals over the age of eight...

  12. Comparative analysis of SIV-specific cellular immune responses induced by different vaccine platforms in rhesus macaques.

    Science.gov (United States)

    Valentin, Antonio; McKinnon, Katherine; Li, Jinyao; Rosati, Margherita; Kulkarni, Viraj; Pilkington, Guy R; Bear, Jenifer; Alicea, Candido; Vargas-Inchaustegui, Diego A; Jean Patterson, L; Pegu, Poonam; Liyanage, Namal P M; Gordon, Shari N; Vaccari, Monica; Wang, Yichuan; Hogg, Alison E; Frey, Blake; Sui, Yongjun; Reed, Steven G; Sardesai, Niranjan Y; Berzofsky, Jay A; Franchini, Genoveffa; Robert-Guroff, Marjorie; Felber, Barbara K; Pavlakis, George N

    2014-11-01

    To identify the most promising vaccine candidates for combinatorial strategies, we compared five SIV vaccine platforms including recombinant canary pox virus ALVAC, replication-competent adenovirus type 5 host range mutant RepAd, DNA, modified vaccinia Ankara (MVA), peptides and protein in distinct combinations. Three regimens used viral vectors (prime or boost) and two regimens used plasmid DNA. Analysis at necropsy showed that the DNA-based vaccine regimens elicited significantly higher cellular responses against Gag and Env than any of the other vaccine platforms. The T cell responses induced by most vaccine regimens disseminated systemically into secondary lymphoid tissues (lymph nodes, spleen) and effector anatomical sites (including liver, vaginal tissue), indicative of their role in viral containment at the portal of entry. The cellular and reported humoral immune response data suggest that combination of DNA and viral vectors elicits a balanced immunity with strong and durable responses able to disseminate into relevant mucosal sites.

  13. Physiological responses of macroalga Gracilaria lemaneiformis (Rhodophyta) to UV-B radiation exposure

    Science.gov (United States)

    Zhu, Lin; Xiao, Hui; Wang, Ying; Jian, Xiaoyang; Zhang, Zhipeng; Zhang, Huanxin; Tang, Xuexi

    2015-03-01

    This paper aims to evaluate the effects of ultraviolet-B radiation (UVBR) on Gracilaria lemaneiformis, a commercial red macroalga and an important source of agar. To study the in-vitro effect of UVBR on G. lemaneiformis, this plant was cultivated and exposed to photosynthetically active radiation (PAR) at 40 μmol photons/(m2 ·s) and enhanced UVBR (0, 0.36, 0.72, 1.08, 1.44, and 1.80 kJ/(m2 ·d)) for 13 days. The samples were processed for histochemical analysis, and the growth rate, photosynthetic pigment contents, photosynthetic performance, reactive oxygen species levels, membrane permeability, malonyl dialdehyde contents and antioxidant capacity of G. lemaneiformis were investigated. After 13 days of exposure to PAR+UVBR, G. lemaneiformis showed photodamage and photoinhibition of photosynthetic pigments (chlorophyll a and phycoerythrin), leading to a decreased photosynthetic efficiency. Further, there was a corresponding decrease in the relative growth rates and depigmentation and partial necrosis of the apical segments were noted after exposure to PAR+UVBR. Additionally, UVBR induced excess production of superoxide radicals and hydrogen peroxide, eliciting a marked cellular membrane damage and antioxidative response.

  14. Biological stress responses to radio frequency electromagnetic radiation: are mobile phones really so (heat) shocking?

    Science.gov (United States)

    Cotgreave, Ian A

    2005-03-01

    Cells phenotypically adapt to alterations in their intra- and extracellular environment via organised alterations to gene and protein expression. Many chemical and physical stimuli are known to drive such responses, including the induction of oxidative stress and heat shock. Increasing use of mobile telephones in our society, has brought focus on the potential for radio frequency (microwave) electromagnetic radiation to elicit biological stress responses, in association with potentially detrimental effects of this to human health. Here we review evidence suggesting altered gene and protein expression in response to such emissions, with particular focus on heat shock proteins. Non-thermal induction of heat shock proteins has been claimed by a number of investigations in in vitro cellular systems, and appears pleiotropic for many other regulatory events. However, many of these studies are flawed by inconsistencies in exposure models, cell types used and the independent reproducibility of the findings. Further, the paucity of evidence from in vivo experimentation is largely contradictory. Therefore, the validity of these effects in human health risk assessment remain unsubstantiated. Where possible, suggestions for further experimental clarification have been provided.

  15. Negative Regulation of IRF7 Activation by ATF4 Suggests a Cross Regulation Between the Interferon Responses and the Cellular Integrated Stress Responses

    OpenAIRE

    Liang, Qiming; Deng, Hongying; Sun, Chiao-Wang; Tim M. Townes; Zhu, Fanxiu

    2010-01-01

    Cells react to viral infection by exhibiting interferon (IFN)-based innate immune responses and integrated stress responses, but little is known about the interrelationships between the two. We here report a linkage between these two host protective cellular mechanisms. We found that IRF7, the master regulator of type I IFN gene expression, interacts with ATF4, a key component of the integrated stress responses whose translation is induced by viral infection and various stresses. We have demo...

  16. Comparison of Cellular Uptake and Inflammatory Response via Toll-Like Receptor 4 to Lipopolysaccharide and Titanium Dioxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Akiyoshi Taniguchi

    2013-06-01

    Full Text Available The innate immune response is the earliest cellular response to infectious agents and mediates the interactions between microbes and cells. Toll-like receptors (TLRs play an important role in these interactions. We have already shown that TLRs are involved with the uptake of titanium dioxide nanoparticles (TiO2 NPs and promote inflammatory responses. In this paper, we compared role of cellular uptake and inflammatory response via TLR 4 to lipopolysaccharide (LPS and TiO2 NPs. In the case of LPS, LPS binds to LPS binding protein (LBP and CD 14, and then this complex binds to TLR 4. In the case of TiO2 NPs, the necessity of LBP and CD 14 to induce the inflammatory response and for uptake by cells was investigated using over-expression, antibody blocking, and siRNA knockdown experiments. Our results suggested that for cellular uptake of TiO2 NPs, TLR 4 did not form a complex with LBP and CD 14. In the TiO2 NP-mediated inflammatory response, TLR 4 acted as the signaling receptor without protein complex of LPS, LBP and CD 14. The results suggested that character of TiO2 NPs might be similar to the complex of LPS, LBP and CD 14. These results are important for development of safer nanomaterials.

  17. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, R.P.

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute {gamma}-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  18. Cellular responses to modified Plasmodium falciparum MSP119 antigens in individuals previously exposed to natural malaria infection

    Directory of Open Access Journals (Sweden)

    Awobode Henrietta O

    2009-11-01

    Full Text Available Abstract Background MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP119, inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP119 had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP119 would affect critical T-cell responses to epitopes in this antigen. Methods The cellular responses to wild-type MSP119 and a panel of modified MSP119 antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. Results Interestingly, stimulation indices (SI for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP119. A protein with four amino acid substitutions (Glu27→Tyr, Leu31→Arg, Tyr34→Ser and Glu43→Leu had the highest stimulation index (SI up to 360 and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. Conclusion This study suggests that specific MSP119 variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.

  19. Stratospheric Response to Intraseasonal Changes in Incoming Solar Radiation

    Science.gov (United States)

    Garfinkel, Chaim; silverman, vered; harnik, nili; Erlich, caryn

    2016-04-01

    Superposed epoch analysis of meteorological reanalysis data is used to demonstrate a significant connection between intraseasonal solar variability and temperatures in the stratosphere. Decreasing solar flux leads to a cooling of the tropical upper stratosphere above 7hPa, while increasing solar flux leads to a warming of the tropical upper stratosphere above 7hPa, after a lag of approximately six to ten days. Late winter (February-March) Arctic stratospheric temperatures also change in response to changing incoming solar flux in a manner consistent with that seen on the 11 year timescale: ten to thirty days after the start of decreasing solar flux, the polar cap warms during the easterly phase of the Quasi-Biennal Oscillation. In contrast, cooling is present after decreasing solar flux during the westerly phase of the Quasi-Biennal Oscillation (though it is less robust than the warming during the easterly phase). The estimated composite mean changes in Northern Hemisphere upper stratospheric (~ 5hPa) polar temperatures exceed 8K, and are potentially a source of intraseasonal predictability for the surface. These changes in polar temperature are consistent with the changes in wave driving entering the stratosphere. Garfinkel, C.I., V. Silverman, N. Harnik, C. Erlich, Y. Riz (2015), Stratospheric Response to Intraseasonal Changes in Incoming Solar Radiation, J. Geophys. Res. Atmos., 120, 7648-7660. doi: 10.1002/2015JD023244.

  20. The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine.

    Science.gov (United States)

    Requena, Cristina E; Pérez-Moreno, Guiomar; Horváth, András; Vértessy, Beáta G; Ruiz-Pérez, Luis M; González-Pacanowska, Dolores; Vidal, Antonio E

    2016-09-01

    Decitabine (5-aza-2'-deoxycytidine, aza-dCyd) is an anti-cancer drug used clinically for the treatment of myelodysplastic syndromes and acute myeloid leukaemia that can act as a DNA-demethylating or genotoxic agent in a dose-dependent manner. On the other hand, DCTPP1 (dCTP pyrophosphatase 1) and dUTPase are two 'house-cleaning' nucleotidohydrolases involved in the elimination of non-canonical nucleotides. In the present study, we show that exposure of HeLa cells to decitabine up-regulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase, thus suggesting their contribution to the cellular response to this anti-cancer nucleoside. We present several lines of evidence supporting that, in addition to the formation of aza-dCTP (5-aza-2'-deoxycytidine-5'-triphosphate), an alternative cytotoxic mechanism for decitabine may involve the formation of aza-dUMP, a potential thymidylate synthase inhibitor. Indeed, dUTPase or DCTPP1 down-regulation enhanced the cytotoxic effect of decitabine producing an accumulation of nucleoside triphosphates containing uracil as well as uracil misincorporation and double-strand breaks in genomic DNA. Moreover, DCTPP1 hydrolyses the triphosphate form of decitabine with similar kinetic efficiency to its natural substrate dCTP and prevents decitabine-induced global DNA demethylation. The data suggest that the nucleotidohydrolases DCTPP1 and dUTPase are factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy.

  1. The cellular immune response plays an important role in protecting against dengue virus in the mouse encephalitis model.

    Science.gov (United States)

    Gil, Lázaro; López, Carlos; Blanco, Aracelys; Lazo, Laura; Martín, Jorge; Valdés, Iris; Romero, Yaremis; Figueroa, Yassel; Guillén, Gerardo; Hermida, Lisset

    2009-02-01

    For several years, researchers have known that the generation of neutralizing antibodies is a prerequisite for attaining adequate protection against dengue virus. Nevertheless, the cellular immune response is the principal arm of the adaptive immune system against non-cytopathic viruses such as dengue, as once the virus enters into the cell it is necessary to destroy it to eliminate the virus. To define the role of the cellular immune response in the protection against dengue, we selected the mouse encephalitis model. Mice were immunized with a single dose of infective dengue 2 virus and different markers of both branches of the induced adaptive immunity were measured. Animals elicited a broad antibody response against the four dengue virus serotypes, but neutralizing activity was only detected against the homologous serotype. On the other hand, the splenocytes of the infected animals strongly proliferated after in vitro stimulation with the homologous virus, and specifically the CD8 T-cell subset was responsible for the secretion of the cytokine IFN-gamma. Finally, to define the role of T cells in in vivo protection, groups of animals were inoculated with the depleting monoclonal antibodies anti-CD4 or anti-CD8. Only depletion with anti-CD8 decreased to 50% the level of protection reached in the non-depleted mice. The present work constitutes the first report defining the role of the cellular immune response in protection against dengue virus in the mouse model.

  2. p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xu Rui; LIU Yong Ai; SUN Fang; LI He; LEI Su Wen; WANG Ju Fang

    2016-01-01

    Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest. Methods Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence-associated-β-galactosidase (SA-β-gal) staining combined with Ki67 staining, a cell proliferation marker. Results Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells. Conclusion Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis.

  3. Activation of WIP1 phosphatase by HTLV-1 Tax mitigates the cellular response to DNA damage.

    Directory of Open Access Journals (Sweden)

    Tajhal Dayaram

    Full Text Available Genomic instability stemming from dysregulation of cell cycle checkpoints and DNA damage response (DDR is a common feature of many cancers. The cancer adult T cell leukemia (ATL can occur in individuals infected with human T cell leukemia virus type 1 (HTLV-1, and ATL cells contain extensive chromosomal abnormalities, suggesting that they have defects in the recognition or repair of DNA damage. Since Tax is the transforming protein encoded by HTLV-1, we asked whether Tax can affect cell cycle checkpoints and the DDR. Using a combination of flow cytometry and DNA repair assays we showed that Tax-expressing cells exit G(1 phase and initiate DNA replication prematurely following damage. Reduced phosphorylation of H2AX (γH2AX and RPA2, phosphoproteins that are essential to properly initiate the DDR, was also observed in Tax-expressing cells. To determine the cause of decreased DDR protein phosphorylation in Tax-expressing cells, we examined the cellular phosphatase, WIP1, which is known to dephosphorylate γH2AX. We found that Tax can interact with Wip1 in vivo and in vitro, and that Tax-expressing cells display elevated levels of Wip1 mRNA. In vitro phosphatase assays showed that Tax can enhance Wip1 activity on a γH2AX peptide target by 2-fold. Thus, loss of γH2AX in vivo could be due, in part, to increased expression and activity of WIP1 in the presence of Tax. siRNA knockdown of WIP1 in Tax-expressing cells rescued γH2AX in response to damage, confirming the role of WIP1 in the DDR. These studies demonstrate that Tax can disengage the G(1/S checkpoint by enhancing WIP1 activity, resulting in reduced DDR. Premature G(1 exit of Tax-expressing cells in the presence of DNA lesions creates an environment that tolerates incorporation of random mutations into the host genome.

  4. Effects of levamisole hydrochloride on cellular immune response and flock performance of commercial broilers

    Directory of Open Access Journals (Sweden)

    OA Oladele

    2012-12-01

    Full Text Available Levamisole hydrochloride (Lev.HCl has been acclaimed to boost immune response particularly in immunocompromised state. Its routine use as an immunomodulator in poultry production is yet to be well embraced, thus its effects of on cellular immunity and flock performance of commercial broilers were evaluated. One hundred and fifty Anak broiler chicks were separated into two groups of 75 each. Broilers in group 1 were sensitized with 150µg of Staphylococcus aureus antigen each at 4 and 5 weeks, while those in group 2 were not sensitized. Each group was further divided into subgroups A, B, and C. Levamisole hydrochloride (40 mg/kg was administered orally to 1A and 2A at 45 and 46 days of age and to 1B and 2B at 47 and 48 days of age, while 1C and 2C were not treated. At 47 days of age, 12 broilers from all subgroups were challenged with 75µg of S. aureus antigen each at the right wattle. Wattle thickness was measured till 72 hours post challenge (pc and delayed wattle reaction (DWR was determined. Tissues were harvested at 72 hours pc for histopathology. Morbidity, mortality and live weights at 8 weeks of age were recorded. DWR peaked at 4 hours pc in 1A (2.22 ± 0.21 mm and 1B (2.96 ± 0.21 mm and 24 hours pc in 1C (3.39 ± 0.34 mm, the difference being significant (p<0.05. Inflammatory lesions were observed in wattles of sensitized subgroups and were more severe in 1C. Mortality rates were 4.17% and 29.17% in 1A and 1C respectively. Mean live weights in A and B i.e. 1.57± 0.06 kg and 1.56 ± 0.06 kg respectively, were significantly higher (p<0.0 than 1.43 ± 0.08 kg in C. Levamisole enhanced DTH via an early response, improved broiler liveability, and its anti-inflammatory property was confirmed.

  5. ULTRAVIOLET PROTECTIVE PIGMENTS AND DNA DIMER INDUCTION AS RESPONSES TO ULTRAVIOLET RADIATION

    Science.gov (United States)

    Life on Earth has evolved adaptations to many environmental stresses over the epochs. One consistent stress has been exposure to ultraviolet (UV) radiation. The most basic effect of UV radiation on biological systems is damage to DNA. In response to UV radiation organisms have ad...

  6. Interleukin-27 inhibits vaccine-enhanced pulmonary disease following respiratory syncytial virus infection by regulating cellular memory responses.

    Science.gov (United States)

    Zeng, Ruihong; Zhang, Huixian; Hai, Yan; Cui, Yuxiu; Wei, Lin; Li, Na; Liu, Jianxun; Li, Caixia; Liu, Ying

    2012-04-01

    Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract disease in young children. In the 1960s, infants vaccinated with formalin-inactivated RSV developed a more severe disease characterized by excessive inflammatory immunopathology in lungs upon natural RSV infection. The fear of causing the vaccine-enhanced disease (VED) is an important obstacle for development of safe and effective RSV vaccines. The recombinant vaccine candidate G1F/M2 immunization also led to VED. It has been proved that cellular memory induced by RSV vaccines contributed to VED. Interleukin-27 (IL-27) and IL-23 regulate Th1, Th17, and/or Th2 cellular immune responses. In this study, mice coimmunized with pcDNA3-IL-27 and G1F/M2 were fully protected and, importantly, did not develop vaccine-enhanced inflammatory responses and immunopathology in lungs after RSV challenge, which was correlated with moderate Th1-, suppressed Th2-, and Th17-like memory responses activated by RSV. In contrast, G1F/M2- or pcDNA3-IL-23+G1F/M2-immunized mice, in which robust Th2- and Th17-like memory responses were induced, developed enhanced pulmonary inflammation and severe immunopathology. Mice coimmunized with G1F/M2 and the two cytokine plasmids exhibited mild inflammatory responses as well as remarkable Th1-, suppressed Th2-, and Th17-like memory responses. These results suggested that Th1-, Th2-, and Th17-like memory responses and, in particular, excessive Th2- and Th17-like memory responses were closely associated with VED; IL-27 may inhibit VED following respiratory syncytial virus infection by regulating cellular memory responses.

  7. The interplay among chromatin dynamics, cell cycle checkpoints and repair mechanisms modulates the cellular response to DNA damage.

    Science.gov (United States)

    Lazzaro, Federico; Giannattasio, Michele; Muzi-Falconi, Marco; Plevani, Paolo

    2007-06-01

    Cells are continuously under the assault of endogenous and exogenous genotoxic stress that challenges the integrity of DNA. To cope with such a formidable task cells have evolved surveillance mechanisms, known as checkpoints, and a variety of DNA repair systems responding to different types of DNA lesions. These lesions occur in the context of the chromatin structure and, as expected for all DNA transactions, the cellular response to DNA damage is going to be influenced by the chromatin enviroment. In this review, we will discuss recent studies implicating chromatin remodelling factors and histone modifications in the response to DNA double-strand breaks (DSBs) and in checkpoint activation in response to UV lesions.

