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Sample records for induced bystander effect

  1. Neutron induced bystander effect among zebrafish embryos

    NASA Astrophysics Data System (ADS)

    Ng, C. Y. P.; Kong, E. Y.; Kobayashi, A.; Suya, N.; Uchihori, Y.; Cheng, S. H.; Konishi, T.; Yu, K. N.

    2015-12-01

    The present paper reported the first-ever observation of neutron induced bystander effect (NIBE) using zebrafish (Danio rerio) embryos as the in vivo model. The neutron exposure in the present work was provided by the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. Two different strategies were employed to induce NIBE, namely, through directly partnering and through medium transfer. Both results agreed with a neutron-dose window (20-50 mGy) which could induce NIBE. The lower dose limit corresponded to the threshold amount of neutron-induced damages to trigger significant bystander signals, while the upper limit corresponded to the onset of gamma-ray hormesis which could mitigate the neutron-induced damages and thereby suppress the bystander signals. Failures to observe NIBE in previous studies were due to using neutron doses outside the dose-window. Strategies to enhance the chance of observing NIBE included (1) use of a mono-energetic high-energy (e.g., between 100 keV and 2 MeV) neutron source, and (2) use of a neutron source with a small gamma-ray contamination. It appeared that the NASBEE facility used in the present study fulfilled both conditions, and was thus ideal for triggering NIBE.

  2. Heavy-ion radiation induced bystander effect in mice

    NASA Astrophysics Data System (ADS)

    Liang, Shujian; Sun, Yeqing; Zhang, Meng; Wang, Wei; Cui, Changna

    2012-07-01

    Radiation-induced bystander effect is defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, Low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic, metabolomics and proteomics play significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male mice head were exposed to 2000mGy dose of 12C heavy-ion radiation and the distant organ liver was detected on 1h, 6h, 12h and 24h after radiation, respectively. MSAP was used to monitor the level of polymorphic DNA methylation changes. The results show that heavy-ion irradiate mouse head can induce liver DNA methylation changes significantly. The percent of DNA methylation changes are time-dependent and highest at 6h after radiation. We also prove that the hypo-methylation changes on 1h and 6h after irradiation. But the expression level of DNA methyltransferase DNMT3a is not changed. UPLC/Synapt HDMS G2 was employed to detect the proteomics of bystander liver 1h after irradiation. 64 proteins are found significantly different between treatment and control group. GO process show that six of 64 which were unique in irradiation group are associated with apoptosis and DNA damage response. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo.

  3. The Mechanisms of Radiation-Induced Bystander Effect

    PubMed Central

    Najafi, M; Fardid, R; Hadadi, Gh; Fardid, M

    2014-01-01

    The radiation-induced bystander effect is the phenomenon which non-irradiated cells exhibit effects along with their different levels as a result of signals received from nearby irradiated cells. Responses of non-irradiated cells may include changes in process of translation, gene expression, cell proliferation, apoptosis and cells death. These changes are confirmed by results of some In-Vivo studies. Most well-known important factors affecting radiation-induced bystander effect include free radicals, immune system factors, expression changes of some genes involved in inflammation pathway and epigenetic factors. PMID:25599062

  4. Vincristine-induced bystander effect in human lymphocytes.

    PubMed

    Testi, Serena; Azzarà, Alessia; Giovannini, Caterina; Lombardi, Sara; Piaggi, Simona; Facioni, Maria Sole; Scarpato, Roberto

    2016-07-01

    Bystander effect is a known radiobiological effect, widely described using ionizing radiations and which, more recently, has also been related to chemical mutagens. In this study, we aimed to assess whether or not a bystander response can be induced in cultured human peripheral lymphocytes by vincristine, a chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an alkylating agent already known to induce this response in human lymphoblastoid cells. Designing a modified ad hoc protocol for the cytokinesis blocked micronucleus (MN) assay, we detected the presence of a dose-dependent bystander response in untreated cultures receiving the conditioned medium (CM) from mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN frequencies, expressed as micronucleated binucleates, were: 13.5±1.41 at 6μM, 22±2.12 at 12μM or 28.25±5.13 at 15μM vs. a control value of 4.75±1.59. MN levels for VCR, expressed as micronucleated mononucleates were: 2.75±0.88 at 0.0μM, 27.25±2.30 at 0.4μM, 46.25±1.94 at 0.8μM, 98.25±7.25 at 1.6μM. To verify that no mutagen residual was transferred to recipient cultures together with the CM, we evaluated MN levels in cultures receiving the medium immediately after three washings following the chemical treatment (unconditioned medium). We further confirmed these results using a cell-mixing approach where untreated lymphocytes were co-cultured with donor cells treated with an effect-inducing dose of MMC or VCR. A distinct production pattern of both reactive oxygen species and soluble mediator proteins by treated cells may account for the differences observed in the manifestation of the bystander effect induced by VCR. In fact, we observed an increased level of ROS, IL-32 and TGF-β in the CM from VCR treated cultures, not present in MMC treated cultures. PMID:27050754

  5. MiR-21 is involved in radiation-induced bystander effects

    PubMed Central

    Xu, Shuai; Ding, Nan; Pei, Hailong; Hu, Wentao; Wei, Wenjun; Zhang, Xurui; Zhou, Guangming; Wang, Jufang

    2014-01-01

    Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication. PMID:25483031

  6. Are Epigenetic Mechanisms Involved in Radiation-Induced Bystander Effects?

    PubMed Central

    Mothersill, Carmel; Seymour, Colin

    2012-01-01

    The “non-targeted effects” of ionizing radiation including bystander effects and genomic instability are unique in that no classic mutagenic event occurs in the cell showing the effect. In the case of bystander effects, cells which were not in the field affected by the radiation show high levels of mutations, chromosome aberrations, and membrane signaling changes leading to what is termed “horizontal transmission” of mutations and information which may be damaging while in the case of genomic instability, generations of cells derived from an irradiated progenitor appear normal but then lethal and non-lethal mutations appear in distant progeny. This is known as “vertical transmission.” In both situations high yields of non-clonal mutations leading to distant occurrence of mutation events both in space and time. This precludes a mutator phenotype or other conventional explanation and appears to indicate a generalized form of stress-induced mutagenesis which is well documented in bacteria. This review will discuss the phenomenology of what we term “non-targeted effects,” and will consider to what extent they challenge conventional ideas in genetics and epigenetics. PMID:22629281