  8. Characterization of ionizing radiation-induced unfolded protein response in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ju; Lee, Yoon Jin; Kang, Seong Man [Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-04-15

    Misfolded or unfolded proteins within the endoplasmic reticulum (ER stress), viral infection, or amino acid deprivation induce eukaryotic translation initiation factor 2α phosphorylation (eIF2α) in eukaryotic cells, repressing global protein synthesis coincident with preferential translation of activating transcription factor 4 (ATF4). ATF4 is a transcriptional activator of genes involved in amino acid metabolism, cellular redox homeostasis, and regulation of apoptosis. When the eIF2α/ATF4 pathway is initiated by ER stress, the pathway is referred toas the unfolded protein response (UPR). In addition to DNA, proteins may be initial and important targets of ionizing radiation (IR), and the damaged protein can trigger ER stress pathway. Recent investigations suggested that IR induces ER stress followed by UPR in various cell types including intestinal epithelial cells. We conducted this study to determine whether IR can activate UPR in human vascular endothelial cells. Our data have shown that IR increased PERK-dependent eIF2α phosphorylation accompanied by induction in ATF4 protein levels in human vascular endothelial cells without alterations in expressions of XBP-1s and GRP78. Based on these data, we suggest that IR selectively activates PERK branch of unfolded protein response in human vascular endothelial cells.

  9. Toxicity potentials from waste cellular phones, and a waste management policy integrating consumer, corporate, and government responsibilities.

    Science.gov (United States)

    Lim, Seong-Rin; Schoenung, Julie M

    2010-01-01

    Cellular phones have high environmental impact potentials because of their heavy metal content and current consumer attitudes toward purchasing new phones with higher functionality and neglecting to return waste phones into proper take-back systems. This study evaluates human health and ecological toxicity potentials from waste cellular phones; highlights consumer, corporate, and government responsibilities for effective waste management; and identifies key elements needed for an effective waste management strategy. The toxicity potentials are evaluated by using heavy metal content, respective characterization factors, and a pathway and impact model for heavy metals that considers end-of-life disposal in landfills or by incineration. Cancer potentials derive primarily from Pb and As; non-cancer potentials primarily from Cu and Pb; and ecotoxicity potentials primarily from Cu and Hg. These results are not completely in agreement with previous work in which leachability thresholds were the metric used to establish priority, thereby indicating the need for multiple or revised metrics. The triple bottom line of consumer, corporate, and government responsibilities is emphasized in terms of consumer attitudes, design for environment (DfE), and establishment and implementation of waste management systems including recycling streams, respectively. The key strategic elements for effective waste management include environmental taxation and a deposit-refund system to motivate consumer responsibility, which is linked and integrated with corporate and government responsibilities. The results of this study can contribute to DfE and waste management policy for cellular phones.

  10. SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Park, J [Dept. of Pediatrics, Stanford University School of Medicine, Stanford, CA (United States); Molecular Imaging Program at Stanford, Stanford, CA (United States); Bio-X Program, Stanford, CA (United States); Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Park, J [Proton Therapy Center, National Cancer Center, Goyang (Korea, Republic of); Rogalla, S; Contag, C [Dept. of Pediatrics, Stanford University School of Medicine, Stanford, CA (United States); Molecular Imaging Program at Stanford, Stanford, CA (United States); Bio-X Program, Stanford, CA (United States); Woo, D [Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Lee, D [Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Park, H [Dept. of Radiation Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Suh, T [Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Dept. of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/min was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.

  11. Regulation of Cellular Response Pattern to Phosphorus Ion is a New Target for the Design of Tissue-Engineered Blood Vessel.

    Science.gov (United States)

    Chen, Wen; Wang, Fangjuan; Zeng, Wen; Sun, Jun; Li, Li; Yang, Mingcan; Sun, Jiansen; Wu, Yangxiao; Zhao, Xiaohui; Zhu, Chuhong

    2015-05-01

    Regulation of cellular response pattern to phosphorus ion (PI) is a new target for the design of tissue-engineered materials. Changing cellular response pattern to high PI can maintain monocyte/macrophage survival in TEBV and the signal of increasing PI can be converted by klotho to the adenosine signals through the regulation of energy metabolism in monocytes/macrophages.

  12. In vitro testing of cellular response to ultra high frequency electromagnetic field radiation.

    Science.gov (United States)

    Pavicic, Ivan; Trosic, Ivancica

    2008-08-01

    The aim of this study was to evaluate whether low-level, ultra high frequency (UHF) irradiation of 935 MHz influences the cell structure and growth of V79 cells. UHF field was generated inside a Gigahertz Transversal Electromagnetic Mode cell (GTEM-cell) with a Hewlett-Packard signal generator. The electric field strength was 8.2+/-0.3 V/cm and the average specific absorption rate (SAR) was calculated to be 0.12 W/kg. Cell samples were cultivated in a humidified atmosphere at 37 degrees C with 5% CO2. Prepared cell samples were exposed to a 935 MHz continuous wave frequency field for 1, 2, and 3 h. The structure of microtubule proteins has been determined using the immunocytochemical method. Cell growth was determined by cell counts for each hour of exposure during five post-exposure days. Negative- and positive-cell controls were included into the experimental procedure. In comparison with control cells, the microtubule structure clearly altered after 3h of irradiation (pgrowth was noted in cells exposed for 3h three days after irradiation (pcell growth.

  13. SINGLE-CELL LEVEL INVESTIGATION OF CYTOSKELETAL/CELLULAR RESPONSE TO EXTERNAL STIMULI

    Energy Technology Data Exchange (ETDEWEB)

    Hiddessen, A L

    2007-02-26

    A detailed understanding of the molecular mechanisms by which chemical signals control cell behavior is needed if the complex biological processes of embryogenesis, development, health and disease are to be completely understood. Yet, if we are to fully understand the molecular mechanisms controlling cell behavior, measurements at the single cell level are needed to supplement information gained from population level studies. One of the major challenges to accomplishing studies at the single cell level has been a lack of physical tools to complement the powerful molecular biological assays which have provided much of what we currently know about cell behavior. The goal of this exploratory project is the development of an experimental platform that facilitates integrated observation, tracking and analysis of the responses of many individual cells to controlled environmental factors (e.g. extracellular signals). Toward this goal, we developed chemically-patterned microarrays of both adherent and suspension mammalian cell types. A novel chemical patterning methodology, based on photocatalytic lithography, was developed to construct biomolecule and cell arrays that facilitate analysis of biological function. Our patterning techniques rely on inexpensive stamp materials and visible light, and do not necessitate mass transport or specified substrates. Patterned silicon and glass substrates are modified such that there is a non-biofouling polymer matrix surrounding the adhesive regions that target biomolecules and cells. Fluorescence and reflectance microscopy reveal successful patterning of proteins and single to small clusters of mammalian cells. In vitro assays conducted upon cells on the patterned arrays demonstrate the viability of cells interfacing with this synthetic system. Hence, we have successfully established a versatile cell measurement platform which can be used to characterize the molecular regulators of cellular behavior in a variety of important

  14. Radiation response of SiC-based fibers

    Energy Technology Data Exchange (ETDEWEB)

    Youngblood, G.E.; Jones, R.H. [Pacific Northwest National Lab., Richland, WA (United States); Kohyama, Akira [Inst. of Advanced Energy, Kyoto (Japan); Snead, L.L. [Oak Ridge National Lab., TN (United States)

    1998-03-01

    The radiation response of a base-line carbide composite (SiC/SiC) made with Nicalon{trademark} CG fiber reinforcement was presented for a broad range of dose and irradiation temperatures. Strength loss in this composite and a similar composite made with Tyranno{trademark} fiber was related to shrinkage and a predicted mass loss in the Nicalon CG or Tyranno fibers. In Table 1, measured relative density and length changes ({Delta}p/p{sub o} and {Delta}L/L{sub o}, respectively) for coated and uncoated fibers irradiated at high doses and temperatures (43 dpa-SiC at 1000 C and 80 dpa-SiC at 800 C) are given. Also given are the relative mass loss changes {Delta}m/m{sub o}, calculated from {Delta}p/p{sub o} and {Delta}L/L{sub o} by the expression {Delta}m/m{sub o} = 3 {Delta}L/L{sub o} + {Delta}p/p{sub o}.

  15. A cellular stress response (CSR) that interacts with NADPH-P450 reductase (NPR) is a new regulator of hypoxic response.

    Science.gov (United States)

    Oguro, Ami; Koyama, Chika; Xu, Jing; Imaoka, Susumu

    2014-02-28

    NADPH-P450 reductase (NPR) was previously found to contribute to the hypoxic response of cells, but the mechanism was not clarified. In this study, we identified a cellular stress response (CSR) as a new factor interacting with NPR by a yeast two-hybrid system. Overexpression of CSR enhanced the induction of erythropoietin and hypoxia response element (HRE) activity under hypoxia in human hepatocarcinoma cell lines (Hep3B), while knockdown of CSR suppressed them. This new finding regarding the interaction of NPR with CSR provides insight into the function of NPR in hypoxic response.

  16. Increased cellular proliferation in rat skeletal muscle and tendon in response to exercise

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Bayer, Monika L; Mackey, Abigail

    2010-01-01

    PURPOSE: The purpose of this study is to investigate exercise-induced cellular proliferation in rat skeletal muscle/tendon with the use of 3'-[F-18]fluoro-3'deoxythymidine (FLT) and to quantitatively study concomitant changes in the proliferation-associated factor, Ki67. PROCEDURES: Wistar rats (......-derived results were supported by a correlation in calf muscle to Ki67 (protein and mRNA level), while this coherence was not found in tendon. CONCLUSION: FLT-PET seems to be a promising tool for imaging of exercise-induced cellular proliferation in musculo-tendinous tissue....

  17. Familial Parkinson's disease iPSCs show cellular deficits in mitochondrial responses that can be pharmacologically rescued

    Science.gov (United States)

    Cooper, Oliver; Seo, Hyemyung; Andrabi, Shaida; Guardia-Laguarta, Cristina; Graziotto, John; Sundberg, Maria; McLean, Jesse R.; Carrillo-Reid, Luis; Xie, Zhong; Osborn, Teresia; Hargus, Gunnar; Deleidi, Michela; Lawson, Tristan; Bogetofte, Helle; Perez-Torres, Eduardo; Clark, Lorraine; Moskowitz, Carol; Mazzulli, Joseph; Chen, Li; Volpicelli-Daley, Laura; Romero, Norma; Jiang, Houbo; Uitti, Ryan J.; Huang, Zhigao; Opala, Grzegorz; Scarffe, Leslie A.; Dawson, Valina L.; Klein, Christine; Feng, Jian; Ross, Owen A.; Trojanowski, John Q.; Lee, Virginia M.-Y.; Marder, Karen; Surmeier, D. James; Wszolek, Zbigniew K.; Przedborski, Serge; Krainc, Dimitri; Dawson, Ted M.; Isacson, Ole

    2012-01-01

    Parkinson's disease (PD) is a common neurodegenerative disease caused by genetic and environmental factors. We analyzed induced pluripotent stem cell (iPSC)-derived neural cells from PD patients and presymptomatic individuals carrying mutations in the PINK1 and LRRK2 genes, and healthy control subjects. We measured several aspects of mitochondrial responses in the iPSC-derived neural cells including production of reactive oxygen species, mitochondrial respiration, proton leakage and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial function in iPSC-derived neural cells from PD patients and at-risk individuals could be rescued with coenzyme Q10, rapamycin or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insights into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in PD. PMID:22764206

  18. Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae

    Science.gov (United States)

    López, Javier Hernández; Krainer, Sophie; Engert, Antonia; Schuehly, Wolfgang; Riessberger-Gallé, Ulrike; Crailsheim, Karl

    2017-01-01

    Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health. PMID:28145462

  19. Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae

    Science.gov (United States)

    López, Javier Hernández; Krainer, Sophie; Engert, Antonia; Schuehly, Wolfgang; Riessberger-Gallé, Ulrike; Crailsheim, Karl

    2017-02-01

    Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.

  20. Development of mechano-responsive polymeric scaffolds using functionalized silica nano-fillers for the control of cellular functions.

    Science.gov (United States)

    Griffin, Michelle; Nayyer, Leila; Butler, Peter E; Palgrave, Robert G; Seifalian, Alexander M; Kalaskar, Deepak M

    2016-08-01

    We demonstrate an efficient method to produce mechano-responsive polymeric scaffolds which can alter cellular functions using two different functionalized (OH and NH2) silica nano-fillers. Fumed silica-hydroxyl and fumed silica-amine nano-fillers were mixed with a biocompatible polymer (POSS-PCU) at various wt% to produce scaffolds. XPS and mechanical testing demonstrate that bulk mechanical properties are modified without changing the scaffold's surface chemistry. Mechanical testing showed significant change in bulk properties of POSS-PCU scaffolds with an addition of silica nanofillers as low as 1% (PScaffolds modified with NH2 silica showed significantly higher bulk mechanical properties compared to the one modified with the OH group. Enhanced cell adhesion, proliferation and collagen production over 14days were observed on scaffolds with higher bulk mechanical properties (NH2) compared to those with lower ones (unmodified and OH modified) (Ppolymeric scaffolds, which can help to customize cellular responses for biomaterial applications.

  1. Proteomic analysis of cellular response induced by boron neutron capture reaction in human squamous cell carcinoma SAS cells.

    Science.gov (United States)

    Sato, Akira; Itoh, Tasuku; Imamichi, Shoji; Kikuhara, Sota; Fujimori, Hiroaki; Hirai, Takahisa; Saito, Soichiro; Sakurai, Yoshinori; Tanaka, Hiroki; Nakamura, Hiroyuki; Suzuki, Minoru; Murakami, Yasufumi; Baiseitov, Diaz; Berikkhanova, Kulzhan; Zhumadilov, Zhaxybay; Imahori, Yoshio; Itami, Jun; Ono, Koji; Masunaga, Shinichiro; Masutani, Mitsuko

    2015-12-01

    To understand the mechanism of cell death induced by boron neutron capture reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells after BNCR. Cells were irradiated with thermal neutron beam at KUR after incubation under boronophenylalanine (BPA)(+) and BPA(-) conditions. BNCR mainly induced typical apoptosis in SAS cells 24h post-irradiation. Proteomic analysis in SAS cells suggested that proteins functioning in endoplasmic reticulum, DNA repair, and RNA processing showed dynamic changes at early phase after BNCR and could be involved in the regulation of cellular response to BNCR. We found that the BNCR induces fragments of endoplasmic reticulum-localized lymphoid-restricted protein (LRMP). The fragmentation of LRMP was also observed in the rat tumor graft model 20 hours after BNCT treatment carried out at the National Nuclear Center of the Republic of Kazakhstan. These data suggest that dynamic changes of LRMP could be involved during cellular response to BNCR.

  2. Expression of early and late cellular damage markers by ARPE-19 cells following prolonged treatment with UV-A radiation.

    Science.gov (United States)

    Tringali, Giuseppe; Sampaolese, Beatrice; Clementi, Maria Elisabetta

    2016-10-01

    Pathological alterations to the retinal pigment epithelium underlie several eye diseases, which lead to visual impairment and even blindness. Exposure to ultraviolet (UV) radiation is associated with some skin and ocular pathologies; UV radiation may induce DNA breakdown and cause cellular damage through the production of reactive oxygen species (ROS), thus leading to programmed cell death. The present study aimed to investigate the production of ROS and the gene expression levels of anti‑ and proapoptotic proteins [B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and caspase‑3] in human retinal pigment epithelial cells (ARPE‑19) treated with UV‑A for 5 h consecutively. The results demonstrated that prolonged exposure to UV‑A induced: i) Cell death, the decrease in cell viability was time‑dependent and reached statistical significance after 3 h; ii) a significant and substantial increase in ROS levels that remained constant for the duration of the experiment, the levels were significantly increased after 1 h of exposure; iii) an activation of apoptotic genes (Bax and caspase‑3) after 1 h of treatment, which was accompanied by a decrease in the anti‑apoptotic gene Bcl‑2; and iv) a loss of apoptotic signals and a rapid decrease in cellular viability after 3 h of consecutive treatment. These processes may trigger necrosis, which was observed in the cells following treatment with UV‑A for 5 consecutive hours. In conclusion, the present study is the first, to the best of our knowledge, to provide in vitro evidence regarding the sequence of events that underlie the cellular damage induced by prolonged UV‑A radiation, starting from the first 30 min of treatment. UV‑A radiation resulted in the activation of apoptotic events, and subsequently led to irreversible cell necrosis.

  3. Human Xip1 (C2orf13) is a novel regulator of cellular responses to DNA strand breaks

    DEFF Research Database (Denmark)

    Bekker-Jensen, Simon; Fugger, Kasper; Danielsen, Jannie Rendtlew;

    2007-01-01

    interacted through recognition of CK2 phosphorylation sites in XRCC1 by the Forkhead-associated (FHA) domain of Xip1, and XRCC1 was required to maintain steady-state levels of Xip1. Moreover, Xip1 was phosphorylated on Ser-116 by ataxia telangiectasia-mutated in response to ionizing radiation, further...

  4. Rutin as a Mediator of Lipid Metabolism and Cellular Signaling Pathways Interactions in Fibroblasts Altered by UVA and UVB Radiation

    Science.gov (United States)

    Rybałtowska-Kawałko, Paula

    2017-01-01

    Background. Rutin is a natural nutraceutical that is a promising compound for the prevention of UV-induced metabolic changes in skin cells. The aim of this study was to examine the effects of rutin on redox and endocannabinoid systems, as well as proinflammatory and proapoptotic processes, in UV-irradiated fibroblasts. Methods. Fibroblasts exposed to UVA and UVB radiation were treated with rutin. The activities and levels of oxidants/antioxidants and endocannabinoid system components, as well as lipid, DNA, and protein oxidation products, and the proinflammatory and pro/antiapoptotic proteins expression were measured. Results. Rutin reduced UV-induced proinflammatory response and ROS generation and enhanced the activity/levels of antioxidants (SOD, GSH-Px, vitamin E, GSH, and Trx). Rutin also normalized UV-induced Nrf2 expression. Its biological activity prevented changes in the levels of the lipid mediators: MDA, 4-HNE, and endocannabinoids, as well as the endocannabinoid receptors CB1/2, VR1, and GPR55 expression. Furthermore, rutin prevented the protein modifications (tyrosine derivatives formation in particular) and decreased the levels of the proapoptotic markers—caspase-3 and cytochrome c. Conclusion. Rutin prevents UV-induced inflammation and redox imbalance at protein and transcriptional level which favors lipid, protein, and DNA protection. In consequence rutin regulates endocannabinoid system and apoptotic balance. PMID:28168010

  5. Rutin as a Mediator of Lipid Metabolism and Cellular Signaling Pathways Interactions in Fibroblasts Altered by UVA and UVB Radiation

    Directory of Open Access Journals (Sweden)

    Agnieszka Gęgotek

    2017-01-01

    Full Text Available Background. Rutin is a natural nutraceutical that is a promising compound for the prevention of UV-induced metabolic changes in skin cells. The aim of this study was to examine the effects of rutin on redox and endocannabinoid systems, as well as proinflammatory and proapoptotic processes, in UV-irradiated fibroblasts. Methods. Fibroblasts exposed to UVA and UVB radiation were treated with rutin. The activities and levels of oxidants/antioxidants and endocannabinoid system components, as well as lipid, DNA, and protein oxidation products, and the proinflammatory and pro/antiapoptotic proteins expression were measured. Results. Rutin reduced UV-induced proinflammatory response and ROS generation and enhanced the activity/levels of antioxidants (SOD, GSH-Px, vitamin E, GSH, and Trx. Rutin also normalized UV-induced Nrf2 expression. Its biological activity prevented changes in the levels of the lipid mediators: MDA, 4-HNE, and endocannabinoids, as well as the endocannabinoid receptors CB1/2, VR1, and GPR55 expression. Furthermore, rutin prevented the protein modifications (tyrosine derivatives formation in particular and decreased the levels of the proapoptotic markers—caspase-3 and cytochrome c. Conclusion. Rutin prevents UV-induced inflammation and redox imbalance at protein and transcriptional level which favors lipid, protein, and DNA protection. In consequence rutin regulates endocannabinoid system and apoptotic balance.

  6. Chemical Genomics Identifies the PERK-Mediated Unfolded Protein Stress Response as a Cellular Target for Influenza Virus Inhibition

    Directory of Open Access Journals (Sweden)

    Sara Landeras-Bueno

    2016-04-01

    Full Text Available Influenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and the economy. Therefore, a large effort has been devoted to the development of new anti-influenza virus drugs directed to viral targets, as well as to the identification of cellular targets amenable to anti-influenza virus therapy. Here we have addressed the identification of such potential cellular targets by screening collections of drugs approved for human use. We reasoned that screening with a green fluorescent protein-based recombinant replicon system would identify cellular targets involved in virus transcription/replication and/or gene expression and hence address an early stage of virus infection. By using such a strategy, we identified Montelukast (MK as an inhibitor of virus multiplication. MK inhibited virus gene expression but did not alter viral RNA synthesis in vitro or viral RNA accumulation in vivo. The low selectivity index of MK prevented its use as an antiviral, but it was sufficient to identify a new cellular pathway suitable for anti-influenza virus intervention. By deep sequencing of RNA isolated from mock- and virus-infected human cells, treated with MK or left untreated, we showed that it stimulates the PERK-mediated unfolded protein stress response. The phosphorylation of PERK was partly inhibited in virus-infected cells but stimulated in MK-treated cells. Accordingly, pharmacological inhibition of PERK phosphorylation led to increased viral gene expression, while inhibition of PERK phosphatase reduced viral protein synthesis. These results suggest the PERK-mediated unfolded protein response as a potential cellular target to modulate influenza virus infection.

  7. IFI16, an amplifier of DNA-damage response: Role in cellular senescence and aging-associated inflammatory diseases.

    Science.gov (United States)

    Choubey, Divaker; Panchanathan, Ravichandran

    2016-07-01

    DNA-damage induces a DNA-damage response (DDR) in mammalian cells. The response, depending upon the cell-type and the extent of DNA-damage, ultimately results in cell death or cellular senescence. DDR-induced signaling in cells activates the ATM-p53 and ATM-IKKα/β-interferon (IFN)-β signaling pathways, thus leading to an induction of the p53 and IFN-inducible IFI16 gene. Further, upon DNA-damage, DNA accumulates in the cytoplasm, thereby inducing the IFI16 protein and STING-dependent IFN-β production and activation of the IFI16 inflammasome, resulting in the production of proinflammatory cytokines (e.g., IL-1β and IL-18). Increased expression of IFI16 protein in a variety of cell-types promotes cellular senescence. However, reduced expression of IFI16 in cells promotes cell proliferation. Because expression of the IFI16 gene is induced by activation of DNA-damage response in cells and increased levels of IFI16 protein in cells potentiate the p53-mediated transcriptional activation of genes and p53 and pRb-mediated cell cycle arrest, we discuss how an improved understanding of the role of IFI16 protein in cellular senescence and associated inflammatory secretory phenotype is likely to identify the molecular mechanisms that contribute to the development of aging-associated human inflammatory diseases and a failure to cancer therapy.

  8. Adult neurogenesis and the unfolded protein response; new cellular and molecular avenues in sleep research

    NARCIS (Netherlands)

    Lucassen, P.J.; Scheper, W.; van Someren, E.J.W.

    2009-01-01

    Two recent publications in this journal highlight the impact of new developments for our understanding of the mechanisms underlying the consequences of sleep disturbance and sleep loss. Meerlo et al. discuss effects of sleep disturbance at the cellular level, focusing mainly on adult neurogenesis an

  9. Airway cellular response to two different immunosuppressive regimens in lung transplant recipients

    NARCIS (Netherlands)

    Slebos, DJ; Kauffman, HF; Koeter, GH; Verschuuren, EAM; van der Bij, W; Postma, DS

    2005-01-01

    A number of new immunosuppressive drugs have become available in transplant medicine. We investigated the effects of two different immunosuppressive protocols on bronchoalveolar lavage fluid cellular characteristics in 34 lung transplant recipients who were treated with anti-thymocyte globulin induc

  10. Identification of genes that regulate multiple cellular processes/responses in the context of lipotoxicity to hepatoma cells

    Directory of Open Access Journals (Sweden)

    Yedwabnick Matthew

    2007-10-01

    Full Text Available Abstract Background In order to devise efficient treatments for complex, multi-factorial diseases, it is important to identify the genes which regulate multiple cellular processes. Exposure to elevated levels of free fatty acids (FFAs and tumor necrosis factor alpha (TNF-α alters multiple cellular processes, causing lipotoxicity. Intracellular lipid accumulation has been shown to reduce the lipotoxicity of saturated FFA. We hypothesized that the genes which simultaneously regulate lipid accumulation as well as cytotoxicity may provide better targets to counter lipotoxicity of saturated FFA. Results As a model system to test this hypothesis, human hepatoblastoma cells (HepG2 were exposed to elevated physiological levels of FFAs and TNF-α. Triglyceride (TG accumulation, toxicity and the genomic responses to the treatments were measured. Here, we present a framework to identify such genes in the context of lipotoxicity. The aim of the current study is to identify the genes that could be altered to treat or ameliorate the cellular responses affected by a complex disease rather than to identify the causal genes. Genes that regulate the TG accumulation, cytotoxicity or both were identified by a modified genetic algorithm partial least squares (GA/PLS analysis. The analyses identified NADH dehydrogenase and mitogen activated protein kinases (MAPKs as important regulators of both cytotoxicity and lipid accumulation in response to FFA and TNF-α exposure. In agreement with the predictions, inhibiting NADH dehydrogenase and c-Jun N-terminal kinase (JNK reduced cytotoxicity significantly and increased intracellular TG accumulation. Inhibiting another MAPK pathway, the extracellular signal regulated kinase (ERK, on the other hand, improved the cytotoxicity without changing TG accumulation. Much greater reduction in the toxicity was observed upon inhibiting the NADH dehydrogenase and MAPK (which were identified by the dual-response analysis, than for the

  11. The radiation response of mesoporous nanocrystalline zirconia thin films

    Science.gov (United States)

    Manzini, Ayelén M.; Alurralde, Martin A.; Giménez, Gustavo; Luca, Vittorio

    2016-12-01

    The next generation of nuclear systems will require materials capable of withstanding hostile chemical, physical and radiation environments over long time-frames. Aside from its chemical and physical stability, crystalline zirconia is one of the most radiation tolerant materials known. Here we report the first ever study of the radiation response of nanocrystalline and mesoporous zirconia and Ce3+-stabilized nanocrystalline zirconia (Ce0.1Zr0.9O2) thin films supported on silicon wafers. Zirconia films prepared using the block copolymer Brij-58 as the template had a thickness of around 60-80 nm. In the absence of a stabilizing trivalent cation they consisted of monoclinic and tetragonal zirconia nanocrystals with diameters in the range 8-10 nm. Films stabilized with Ce3+ contained only the tetragonal phase. The thin films were irradiated with iodine ions of energies of 70 MeV and 132 keV at low fluences (1013 - 1014 cm-2) corresponding to doses of 0.002 and 1.73 dpa respectively, and at 180 keV and high fluences (2 × 1016 cm-2) corresponding to 82.4 dpa. The influence of heavy ion irradiation on the nanocrystalline structure was monitored through Rietveld analysis of grazing incidence X-ray diffraction (GIXRD) patterns recorded at angles close to the critical angle to ensure minimum contribution to the diffraction pattern from the substrate. Irradiation of the mesoporous nanocrystalline zirconia thin films with 70 MeV iodine ions, for which electronic energy loss is dominant, resulted in slight changes in phase composition and virtually no change in crystallographic parameters as determined by Rietveld analysis. Iodine ion bombardment in the nuclear energy loss regime (132-180 keV) at low fluences did not provoke significant changes in phase composition or crystallographic parameters. However, at 180 keV and high fluences the monoclinic phase was totally eliminated from the GIXRD pattern of films prepared at both 350 and 500 °C implying either a monoclinic

  12. Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Horton, Janet K., E-mail: janet.horton@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Blitzblau, Rachel C.; Yoo, Sua [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Geradts, Joseph [Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Chang, Zheng [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Baker, Jay A. [Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Georgiade, Gregory S. [Department of Surgery, Duke University Medical Center, Durham, North Carolina (United States); Chen, Wei [Department of Bioinformatics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Siamakpour-Reihani, Sharareh; Wang, Chunhao [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Broadwater, Gloria [Department of Biostatistics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Groth, Jeff [Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Palta, Manisha; Dewhirst, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Barry, William T. [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Duffy, Eileen A. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); and others

    2015-07-15

    Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should

  13. [Pulse-modulated Electromagnetic Radiation of Extremely High Frequencies Protects Cellular DNA against Damaging Effect of Physico-Chemical Factors in vitro].

    Science.gov (United States)

    Gapeyev, A B; Lukyanova, N A

    2015-01-01

    Using a comet assay technique, we investigated protective effects of. extremely high frequency electromagnetic radiation in combination with the damaging effect of X-ray irradiation, the effect of damaging agents hydrogen peroxide and methyl methanesulfonate on DNA in mouse whole blood leukocytes. It was shown that the preliminary exposure of the cells to low intensity pulse-modulated electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20-min exposure, modulation frequencies of 1 and 16 Hz) caused protective effects decreasing the DNA damage by 20-45%. The efficacy of pulse-modulated electromagnetic radiation depended on the type of genotoxic agent and increased in a row methyl methanesulfonate--X-rays--hydrogen peroxide. Continuous electromagnetic radiation was ineffective. The mechanisms of protective effects may be connected with an induction of the adaptive response by nanomolar concentrations of reactive oxygen species formed by pulse-modulated electromagnetic radiation.

  14. Changes in Stoichiometry, Cellular RNA, and Alkaline Phosphatase Activity of Chlamydomonas in Response to Temperature and Nutrients

    Science.gov (United States)

    Hessen, Dag O.; Hafslund, Ola T.; Andersen, Tom; Broch, Catharina; Shala, Nita K.; Wojewodzic, Marcin W.

    2017-01-01

    Phytoplankton may respond both to elevated temperatures and reduced nutrients by changing their cellular stoichiometry and cell sizes. Since increased temperatures often cause increased thermal stratification and reduced vertical flux of nutrients into the mixed zone, it is difficult to disentangle these drivers in nature. In this study, we used a factorial design with high and low levels of phosphorus (P) and high and low temperature to assess responses in cellular stoichiometry, levels of RNA, and alkaline phosphatase activity (APA) in the chlorophyte Chlamydomonas reinhardtii. Growth rate, C:P, C:N, N:P, RNA, and APA all responded primarily to P treatment, but except for N:P and APA, also temperature contributed significantly. For RNA, the contribution from temperature was particularly strong with higher cellular levels of RNA at low temperatures, suggesting a compensatory allocation to ribosomes to maintain protein synthesis and growth. These experiments suggest that although P-limitation is the major determinant of growth rate and cellular stoichiometry, there are pronounced effects of temperature also via interaction with P. At the ecosystem level, nutrients and temperature will thus interact, but temperatures would likely exert a stronger impact on these phytoplankton traits indirectly via its force on stratification regimes and vertical nutrient fluxes. PMID:28167934

  15. Proteomic analysis of cellular response induced by multi-walled carbon nanotubes exposure in A549 cells.

    Directory of Open Access Journals (Sweden)

    Li Ju

    Full Text Available The wide application of multi-walled carbon nanotubes (MWCNT has raised serious concerns about their safety on human health and the environment. However, the potential harmful effects of MWCNT remain unclear and contradictory. To clarify the potentially toxic effects of MWCNT and to elucidate the associated underlying mechanisms, the effects of MWCNT on human lung adenocarcinoma A549 cells were examined at both the cellular and the protein level. Cytotoxicity and genotoxicity were examined, followed by a proteomic analysis (2-DE coupled with LC-MS/MS of the cellular response to MWCNT. Our results demonstrate that MWCNT induces cytotoxicity in A549 cells only at relatively high concentrations and longer exposure time. Within a relatively low dosage range (30 µg/ml and short time period (24 h, MWCNT treatment does not induce significant cytotoxicity, cell cycle changes, apoptosis, or DNA damage. However, at these low doses and times, MWCNT treatment causes significant changes in protein expression. A total of 106 proteins show altered expression at various time points and dosages, and of these, 52 proteins were further identified by MS. Identified proteins are involved in several cellular processes including proliferation, stress, and cellular skeleton organization. In particular, MWCNT treatment causes increases in actin expression. This increase has the potential to contribute to increased migration capacity and may be mediated by reactive oxygen species (ROS.

  16. Opposite roles for p38MAPK-driven responses and reactive oxygen species in the persistence and resolution of radiation-induced genomic instability.

    Directory of Open Access Journals (Sweden)

    Erica Werner

    Full Text Available We report the functional and temporal relationship between cellular phenotypes such as oxidative stress, p38MAPK-dependent responses and genomic instability persisting in the progeny of cells exposed to sparsely ionizing low-Linear Energy Transfer (LET radiation such as X-rays or high-charge and high-energy (HZE particle high-LET radiation such as (56Fe ions. We found that exposure to low and high-LET radiation increased reactive oxygen species (ROS levels as a threshold-like response induced independently of radiation quality and dose. This response was sustained for two weeks, which is the period of time when genomic instability is evidenced by increased micronucleus formation frequency and DNA damage associated foci. Indicators for another persisting response sharing phenotypes with stress-induced senescence, including beta galactosidase induction, increased nuclear size, p38MAPK activation and IL-8 production, were induced in the absence of cell proliferation arrest during the first, but not the second week following exposure to high-LET radiation. This response was driven by a p38MAPK-dependent mechanism and was affected by radiation quality and dose. This stress response and elevation of ROS affected genomic instability by distinct pathways. Through interference with p38MAPK activity, we show that radiation-induced stress phenotypes promote genomic instability. In contrast, exposure to physiologically relevant doses of hydrogen peroxide or increasing endogenous ROS levels with a catalase inhibitor reduced the level of genomic instability. Our results implicate persistently elevated ROS following exposure to radiation as a factor contributing to genome stabilization.

  17. Cellular biomarker responses of limpets (Mollusca as measure of sensitivity to cadmiumcontamination

    Directory of Open Access Journals (Sweden)

    Koot Reinecke

    2008-09-01

    Full Text Available Due to the availability and chemical nature of some heavy metals, sub-lethal toxicant levels may persist in the ocean waters and may cause physiological problems and toxicity in invertebrates and other marine organisms. Although studies of metal concentrations in False Bay showed relatively low mean concentrations of Cd, invertebrates such as molluscs, crustaceans and many other groups are able to accumulate high levels of heavy metals in their tissues and still survive in the heaviest polluted areas. They can accumulate numerous pollutants from natural waters in quantities that are many orders of magnitude higher than background levels. Bioaccumulation ofcadmium in intertidal species could cause stress which may be measurable at the cellular level. A variety of limpet species that may serve as suitable ecotoxicological monitoring species occur in abundance on rocky shores along the South African coastline. The aim of this study was to obtain sensitivity data which could contribute to the selection of a suitable monitoring species and the eventual establishment of a species sensitivity distribution model (SSD with a biomarker responseas endpoint. The limpets Cymbula oculus, Scutellastra longicosta, Cymbula granatina and Scutellastragranularis as well as water samples were collected at two localities in False Bay, South Africa. Analysis of water and biological samples were done by atomic absorption spectrometry. Exposures were done to three different sublethal concentrations of cadmium in the laboratory in static flow tanks over three days. There was a moderate increase in cadmium body concentrations over time. Results obtained at three exposure concentrations showed no significant differences in metal concentrations between the different C. oculus samples. Significant differences were obtained between the control and the exposure groups for each exposure time except between the control and the 1mg/L CdCl2 exposure group after 24 and 72 hours of

  18. Interaction of cellular-localized signature modules in response to prostate cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Rapid progress in high-throughput biotechnologies (e. g. microarrays) and exponential accumulation of gene functional knowledge makes it promising for systematic understanding of complex human diseases at the functional modules level. Current modular categorizations can be defined and selected more specifically and precisely in terms of both biological processes and cellular locations, aiming at uncovering the modular molecular networks highly relevant to cancers. Based on Gene Ontology, we identifed the functional modules enriched with differentially expressed genes and characterized by biological processes and specific cellular locations. Then, according to the ranking of the disease discriminating abilities of the pre-selected functional modules, we further defined and filtered signature modules which have higher relevance to the cancer under study. Applications of the proposed method to the analysis of a prostate cancer dataset revealed insightful biological modules.

  19. Discovering the cellular-localized functional modules and modular interactions in response to liver cancer

    Institute of Scientific and Technical Information of China (English)

    Zhu Jing; Guo Zheng; Yang Da; Zhang Min; Wang Jing; Wang Chenguang

    2008-01-01

    In this paper, we firstly identify the functional modules enriched with differentially expressed genes (DEGs) and characterized by biological processes in specific cellular locations, based on gene ontology (GO) and microarray data. Then, we further define and filter disease relevant signature modules according to the ranking of the disease discriminating abilities of the pre-selected functional modules. At last, we analyze the potential way by which they cooperate towards human disease. Application of the proposed method to the analysis of a liver cancer dataset shows that, using the same false discovery rate (FDR) threshold, we can find more biologically meaningful and detailed processes by using the cellular localization information. Some biological evidences support the relevancy of our biological modules to the disease mechanism.

  20. Impaired cellular immune response to diphtheria and tetanus vaccines in children after thoracic transplantation.

    Science.gov (United States)

    Urschel, Simon; Rieck, Birgit D; Birnbaum, Julia; Dalla Pozza, Robert; Rieber, Nikolaus; Januszewska, Katarzyna; Fuchs, Alexandra; West, Lori J; Netz, Heinrich; Belohradsky, Bernd H

    2011-05-01

    Safety and immunogenicity of diphtheria and tetanus booster vaccination were evaluated in 28 children after thoracic transplantation. Adverse events were documented in a patient diary. Blood was collected prior to and four wk after vaccination. Specific antibody concentrations were measured by ELISA. Lymphocytes were investigated for expression of activation markers (CD25, HLA-DR) by flow cytometry and proliferation assays with and without stimulation. Post-vaccination antibody titers were higher than prevaccination (p antibody levels against diphtheria (p antibodies was negatively correlated with tacrolimus dose, and impaired cellular immunity was associated with higher tacrolimus dose and steroid use. Adverse events were similar to the general population; serious adverse events and rejection did not occur. Vaccination with inactivated vaccines can be performed safely in immunosuppressed children after thoracic transplantation and induces protective antibody levels in the majority of patients. Impaired induction of specific cellular immunity is correlated with intensity of immunosuppression and may explain reduced sustainability of antibodies.