  7. Bystander effect induced by UV radiation; why should we be interested?

    PubMed

    Widel, Maria

    2012-01-01

    The bystander effect, whose essence is an interaction of cells directly subjected to radiation with adjacent non-subjected cells, via molecular signals, is an important component of ionizing radiation action. However, knowledge of the bystander effect in the case of ultraviolet (UV) radiation is quite limited. Reactive oxygen and nitrogen species generated by UV in exposed cells induce bystander effects in non-exposed cells, such as reduction in clonogenic cell survival and delayed cell death, oxidative DNA damage and gene mutations, induction of micronuclei, lipid peroxidation and apoptosis. Although the bystander effect after UV radiation has been recognized in cell culture systems, its occurrence in vivo has not been studied. However, solar UV radiation, which is the main source of UV in the environment, may induce in human dermal tissue an inflammatory response and immune suppression, events which can be considered as bystander effects of UV radiation. The oxidative damage to DNA, genomic instability and the inflammatory response may lead to carcinogenesis. UV radiation is considered one of the important etiologic factors for skin cancers, basal- and squamous-cell carcinomas and malignant melanoma. Based on the mechanisms of actions it seems that the UV-induced bystander effect can have some impact on skin damage (carcinogenesis?), and probably on cells of other tissues. The paper reviews the existing data about the UV-induced bystander effect and discusses a possible implication of this phenomenon for health risk.  PMID:23175338

  8. Radiation-induced bystander effect in non-irradiated glioblastoma spheroid cells

    PubMed Central

    Faqihi, Fahime; Neshastehriz, Ali; Soleymanifard, Shokouhozaman; Shabani, Robabeh; Eivazzadeh, Nazila

    2015-01-01

    Radiation-induced bystander effects (RIBEs) are detected in cells that are not irradiated but receive signals from treated cells. The present study explored these bystander effects in a U87MG multicellular tumour spheroid model. A medium transfer technique was employed to induce the bystander effect, and colony formation assay was used to evaluate the effect. Relative changes in expression of BAX, BCL2, JNK and ERK genes were analysed using RT-PCR to investigate the RIBE mechanism. A significant decrease in plating efficiency was observed for both bystander and irradiated cells. The survival fraction was calculated for bystander cells to be 69.48% and for irradiated cells to be 34.68%. There was no change in pro-apoptotic BAX relative expression, but anti-apoptotic BCL2 showed downregulation in both irradiated and bystander cells. Pro-apoptotic JNK in bystander samples and ERK in irradiated samples were upregulated. The clonogenic survival data suggests that there was a classic RIBE in U87MG spheroids exposed to 4 Gy of X-rays, using a medium transfer technique. Changes in the expression of pro- and anti-apoptotic genes indicate involvement of both intrinsic apoptotic and MAPK pathways in inducing these effects. PMID:26160180

  9. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

    PubMed Central

    Huang, Yao-Huei; Yang, Pei-Ming; Chuah, Qiu-Yu; Lee, Yi-Jang; Hsieh, Yi-Fen; Peng, Chih-Wen; Chiu, Shu-Jun

    2014-01-01

    Ionizing radiation induces cellular senescence to suppress cancer cell proliferation. However, it also induces deleterious bystander effects in the unirradiated neighboring cells through the release of senescence-associated secretory phenotypes (SASPs) that promote tumor progression. Although autophagy has been reported to promote senescence, its role is still unclear. We previously showed that radiation induces senescence in PTTG1-depleted cancer cells. In this study, we found that autophagy was required for the radiation-induced senescence in PTTG1-depleted breast cancer cells. Inhibition of autophagy caused the cells to switch from radiation-induced senescence to apoptosis. Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways. However, the radiation-induced bystander effects were correlated with the inhibition of endogenous autophagy in bystander cells, which also resulted from the activation of the CSF2-JAK2 pathway. The induction of autophagy by rapamycin reduced the radiation-induced bystander effects. This study reveals, for the first time, the dual role of autophagy in radiation-induced senescence and bystander effects. PMID:24813621

  10. The role of protein kinase C alpha translocation in radiation-induced bystander effect

    PubMed Central

    Fang, Zihui; Xu, An; Wu, Lijun; Hei, Tom K.; Hong, Mei

    2016-01-01

    Ionizing radiation is a well known human carcinogen. Evidence accumulated over the past decade suggested that extranuclear/extracellular targets and events may also play a critical role in modulating biological responses to ionizing radiation. However, the underlying mechanism(s) of radiation-induced bystander effect is still unclear. In the current study, AL cells were irradiated with alpha particles and responses of bystander cells were investigated. We found out that in bystander AL cells, protein kinase C alpha (PKCα) translocated from cytosol to membrane fraction. Pre-treatment of cells with PKC translocation inhibitor chelerythrine chloride suppressed the induced extracellular signal-regulated kinases (ERK) activity and the increased cyclooxygenase 2 (COX-2) expression as well as the mutagenic effect in bystander cells. Furthermore, tumor necrosis factor alpha (TNFα) was elevated in directly irradiated but not bystander cells; while TNFα receptor 1 (TNFR1) increased in the membrane fraction of bystander cells. Further analysis revealed that PKC activation caused accelerated internalization and recycling of TNFR1. Our data suggested that PKCα translocation may occur as an early event in radiation-induced bystander responses and mediate TNFα-induced signaling pathways that lead to the activation of ERK and up-regulation of COX-2. PMID:27165942

  11. Bystander Effects Induced by Medium From Irradiated Cells: Similar Transcriptome Responses in Irradiated and Bystander K562 Cells

    SciTech Connect

    Herok, Robert; Konopacka, Maria; Polanska, Joanna; Swierniak, Andrzej; Rogolinski, Jacek; Jaksik, Roman; Hancock, Ronald; Rzeszowska-Wolny, Joanna