  1. Response of cellular stoichiometry and phosphorus storage of the cyanobacteria Aphanizomenon flos-aquae to small-scale turbulence

    Science.gov (United States)

    Li, Zhe; Xiao, Yan; Yang, Jixiang; Li, Chao; Gao, Xia; Guo, Jinsong

    2017-01-01

    Turbulent mixing, in particular on a small scale, affects the growth of microalgae by changing diffusive sublayers and regulating nutrient fluxes of cells. We tested the nutrient flux hypothesis by evaluating the cellular stoichiometry and phosphorus storage of microalgae under different turbulent mixing conditions. Aphanizomenon flos-aquae were cultivated in different stirring batch reactors with turbulent dissipation rates ranging from 0.001 51 m2/s3 to 0.050 58 m2/s3, the latter being the highest range observed in natural aquatic systems. Samples were taken in the exponential growth phase and compared with samples taken when the reactor was completely stagnant. Results indicate that, within a certain range, turbulent mixing stimulates the growth of A. flos-aquae. An inhibitory effect on growth rate was observed at the higher range. Photosynthesis activity, in terms of maximum effective quantum yield of PSII (the ratio of F v/F m) and cellular chlorophyll a, did not change significantly in response to turbulence. However, Chl a/C mass ratio and C/N molar ratio, showed a unimodal response under a gradient of turbulent mixing, similar to growth rate. Moreover, we found that increases in turbulent mixing might stimulate respiration rates, which might lead to the use of polyphosphate for the synthesis of cellular constituents. More research is required to test and verify the hypothesis that turbulent mixing changes the diffusive sublayer, regulating the nutrient flux of cells.

  2. Modeling marrow damage from response data: Morphallaxis from radiation biology to benzene toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T.D.; Morris, M.D.; Hasan, J.S.

    1995-12-01

    Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is ``critical`` to hematopoietic recovery does not resemble stem-like cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD{sub 50} and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in the fitting of model coefficients.

  3. Cell-directed assembly on an integrated nanoelectronic/nanophotonic device for probing cellular responses on the nanoscale.

    Energy Technology Data Exchange (ETDEWEB)

    Brinker, C. Jeffrey; Dunphy, Darren Robert; Ashley, Carlee E. (University of New Mexico, Albuquerque, NM); Fan, Hongyou; Lopez, DeAnna (University of New Mexico, Albuquerque, NM); Simpson, Regina Lynn; Tallant, David Robert; Burckel, David Bruce; Baca, Helen Kennicott (University of New Mexico, Albuquerque, NM); Carnes, Eric C. (University of New Mexico, Albuquerque, NM); Singh, Seema

    2006-01-01

    Our discovery that the introduction of living cells (Saccharomyces cerevisiae) alters dramatically the evaporation driven self-assembly of lipid-silica nanostructures suggested the formation of novel bio/nano interfaces useful for cellular interrogation at the nanoscale. This one year ''out of the box'' LDRD focused on the localization of metallic and semi-conducting nanocrystals at the fluid, lipid-rich interface between S. cerevisiae and the surrounding phospholipid-templated silica nanostructure with the primary goal of creating Surface Enhanced Raman Spectroscopy (SERS)-active nanostructures and platforms for cellular integration into electrode arrays. Such structures are of interest for probing cellular responses to the onset of disease, understanding of cell-cell communication, and the development of cell-based bio-sensors. As SERS is known to be sensitive to the size and shape of metallic (principally gold and silver) nanocrystals, various sizes and shapes of nanocrystals were synthesized, functionalized and localized at the cellular surface by our ''cell-directed assembly'' approach. Laser scanning confocal microscopy, SEM, and in situ grazing incidence small angle x-ray scattering (GISAXS) experiments were performed to study metallic nanocrystal localization. Preliminary Raman spectroscopy studies were conducted to test for SERS activity. Interferometric lithography was used to construct high aspect ratio cylindrical holes on patterned gold substrates and electro-deposition experiments were performed in a preliminary attempt to create electrode arrays. A new printing procedure was also developed for cellular integration into nanostructured platforms that avoids solvent exposure and may mitigate osmotic stress. Using a different approach, substrates comprised of self-assembled nanoparticles in a phospholipid templated silica film were also developed. When printed on top of these substrates, the cells integrate

  4. SU-E-T-320: The Effect of Survivin Perturbation On the Radiation Response of Breast Cancer Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D; Debeb, B; Woodward, W [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX (United States)

    2014-06-01

    Purpose: Survivin is the smallest member of the inhibitor of apoptosis protein family and is well-known for its universal over-expression in human cancers. Due to its role in apoptosis and cellular proliferation, survivin is implicated in the radiation response in several cancer types, and antisurvivin treatments have had success as a radiation sensitizer in many preclinical cancer models. As no studies to date have reported survivin as a factor affecting radiation resistance in breast cancer models, we sought to evaluate the synergistic relationship between survivin function and irradiation in breast cancer cell lines. Methods: Information regarding survivin protein expression in breast cancer was retrieved from three public databases: Oncomine, Kaplan-Meier Plotter, and GOBO. For the in vitro studies, survivin function was compromised by transducing a non-functional mutant form (survivin-DN) into two breast cancer cell lines, the estrogen receptor-positive MCF7 and the triple-negative, inflammatory SUM149. Cell growth was compared in the survivin-DN and control populations with colony-formation assays. To assess how survivin affects radiation response, clonogenic assays were performed by irradiating the cell lines up to 6 Gy. Results: From the public databases, survivin is more highly expressed in triple-negative breast cancer compared to all other subtypes, and is prognostic of poor survival in all breast cancer patients. In MCF7, the survivin-DN population had decreased colony-formation potential; the opposite was true in SUM149. In the clonogenic assays, abrogation of survivin function radio-protected MCF7 cells in monolayer and 3D growth conditions, while SUM149 survivin-DN cells were radiosensitized in monolayer conditions. Conclusion: We observed synergy between survivin function and radiation, although the results between the two cell lines were disparate. Further investigation is required to identify the mechanism of this discrepancy, including evaluation

  5. High atomic weight, high-energy radiation (HZE induces transcriptional responses shared with conventional stresses in addition to a core DSB response specific to clastogenic treatments.

    Directory of Open Access Journals (Sweden)

    Victor eMissirian

    2014-08-01

    Full Text Available Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as collateral damage to other cellular components and therefore are not expected to provoke identical responses by the cell. Here we study the effects of two different types of ionizing radiation (IR treatment, HZE (1 GeV Fe26+ high mass, high charge, and high energy relativistic particles and gamma photons, on the transcriptome of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of radicals that can result in the formation of double strand breaks (DSBs, but HZE also produces linear arrays of extremely clustered damage. We performed these experiments across a range of time points (1.5 to 24 hours after irradiation in both wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM. The two types of IR exhibit a shared double strand break-repair-related damage response, although they differ slightly in the timing, degree, and ATM-dependence of the response. The ATM-dependent, DNA metabolism-related transcripts of the DSB response were also induced by other DNA damaging agents, but were not induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 hours post-irradiation, ATM-dependent transcripts associated with a variety of conventional stresses; these were overrepresented for pathogen response, rather than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 hr after irradiation, exhibited an additional and very extensive transcriptional response, shared with plants experiencing extended night. This response was not apparent in gamma-irradiated plants.

  6. High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments.

    Science.gov (United States)

    Missirian, Victor; Conklin, Phillip A; Culligan, Kevin M; Huefner, Neil D; Britt, Anne B

    2014-01-01

    Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as "collateral" damage to other cellular components and therefore are not expected to provoke identical responses by the cell. Here we study the effects of two different types of ionizing radiation (IR) treatment, HZE (1 GeV Fe(26+) high mass, high charge, and high energy relativistic particles) and gamma photons, on the transcriptome of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of radicals that can result in the formation of double strand breaks (DSBs), but HZE also produces linear arrays of extremely clustered damage. We performed these experiments across a range of time points (1.5-24 h after irradiation) in both wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM. The two types of IR exhibit a shared double strand break-repair-related damage response, although they differ slightly in the timing, degree, and ATM-dependence of the response. The ATM-dependent, DNA metabolism-related transcripts of the "DSB response" were also induced by other DNA damaging agents, but were not induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 h post-irradiation, ATM-dependent transcripts associated with a variety of conventional stresses; these were overrepresented for pathogen response, rather than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 h after irradiation, exhibited an additional and very extensive transcriptional response, shared with plants experiencing "extended night." This response was not apparent in gamma-irradiated plants.

  7. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    Directory of Open Access Journals (Sweden)

    Hae Mi Joo

    Full Text Available Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6 and LAD2 cells, mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6 and LAD2 cells that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i. The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13, and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.

  8. Differential regulation of the cellular response to DNA double-strand breaks in G1

    DEFF Research Database (Denmark)

    Barlow, Jacqueline H; Lisby, Michael; Rothstein, Rodney

    2008-01-01

    Double-strand breaks (DSBs) are potentially lethal DNA lesions that can be repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). We show that DSBs induced by ionizing radiation (IR) are efficiently processed for HR and bound by Rfa1 during G1, while endonuclease-in...

  9. Toxicologic study of electromagnetic radiation emitted by television and video display screens and cellular telephones on chickens and mice

    Energy Technology Data Exchange (ETDEWEB)

    Bastide, M.; Youbicier-Simo, B.J.; Lebecq, J.C.; Giaimis, J. [Laboratoire d' Immunologie et Parasitologie, Faculte de Pharmacie, Universite de Montpellier, Montpellier (France); Youbicier-Simo, B.J. [Tecnolab, Chateau de l' Orbize, Dracy-le-Fort (France)

    2001-07-01

    The effects of continuous exposure of chick embryos and young chickens to the electromagnetic fields (EMFs) emitted by video display units (VDUs) and GSM cell phone radiation, either the whole spectrum emitted or attenuated by a copper gauze, were investigated. Permanent exposure to the EMFs radiated by a VDU was associated with significantly increased fetal loss (47-68%) and markedly depressed levels of circulating specific antibodies (lgG), corticosterone and melatonin. We have also shown that under chronic exposure conditions, GSM cell phone radiation was harmful to chick embryos, stressful for healthy mice and, in this species, synergistic with cancer insofar as it depleted stress hormones. The same pathological results were observed after substantial reduction of the microwaves radiated from the cell phone by attenuating them with a copper gauze. (author)

  10. Enhanced cellular responses and distinct gene profiles in human fetoplacental artery endothelial cells under chronic low oxygen.

    Science.gov (United States)

    Jiang, Yi-Zhou; Wang, Kai; Li, Yan; Dai, Cai-Feng; Wang, Ping; Kendziorski, Christina; Chen, Dong-Bao; Zheng, Jing

    2013-12-01

    Fetoplacental endothelial cells are exposed to oxygen levels ranging from 2% to 8% in vivo. However, little is known regarding endothelial function within this range of oxygen because most laboratories use ambient air (21% O2) as a standard culture condition (SCN). We asked whether human umbilical artery endothelial cells (HUAECs) that were steadily exposed to the physiological chronic normoxia (PCN, 3% O2) for ∼20-25 days differed in their proliferative and migratory responses to FGF2 and VEGFA as well as in their global gene expression compared with those in the SCN. We observed that PCN enhanced FGF2- and VEGFA-stimulated cell proliferation and migration. In oxygen reversal experiments (i.e., when PCN cells were exposed to SCN for 24 h and vice versa), we found that preexposure to 21% O2 decreased the migratory ability, but not the proliferative ability, of the PCN-HUAECs in response to FGF2 and VEGFA. These PCN-enhanced cellular responses were associated with increased protein levels of HIF1A and NOS3, but not FGFR1, VEGFR1, and VEGFR2. Microarray analysis demonstrated that PCN up-regulated 74 genes and down-regulated 86, 14 of which were directly regulated by hypoxia-inducible factors as evaluated using in silico analysis. Gene function analysis further indicated that the PCN-regulated genes were highly related to cell proliferation and migration, consistent with the results from our functional assays. Given that PCN significantly alters cellular responses to FGF2 and VEGFA as well as transcription in HUAECs, it is likely that we may need to reexamine the current cellular and molecular mechanisms controlling fetoplacental endothelial functions, which were largely derived from endothelial models established under ambient O2.

  11. Synergistic and additive effects of cimetidine and levamisole on cellular immune responses to hepatitis B virus DNA vaccine in mice.

    Science.gov (United States)

    Niu, X; Yang, Y; Wang, J

    2013-02-01

    We and others have previously shown that both cimetidine (CIM) and levamisole (LMS) enhance humoral and cellular responses to DNA vaccines via different mechanisms. In this study, we investigated the synergistic and additive effects of CIM and LMS on the potency of antigen-specific immunities generated by a DNA vaccine encoding the hepatitis B surface antigen (HBsAg, pVax-S2). Compared with CIM or LMS alone, the combination of CIM and LMS elicited a robust HBsAg-specific cellular response that was characterized by higher IgG2a, but did not further increase HBsAg-specific antibody IgG and IgG1 production. Consistent with these results, the combination of CIM and LMS produced the highest level of IL-2 and IFN-γ in antigen-specific CD4(+) T cells, whereas the combination of CIM and LMS did not further increase IL-4 production. Significantly, a robust HBsAg-specific cytotoxic response was also observed in the animals immunized with pVax-S2 in the presence of the combination of CIM and LMS. Further mechanistic studies demonstrated that the combination of CIM and LMS promoted dendritic cell (DC) activation and blocked anti-inflammatory cytokine IL-10 and TGF-β production in CD4(+) CD25(+) T cells. These findings suggest that CIM and LMS have the synergistic and additive ability to enhance cellular response to hepatitis B virus DNA vaccine, which may be mediated by DC activation and inhibition of anti-inflammatory cytokine expression. Thus, the combination of cimetidine and levamisole may be useful as an effective adjuvant in DNA vaccinations for chronic hepatitis B virus infection.

  12. Specific cellular stimulation in the primary immune response: experimental test of a quantized model.

    OpenAIRE

    Dintzis, R Z; Vogelstein, B; Dintzis, H M

    1982-01-01

    Dose-response and dose-suppression curves have been measured for the primary immune response in mice, in vivo and in vitro, by using size-fractionated linear polymers of acrylamide substituted with hapten. The results are in general agreement with a simple theory based on the premise that the specific primary immunological response is quantized at some fundamental and limiting step, requiring a minimum number of linked antigen receptors for response.

  13. Up-stream and Down-stream Events in the NF-kB Activation Cascade in Response to Sparsely and Densely Ionizing Radiation

    Science.gov (United States)

    Langen, Britta; Hellweg, Christine; Baumstark-Khan, Christa; Ruscher, Roland; Schmitz, Claudia; Arenz, Andrea; Lau, Patrick; Meier, Matthias M.; Testard, Isabelle; Reitz, Guenther

    Radiation is a potentially limiting factor for long term orbital and interplanetary missions. Long-term exposure to galactic cosmic rays may shorten the healthy life-span after return to Earth due to cancer induction. During the mission, a solar flare can be life threatening. For better risk estimation and development of appropriate countermeasures, the study of the cellular radiation response is necessary. As an antiapoptotic factor, if activated in human cells by exposure to components of cosmic rays, the transcription factor nuclear factor κB (NF- κB) could influence the cancer risk of astronauts exposed to cosmic radiation and improve cellular survival after exposure to high radiation doses. In previous studies using a screening assay for the detection of NF-κB-dependent gene induction (HEK-pNF-κB-d2EGFP/Neo cells), the activation of this transcription factor by heavy ions was shown (Radiat. Res. 164: 527- 530, 2005). In this work, the events upstream of NF-κB attachment to its promoter and enhancer binding sites, and downstream expression of target genes were analysed. It is supposed that the ATM kinase mediates the signal from damaged DNA in the nucleus to kinases in the cytoplasm, such as NF-κB essential modulator (NEMO). For liberation of NF-κB and its nuclear translocation, the inhibitor of NF-κB (IκB) has to be degraded in the proteasom. In order to evaluate a role of NEMO in the radiation response, the survival of murine embryonic fibroblasts expressing wildtype NEMO and lacking NEMO in response to ionizing radiation was analyzed. Lack of NEMO impairs survival after X-ray exposure. The inhibition of ATM by KU-55933 suppresses the X-ray and heavy ion (13C, 35 MeV/u, LET 70 keV/µm) induced activation of NF-κB dependent gene expression, indicating the central position of ATM in radiation induced NF-κB activation. Short-term incubation with the proteasome inhibitor MG-132 also blocks NF-κB activation by radiation. These results suggest a role of

  14. Radiation impedance of condenser microphones and their diffuse-field responses

    DEFF Research Database (Denmark)

    Barrera Figueroa, Salvador; Rasmussen, Knud; Jacobsen, Finn

    2010-01-01

    The relation between the diffuse-field response and the radiation impedance of a microphone has been investigated. Such a relation can be derived from classical theory. The practical measurement of the radiation impedance requires (a) measuring the volume velocity of the membrane of the microphone....... In this way, a hybrid estimate of the radiation impedance is obtained. The resulting estimate of the diffuse-field response is compared with experimental estimates of the diffuse-field response determined using reciprocity and the random-incidence method. The different estimates are in good agreement...

  15. Phenylalanine is required to promote specific developmental responses and prevents cellular damage in response to ultraviolet light in soybean (Glycine max) during the seed-to-seedling transition.

    Science.gov (United States)

    Sullivan, Joe H; Muhammad, DurreShahwar; Warpeha, Katherine M

    2014-01-01

    UV-radiation elicits a suite of developmental (photomorphogenic) and protective responses in plants, but responses early post-germination have received little attention, particularly in intensively bred plants of economic importance. We examined germination, hypocotyl elongation, leaf pubescence and subcellular responses of germinating and/or etiolated soybean (Glycine max (L.) Merr.) seedlings in response to treatment with discrete wavelengths of UV-A or UV-B radiation. We demonstrate differential responses of germinating/young soybean seedlings to a range of UV wavelengths that indicate unique signal transduction mechanisms regulate UV-initiated responses. We have investigated how phenylalanine, a key substrate in the phenylpropanoid pathway, may be involved in these responses. Pubescence may be a key location for phenylalanine-derived protective compounds, as UV-B irradiation increased pubescence and accumulation of UV-absorbing compounds within primary leaf pubescence, visualized by microscopy and absorbance spectra. Mass spectrometry analysis of pubescence indicated that sinapic esters accumulate in the UV-irradiated hairs compared to unirradiated primary leaf tissue. Deleterious effects of some UV-B wavelengths on germination and seedling responses were reduced or entirely prevented by inclusion of phenylalanine in the growth media. Key effects of phenylalanine were not duplicated by tyrosine or tryptophan or sucrose, nor is the specificity of response due to the absorbance of phenylalanine itself. These results suggest that in the seed-to-seedling transition, phenylalanine may be a limiting factor in the development of initial mechanisms of UV protection in the developing leaf.

  16. Cellular and molecular immune responses of the sea bass (Dicentrarchus labrax) experimentally infected with betanodavirus

    DEFF Research Database (Denmark)

    Scapigliati, G.; Buonocore, F.; Randelli, E.;

    2010-01-01

    Naïve sea bass juveniles (38.4 ± 4.5 g) were intramuscularly infected with a sublethal dose of betanodavirus isolate 378/I03, followed after 43 days by a similar boosting. This infection resulted in an overall mortality of 7.6%. At various intervals, sampling of fish tissues was performed to inve...... was also observed, while the other tested genes did not show any significant variations with respect to mock-treated fish. Overall, our work represents a first comprehensive analysis of cellular and molecular immune parameters in a fish species exposed to a pathogenic virus....

  17. Gamma response study of radiation sensitive MOSFETs for their use as gamma radiation sensor

    Science.gov (United States)

    Srivastava, Saurabh; Aggarwal, Bharti; Singh, Arvind; Kumar, A. Vinod; Topkar, Anita

    2016-05-01

    Continuous monitoring of gamma dose is important in various fields like radiation therapy, space-related research, nuclear energy programs and high energy physics experiment facilities. The present work is focused on utilization of radiation-sensitive Metal-Oxide-Semiconductor Field Effect Transistors (MOSFETs) to monitor gamma radiation doses. Static characterization of these detectors was performed to check their expected current-voltage relationship. Threshold voltage and transconductance per unit gate to source voltage (K factor) were calculated from the experimental data. The detector was exposed to gamma radiation in both, with and without gate bias voltage conditions, and change in threshold voltage was monitored at different gamma doses. The experimental data was fitted to obtain equation for dependence of threshold voltage on gamma dose. More than ten times increase in sensitivity was observed in biased condition (+3 V) compared to the unbiased case.

  18. High content analysis at single cell level identifies different cellular responses dependent on nanomaterial concentrations

    Science.gov (United States)

    Manshian, Bella B.; Munck, Sebastian; Agostinis, Patrizia; Himmelreich, Uwe; Soenen, Stefaan J.

    2015-09-01

    A mechanistic understanding of nanomaterial (NM) interaction with biological environments is pivotal for the safe transition from basic science to applied nanomedicine. NM exposure results in varying levels of internalized NM in different neighboring cells, due to variances in cell size, cell cycle phase and NM agglomeration. Using high-content analysis, we investigated the cytotoxic effects of fluorescent quantum dots on cultured cells, where all effects were correlated with the concentration of NMs at the single cell level. Upon binning the single cell data into different categories related to NM concentration, this study demonstrates, for the first time, that quantum dots activate both cytoprotective and cytotoxic mechanisms, resulting in a zero net result on the overall cell population, yet with significant effects in cells with higher cellular NM levels. Our results suggest that future NM cytotoxicity studies should correlate NM toxicity with cellular NM numbers on the single cell level, as conflicting mechanisms in particular cell subpopulations are commonly overlooked using classical toxicological methods.

  19. Climate response to imposed solar radiation reductions in high latitudes

    Directory of Open Access Journals (Sweden)

    M. C. MacCracken

    2012-07-01

    Full Text Available Increasing concentrations of greenhouse gases are the primary contributor to the 0.8 °C increase in the global average temperature since the late 19th century, shortening cold seasons and lengthening warm seasons. The warming is amplified in polar regions, causing retreat of sea ice, snow cover, permafrost, mountain glaciers, and ice sheets, while also modifying mid-latitude weather, amplifying global sea level rise, and initiating high-latitude carbon feedbacks. Model simulations in which we reduced solar insolation over high latitudes not only cooled those regions, but also drew energy from lower latitudes, exerting a cooling influence over much of the hemisphere in which the reduction was imposed. Our simulations, which used the National Center for Atmospheric Research's CAM3.1 atmospheric model coupled to a slab ocean, indicated that, on a normalized basis, high-latitude reductions in absorbed solar radiation have a significantly larger cooling influence than equivalent solar reductions spread evenly over the Earth. This amplified influence occurred because high-latitude surface cooling preferentially increased sea ice fraction and, therefore, surface albedo, leading to a larger deficit in the radiation budget at the top of the atmosphere than from an equivalent global reduction in solar radiation. Reductions in incoming solar radiation in one polar region (either north or south resulted in increased poleward energy transport during that hemisphere's cold season and shifted the Inter-Tropical Convergence Zone (ITCZ away from that pole, whereas equivalent reductions in both polar regions tended to leave the ITCZ approximately in place. Together, these results suggest that, until emissions reductions are sufficient to limit the warming influence of greenhouse gas concentrations, polar reductions in solar radiation, if they can be efficiently and effectively implemented, might, because of fewer undesirable side effects than for global solar

  20. Mapping Variation in Cellular and Transcriptional Response to 1,25-Dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells.

    Directory of Open Access Journals (Sweden)

    Silvia N Kariuki

    Full Text Available The active hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D is an important modulator of the immune system, inhibiting cellular proliferation and regulating transcription of immune response genes. In order to characterize the genetic basis of variation in the immunomodulatory effects of 1,25D, we mapped quantitative traits of 1,25D response at both the cellular and the transcriptional level. We carried out a genome-wide association scan of percent inhibition of cell proliferation (Imax induced by 1,25D treatment of peripheral blood mononuclear cells from 88 healthy African-American individuals. Two genome-wide significant variants were identified: rs1893662 in a gene desert on chromosome 18 (p = 2.32 x 10-8 and rs6451692 on chromosome 5 (p = 2.55 x 10-8, which may influence the anti-proliferative activity of 1,25D by regulating the expression of nearby genes such as the chemokine gene, CCL28, and the translation initiation gene, PAIP1. We also identified 8 expression quantitative trait loci at a FDR<0.10 for transcriptional response to 1,25D treatment, which include the transcriptional regulator ets variant 3-like (ETV3L and EH-domain containing 4 (EHD4. In addition, we identified response eQTLs in vitamin D receptor binding sites near genes differentially expressed in response to 1,25D, such as FERM Domain Containing 6 (FRMD6, which plays a critical role in regulating both cell proliferation and apoptosis. Combining information from the GWAS of Imax and the response eQTL mapping enabled identification of putative Imax-associated candidate genes such as PAIP1 and the transcriptional repressor gene ZNF649. Overall, the variants identified in this study are strong candidates for immune traits and diseases linked to vitamin D, such as multiple sclerosis.

  1. Novel metastasis-related gene CIM functions in the regulation of multiple cellular stress-response pathways.

    Science.gov (United States)

    Yanagisawa, Kiyoshi; Konishi, Hiroyuki; Arima, Chinatsu; Tomida, Shuta; Takeuchi, Toshiyuki; Shimada, Yukako; Yatabe, Yasushi; Mitsudomi, Tetsuya; Osada, Hirotaka; Takahashi, Takashi

    2010-12-01

    Various stresses of the tumor microenvironment produced by insufficient nutrients, pH, and oxygen can contribute to the generation of altered metabolic and proliferative states that promote the survival of metastatic cells. Among many cellular stress-response pathways activated under such conditions are the hypoxia-inducible factor (HIF) pathway and the unfolded protein response (UPR), which is elicited as a response to endoplasmic reticulum (ER) stress. In this study, we report the identification of a novel cancer invasion and metastasis-related gene (hereafter referred to as CIM, also called ERLEC1), which influences both of these stress-response pathways to promote metastasis. CIM was identified by comparing the gene expression profile of a highly metastatic human lung cancer cell line with its weakly metastatic parental clone. We showed that CIM is critical for metastatic properties in this system. Proteomic approaches combined with bioinformatic analyses revealed that CIM has multifaceted roles in controlling the response to hypoxia and ER stress. Specifically, CIM sequestered OS-9 from the HIF-1α complex and PHD2, permitting HIF-1α accumulation by preventing its degradation. Ectopic expression of CIM in lung cancer cells increased their tolerance to hypoxia. CIM also modulated UPR through interaction with the key ER stress protein BiP, influencing cell proliferation under ER stress conditions. Our findings shed light on how tolerance to multiple cellular stresses at a metastatic site can be evoked by an integrated mechanism involving CIM, which can function to coordinate those responses in a manner that promotes metastatic cell survival.

  2. Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

    Energy Technology Data Exchange (ETDEWEB)

    Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Gilbert, Ethel; Curtis, Rochelle; Inskip, Peter; Kleinerman, Ruth; Morton, Lindsay; Rajaraman, Preetha; Little, Mark P. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-06-01

    Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.

  3. Immunosuppressive activity of Semen Persicae ethanol extract on specific antibody and cellular response to ovalbumin in mice.

    Science.gov (United States)

    Zhang, Yi-Bin; Qin, Feng; Sun, Hong-Xiang

    2006-09-01

    The immunosuppressive activity of the ethanol extract of Semen Persicae (EESP) was studied with respect to specific antibody and cellular response to ovalbumin (OVA) in mice. The effects of EESP on mice splenocyte proliferation in vitro were measured. EESP significantly suppressed concanavalin A (ConA)- and lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro in a concentration-dependent manner. Furthermore, the effects of EESP at three dose levels on the humoral and cellular immune responses in the OVA-immunized mice were examined. ICR Mice were immunized subcutaneously with OVA on day 0 and 14. Starting on the day of immunization, the mice were administered intraperitoneally with EESP at a single dose of 0.25, 0.5, and 1.0 mg, and cyclosporin A (CsA, positive drug) at a single dose of 0.1 mg at intervals of 7 days. On day 28, mitogen- and OVA-induced splenocyte proliferation and OVA-specific antibody level in serum were measured. EESP significantly decreased ConA-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice at the dose of 1.0 mg. Meanwhile, the OVA-specific serum IgG, IgG1, and IgG2b antibody levels in the OVA-immunized mice were markedly reduced by EESP in a dose-dependent manner. The results suggest that EESP could suppress the cellular and humoral immune response in mice, and deserve further research to be developed as immunosuppressant.

  4. Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

    Directory of Open Access Journals (Sweden)

    Geferson Fischer

    2010-11-01

    Full Text Available Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1. When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05 neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01. Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05. Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.

  5. Investigation on the role of IGF-1 signal transduction in the biological radiation responses

    Energy Technology Data Exchange (ETDEWEB)

    Jung, U Hee; Jo, Sung Kee; Park, Hae Ran; Oh, Soo Jin; Cho, Eun Hee; Eom, Hyun Soo; Ju, Eun Jin

    2009-05-15

    Effects of {gamma}-irradiation on the IGF-1 related gene expressions and activations in various cell lines - Various expression patterns of IGF-1 and IGF-1R following {gamma}-irradiation were observed according to the cell lines - The increased expressions of IGF-1 and IGF-1R were observed in Balb/3T3 and NIH/3T3 cells - Among the IGF-1 downstream signaling molecules, the phosphorylated ERK5 were not changed by {gamma}-irradiation in all three examined cell lines, whereas the phosphorylated p65 were increased by {gamma} -irradiation in all cell lines. The role of IGF-1 and p38 signaling in {gamma}-irradiated mouse embryonic fibroblast (MEF) cells - In MEF cells, IGF-1 signaling molecules were decreased and p21/phosphorylated p38 were increased by {gamma}-irradiation - The experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 signaling is involved but not essential in radiation-induced cell growth arrest and senescence and that p38 MAP kinase play a important role in this cellular radiation response. The role of IGF-1 and p38 signaling in {gamma}-irradiated mouse fibroblast (NIH/3T3) cell - In NIH/3T3 cells, IGF-1 signaling molecules and p21/phosphorylated p38 were increased by {gamma} -irradiation. - However, the experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 and p38 signaling do not play a crucial role in radiation-induced cell growth arrest and senescence in NIH/3T3 cells. Effects of {gamma}-irradiation on the expressions and activations on the genes related to the IGF-1 signaling in mouse tissues - In {gamma}-irradiated mice, the increased expressions of IGF-1 and IGF-1R were observed in the lung and kidney at 2 months after irradiation, and in all the tissues examined (lung, liver and kidney) at 6 months after irradiation. - In the lung of {gamma}-irradiated mice at 6 months after irradiation, the increases of IGF-1R, phosphorylated FOXO3a, p65, p38, p21 were observed. - The

  6. Assessing Response to Radiation Therapy Treatment of Bone Metastases: Short-Term Followup of Radiation Therapy Treatment of Bone Metastases with Diffusion-Weighted Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Salvatore Cappabianca

    2014-01-01

    Full Text Available This study examined the usefulness of diffusion-weighted (DW Magnetic Resonance Imaging (MRI in monitoring bone metastases response to radiation therapy in 15 oligometastatic patients. For each metastasis, both mean apparent diffusion coefficient (ADC changes and high b-value DW metastasis/muscle signal intensity ratio (SIR variations were evaluated at 30 ± 5 days and 60 ± 7 days after the end of treatment. On baseline DW-MRI, all bone metastases were hyperintense and had signal intensities higher than normal bone marrow on calculated ADC maps. At follow-up evaluations, 4 patterns of response were identified: (I decreased high b-value DW SIR associated with increased mean ADC (83.3% of cases; (II increased mean ADC with no change of high b-value DW SIR (10% of cases; (III decreased both high b-value DW SIR and mean ADC (3.3% of cases; (IV a reduction in mean ADC associated with an increase in high b-value DW SIR compared to pretreatment values (3.3% of cases. Patterns (I and (II suggested a good response to therapy; pattern (III was classified as indeterminate, while pattern (IV was suggestive of disease progression. This pattern approach may represent a useful tool in the differentiation between treatment-induced necrosis and highly cellular residual tumor.

  7. Specific cellular stimulation in the primary immune response: a quantized model.

    OpenAIRE

    1982-01-01

    A general theory for the initial phase of T cell independent immune response is derived from elementary physical-chemical considerations and from the premise that response entails a quantized linkage of cell surface receptors. The theory leads to the construction of explicit antigen dose--response and antigen dose--suppression curves, to the calculation of intrinsic affinities for receptors, and to the deduction that receptors are divalent in character. The theory may be applicable to other c...

  8. Tetanus toxoid-loaded cationic non-aggregated nanostructured lipid particles triggered strong humoral and cellular immune responses.

    Science.gov (United States)

    Kaur, Amandeep; Jyoti, Kiran; Rai, Shweta; Sidhu, Rupinder; Pandey, Ravi Shankar; Jain, Upendra Kumar; Katyal, Anju; Madan, Jitender

    2016-05-01

    In the present investigation, non-aggregated cationic and unmodified nanoparticles (TT-C-NLPs4 and TT-NLPs1) were prepared of about 49.2 ± 6.8-nm and 40.8 ± 8.3-nm, respectively. In addition, spherical shape, crystalline architecture and cationic charge were also noticed. Furthermore, integrity and conformational stability of TT were maintained in both TT-C-NLPs4 and TT-NLPs1, as evidenced by symmetrical position of bands and superimposed spectra, respectively in SDS-PAGE and circular dichroism. Cellular uptake in RAW264.7 cells indicating the concentration-dependent internalisation of nanoparticles. Qualitatively, CLSM exhibited enhanced cellular uptake of non-aggregated TT-C-NLPs4 owing to interaction with negatively charged plasma membrane and clevaloe mediated/independent endocytosis. In last, in vivo immunisation with non-aggregated TT-C-NLPs4 elicited strong humoral (anti-TT IgG) and cellular (IFN-γ) immune responses at day 42, as compared to non-aggregated TT-NLPs1 and TT-Alum following booster immunisation at day 14 and 28. Thus, non-aggregated cationic lipid nanoparticles may be a potent immune-adjuvant for parenteral delivery of weak antigens.

  9. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

    Energy Technology Data Exchange (ETDEWEB)

    Kiran, Shashi; Oddi, Vineesha [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Laboratory of Cancer Cell Biology, Department of Research, Institute of Liver and Biliary Sciences, Delhi 110070 (India)

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

  10. Report on NCI symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. II. Cellular and animal models

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1984-01-01

    The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could be demonstrated after exposure to low-LET radiation but not after exposure to chemical carcinogens.

  11. The responsibility of the radiation protection expert; La responsabilite de la personne competente en radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Varescon, M. [AREVA NC, Direction Juridique, Departement Droit Nucleaire et de l' Environnement, 75 - Paris (France)

    2008-07-01

    After having recalled the two main different types of responsibility in the French law system (civil liability and criminal responsibility), and how criminal law has been gradually introduced in companies, the author analyzes and describes how the radiation protection expert's responsibility is tightly related to that of his employer, and how both can be committed on a disciplinary and criminal level

  12. MECANISMOS CELULARES EN RESPUESTA AL ESTRÉS:: SIRTUINAS Cellular mechanisms in response to stress: sirtuin

    Directory of Open Access Journals (Sweden)

    Nancy Paola Echeverri-Ruíz

    2010-07-01

    Full Text Available Desde hace algún tiempo se conoce el papel de la restricción calórica sobre la longevidad y la prevención de enfermedades crónicas, pero hasta hace poco los mecanismos celulares involucrados comienzan a ser elucidados. El estrés celular se podría definir como el estado en el que la célula no presenta las condiciones óptimas de supervivencia, siendo el oxidativo un tipo de estrés en el que se generan radicales libres nocivos para las estructuras celulares. La restricción calórica podría incrementar la resistencia celular a diferentes formas de estrés. Las sirtuinas, proteínas deacetilasas de histonas tipo III, están involucradas en la relación entre balance energético y transcripción génica, permitiendo que la célula responda a la restricción calórica y sobreviva a situaciones de estrés oxidativo. En esta relación las sirtuinas regulan genes de la familia FOXO, cMYC, hTERT, p53, entre otros. La activación o silenciamiento de estos genes es importante en los procesos de apoptosis, reparación y muerte celular.The role of caloric restriction on longevity and prevention of chronic diseases has been known for some time; recently, cellular mechanisms involved are beginning to be elucidated. Cellular stress could be defined as the state in which the cell does not present optimal survival conditions; oxidative stress is a type of stress in which free radicals harmful cell structures. Caloric restriction might increase cellular resistance to various forms of stress. Sirtuins, histone deacetylases type III proteins are involved in the relationship between energy balance and gene transcription, allowing cell to respond to caloric restriction and to survive to oxidative stress. In this relationship, sirtuins regulate FOXO family genes, cMYC, hTERT, p53, among others. Activation or silencing of those genes is important in the process of apoptosis, repair and cell death

  13. Role for DNA polymerase beta in response to ionizing radiation.

    NARCIS (Netherlands)

    Vermeulen, C.; Verwijs-Janssen, M.; Cramers, P.; Begg, A.C.; Vens, C.