    2010-05-01

    Purpose: Cells exposed to ionizing radiation release factors that induce deoxyribonucleic acid damage, chromosomal instability, apoptosis, and changes in the proliferation rate of neighboring unexposed cells, phenomena known as bystander effects. This work analyzes and compares changes in global transcript levels induced by direct irradiation and by bystander effects in K562 (human erythroleukemia) cells. Methods and Materials: Cells were X-irradiated with 4 Gy or transferred into culture medium collected from cells 1 h after irradiation (irradiation-conditioned medium). Global transcript profiles were assessed after 36 h of growth by use of Affymetrix microarrays (Affymetrix, Santa Clara, CA) and the kinetics of change of selected transcripts by quantitative reverse transcriptase-polymerase chain reaction. Results: The level of the majority (72%) of transcripts changed similarly (increase, decrease, or no change) in cells grown in irradiation-conditioned medium or irradiated, whereas only 0.6% showed an opposite response. Transcript level changes in bystander and irradiated cells were significantly different from those in untreated cells grown for the same amount of time and were confirmed by quantitative reverse transcriptase-polymerase chain reaction for selected genes. Signaling pathways in which the highest number of transcripts changed in both conditions were found in the following groups: neuroactive ligand-receptor, cytokine-cytokine receptor interaction, Janus Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) and Mitogen-Activated Protein Kinase (MAPK) In control cells more transcripts were downregulated than in irradiated and bystander cells with transcription factors YBX1 and STAT5B, heat shock protein HSPA1A, and ribonucleic acid helicase DDX3X as examples. Conclusions: The transcriptomes of cells grown in medium from X-irradiated cells or directly irradiated show very similar changes. Signals released by irradiated cells may cause

  12. Bystander effects in radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Morgan, William F.; Hartmann, Andreas; Limoli, Charles L.; Nagar, Shruti; Ponnaiya, Brian

    2002-01-01

    Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.

  13. Role of nitric oxide in the radiation-induced bystander effect.

    PubMed

    Yakovlev, Vasily A

    2015-12-01

    Cells that are not irradiated but are affected by "stress signal factors" released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role in the stimulation and propagation of RIBE. The hydrophobic properties of NO, which permit its diffusion through the cytoplasm and plasma membranes, allow this signaling molecule to easily spread from irradiated cells to bystander cells without the involvement of gap junction intercellular communication. NO produced in irradiated tissues mediates cellular regulation through posttranslational modification of a number of regulatory proteins. The best studied of these modifications are S-nitrosylation (reversible oxidation of cysteine) and tyrosine nitration. These modifications can up- or down-regulate the functions of many proteins modulating different NO-dependent effects. These NO-dependent effects include the stimulation of genomic instability (GI) and the accumulation of DNA errors in bystander cells without direct DNA damage. PMID:26355395

  14. Epigenetic Analysis of Heavy-ion Radiation Induced Bystander Effects in Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Cui, Changna; Xue, Bei

    Abstract: Radiation-induced bystander effect was defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic and proteomics plays significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were exposed head-only to 40, 200, 2000mGy dose of (12) C heavy-ion radiation, while the rest of the animal body was shielded. Directly radiation organ ear and the distant organ liver were detected on 1h, 6h, 12h and 24h after radiation, respectively. Methylation-sensitive amplification polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that heavy-ion irradiated mouse head could induce genomic DNA methylation changes significantly in both the directly radiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate was highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation. The global DNA methylation changes tended to occur in the CG sites. The results illustrated that genomic methylation changes of heavy ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of

  15. The Role of DNA Methylation Changes in Radiation-Induced Bystander Effects in cranial irradiated Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Xue, Bei; Wang, Xinwen; Wang, Jiawen

    2016-07-01

    Heavy-ion radiation could lead to bystander effect in neighboring non-hit cells by signals released from directly-irradiated cells. The exact mechanisms of radiation-induced bystander effect in distant organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in bystander effect. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were cranial exposed to 40, 200, 2000mGy dose of carbon heavy-ion radiation, while the rest of the animal body was shielded. The γH2AX foci as the DNA damage biomarker in directly irradiation organ ear and the distant organ liver were detected on 0, 1, 2, 6, 12 and 24h after radiation, respectively. Methylation-sensitive amplifcation polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that cranial irradiated mice could induce the γH2AX foci and genomic DNA methylation changes significantly in both the directly irradiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate were highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation in ear. The global DNA methylation changes tended to occur in the CG sites. We also found that the numbers of γH2AX foci and the genomic methylation changes of heavy-ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo. Keywords: Heavy-ion radiation; Bystander effect; DNA methylation; γH2

  16. Radiation induced bystander effect by GAP junction channels in human fibroblast cell

    NASA Astrophysics Data System (ADS)

    Furusawa, Y.; Shao, C.; Aoki, M.; Kobayashi, Y.; Funayama, T.; Ando, K.

    The chemical factor involved in bystander effect and its transfer pathway were investigated in a confluent human fibroblast cell (AG1522) population. Micronuclei (MN) and G1-phase arrest were detected in cells irradiated by carbon (~100 keV/μm) ions at HIMAC. A very low dose irradiation showed a high effectiveness in producing MN, suggesting a bystander effect. This effectiveness was enhanced by 8-Br-cAMP treatment that increases gap junctional intercellular communication (GJIC). On the other hand, the effect was reduced by 5% DMSO treatment, which reduce the reactive oxygen species (ROS), and suppressed by 100 μM lindane treatment, an inhibitor of GJIC. In addition, the radiation-induced G1-phase arrest was also enhanced by cAMP, and reduced or suppressed by DMSO or lindane. A microbeam device (JAERI) was also used for these studies. It was found that exposing one single cell in a confluent cell population to exactly one argon (~1260 keV/μm) or neon (~430 keV/ μm) ion, additional MN could be detected in many other unirradiated cells. The yield of MN increased with the number of irradiated cells. However, there was no significant difference in the MN induction when the cells were irradiated by increasing number of particles. MN induction by bystander effect was partly reduced by DMSO, and effectively suppressed by lindane. Our results obtained from both random irradiation and precise numbered irradiation indicate that both GJIC and ROS contributed to the radiation-induced bystander effect, but the cell gap junction channels likely play an essential role in the release and transfer of radiation-induced chemical factors.

  17. Time-lapse microscopy studies of bystander effects induced by photosensitization

    NASA Astrophysics Data System (ADS)

    Chen, Yin-Chu; Redmond, Robert W.

    2006-02-01

    Reactive oxygen species (ROS) are involved in the pathogenesis of many critical diseases and are also utilized as cytotoxic agents in a variety of treatments for eradication of diseased tissue, including cancer. Oxidative stress ensues when the level of ROS in a system exceeds the antioxidant capacity. Oxidative stress can have local (direct) and long-range (bystander) effects in cells and tissue and this research was carried out to determine the spatial and temporal nature of the photosensitized bystander effect using time-lapse fluorescence microscopy. By initiating photosensitization in only a portion of the microscopic imaging field it was possible to differentiate direct from bystander effects in EMT-6 murine breast cancer cells in 6-well plates. Elevated ROS levels are seen immediately following photodynamic treatment in direct cells with a delayed increase in oxidative stress observed in bystander cells. Cytotoxicity is also seen at earlier times in direct cells and occurs in bystander cells in a delayed fashion. These studies confirm the existence of a bystander effect following photosensitization and implicate mediators capable of diffusing in an intercellular manner from directly photosensitized cells to bystander cells and also implicate increased oxidative stress as a mechanistic factor in generating damage in bystander cells.