    2007-01-01

    Evidence for a role of DNA polymerase beta in determining radiosensitivity is conflicting. In vitro assays show an involvement of DNA polymerase beta in single strand break repair and base excision repair of oxidative damages, both products of ionizing radiation. Nevertheless the lack of DNA polymer

  14. Response of Marine Microalgae, Heterotrophic Bacteria and Their Relationship to Enhanced UV-B Radiation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Wenli; TANG Xuexi; XIAO Hui; WANG You; WANG Renjun

    2009-01-01

    Ozone depletion in the stratosphere has enhanced solar UV-B radiation reaching the Earth surface and has brought about significant effects to marine ecosystems. The effects of enhanced UV-B radiation on marine microalgae, heterotrophic bacteria and the interaction between them are discussed. The effects on marine microalgae have been proved to occur at molecular, cellular and population levels. Enhanced UV-B radiation increases microalgal flavonoid content but decreases their chlorophyll content and pho-tosynthesis rate; this rachation induces genetic change and results in DNA damage and change of protein content. There have been fewer studies on the effects of UV-B radiation on marine heterotrophic bacteria. Establishment of a nucroalgal ecological dynamic model at population and community levels under UV-B radiation has gradually become a hotspot. The effects of enhanced UV-B radiation on microalgae communities, heterotrophic bacterial populations and interaction between them will become a focus in the near future. This paper will make an overview on the studies concerning the effects of enhanced UV-B radiation on marine microal-gae and heterotrophic bacteria and the interaction between them.

  15. RETRACTED: The Nonlinear Compressive Response and Deformation of an Auxetic Cellular Structure under In-Plane Loading

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2015-01-01

    Full Text Available At the request of the Author, the following article Zhang, W, Hou, W, Hu, Ping and Ma, Z (2014 The Nonlinear Compressive Response and Deformation of an Auxetic Cellular Structure under In-Plane Loading Advances in Mechanical Engineering published 17 November 2014. doi: 10.1155/2014/214681has been retracted due to errors discovered by the authors. On Page 3, the definition of component force in Equation 4 is incorrect. (2 On Page 4, the definition of component force in Equation 11 is incorrect. Moreover this equation should not have parameterM(length of cell wall, because a mistake was made in the process of calculation. Because of the above reasons, the conclusion obtained from the mechanical model is incorrect and should instead state that the Elastic Buckling and Plastic Collapse are both yield modes of this structure (3 On Page 5, the FEA model used in this article is not appropriate, because the deformation of single cell is not homogeneous, which means that the geometrical non-linear effect on single cell model is greater. So in the actual whole structure we may not obtain the results that were described in Page 6 Paragraph 2. (4 The data in figures 8 (page 6 and 9 (page 7 is incorrect and the values of effective Young’s modulus and plateau stress are much larger than reasonable values. The definition of effective stress is wrong in the FEA model, which means the effective stress should be calculated by the total width of cell instead of length of horizontal cell wall. For example, in Figure 8, the plateau stress can reach 140Mpa, this is not reasonable because there are many holes in this cellular structure, and its mechanical properties should be much lower than material properties of cell wall. The reasonable plateau stress should be around 2Mpa. The authors takes responsibility for these errors and regret the publication of invalid results. The nonlinear compressive response and deformation of an auxetic cellular structure that has

  16. Response of asymmetric carbon nanotube network devices to sub-terahertz and terahertz radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gayduchenko, I., E-mail: igorandg@gmail.com, E-mail: gefedorov@mail.ru [Physics Department, Moscow State Pedagogical University, Moscow 119991 (Russian Federation); National Research Centre “Kurchatov Institute,” Moscow 123128 (Russian Federation); Kardakova, A.; Voronov, B.; Finkel, M. [Physics Department, Moscow State Pedagogical University, Moscow 119991 (Russian Federation); Fedorov, G., E-mail: igorandg@gmail.com, E-mail: gefedorov@mail.ru [Physics Department, Moscow State Pedagogical University, Moscow 119991 (Russian Federation); Moscow Institute of Physics and Technology (State University), Dolgoprudny 141700 (Russian Federation); Jiménez, D. [Departament d' Enginyeria Electrònica, Escola d' Enginyeria, Universitat Autònoma de Barcelona, 08193 Bellaterra (Spain); Morozov, S. [Moscow Institute of Physics and Technology (State University), Dolgoprudny 141700 (Russian Federation); Presniakov, M. [National Research Centre “Kurchatov Institute,” Moscow 123128 (Russian Federation); Goltsman, G. [Physics Department, Moscow State Pedagogical University, Moscow 119991 (Russian Federation); Moscow Institute of Electronics and Mathematics, National Research University Higher School of Economics, Moscow 109028 (Russian Federation)

    2015-11-21

    Demand for efficient terahertz radiation detectors resulted in intensive study of the asymmetric carbon nanostructures as a possible solution for that problem. It was maintained that photothermoelectric effect under certain conditions results in strong response of such devices to terahertz radiation even at room temperature. In this work, we investigate different mechanisms underlying the response of asymmetric carbon nanotube (CNT) based devices to sub-terahertz and terahertz radiation. Our structures are formed with CNT networks instead of individual CNTs so that effects probed are more generic and not caused by peculiarities of an individual nanoscale object. We conclude that the DC voltage response observed in our structures is not only thermal in origin. So called diode-type response caused by asymmetry of the device IV characteristic turns out to be dominant at room temperature. Quantitative analysis provides further routes for the optimization of the device configuration, which may result in appearance of novel terahertz radiation detectors.

  17. Tunable Radiation Response in Hybrid Organic-Inorganic Gate Dielectrics for Low-Voltage Graphene Electronics.

    Science.gov (United States)

    Arnold, Heather N; Cress, Cory D; McMorrow, Julian J; Schmucker, Scott W; Sangwan, Vinod K; Jaber-Ansari, Laila; Kumar, Rajan; Puntambekar, Kanan P; Luck, Kyle A; Marks, Tobin J; Hersam, Mark C

    2016-03-01

    Solution-processed semiconductor and dielectric materials are attractive for future lightweight, low-voltage, flexible electronics, but their response to ionizing radiation environments is not well understood. Here, we investigate the radiation response of graphene field-effect transistors employing multilayer, solution-processed zirconia self-assembled nanodielectrics (Zr-SANDs) with ZrOx as a control. Total ionizing dose (TID) testing is carried out in situ using a vacuum ultraviolet source to a total radiant exposure (RE) of 23.1 μJ/cm(2). The data reveal competing charge density accumulation within and between the individual dielectric layers. Additional measurements of a modified Zr-SAND show that varying individual layer thicknesses within the gate dielectric tuned the TID response. This study thus establishes that the radiation response of graphene electronics can be tailored to achieve a desired radiation sensitivity by incorporating hybrid organic-inorganic gate dielectrics.

  18. The effects of emitter-tied field plates on lateral PNP ionizing radiation response

    Energy Technology Data Exchange (ETDEWEB)

    Barnaby, H.J.; Schrimpf, R.D.; Cirba, C.R. [Vanderbilt Univ., Nashville, TN (United States); Pease, R.L. [RLP Research, Inc., Albuquerque, NM (United States); Fleetwood, D.M. [Sandia National Labs., Albuquerque, NM (United States); Kosier, S.L. [VTC Inc., Bloomington, MN (United States)

    1998-03-01

    Radiation response comparisons of lateral PNP bipolar technologies reveal that device hardening may be achieved by extending the emitter contact over the active base. The emitter-tied field plate suppresses recombination of carriers with interface traps.

  19. Deconvolving the temporal response of photoelectric x-ray detectors for the diagnosis of pulsed radiations.

    Science.gov (United States)

    Zou, Shiyang; Song, Peng; Guo, Liang; Pei, Wenbing

    2013-09-01

    Based on the conjugate gradient method, a simple algorithm is presented for deconvolving the temporal response of photoelectric x-ray detectors (XRDs) to reconstruct the resolved time-dependent x-ray fluxes. With this algorithm, we have studied the impact of temporal response of XRD on the radiation diagnosis of hohlraum heated by a short intense laser pulse. It is found that the limiting temporal response of XRD not only postpones the rising edge and peak position of x-ray pulses but also smoothes the possible fluctuations of radiation fluxes. Without a proper consideration of the temporal response of XRD, the measured radiation flux can be largely misinterpreted for radiation pulses of a hohlraum heated by short or shaped laser pulses.

  20. Tumor Necrosis Factor-α -and Interleukin-1-Induced Cellular Responses: Coupling Proteomic and Genomic Information

    Science.gov (United States)

    Ott, Lee W.; Resing, Katheryn A.; Sizemore, Alecia W.; Heyen, Joshua W.; Cocklin, Ross R.; Pedrick, Nathan M.; Woods, H. Cary; Chen, Jake Y.; Goebl, Mark G.; Witzmann, Frank A.; Harrington, Maureen A.

    2010-01-01

    The pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNFα) and Interleukin-1 (IL-1) mediate the innate immune response. Dysregulation of the innate immune response contributes to the pathogenesis of cancer, arthritis, and congestive heart failure. TNFα- and IL-1-induced changes in gene expression are mediated by similar transcription factors; however, TNFα and IL-1 receptor knock-out mice differ in their sensitivities to a known initiator (lipopolysaccharide, LPS) of the innate immune response. The contrasting responses to LPS indicate that TNFα and IL-1 regulate different processes. A large-scale proteomic analysis of TNFα- and IL-1-induced responses was undertaken to identify processes uniquely regulated by TNFα and IL-1. When combined with genomic studies, our results indicate that TNFα, but not IL-1, mediates cell cycle arrest. PMID:17503796

  1. Tumor Necrosis Factor-alpha- and interleukin-1-induced cellular responses: coupling proteomic and genomic information.

    Science.gov (United States)

    Ott, Lee W; Resing, Katheryn A; Sizemore, Alecia W; Heyen, Joshua W; Cocklin, Ross R; Pedrick, Nathan M; Woods, H Cary; Chen, Jake Y; Goebl, Mark G; Witzmann, Frank A; Harrington, Maureen A

    2007-06-01

    The pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNFalpha) and Interleukin-1 (IL-1) mediate the innate immune response. Dysregulation of the innate immune response contributes to the pathogenesis of cancer, arthritis, and congestive heart failure. TNFalpha- and IL-1-induced changes in gene expression are mediated by similar transcription factors; however, TNFalpha and IL-1 receptor knock-out mice differ in their sensitivities to a known initiator (lipopolysaccharide, LPS) of the innate immune response. The contrasting responses to LPS indicate that TNFalpha and IL-1 regulate different processes. A large-scale proteomic analysis of TNFalpha- and IL-1-induced responses was undertaken to identify processes uniquely regulated by TNFalpha and IL-1. When combined with genomic studies, our results indicate that TNFalpha, but not IL-1, mediates cell cycle arrest.

  2. Effect of tylosin tartrate (Tylan Soluble) on cellular immune responses in chickens.

    Science.gov (United States)

    Baba, T; Yamashita, N; Kodama, H; Mukamoto, M; Asada, M; Nakamoto, K; Nose, Y; McGruder, E D

    1998-09-01

    Although many antimicrobial agents have been reported to cause immunosuppression in animals, macrolide antibiotics enhance immune function. Tylosin is a macrolide antibiotic approved for the control of mycoplasmosis in poultry. The purpose of this investigation was to determine the effect of tylosin on cellular immune functions in chickens. There was no significant difference in adherent splenocyte chemotaxis between tylosin-treated and untreated (control) chickens. Tylosin increased splenocyte proliferation and splenocyte conditioned medium (CM) proliferative activity above control levels. Removal of adherent splenocytes before preparation of CM caused a reduction in CM proliferative activity. Tylosin also increased antitumor activity of splenocytes. These data are the first to suggest that the macrolide antibiotic, tylosin tartrate, has a modulatory effect in chickens on the immune parameters studied.

  3. Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds

    Science.gov (United States)

    Moore, Laura; Grobárová, Valéria; Shen, Helen; Man, Han Bin; Míčová, Júlia; Ledvina, Miroslav; Štursa, Jan; Nesladek, Milos; Fišerová, Anna; Ho, Dean

    2014-09-01

    Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, thus demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.

  4. Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds.

    Science.gov (United States)

    Moore, Laura; Grobárová, Valéria; Shen, Helen; Man, Han Bin; Míčová, Júlia; Ledvina, Miroslav; Štursa, Jan; Nesladek, Milos; Fišerová, Anna; Ho, Dean

    2014-10-21

    Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, thus demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.

  5. Polyacrylamide scaffolds for studying cellular response to substrate stiffness in three dimensions

    Science.gov (United States)

    Lin, Keng-Hui

    2013-03-01

    Recent developments in two-dimensional (2D) culture substrates with tunable stiffness and patterned adhesion ligands have demonstrated that biochemical and mechanical cues regulate the biological functions of living cells. We have extended these cell culture platforms into three dimensions (3D), as in complex biological systems, by producing highly ordered scaffolds of polyacrylamide coated with extracellular matrix proteins. We characterized parameters for the scaffold fabrication. We then grew individual fibroblasts in the identical pores of our scaffolds, examing cellular morphological, cytoskeletal, and adhesion properties. We have observed rich variety of morphologies and anchoring strategies assumed by cells growing on our tunable 3D polyacrylamide scaffolds to demonstrate the richness of cell-mciroenvironment interactions when cell adhesions are not confined to 2D surfaces.

  6. Molecular and cellular response of earthworm Eisenia andrei (Oligochaeta, Lumbricidae) to PCDD/Fs exposure.

    Science.gov (United States)

    Nusair, Shreen Deeb; Abu Zarour, Yousef Sa'id

    2017-01-01

    The acute toxicity of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) was investigated in the earthworm Eisenia andrei using filter paper toxicity test. Protein content, catalase (CAT) activity, and histology of intestinal wall (chloragogen cells and intestinal epithelium) were investigated in earthworms exposed for 48 h to 0 (control), 0.5, 1.0, and 1.5 ng/cm(2) PCDD/Fs. The results showed an increase in the total protein content 1.56- (p = 0.104), 1.66- (p = 0.042), and 2.26-fold (p biomarkers of E. andrei within 48 h, the cellular and molecular alterations resulted from the filter paper contact test could be utilized as a rapid toxicity assessment tool of environmental contamination with dioxins/furans and to assess consequent potential adverse effects on soil biota and other organisms in the ecosystem.

  7. Modification to the capsid of the adenovirus vector that enhances dendritic cell infection and transgene-specific cellular immune responses.

    Science.gov (United States)

    Worgall, Stefan; Busch, Annette; Rivara, Michael; Bonnyay, David; Leopold, Philip L; Merritt, Robert; Hackett, Neil R; Rovelink, Peter W; Bruder, Joseph T; Wickham, Thomas J; Kovesdi, Imi; Crystal, Ronald G

    2004-03-01

    Adenovirus (Ad) gene transfer vectors can be used to transfer and express antigens and function as strong adjuvants and thus are useful platforms for the development of genetic vaccines. Based on the hypothesis that Ad vectors with enhanced infectibility of dendritic cells (DC) may be able to evoke enhanced immune responses against antigens encoded by the vector in vivo, the present study analyzes the vaccine potential of an Ad vector expressing beta-galactosidase as a model antigen and genetically modified with RGD on the fiber knob [AdZ.F(RGD)] to more selectively infect DC and consequently enhance immunity against the beta-galactosidase antigen. Infection of murine DC in vitro with AdZ.F(RGD) showed an eightfold-increased transgene expression following infection compared to AdZ (also expressing beta-galactosidase, but with a wild-type capsid). Binding, cellular uptake, and trafficking in DC were also increased with AdZ.F(RGD) compared to AdZ. To determine whether AdZ.F(RGD) could evoke enhanced immune responses to beta-galactosidase in vivo, C57BL/6 mice were immunized with AdZ.F(RGD) or AdZ subcutaneously via the footpad. Humoral responses with both vectors were comparable, with similar anti-beta-galactosidase antibody levels following vector administration. However, cellular responses to beta-galactosidase were significantly enhanced, with the frequency of CD4(+) as well as the CD8(+) beta-galactosidase-specific gamma interferon response in cells isolated from the draining lymph nodes increased following immunization with AdZ.F(RGD) compared to Ad.Z (P AdZ.F(RGD) vector was sufficient to evoke enhanced inhibition of the growth of preexisting tumors expressing beta-galactosidase: BALB/c mice implanted with the CT26 syngeneic beta-galactosidase-expressing colon carcinoma cell line and subsequently immunized with AdZ.F(RGD) showed decreased tumor growth and improved survival compared to mice immunized with AdZ. These data demonstrate that addition of an RGD motif

  8. Redox regulation of human OGG1 activity in response to cellular oxidative stress.

    Science.gov (United States)

    Bravard, Anne; Vacher, Monique; Gouget, Barbara; Coutant, Alexandre; de Boisferon, Florence Hillairet; Marsin, Stéphanie; Chevillard, Sylvie; Radicella, J Pablo

    2006-10-01

    8-Oxoguanine (8-oxoG), a common and mutagenic form of oxidized guanine in DNA, is eliminated mainly through base excision repair. In human cells its repair is initiated by human OGG1 (hOGG1), an 8-oxoG DNA glycosylase. We investigated the effects of an acute cadmium exposure of human lymphoblastoid cells on the activity of hOGG1. We show that coinciding with alteration of the redox cellular status, the 8-oxoG DNA glycosylase activity of hOGG1 was nearly completely inhibited. However, the hOGG1 activity returned to normal levels once the redox cellular status was normalized. In vitro, the activity of purified hOGG1 was abolished by cadmium and could not be recovered by EDTA. In cells, however, the reversible inactivation of OGG1 activity by cadmium was strictly associated with reversible oxidation of the protein. Moreover, the 8-oxoG DNA glycosylase activity of purified OGG1 and that from crude extracts were modulated by cysteine-modifying agents. Oxidation of OGG1 by the thiol oxidant diamide led to inhibition of the activity and a protein migration pattern similar to that seen in cadmium-treated cells. These results suggest that cadmium inhibits hOGG1 activity mainly by indirect oxidation of critical cysteine residues and that excretion of the metal from the cells leads to normalization of the redox cell status and restoration of an active hOGG1. The results presented here unveil a novel redox-dependent mechanism for the regulation of OGG1 activity.

  9. Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans.

    Science.gov (United States)

    Gullón, Sonia; Marín, Silvia; Mellado, Rafael P

    2015-01-01

    Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase) and a Tat-dependent model protein (agarase) in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients' depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host.

  10. Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans

    Science.gov (United States)

    Gullón, Sonia; Marín, Silvia; Mellado, Rafael P.

    2015-01-01

    Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase) and a Tat-dependent model protein (agarase) in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients’ depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host. PMID:26200356

  11. Mechanisms underlying the adaptive response against spontaneous neoplastic transformation induced by low doses of low LET radiation, Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    J. Leslie Redpath, Ph.D.

    2006-01-23

    The goal of this project was to investigate mechanisms underlying the adaptive response seen following exposure of HeLa x skin fibroblast human hybrid cells to low doses of low LET radiation. It was proposed to investigate the contributions of three possible mechanisms. These were: 1. Upregulation of cellular antioxidant status. 2. Upregulation of DNA repair. 3. Upregulation of gap junction intracellular communication. We have completed the study of the role of upregulation of reduced glutathione (GSH) as a possible mechanism underlying our observed suppression of transformation frequency at low radiation doses. We have also completed our study of the possible role of upregulation of DNA repair in the observed adaptive response against neoplastic transformation. We concluded that upregulation of DNA repair may be more important in modulating transformation at the higher dose. A manuscript describing the above studies has been submitted published in Carcinogenesis 24:1961-1965, 2003. Finally, we have completed two studies of the possible role of upregulation of gap junction intercellular communication (GJIC) in modulating transformation frequency at low doses of low LET radiation. This research was published in Radiation Research 162:646-654, 2004. In order to optimize the opportunity for GJIC, we then carried out a study where confluent cultures were irradiated. The results indicated, that while the degree of low dose suppression was somewhat reduced compared to that seen for subconfluent cultures, it was not completely absent. This research has been submitted for publication. Our research program was of sufficient interest to generate two invited reviews, and five invited presentations.