  18. Differential effects of p53 on bystander phenotypes induced by gamma ray and high LET heavy ion radiation

    NASA Astrophysics Data System (ADS)

    He, Mingyuan; Dong, Chen; Konishi, Teruaki; Tu, Wenzhi; Liu, Weili; Shiomi, Naoko; Kobayashi, Alisa; Uchihori, Yukio; Furusawa, Yoshiya; Hei, Tom K.; Dang, Bingrong; Shao, Chunlin

    2014-04-01

    High LET particle irradiation has several potential advantages over γ-rays such as p53-independent response. The purpose of this work is to disclose the effect of p53 on the bystander effect induced by different LET irradiations and underlying mechanism. Lymphocyte cells of TK6 (wild type p53) and HMy2.CIR (mutated p53) were exposed to either low or high LET irradiation, then their mitochondrial dysfunction and ROS generation were detected. The micronuclei (MN) induction in HL-7702 hepatocytes co-cultured with irradiated lymphocytes was also measured. It was found that the mitochondrial dysfunction, p66Shc activation, and intracellular ROS were enhanced in TK6 but not in HMy2.CIR cells after γ-ray irradiation, but all of them were increased in both cell lines after carbon and iron irradiation. Consistently, the bystander effect of MN formation in HL-7702 cells was only triggered by γ-irradiated TK6 cells but not by γ-irradiated HMy2.CIR cells. But this bystander effect was induced by both lymphocyte cell lines after heavy ion irradiation. PFT-μ, an inhibitor of p53, only partly inhibited ROS generation and bystander effect induced by 30 keV/μm carbon-irradiated TK6 cells but failed to suppress the bystander effect induced by the TK6 cells irradiated with either 70 keV/μm carbon or 180 keV/μm iron. The mitochondrial inhibitors of rotenone and oligomycin eliminated heavy ion induced ROS generation in TK6 and HMy2.CIR cells and hence diminished the bystander effect on HL-7702 cells. These results clearly demonstrate that the bystander effect is p53-dependent for low LET irradiation, but it is p53-independent for high LET irradiation which may be because of p53-independent ROS generation due to mitochondrial dysfunction.

  19. Proteomic overview and perspectives of the radiation-induced bystander effects.

    PubMed

    Chevalier, François; Hamdi, Dounia Houria; Saintigny, Yannick; Lefaix, Jean-Louis

    2015-01-01

    Radiation proteomics is a recent, promising and powerful tool to identify protein markers of direct and indirect consequences of ionizing radiation. The main challenges of modern radiobiology is to predict radio-sensitivity of patients and radio-resistance of tumor to be treated, but considerable evidences are now available regarding the significance of a bystander effect at low and high doses. This "radiation-induced bystander effect" (RIBE) is defined as the biological responses of non-irradiated cells that received signals from neighboring irradiated cells. Such intercellular signal is no more considered as a minor side-effect of radiotherapy in surrounding healthy tissue and its occurrence should be considered in adapting radiotherapy protocols, to limit the risk for radiation-induced secondary cancer. There is no consensus on a precise designation of RIBE, which involves a number of distinct signal-mediated effects within or outside the irradiated volume. Indeed, several cellular mechanisms were proposed, including the secretion of soluble factors by irradiated cells in the extracellular matrix, or the direct communication between irradiated and neighboring non-irradiated cells via gap junctions. This phenomenon is observed in a context of major local inflammation, linked with a global imbalance of oxidative metabolism which makes its analysis challenging using in vitro model systems. In this review article, the authors first define the radiation-induced bystander effect as a function of radiation type, in vitro analysis protocols, and cell type. In a second time, the authors present the current status of protein biomarkers and proteomic-based findings and discuss the capacities, limits and perspectives of such global approaches to explore these complex intercellular mechanisms. PMID:25795126

  20. Spatio-temporal analysis of tamoxifen-induced bystander effects in breast cancer cells using microfluidics.

    PubMed

    Rios-Mondragon, Ivan; Wang, Xiang; Gerdes, Hans-Hermann

    2012-06-01

    The bystander effect in cancer therapy is the inhibition or killing of tumor cells that are adjacent to those directly affected by the agent used for treatment. In the case of chemotherapy, little is known as to how much and by which mechanisms bystander effects contribute to the elimination of tumor cells. This is mainly due to the difficulty to distinguish between targeted and bystander cells since both are exposed to the pharmaceutical compound. We here studied the interaction of tamoxifen-treated human breast cancer MCF-7 cells with their neighboring counterparts by exploiting laminar flow patterning in a microfluidic chip to ensure selective drug delivery. The spatio-temporal evolution of the bystander response in non-targeted cells was analyzed by measuring the mitochondrial membrane potential under conditions of free diffusion. Our data show that the bystander response is detectable as early as 1 hour after drug treatment and reached effective distances of at least 2.8 mm. Furthermore, the bystander effect was merely dependent on diffusible factors rather than cell contact-dependent signaling. Taken together, our study illustrates that this microfluidic approach is a promising tool for screening and optimization of putative chemotherapeutic drugs to maximize the bystander response in cancer therapy. PMID:23750189

  1. Characterization of a bystander effect induced by the endocrine-disrupting chemical 6-propyl-2-thiouracil in zebrafish embryos.