  12. Modulating Radiation Resistance: Novel Protection Paradigms Based on Defenses against Ionizing Radiation in the Extremophile Deinococcus radiodurans

    Science.gov (United States)

    2010-05-10

    cellular damge caused by ionizing radiation and ultraviolet light. Deinococcus radiodurans; Lactobacillus plantarurn; cyanobacteria ; radiation...6 3. K. S. Makarova and MICHAEL J. DALY (2010) Comparative genomics of stress response systems in Deinococcus bacteria. Bacterial Stress Responses...In Press) Abstract | The prospect of comparative genomics resolving the seemingly paradoxical mechanism of extreme radiation resistance in

  13. Skin Blood Perfusion and Cellular Response to Insertion of Insulin Pen Needles With Different Diameters

    DEFF Research Database (Denmark)

    Præstmark, Kezia Ann; Stallknecht, Bente Merete; Bo Jensen, Casper;

    2014-01-01

    Today most research on pen needle design revolves around pain perception statements through clinical trials, but these are both costly, timely, and require high sample sizes. The purpose of this study was to test if tissue damage, caused by different types of needles, can be assessed by evaluating...... skin blood perfusion response around needle insertion sites. Three common sized pen needles of 28G, 30G, and 32G as well as hooked 32G needles, were inserted into the neck skin of pigs and then removed. Laser Speckle Contrast Analysis was used to measure skin blood perfusion for 20 minutes after......, but there was a trend of an increased response with increasing needle diameter. Skin blood perfusion response to pen needle insertions rank according to needle diameter, and the tissue response caused by hooked 32G needles corresponds to that of 28G needles. The relation between needle diameter and trauma when...

  14. Establishing cellular stress response profiles as biomarkers of homeodynamics, health, and hormesis

    OpenAIRE

    Demirovic, Dino; Rattan, Suresh

    2013-01-01

    Aging is the progressive shrinkage of the homeodynamic space. A crucial component of the homeodynamic space is the stress response (SR), by virtue of which a living system senses disturbance and initiates a series of events for maintenance, repair, adaptation, remodeling and survival. Here we discuss the main intracellular SR pathways in human cells, and argue for the need to define and establish the immediate and delayed stress response profiles (SRP) during aging. Such SRP are required to b...

  15. Transcriptomal profiling of the cellular response to DNA damage mediated by Slug (Snai2)

    OpenAIRE

    Pérez-Caro, M.; Bermejo-Rodríguez, C.; González-Herrero, I; Sánchez-Beato, M; Piris, M. A.; Sánchez-García, I

    2008-01-01

    Snai2-deficient cells are radiosensitive to DNA damage. The function of Snai2 in response to DNA damage seems to be critical for its function in normal development and cancer. Here, we applied a functional genomics approach that combined gene-expression profiling and computational molecular network analysis to obtain global dissection of the Snai2-dependent transcriptional response to DNA damage in primary mouse embryonic fibroblasts (MEFs), which undergo p53-dependent growth arrest in respon...

  16. Tumor Necrosis Factor-α -and Interleukin-1-Induced Cellular Responses: Coupling Proteomic and Genomic Information

    OpenAIRE

    2007-01-01

    The pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNFα) and Interleukin-1 (IL-1) mediate the innate immune response. Dysregulation of the innate immune response contributes to the pathogenesis of cancer, arthritis, and congestive heart failure. TNFα- and IL-1-induced changes in gene expression are mediated by similar transcription factors; however, TNFα and IL-1 receptor knock-out mice differ in their sensitivities to a known initiator (lipopolysaccharide, LPS) of the innate immune...

  17. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    Energy Technology Data Exchange (ETDEWEB)

    Latham, Antony M.; Odell, Adam F. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Mughal, Nadeem A. [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Issitt, Theo; Ulyatt, Clare; Walker, John H. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Homer-Vanniasinkam, Shervanthi [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Ponnambalam, Sreenivasan, E-mail: s.ponnambalam@leeds.ac.uk [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2012-11-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black

  18. Development, Verification and Validation of Enclosure Radiation Capabilities in the CHarring Ablator Response (CHAR) Code

    Science.gov (United States)

    Salazar, Giovanni; Droba, Justin C.; Oliver, Brandon; Amar, Adam J.

    2016-01-01

    With the recent development of multi-dimensional thermal protection system (TPS) material response codes including the capabilities to account for radiative heating is a requirement. This paper presents the recent efforts to implement such capabilities in the CHarring Ablator Response (CHAR) code developed at NASA's Johnson Space Center. This work also describes the different numerical methods implemented in the code to compute view factors for radiation problems involving multiple surfaces. Furthermore, verification and validation of the code's radiation capabilities are demonstrated by comparing solutions to analytical results, to other codes, and to radiant test data.

  19. Tetanus toxoid-loaded layer-by-layer nanoassemblies for efficient systemic, mucosal, and cellular immunostimulatory response following oral administration.

    Science.gov (United States)

    Harde, Harshad; Agrawal, Ashish Kumar; Jain, Sanyog

    2015-10-01

    The present study reports the tetanus toxoid (TT)-loaded layer-by-layer nanoassemblies (layersomes) with enhanced protection, permeation, and presentation for comprehensive oral immunization. The stable and lyophilized TT-loaded layersomes were prepared by a thin-film hydration method followed by alternate layer-by-layer coating of an electrolyte. The developed system was assessed for in vitro stability of antigen and formulation, cellular uptake, ex vivo intestinal uptake, and immunostimulatory response using a suitable experimental protocol. Layersomes improved the stability in simulated biological media as well as protected the integrity/conformation and native 3D structure of TT as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence spectroscopy, respectively. The cell culture studies demonstrated a 3.8-fold higher permeation of layersomes in Caco-2 cells and an 8.5-fold higher uptake by antigen-presenting cells (RAW 264.7). The TT-loaded layersomes elicited a complete immunostimulatory profile consisting of higher systemic (serum IgG titer), mucosal (sIgA titer), and cellular (interleukin-2 (IL-2) and interferon-γ (IFN-γ) levels) immune response after peroral administration in mice. The modified TT inhibition assay further confirmed the elicitation of complete protective levels of anti-TT antibody (>0.1 IU/mL) by layersomes. In conclusion, the proposed strategy is expected to contribute significantly in the field of stable liposome technology for mass immunization through the oral route.

  20. Cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells.

    Science.gov (United States)

    Lim, Young-Cheol; Yoo, Je-Ok; Kang, Seong-Sik; Kim, Young-Myeong; Ha, Kwon-Soo

    2011-03-01

    We investigated cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells. Cells were loaded with 0.5-10 μg/mL DH-II-24 for 12 h, and intracellular reactive oxygen species (ROS) and intracellular Ca(2+) levels, in situ tissue transglutaminase (tTGase) activity, cell viability, cell morphology and cell cycle were examined. DH-II-24 treatment had no effect on intracellular ROS production or cell morphology, and did not induce cell detachment at any concentrations tested. In addition, cell viability and cell cycle progression were not altered by the photosensitizer. However, DH-II-24 treatment elevated the basal level of intracellular Ca(2+) in a dose-dependent manner and inhibited tTGase activity without affecting tTGase expression levels. Furthermore, DH-II-24 inhibited lysophosphatidic acid-induced activation of tTGase in a dose-dependent manner. In contrast, photodynamic therapy (PDT) with 1 μg/mL DH-II-24 significantly elevated intracellular ROS and in situ tTGase activity in parallel with a rapid and large increase in intracellular Ca(2+) levels. DH-II-24-mediated PDT decreased cell viability and induced cell detachment. These results demonstrate that DH-II-24 treatment alone under darkness induced different cellular responses to DH-II-24-mediated PDT.

  1. Study on biological response to space radiation and its countermeasure

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jong Il; Lee, Ju Woon; Kim, Dong Ho; Kim, Jae Hun; Song, Beom Suk; Kim, Jae Kyung; Park, Jong Heum; Kim, Jin Kyu [KAERI, Daejeon (Korea, Republic of)

    2011-12-15

    The purpose is to develop the core technologies for the advanced life supporting system based on radiation technology by 2015 and to be a member of G7 in the space technology research field. And it is the final aim that contribution for establishment of the self-supporting technology and national strength by 2020. To simulate the space environment of microgravity and expose to space radiation, denervation model was established in Gamma Phytotron. The changes in microflora population in animal model was shown. The effect of simulated microgravity and long-term exposure to irradiation was investigated. In the experiment of MARS 500, crews for expedition to Mars had been served by Korean space foods (Bulgogi, Bibimbap, Seaweed soup, Mulberry beverage, Kimchi, Sujeonggwa) for 120 days, then their immunity will be examined and compared with it on the ground.

  2. A possible role for extra-cellular ATP in plant responses to high frequency, low amplitude electromagnetic field.

    Science.gov (United States)

    Roux, David; Faure, Catherine; Bonnet, Pierre; Girard, Sébastien; Ledoigt, Gérard; Davies, Eric; Gendraud, Michel; Paladian, Françoise; Vian, Alain

    2008-06-01

    In parallel to evoking the accumulation of stress-related transcripts, exposure to low level 900 MHz EMF affected the levels of ATP, the main energy molecule of the cell. Its concentration dropped rapidly (27% after 30 min) in response to EMF exposure, along with a 18% decrease in the adenylate energy charge (AEC), a good marker of cell energy status. One could interpret this decrease in ATP and AEC in a classical way, i.e., as the result of an increase in cellular energy usage, but recent work brings exciting new insights in pointing out a signalling function for ATP, especially in the stress physiology context where it could trigger both reactive oxygen species and calcium movement (this latter being involved in plant responses to EMF exposure). In this addendum, we discuss our results within this new perspective for ATP function.

  3. Blood Group O-Dependent Cellular Responses to Cholera Toxin: Parallel Clinical and Epidemiological Links to Severe Cholera.

    Science.gov (United States)

    Kuhlmann, F Matthew; Santhanam, Srikanth; Kumar, Pardeep; Luo, Qingwei; Ciorba, Matthew A; Fleckenstein, James M

    2016-08-03

    Because O blood group has been associated with more severe cholera infections, it has been hypothesized that cholera toxin (CT) may bind non-O blood group antigens of the intestinal mucosae, thereby preventing efficient interaction with target GM1 gangliosides required for uptake of the toxin and activation of cyclic adenosine monophosphate (cAMP) signaling in target epithelia. Herein, we show that after exposure to CT, human enteroids expressing O blood group exhibited marked increase in cAMP relative to cells derived from blood group A individuals. Likewise, using CRISPR/Cas9 engineering, a functional group O line (HT-29-A(-/-)) was generated from a parent group A HT-29 line. CT stimulated robust cAMP responses in HT-29-A(-/-) cells relative to HT-29 cells. These findings provide a direct molecular link between blood group O expression and differential cellular responses to CT, recapitulating clinical and epidemiologic observations.

  4. OSTEOPOROSIS AND ALZHEIMER PATHOLOGY: ROLE OF CELLULAR STRESS RESPONSE AND HORMETIC REDOX SIGNALING IN AGING AND BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Vittorio eCalabrese

    2014-06-01

    Full Text Available Alzheimer’s disease (AD as well as osteoporosis are multifactorial progressive degenerative disorders characterized by low parenchymal density and microarchitectural deterioration of tissue. Though not referred to as one of the major complications of AD, osteoporosis and hip fracture are commonly observed in patients with AD, however, the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS are generally recognized as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-kB ligand (RANKL-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways which regulate life span across species including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in bone remodeling and activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysruption with consequent impact on

  5. Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Gerdil, Adèle; Diemer, Hélène; Proamer, Fabienne; Collin-Faure, Véronique; Habert, Aurélie; Strub, Jean-Marc; Hanau, Daniel; Herlin, Nathalie; Carrière, Marie; van Dorsselaer, Alain; Rabilloud, Thierry

    2014-05-01

    Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations.Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate

  6. Positive and Negative Regulation of Cellular Immune Responses in Physiologic Conditions and Diseases

    Directory of Open Access Journals (Sweden)

    S. Viganò

    2012-01-01

    Full Text Available The immune system has evolved to allow robust responses against pathogens while avoiding autoimmunity. This is notably enabled by stimulatory and inhibitory signals which contribute to the regulation of immune responses. In the presence of a pathogen, a specific and effective immune response must be induced and this leads to antigen-specific T-cell proliferation, cytokines production, and induction of T-cell differentiation toward an effector phenotype. After clearance or control of the pathogen, the effector immune response must be terminated in order to avoid tissue damage and chronic inflammation and this process involves coinhibitory molecules. When the immune system fails to eliminate or control the pathogen, continuous stimulation of T cells prevents the full contraction and leads to the functional exhaustion of effector T cells. Several evidences both in vitro and in vivo suggest that this anergic state can be reverted by blocking the interactions between coinhibitory molecules and their ligands. The potential to revert exhausted or inactivated T-cell responses following selective blocking of their function made these markers interesting targets for therapeutic interventions in patients with persistent viral infections or cancer.

  7. Vitamin D both facilitates and attenuates the cellular response to lipopolysaccharide

    Science.gov (United States)

    Chen, Ling; Eapen, Mathew Suji; Zosky, Graeme R.

    2017-01-01

    Vitamin D has a range of non-skeletal health effects and has been implicated in the response to respiratory infections. The aim of this study was to assess the effect of vitamin D on the response of epithelial cells, neutrophils and macrophages to lipopolysaccharide (LPS) stimulation. BEAS-2B cells (airway epithelial cell line) and primary neutrophils and macrophages isolated from blood samples were cultured and exposed to LPS with and without vitamin D (1,25(OH)2D). The production of IL-6, IL-8, IL-1β and TNF-α of all cells and the phagocytic capacity of neutrophils and macrophages to E. coli were assessed. Vitamin D had no effect on BEAS-2B cells but enhanced the production of IL-8 in neutrophils (p = 0.007) and IL-1β in macrophages (p = 0.007) in response to LPS. Both vitamin D (p = 0.019) and LPS (p vitamin D on responses to infection are complex and that the net effect will depend on the cells that respond, the key response that is necessary for resolution of infection (cytokine production or phagocytosis) and whether there is pre-existing inflammation. PMID:28345644

  8. "Killing the Blues": a role for cellular suicide (apoptosis) in depression and the antidepressant response?

    Science.gov (United States)

    McKernan, Declan P; Dinan, Timothy G; Cryan, John F

    2009-08-01

    Apoptosis or programmed cell death is a critical regulator of tissue homeostasis and emerging evidence is focused on the role of apoptosis mechanisms in the central nervous system. Generally, apoptosis is necessary to prevent cancerous growths. However, excessive apoptosis in post-mitotic cells such as neurons leads to neurodegeneration. Chronic stress, which can precipitate depression, has been shown to increase the susceptibility of certain populations of neurons to cell death while antidepressant treatment, in general, shows the ability to oppose these effects and promote neuroprotection. Here, we discuss the major players in cell death pathways, the physiological implications of chronic stress and depression, chronic stress models in animals which result in cell death and the different classes of antidepressants and mood stabilizers that have been shown to prevent cell death. We discuss the cellular effects of antidepressants and possible modes of action in preventing apoptosis. Investigations on the role of apoptosis in mediating the molecular, physiological and behavioural effects of antidepressants may help gain a better mechanistic insight into drug action and allow refinement of current therapeutics in order to target these pathways in a specific manner.

  9. Investigation of drugs responsible for perioperative anaphylactic reactions using cellular allergen stimulation test

    Institute of Scientific and Technical Information of China (English)

    Xin Xin; Zou Yi; Xing Lijiao; Yin Jia; Gu Jianqing; Wang Zixi; Huang Yuguang

    2014-01-01

    Background Anaphylactic reactions during anesthesia and operation are common and life threatening.Follow-up investigation is necessary for avoiding potential re-exposure of the patients to the offending drugs.The purpose of this study was to assess cellular allergen stimulation test (CAST) as a diagnostic instrument in immunoglobulin E (IgE)-and non-lgE-mediated anaphylactic reactions.Methods This study included 25 patients who developed perioperative anaphylactic reactions and 10 subjects that tolerated anesthetics and other drugs during perioperative period from September 2009 to October 2013 in Peking Union Medical College Hospital.We performed skin tests and flow cytometric analysis of basophil activation-based CAST in all subjects.Results Of the 25 patients,17 had IgE-mediated anaphylactic reactions (causative agent identified by skin tests) and 8 had non-lgE-mediated anaphylactic reactions (negative skin tests).CAST showed a sensitivity of 42.9%,specificity of 90%,and negative predictive value of 80.6% for neuromuscular blocking agents.Conclusions CAST may be useful for the diagnosis of anaphylactic reactions during perioperative period.Our findings call for further investigation to increase the sensitivity of the test.

  10. Improved cellular response of chemically crosslinked collagen incorporated hydroxyethyl cellulose/poly(vinyl) alcohol nanofibers scaffold.

    Science.gov (United States)

    Zulkifli, Farah Hanani; Jahir Hussain, Fathima Shahitha; Abdull Rasad, Mohammad Syaiful Bahari; Mohd Yusoff, Mashitah

    2015-02-01

    The aim of this research is to develop biocompatible nanofibrous mats using hydroxyethyl cellulose with improved cellular adhesion profiles and stability and use these fibrous mats as potential scaffold for skin tissue engineering. Glutaraldehyde was used to treat the scaffolds water insoluble as well as improve their biostability for possible use in biomedical applications. Electrospinning of hydroxyethyl cellulose (5 wt%) with poly(vinyl alcohol) (15 wt%) incorporated with and without collagen was blended at (1:1:1) and (1:1) ratios, respectively, and was evaluated for optimal criteria as tissue engineering scaffolds. The nanofibrous mats were crosslinked and characterized by scanning electron microscope, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Scanning electron microscope images showed that the mean diameters of blend nanofibers were gradually increased after chemically crosslinking with glutaraldehyde. Fourier transform infrared spectroscopy was carried out to understand chemical interactions in the presence of aldehyde groups. Thermal characterization results showed that the stability of hydroxyethyl cellulose/poly(vinyl alcohol) and hydroxyethyl cellulose/poly(vinyl alcohol)/collagen nanofibers was increased with glutaraldehyde treatment. Studies on cell-scaffolds interaction were carried out by culturing human fibroblast (hFOB) cells on the nanofibers by assessing the growth, proliferation, and morphologies of cells. The scanning electron microscope results show that better cell proliferation and attachment appeared on hydroxyethyl cellulose/poly(vinyl alcohol)/collagen substrates after 7 days of culturing, thus, promoting the potential of electrospun scaffolds as a promising candidate for tissue engineering applications.

  11. Antimicrobial activities and cellular responses to natural silicate clays and derivatives modified by cationic alkylamine salts.