    PubMed

    Liu, Chunsheng; Yan, Wei; Zhou, Bingsheng; Guo, Yongyong; Liu, Hongling; Yu, Hongxia; Giesy, John P; Wang, Jianghua; Li, Guangyu; Zhang, Xiaowei

    2012-08-15

    This study was conducted to evaluate possible bystander effects induced by the model chemical 6-propyl-2-thiouracil (PTU) on melanin synthesis. Zebrafish (Danio rerio) embryos were treated with PTU by either microinjection exposure, via waterborne exposure or indirectly through bystander exposure. Melanin content, related mRNA and protein expression were examined at the end of exposure (36 h post-fertilization). Direct exposure to PTU decreased the melanin content, up-regulated mRNA expressions of oculocutaneous albinism type 2 (OCA2), tyrosinase (TYR), dopachrometautomerase (DCT), tyrosinase-related protein 1 (TYRP1) and silver (SILV), and increased the protein expressions of TYR and SILV. Bystander exposure also up-regulated mRNA and protein expressions of TYR and SILV but increased melanin contents. Correlation analysis demonstrated that mRNA expressions of OCA2, TYR, DCT, TYRP1, SILV and protein expressions of TYR and SILV in bystander exposure groups were positively correlated with corresponding expressions in microinjection exposure groups. The results might have environmental implications and highlight the need to consider the bystander effects when assessing potential risks of endocrine-disrupting chemicals. PMID:22542736

  2. Radiation-induced bystander effects and the DNA paradigm: an "out of field" perspective.

    PubMed

    Mothersill, Carmel; Seymour, C B

    2006-05-11

    Over the past 20 years there has been increasing evidence that cells and the progeny of cells surviving a very low dose of ionizing radiation [micro-mGy] can exhibit a wide range of non-monotonic effects such as adaptive responses, low dose hypersensitivity and other delayed effects. These effects are inconsistent with the expected dose-response, when based on extrapolation of high dose data and cast doubt on the reliability of extrapolating from high dose data to predict low dose effects. Recently the cause of many of these effects has been tentatively ascribed to so-called "bystander effects". These are effects that occur in cells not directly hit by an ionizing track but which are influenced by signals from irradiated cells and are thus highly relevant in situations where the dose is very low. Not all bystander effects may be deleterious although most endpoints measured involve cell damage or death. In this commentary, we consider how these effects impact the historical central dogma of radiobiology and radiation protection, which is that DNA double strand breaks are the primary radiation-induced lesion which can be quantifiably related to received dose and which determine the probability that a cancer will result from a radiation exposure. We explore the low dose issues and the evidence and conclude that in the very low dose region, the primary determinant of radiation exposure outcome is the genetic and epigenetic background of the individual and not solely the dose. What this does is to dissociate dose from effect as a quantitative relationship, but it does not necessarily mean that the effect is ultimately unrelated to DNA damage. The fundamental thesis we present is that at low doses fundamentally different mechanisms underlie radiation action and that at these doses, effect is not quantitatively related to dose. PMID:16414088

  3. Modulation of modeled microgravity on radiation-induced bystander effects in Arabidopsis thaliana.

    PubMed

    Wang, Ting; Sun, Qiao; Xu, Wei; Li, Fanghua; Li, Huasheng; Lu, Jinying; Wu, Lijun; Wu, Yuejin; Liu, Min; Bian, Po

    2015-03-01

    Both space radiation and microgravity have been demonstrated to have inevitable impact on living organisms during space flights and should be considered as important factors for estimating the potential health risk for astronauts. Therefore, the question whether radiation effects could be modulated by microgravity is an important aspect in such risk evaluation. Space particles at low dose and fluence rate, directly affect only a fraction of cells in the whole organism, which implement radiation-induced bystander effects (RIBE) in cellular response to space radiation exposure. The fact that all of the RIBE experiments are carried out in a normal gravity condition bring forward the need for evidence regarding the effect of microgravity on RIBE. In the present study, a two-dimensional rotation clinostat was adopted to demonstrate RIBE in microgravity conditions, in which the RIBE was assayed using an experimental system of root-localized irradiation of Arabidopsis thaliana (A. thaliana) plants. The results showed that the modeled microgravity inhibited significantly the RIBE-mediated up-regulation of expression of the AtRAD54 and AtRAD51 genes, generation of reactive oxygen species (ROS) and transcriptional activation of multicopy P35S:GUS, but made no difference to the induction of homologous recombination by RIBE, showing divergent responses of RIBE to the microgravity conditions. The time course of interaction between the modeled microgravity and RIBE was further investigated, and the results showed that the microgravity mainly modulated the processes of the generation or translocation of the bystander signal(s) in roots. PMID:25769184

  4. Radiation-Induced Bystander Effects in A549 Cells Exposed to 6 MV X-rays.

    PubMed

    Yang, Shuning; Xu, Jing; Shao, Weixian; Geng, Chong; Li, Jia; Guo, Feng; Miao, Hui; Shen, Wenbin; Ye, Tao; Liu, Yazhou; Xu, Haiting; Zhang, Xuguang

    2015-07-01

    The aim of the study is to explore the bystander effects in A549 cells that have been exposed to 6MV X-ray. Control group, irradiated group, irradiated conditioned medium (ICM)-received group, and fresh medium group were designed in this study. A549 cells in the logarithmic growth phase were irradiated with 6MV X-ray at 0, 0.5, 1, 1.5, and 2. In ICM-received group, post-irradiation A549 cells were cultured for 3 h and were transferred into non-irradiated A549 cells for further cultivation. Clone forming test was applied to detect the survival fraction of cells. Annexin V-FITC/PI double-staining assay was used to detect the apoptosis of A549 cells 24, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation, and the curves of apoptosis were drawn. The changes in the cell cycles 4, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation were detected using PI staining flow cytometry. With the increase of irradiation dose, the survival fraction of A549 cells after the application of 0.5 Gy irradiation was decreasing continuously. In comparison to the control group, the apoptosis rate of the ICM-received group was increased in a time-dependent pattern, with the highest apoptosis rate observed at 72 h (p < 0.05). Cell count in G2/M stages was obviously increased compared with that of the control group (p < 0.05), with the highest count observed at 72 h, after which G2/M stage arrest was diminished. ICM can cause apparent A549 cell damage, indicating that 6MV X-ray irradiation can induce bystander effect on A549 cells, which reaches a peak at 72 h. PMID:25686868

  5. Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect.

    PubMed

    Tong, Liping; Yu, K N; Bao, Lingzhi; Wu, Wenqing; Wang, Hongzhi; Han, Wei

    2014-01-01

    Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after α-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor β1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy. PMID:24333162

  6. Bystander Effects Induced by Continuous Low-Dose-Rate {sup 125}I Seeds Potentiate the Killing Action of Irradiation on Human Lung Cancer Cells In Vitro

    SciTech Connect

    Chen, H.H. Jia, R.F.; Yu, L.; Zhao, M.J.; Shao, C.L.; Cheng, W.Y.

    2008-12-01

    Purpose: To investigate bystander effects of low-dose-rate (LDR) {sup 125}I seed irradiation on human lung cancer cells in vitro. Methods and Materials: A549 and NCI-H446 cell lines of differing radiosensitivity were directly exposed to LDR {sup 125}I seeds irradiation for 2 or 4 Gy and then cocultured with nonirradiated cells for 24 hours. Induction of micronucleus (MN), {gamma}H2AX foci, and apoptosis were assayed. Results: After 2 and 4 Gy irradiation, micronucleus formation rate (MFR) and apoptotic rate of A549 and NCI-H446 cells were increased, and the MFR and apoptotic rate of NCI-H446 cells was 2.1-2.8 times higher than that of A549 cells. After coculturing nonirradiated bystander cells with {sup 125}I seed irradiated cells for 24 hours, MFR and the mean number of {gamma}H2AX foci/cells of bystander A549 and NCI-H446 cells were similar and significantly higher than those of control (p <0.05), although they did not increase with irradiation dose. However, the proportion of bystander NCI-H446 cells with MN numbers {>=}3 and {gamma}H2AX foci numbers 15-19 and 20-24 was higher than that of bystander A549 cells. In addition, dimethyl sulfoxide (DMSO) treatment could completely suppress the bystander MN of NCI-H446 cells, but it suppressed only partly the bystander MN of A549 cells, indicating that reactive oxygen species are involved in the bystander response to NCI-H446 cells, but other signaling factors may contribute to the bystander response of A549 cells. Conclusions: Continuous LDR irradiation of {sup 125}I seeds could induce bystander effects, which potentiate the killing action on tumor cells and compensate for the influence of nonuniform distribution of radiation dosage on therapeutic outcomes.

  7. Radiation-induced bystander effect and adaptive response in mammalian cells

    NASA Technical Reports Server (NTRS)

    Zhou, H.; Randers-Pehrson, G.; Waldren, C. A.; Hei, T. K.

    2004-01-01

    Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  8. Cytosine Deaminase/5-Fluorocytosine Exposure Induces Bystander and Radiosensitization Effects in Hypoxic Glioblastoma Cells in vitro

    SciTech Connect

    Chen, Jennifer K.; Hu, Lily J.; Wang Dongfang; Lamborn, Kathleen R.; Deen, Dennis F. . E-mail: dennisdeen@juno.com

    2007-04-01

    Purpose: Treatment of glioblastoma (GBM) is limited by therapeutic ratio; therefore, successful therapy must be specifically cytotoxic to cancer cells. Hypoxic cells are ubiquitous in GBM, and resistant to radiation and chemotherapy, and, thus, are logical targets for gene therapy. In this study, we investigated whether cytosine deaminase (CD)/5-fluorocytosine (5-FC) enzyme/prodrug treatment induced a bystander effect (BE) and/or radiosensitization in hypoxic GBM cells. Methods and Materials: We stably transfected cells with a gene construct consisting of the SV40 minimal promoter, nine copies of a hypoxia-responsive element, and the yeast CD gene. During hypoxia, a hypoxia-responsive element regulates expression of the CD gene and facilitates the conversion of 5-FC to 5-fluorouracil, a highly toxic antimetabolite. We used colony-forming efficiency (CFE) and immunofluorescence assays to assess for BE in co-cultures of CD-expressing clone cells and parent, pNeo- or green fluorescent protein-stably transfected GBM cells. We also investigated the radiosensitivity of CD clone cells treated with 5-FC under hypoxic conditions, and we used flow cytometry to investigate treatment-induced cell cycle changes. Results: Both a large BE and radiosensitization occurred in GBM cells under hypoxic conditions. The magnitude of the BE depended on the number of transfected cells producing CD, the functionality of the CD, the administered concentration of 5-FC, and the sensitivity of cell type to 5-fluorouracil. Conclusion: Hypoxia-inducible CD/5-FC therapy in combination with radiation therapy shows both a pronounced BE and a radiosensitizing effect under hypoxic conditions.

  9. Mechanisms of the Bystander Effect

    SciTech Connect

    Hall, Eric J.

    2008-07-15

    Generations of students in radiation biology have been taught that heritable biological damage requires direct damage to DNA. We now know that this is not true. The Bystander Effect is the name given to the phenomenon whereby biological effects are observed in cells that are not themselves traversed by a charged particle, but are in close proximity to cells that are. Several research groups have convincingly demonstrated a bystander effect for alpha particle, which are heavy and high LET, because charged particles can be focused into a tiny beam that can be directed onto individual cells. The biological effects seen in adjacent non-hit cells clearly represents a bystander effect. It is not so easy to demonstrate a similar effect for x-rays or for the electrons set in motion by the absorption of x-rays. In this project we used two types of cell that could be recognized one from the other. One cell type was fed radioactive tritiated thymidine, which is incorporated into the DNA, . The tritium emits electrons which have a very short range so that they do not even get out of the cell. These cells were then mixed with a different type of cell which are routinely used to assess mutations. The mixed cells formed a cluster, where the two types of cells were in close contact, and left for some hours. Subsequently, the two types of cells were separated and studied. A substantial fraction of the cells that had incorporated the tritiated thymidine were killed by the radiation. The interesting finding is that the cells that had not incorporated tritiated thymidine, but had been in close contact with cells that had, exhibited a significant incidence of mutations. These experiments clearly demonstrated a bystander effect for low LET electrons. In further experiments, it was possible to show that the bystander effect was greatest when the two cell types were in gap junction communication.

  10. Exposures involving perturbations of the EM field have non-linear effects on radiation response and can alter the expression of radiation induced bystander effects

    NASA Astrophysics Data System (ADS)

    Mothersill, Carmel; Seymour, Colin

    2012-07-01

    Our recent data suggest there is a physical component to the bystander signal induced by radiation exposure and that alternative medicine techniques such as Reiki and acupuncture or exposures to weak EM fields alter the response of cells to direct irradiation and either altered bystander signal production or altered the response of cells receiving bystander signals. Our proposed mechanism to explain these findings is that perturbation of electromagnetic (EM) fields is central to the induction of low radiation dose responses especially non-targeted bystander effects. In this presentation we review the alternative medicine data and other data sets from our laboratory which test our hypothesis that perturbation of bio-fields will modulate radiation response in the low dose region. The other data sets include exposure to MRI, shielding using lead and or Faraday cages, the use of physical barriers to bystander signal transmission and the use of membrane channel blockers. The data taken together strongly suggest that EM field perturbation can modulate low dose response and that in fact the EM field rather than the targeted deposition of ionizing energy in the DNA may be the key determinant of dose response in a cell or organism The results also lead us to suspect that at least when chemical transmission is blocked, bystander signals can be transmitted by other means. Our recent experiments suggest light signals and volatiles are not likely. We conclude that alternative medicine and other techniques involving electromagnetic perturbations can modify the response of cells to low doses of ionizing radiation and can induce bystander effects similar to those seen in medium transfer experiments. In addition to the obvious implications for mechanistic studies of low dose effects, this could perhaps provide a novel target to exploit in space radiation protection and in optimizing therapeutic gain during radiotherapy.