    Science.gov (United States)

    Hsu, Shan-Hui; Tseng, Hsiang-Jung; Hung, Huey-Shan; Wang, Ming-Chien; Hung, Chiung-Hui; Li, Pei-Ru; Lin, Jiang-Jen

    2009-11-01

    Nanometer-scale silicate platelet (NSP) materials were previously developed by increasing the interlayer space and exfoliation of layered silicate clays such as montmorillonite and synthetic fluorinated mica by the process of polyamine exfoliation. In this study, the antibacterial activity and cytotoxicity of these nanometer-scale silicate clays were evaluated. The derivatives of NSP (NSP-S) which were modified by C18-fatty amine salts via ionic exchange association exhibited the highest antibacterial activity in the aqueous state among all clays. The high antibacterial activity, however, was accompanied by elevated cytotoxicity. The variations of cell surface markers (CD29 and CD44) and type I collagen expression of fibroblasts treated with the clays were measured to clarify the mechanism of the silicate-induced cytotoxicity. The signal transduction pathway involved the downregulation of extracellular-signal-regulated kinase (ERK), which appeared to participate in silicate-induced cytotoxicity. This study helped to understand the antibacterial potential of NSP and the interaction of natural and modified clays with cellular activities.

  12. Cellular mechanisms for the slow phase of the Frank-Starling response.

    Science.gov (United States)

    Bluhm, W F; Sung, D; Lew, W Y; Garfinkel, A; McCulloch, A D

    1998-01-01

    Following a step increase in sarcomere length, isometric cardiac muscle tension increases instantaneously by the Frank-Starling mechanism. In isolated papillary muscle and myocytes, there is an additional significant rise in developed tension over the following 15 min due to an unknown mechanism. This slow change in tension could not be explained by mechanical heterogeneity of the muscle preparations or by an increase in myofilament sensitivity to Ca2+. The slow change in tension was not dependent on sarcoplasmic reticulum Ca2+ loading assessed with rapid cooling contractures, and was not significantly altered by sarcoplasmic reticulum Ca2+ depletion (ryanodine) or inhibition of sarcoplasmic reticulum Ca2+ reuptake (cyclopiazonic acid). We used the Luo-Rudy ionic model of the ventricular myocyte together with a model of the length-dependent myofilament activation by Ca2+ to examine the effects of step changes in the parameters of sarcolemmal ion fluxes as possible mechanisms for the slow change in stress. The slow increase in tension was simulated by step changes in the Na+-K+ pump or Na+ leak currents, suggesting that the slow change in stress may be caused by length induced changes in Na+ fluxes. The model also predicted a slow increase in the magnitude of the initial repolarization during phase 1 of the action potential. The combination of experimental and computational models used in this investigation represents a valuable technique in elucidating the cellular mechanisms of fundamental processes in cardiac excitation-contraction coupling.

  13. Mgat1-dependent N-glycosylation of membrane components primes Drosophila melanogaster blood cells for the cellular encapsulation response.

    Directory of Open Access Journals (Sweden)

    Nathan T Mortimer

    Full Text Available In nature, larvae of the fruitfly Drosophila melanogaster are commonly infected by parasitoid wasps, and so have evolved a robust immune response to counter wasp infection. In this response, fly immune cells form a multilayered capsule surrounding the wasp egg, leading to death of the parasite. Many of the molecular mechanisms underlying this encapsulation response are conserved with human immune responses. Our findings suggest that protein N-glycosylation, a common protein post-translational modification of human immune proteins, may be one such conserved mechanism. We found that membrane proteins on Drosophila immune cells are N-glycosylated in a temporally specific manner following wasp infection. Furthermore we have identified mutations in eight genes encoding enzymes of the N-glycosylation pathway that decrease fly resistance to wasp infection. More specifically, loss of protein N-glycosylation in immune cells following wasp infection led to the formation of defective capsules, which disintegrated over time and were thereby unsuccessful at preventing wasp development. Interestingly, we also found that one species of Drosophila parasitoid wasp, Leptopilina victoriae, targets protein N-glycosylation as part of its virulence mechanism, and that overexpression of an N-glycosylation enzyme could confer resistance against this wasp species to otherwise susceptible flies. Taken together, these findings demonstrate that protein N-glycosylation is a key player in Drosophila cellular encapsulation and suggest that this response may provide a novel model to study conserved roles of protein glycosylation in immunity.

  14. Time course proteomic profiling of cellular responses to immunological challenge in the sea urchin, Heliocidaris erythrogramma.

    Science.gov (United States)

    Dheilly, Nolwenn M; Haynes, Paul A; Raftos, David A; Nair, Sham V

    2012-06-01

    Genome sequences and high diversity cDNA arrays have provided a detailed molecular understanding of immune responses in a number of invertebrates, including sea urchins. However, complementary analyses have not been undertaken at the level of proteins. Here, we use shotgun proteomics to describe changes in the abundance of proteins from coelomocytes of sea urchins after immunological challenge and wounding. The relative abundance of 345 reproducibly identified proteins were measured 6, 24 and 48 h after injection. Significant changes in the relative abundance of 188 proteins were detected. These included pathogen-binding proteins, such as the complement component C3 and scavenger receptor cysteine rich proteins, as well as proteins responsible for cytoskeletal remodeling, endocytosis and intracellular signaling. An initial systemic reaction to wounding was followed by a more specific response to immunological challenge involving proteins such as apolipophorin, dual oxidase, fibrocystin L, aminopeptidase N and α-2-macroglobulin.

  15. Aberrant cellular immune responses in humans infected persistently with parvovirus B19

    DEFF Research Database (Denmark)

    Isa, Adiba; Norbeck, Oscar; Hirbod, Taha;

    2006-01-01

    A subset of parvovirus B19 (B19) infected patients retains the infection for years, as defined by detection of B19 DNA in bone marrow. Thus far, analysis of B19-specific humoral immune responses and viral genome variations has not revealed a mechanism for the absent viral clearance. In this study...

  16. Cellular immune responses to nine Mycobacterium tuberculosis vaccine candidates following intranasal vaccination.

    Directory of Open Access Journals (Sweden)

    Suraj B Sable

    Full Text Available BACKGROUND: The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. METHODS AND PRINCIPAL FINDINGS: In this study, a comparison of intranasal (i.n. and subcutaneous (s.c. vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860 was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. CONCLUSION AND SIGNIFICANCE: Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis.

  17. Inhibition of IRF3-dependent antiviral responses by cellular and viral proteins

    Institute of Scientific and Technical Information of China (English)

    Tetsuo Tsuchida; Taro Kawai; Shizuo Akira

    2009-01-01

    @@ The host evokes innate immune responses to eliminate viruses by detect mg the presence of infection.Host cells respond to nucleic acids derived from infected viruses to produce cytokines known as type I interferons(IFNβ and multiple IFNα),which are the most important cytokines for host defense against viral infection.

  18. Responses in the morphology, physiology and biochemistry of Taxus chinensis var. mairei grown under supplementary UV-B radiation.

    Science.gov (United States)

    Zu, Yuan-gang; Pang, Hai-He; Yu, Jing-Hua; Li, De-Wen; Wei, Xiao-Xue; Gao, Yin-Xiang; Tong, Lu

    2010-02-12

    The effects of supplemental UV-B radiation on Taxus chinensis var. mairei were studied. Leaf traits, gas exchange parameters and the concentrations of photosynthetic pigments, cellular defense system products, secondary metabolites and ultrastructure were determined. UV-B radiation significantly decreased leaf area (psecondary branch number, leaf weight per plant and leaf moisture all increased dramatically (pUV-B radiation. Gas exchange parameters were all dramatically reduced by enhanced UV-B radiation (pUV-B radiation, while carotenoids content significantly decreased (pUV-B treatment induced significant flavonoid accumulation (pUV-B radiation, whereas the aperture size of single stomata was diminished. The number and area of plastoglobuli were apparently reduced by UV-B radiation, but stroma and grana lamellae were not destroyed. Our results demonstrated that T. chinensis var. mairei can activate several defense mechanisms against oxidative stress injury caused by supplemental UV-B radiation.

  19. Phenylalanine is required to promote specific developmental responses and prevents cellular damage in response to ultraviolet light in soybean (Glycine max during the seed-to-seedling transition.

    Directory of Open Access Journals (Sweden)

    Joe H Sullivan

    Full Text Available UV-radiation elicits a suite of developmental (photomorphogenic and protective responses in plants, but responses early post-germination have received little attention, particularly in intensively bred plants of economic importance. We examined germination, hypocotyl elongation, leaf pubescence and subcellular responses of germinating and/or etiolated soybean (Glycine max (L. Merr. seedlings in response to treatment with discrete wavelengths of UV-A or UV-B radiation. We demonstrate differential responses of germinating/young soybean seedlings to a range of UV wavelengths that indicate unique signal transduction mechanisms regulate UV-initiated responses. We have investigated how phenylalanine, a key substrate in the phenylpropanoid pathway, may be involved in these responses. Pubescence may be a key location for phenylalanine-derived protective compounds, as UV-B irradiation increased pubescence and accumulation of UV-absorbing compounds within primary leaf pubescence, visualized by microscopy and absorbance spectra. Mass spectrometry analysis of pubescence indicated that sinapic esters accumulate in the UV-irradiated hairs compared to unirradiated primary leaf tissue. Deleterious effects of some UV-B wavelengths on germination and seedling responses were reduced or entirely prevented by inclusion of phenylalanine in the growth media. Key effects of phenylalanine were not duplicated by tyrosine or tryptophan or sucrose, nor is the specificity of response due to the absorbance of phenylalanine itself. These results suggest that in the seed-to-seedling transition, phenylalanine may be a limiting factor in the development of initial mechanisms of UV protection in the developing leaf.

  20. The cellular immune response of the pea aphid to foreign intrusion and symbiotic challenge.

    Directory of Open Access Journals (Sweden)

    Antonin Schmitz

    Full Text Available Recent studies suggest that the pea aphid (Acyrthosiphon pisum has low immune defenses. However, its immune components are largely undescribed, and notably, extensive characterization of circulating cells has been missing. Here, we report characterization of five cell categories in hemolymph of adults of the LL01 pea aphid clone, devoid of secondary symbionts (SS: prohemocytes, plasmatocytes, granulocytes, spherulocytes and wax cells. Circulating lipid-filed wax cells are rare; they otherwise localize at the basis of the cornicles. Spherulocytes, that are likely sub-cuticular sessile cells, are involved in the coagulation process. Prohemocytes have features of precursor cells. Plasmatocytes and granulocytes, the only adherent cells, can form a layer in vivo around inserted foreign objects and phagocytize latex beads or Escherichia coli bacteria injected into aphid hemolymph. Using digital image analysis, we estimated that the hemolymph from one LL01 aphid contains about 600 adherent cells, 35% being granulocytes. Among aphid YR2 lines differing only in their SS content, similar results to LL01 were observed for YR2-Amp (without SS and YR2-Ss (with Serratia symbiotica, while YR2-Hd (with Hamiltonella defensa and YR2(Ri (with Regiella insecticola had strikingly lower adherent hemocyte numbers and granulocyte proportions. The effect of the presence of SS on A. pisum cellular immunity is thus symbiont-dependent. Interestingly, Buchnera aphidicola (the aphid primary symbiont and all SS, whether naturally present, released during hemolymph collection, or artificially injected, were internalized by adherent hemocytes. Inside hemocytes, SS were observed in phagocytic vesicles, most often in phagolysosomes. Our results thus raise the question whether aphid symbionts in hemolymph are taken up and destroyed by hemocytes, or actively promote their own internalization, for instance as a way of being transmitted to the next generation. Altogether, we

  1. Cellular and Matrix Response of the Mandibular Condylar Cartilage to Botulinum Toxin

    Science.gov (United States)

    Dutra, Eliane H.; O’ Brien, Mara H.; Lima, Alexandro; Kalajzic, Zana; Tadinada, Aditya; Nanda, Ravindra; Yadav, Sumit

    2016-01-01

    Objectives To evaluate the cellular and matrix effects of botulinum toxin type A (Botox) on mandibular condylar cartilage (MCC) and subchondral bone. Materials and Methods Botox (0.3 unit) was injected into the right masseter of 5-week-old transgenic mice (Col10a1-RFPcherry) at day 1. Left side masseter was used as intra-animal control. The following bone labels were intraperitoneally injected: calcein at day 7, alizarin red at day 14 and calcein at day 21. In addition, EdU was injected 48 and 24 hours before sacrifice. Mice were sacrificed 30 days after Botox injection. Experimental and control side mandibles were dissected and examined by x-ray imaging and micro-CT. Subsequently, MCC along with the subchondral bone was sectioned and stained with tartrate resistant acid phosphatase (TRAP), EdU, TUNEL, alkaline phosphatase, toluidine blue and safranin O. In addition, we performed immunohistochemistry for pSMAD and VEGF. Results Bone volume fraction, tissue density and trabecular thickness were significantly decreased on the right side of the subchondral bone and mineralized cartilage (Botox was injected) when compared to the left side. There was no significant difference in the mandibular length and condylar head length; however, the condylar width was significantly decreased after Botox injection. Our histology showed decreased numbers of Col10a1 expressing cells, decreased cell proliferation and increased cell apoptosis in the subchondral bone and mandibular condylar cartilage, decreased TRAP activity and mineralization of Botox injected side cartilage and subchondral bone. Furthermore, we observed reduced proteoglycan and glycosaminoglycan distribution and decreased expression of pSMAD 1/5/8 and VEGF in the MCC of the Botox injected side in comparison to control side. Conclusion Injection of Botox in masseter muscle leads to decreased mineralization and matrix deposition, reduced chondrocyte proliferation and differentiation and increased cell apoptosis in the

  2. Design of parallel microfluidic gradient-generating networks for studying cellular response to chemical stimuli

    Institute of Scientific and Technical Information of China (English)

    Lihui WANG; Dayu LIU; Bo WANG; Jie SUN; Lianhong LI

    2008-01-01

    A microfluidic chip featuring laminar flow-based parallel gradient-generating networks was designed and fabricated. The microchip contains 5 gradient genera-tors and 30 cell chambers where the resulting concentra-tion gradients of drugs are delivered to stimulate on-chip cultured cells. The microfluidics exploits the advantage of lab-on-a-chip technology by integrating the generation of drug concentration gradients and a series of cell opera-tions including seeding, culture, stimulation and staining into a chip. The microfluidic network was patterned on a glass wafer, which was further bonded to a PDMS film. A series of weir structures were fabricated on the cell culture reservoir to facilitate cell positioning and seeding. Cell injection and fluid delivery were controlled by a syringe pump. Steady parallel concentration gradients were gen-erated by flowing two fluids in each network. Over time observation shows that the microchip was suitable for cell seeding and culture. The microchip described above was applied in studying the role of reduced glutathione (GSH) in mediating chemotherapy sensitivity of MCF-7 cells. MCF-7 cells were treated with concentration gradients of As2O3 and N-acetyl cysteine (NAC) for GSH modu-lation, followed by exposure to adriamycin. GSH levels were down-regulated upon As203 treatment and up-regu-lated upon NAC treatment. Suppression of intracellular GSH by treatment with As2O3 has been shown to increase sensitivity to adriamycin. Conversely, elevation of intra-cellular GSH by treatment with NAC leads to increased drug resistance. The integrated microfluidic chip is able to perform multiparametric pharmacological profiling with easy operation, and thus holds great potential for extra-polation to the cell based high-content drug screening.

  3. Response of nickel surface to pulsed fusion plasma radiations

    Science.gov (United States)

    Niranjan, Ram; Rout, R. K.; Srivastava, R.; Chakravarthy, Y.; Patel, N. N.; Alex, P.; Gupta, Satish C.

    2014-04-01

    Nickel based alloys are being projected as suitable materials for some components of the next generation fusion reactor because of compatible thermal, electrical and mechanical properties. Pure nickel material is tested here for possibility of similar application purpose. Nickel samples (> 99.5 % purity) are exposed here to plasma radiations produced due to D-D fusion reaction inside an 11.5 kJ plasma focus device. The changes in the physical properties of the nickel surface at microscopic level which in turn change the mechanical properties are analyzed using scanning electron microscope, optical microscope, glancing incident X-ray diffractometer and Vicker's hardness gauge. The results are reported here.

  4. Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.

    Directory of Open Access Journals (Sweden)

    Nadine T Nehme

    Full Text Available BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd, are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus, we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.

  5.  Evaluation of the humoral and cellular immune responses after implantation of a PTFE vascular prosthesis

    Directory of Open Access Journals (Sweden)

    Jan Skóra

    2012-07-01

    Full Text Available  Introduction:The experiment was designed in order to determine the immunological processes that occur during the healing in synthetic vascular grafts, especially to establish the differences in the location of the complement system proteins between the proximal and distal anastomosis and the differences in the arrangement of inflammatory cells in those anastomoses. The understanding of those processes will provide a true basis for determining risk factors for complications after arterial repair procedures.Material/Methods:The experiment was carried out on 16 dogs that underwent implantation of unilateral aorto-femoral bypass with expanded polytetrafluoroethylene (ePTFE. After 6 months all animals were euthanized to dissect the vascular grafts. Immunohistochemical assays and electron microscopic examinations were performed.Results:Immunohistochemical findings in the structure of neointima between anastomoses of vascular prostheses demonstrated significant differences between humoral and cellular responses. The area of proximal anastomosis revealed the presence of fibroblasts, but no macrophages were detected. The histological structure of the proximal anastomosis indicates that inflammatory processes were ended during the prosthesis healing. The immunological response obtained in the distal anastomosis corresponded to the chronic inflammatory reaction with the presence of macrophages, myofibroblasts and deposits of complement C3.Discussion:The identification of differences in the presence of macrophages and myofibroblasts and the presence of the C3 component between the anastomoses is the original achievement of the present study. In the available literature, no such significant differences have been shown so far in the humoral and cellular immune response caused by the presence of an artificial vessel in the arterial system.

  6. 细胞的缺氧信号转导通路%Cellular signal transduction of the hypoxia response

    Institute of Scientific and Technical Information of China (English)

    韩菲菲(综述); 陈国千(审校)

    2014-01-01

    缺氧是人类诸多疾病中一个重要的病理生理因素。细胞缺氧反应是细胞氧感受器感受缺氧刺激后,激活多条细胞内信号转导通路,进而调控细胞周期及机体呼吸、血液循环、能量代谢等多种生理功能的过程。细胞对缺氧的应答反应具有复杂多样性。细胞在感受缺氧、传递缺氧信号的过程中,缺氧诱导因子(Hypoxia-inducible factor, HIF)具有重要作用。激活非HIF依赖的信号转导通路在维持自身氧平衡和能量代谢平衡中也起重要作用。%Hypoxia is a common physiological and pathological stimulus in many human diseases .The cellular oxygen sensors and the following activation of multiple cellular signal transduction pathways involved in hypoxia responses can regulate cell survival as well as respiration , blood circulation , metabolism and so forth .The cell response to hypoxia has a complex diversity .Hypoxia-induc-ible factor ( HIF) pathway in an oxygen dependent manner plays a central role during the hypoxia response .The HIF-independent path-ways are equally important under hypoxic conditions which can maintain the oxygen balance and metabolism balance .

  7. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

    2015-10-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.