  11. Bystander/abscopal effects induced in intact Arabidopsis seeds by low-energy heavy-ion radiation.

    PubMed

    Yang, Gen; Mei, Tao; Yuan, Hang; Zhang, Weiming; Chen, Lianyun; Xue, Jianming; Wu, Lijun; Wang, Yugang

    2008-09-01

    To date, radiation-induced bystander effects have been observed largely in in vitro single-cell systems; verification of both the effects and the mechanisms in multicellular systems in vivo is important. Previously we showed that bystander/ abscopal effects can be induced by irradiating the shoot apical meristem cells in Arabidopsis embryos. In this study, we investigated the in vivo effects induced by 30 keV 40Ar ions in intact Arabidopsis seeds and traced the postembryonic development of both irradiated and nonirradiated shoot apical meristem and root apical meristem cells. Since the range of 30 keV 40Ar ions in water is about 0.07 microm, which is less than the distance from the testa to shoot apical meristem and root apical meristem in Arabidopsis seeds (about 100 microm), the incident low-energy heavy ions generally stop in the proximal surface. Our results showed that, after the 30 keV 40Ar-ion irradiation of shielded and nonshielded Arabidopsis seeds at a fluence of 1.5 x 10(17) ions/cm2, short- and long-term postembryonic development, including germination, root hair differentiation, primary root elongation, lateral root initiation and survival, was significantly inhibited. Since shoot apical meristem and root apical meristem cells were not damaged directly by radiation, the results suggested that a damage signal(s) is transferred from the irradiated cells to shoot apical meristem and root apical meristem cells and causes the ultimate developmental alterations, indicating that long-distance bystander/ abscopal effects exist in the intact seed. A further study of mechanisms showed that the effects are associated with either enhanced generation of reactive oxygen species (ROS) or decreased auxin-dependent transcription in postembryonic development. Treatment with the ROS scavenger dimethyl sulfoxide (DMSO) or synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D) can significantly reverse both the alterations in postembryonic development and auxin

  12. Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

    PubMed Central

    Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

    2014-01-01

    Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

  13. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    PubMed Central

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  14. Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study

    PubMed Central

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh

    2016-01-01

    Objective Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. Materials and Methods This experimental study irradiated three groups of target cells for one, two and three times with60Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. Results RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. Conclusion The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy). PMID:27602316

  15. Antioxidant enzymes and the mechanism of the bystander effect induced by ultraviolet C irradiation of A375 human melanoma cells.

    PubMed

    Ghosh, Rita; Guha, Dipanjan; Bhowmik, Sudipta; Karmakar, Sayantani

    2013-09-18

    Irradiated cells generate dynamic responses in non-irradiated cells; this signaling phenomenon is known as the bystander effect (BE). Factors secreted by the irradiated cells communicate some of these signals. Conditioned medium from UVC-irradiated A375 human melanoma cells was used to study the BE. Exposure of cells to conditioned medium induce cell-cycle arrest at the G2/M transition. Although conditioned medium treatment, by itself, did not alter cell viability, treated cells were more resistant to the lethal action of UVC or H2O2. This protective effect of conditioned medium was lost within 8h. Apoptotic or autophagic cell death was not involved in this resistance. Exposure to conditioned medium did not influence the rate of DNA repair, as measured by NAD(+) depletion. The activities of catalase and superoxide dismutase were elevated in cells exposed to conditioned medium, but returned to normal levels by 8h post-treatment. These results indicate a close correlation between BE-stimulated antioxidant activity and cellular sensitivity. Cell-cycle arrest and stimulation of antioxidant activity may account for the resistance to killing that was observed in bystander cells exposed to UVC or H2O2 treatment and are consistent with the role of the BE as a natural defense function triggered by UVC irradiation. PMID:23845763

  16. Irradiated fibroblast-induced bystander effects on invasive growth of squamous cell carcinoma under cancer-stromal cell interaction.

    PubMed

    Kamochi, Noriyuki; Nakashima, Masahiro; Aoki, Shigehisa; Uchihashi, Kazuyoshi; Sugihara, Hajime; Toda, Shuji; Kudo, Sho

    2008-12-01

    The irradiated fibroblast-induced response of non-irradiated neighboring cells is called 'radiation-induced bystander effect', but it is unclear in non-irradiated human squamous cell carcinoma (SCC) cells. The present study shows that irradiated fibroblasts promoted the invasive growth of T3M-1 SCC cells, but not their apoptosis, more greatly than non-irradiated fibroblasts, using collagen gel invasion assay, immunohistochemistry and Western blot. The number of irradiated fibroblasts decreased to about 30% of that of non-irradiated fibroblasts, but irradiated fibroblasts increased the growth marker ki-67 display of SCC cells more greatly than non-irradiated fibroblasts. Irradiated fibroblasts did not affect the apoptosis marker ss-DNA expression of SCC cells. Irradiated fibroblasts enhanced the display of the following growth-, invasion- and motility-related molecules in SCC cells more greatly than non-irradiated fibroblasts: c-Met, Ras, mitogen-activated protein kinase (MAPK) cascade (Raf-1, MEK-1 and ERK-1/2), matrix metalloproteinase-1 and -9, laminin 5 and filamin A. Irradiated fibroblasts, but not non-irradiated ones, formed irradiation-induced foci (IRIF) of the genomic instability marker p53-binding protein 1 (53BP1) and expressed transforming growth factor-beta1 (TGF- beta1). Irradiated fibroblasts in turn enabled SCC cells to enhance 53BP1 IRIF formation more extensively than non-irradiated fibroblasts. Finally, effects of irradiated fibroblasts on growth and apoptosis of another HEp-2 SCC cell type were similar to those of T3M-1. These results suggest that irradiated fibroblasts promotes invasion and growth of SCC cells by enhancement of invasive growth-related molecules above through TGF- beta1-mediated bystander mechanism, in which irradiated fibroblast-induced genomic instability of SCC cells may be involved. PMID:19018771

  17. Low Doses of Gamma-Irradiation Induce an Early Bystander Effect in Zebrafish Cells Which Is Sufficient to Radioprotect Cells

    PubMed Central

    Pereira, Sandrine; Malard, Véronique; Ravanat, Jean-Luc; Davin, Anne-Hélène; Armengaud, Jean; Foray, Nicolas; Adam-Guillermin, Christelle

    2014-01-01

    The term “bystander effect” is used to describe an effect in which cells that have not been exposed to radiation are affected by irradiated cells though various intracellular signaling mechanisms. In this study we analyzed the kinetics and mechanisms of bystander effect and radioadaptation in embryonic zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01–0.1 Gy. In two experimental conditions, the transfer of irradiated cells or culture medium from irradiated cells results in the occurrence of DNA double strand breaks in non-irradiated cells (assessed by the number of γ-H2AX foci) that are repaired at 24 hours post-irradiation whatever the dose. At low total irradiation doses the bystander effect observed does not affect DNA repair mechanisms in targeted and bystander cells. An increase in global methylation of ZF4 cells was observed in irradiated cells and bystander cells compared to control cells. We observed that pre-irradiated cells which are then irradiated for a second time with the same doses contained significantly less γ-H2AX foci than in 24 h gamma-irradiated control cells. We also showed that bystander cells that have been in contact with the pre-irradiated cells and then irradiated alone present less γ-H2AX foci compared to the control cells. This radioadaptation effect is significantly more pronounced at the highest doses. To determine the factors involved in the early events of the bystander effect, we performed an extensive comparative proteomic study of the ZF4 secretomes upon irradiation. In the experimental conditions assayed here, we showed that the early events of bystander effect are probably not due to the secretion of specific proteins neither the oxidation of these secreted proteins. These results suggest that early bystander effect may be due probably to a combination of multiple factors. PMID:24667817

  18. Novel mechanism for the radiation-induced bystander effect: nitric oxide and ethylene determine the response in sponge cells.

    PubMed

    Müller, Werner E G; Ushijima, Hiroshi; Batel, Renato; Krasko, Anatoli; Borejko, Alexandra; Müller, Isabel M; Schröder, Heinz-C

    2006-05-11

    Until now the bystander effect had only been described in vertebrates. In the present study the existence of this effect has been demonstrated for the phylogenetically oldest metazoan phylum, the Porifera. We used the demosponge Suberites domuncula for the experiments in the two-chamber-system. The lower dish contained irradiated "donor" cells (single cells) and the upper dish the primmorphs ("recipient" primmorphs). The "donor" cells were treated with UV-B light (40 mJ/cm2) and 100 microM hydrogen peroxide (H2O2), factors that exist also in the natural marine aquatic environment of sponges; these factors caused a high level of DNA strand breaks followed by a reduced viability of the cells. If these cells were added to the "recipient" primmorphs these 3D-cell cultures started to undergo apoptosis. This effect could be abolished by the NO-specific scavenger PTIO and ethylene. The conclusion that NO is synthesized by the UV-B/H2O2-treated cells was supported analytically. The cDNA encoding the enzyme dimethylarginine dimethylaminohydrolase (DDAH) was isolated from the "donor" cells. High levels of DDAH transcripts were measured in UV-B/H2O2-treated "donor" cells while after ethylene treatment the steady-state level of expression drops drastically. We conclude that in the absence of ethylene the concentration of the physiological inhibitor for the NO synthase ADMA is low, due to the high level of DDAH. In consequence, high amounts of NO are released from "donor" cells which cause apoptosis in "recipient" primmorphs. In contrast, ethylene reduces the DDAH expression with the consequence of higher levels of ADMA which prevent the formation of larger amounts of NO. This study describes the radiation-induced bystander effect also for the most basal metazoans and demonstrates that this effect is controlled by the two gases NO and ethylene. PMID:16427660

  19. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    A long-standing dogma in the radiation sciences is that energy from radiation must be deposited in the cell nucleus to elicit a biological effect. A number of non-targeted, delayed effects of ionizing radiation have been described that challenge this dogma and pose new challenges to evaluating potential hazards associated with radiation exposure. These effects include induced genomic instability and non-targeted bystander effects. The in vitro evidence for non-targeted effects in radiation biology will be reviewed, but the question as to how one extrapolates from these in vitro observations to the risk of radiation-induced adverse health effects such as cancer remains open.

  20. SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation.

    PubMed

    Xie, Yuexia; Tu, Wenzhi; Zhang, Jianghong; He, Mingyuan; Ye, Shuang; Dong, Chen; Shao, Chunlin

    2015-02-01

    Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved. PMID:25772107

  1. Use of synchrotron medical microbeam irradiation to investigate radiation-induced bystander and abscopal effects in vivo.

    PubMed

    Fernandez-Palomo, Cristian; Bräuer-Krisch, Elke; Laissue, Jean; Vukmirovic, Dusan; Blattmann, Hans; Seymour, Colin; Schültke, Elisabeth; Mothersill, Carmel

    2015-09-01

    The question of whether bystander and abscopal effects are the same is unclear. Our experimental system enables us to address this question by allowing irradiated organisms to partner with unexposed individuals. Organs from both animals and appropriate sham and scatter dose controls are tested for expression of several endpoints such as calcium flux, role of 5HT, reporter assay cell death and proteomic profile. The results show that membrane related functions of calcium and 5HT are critical for true bystander effect expression. Our original inter-animal experiments used fish species whole body irradiated with low doses of X-rays, which prevented us from addressing the abscopal effect question. Data which are much more relevant in radiotherapy are now available for rats which received high dose local irradiation to the implanted right brain glioma. The data were generated using quasi-parallel microbeams at the biomedical beamline at the European Synchrotron Radiation Facility in Grenoble France. This means we can directly compare abscopal and "true" bystander effects in a rodent tumour model. Analysis of right brain hemisphere, left brain and urinary bladder in the directly irradiated animals and their unirradiated partners strongly suggests that bystander effects (in partner animals) are not the same as abscopal effects (in the irradiated animal). Furthermore, the presence of a tumour in the right brain alters the magnitude of both abscopal and bystander effects in the tissues from the directly irradiated animal and in the unirradiated partners which did not contain tumours, meaning the type of signal was different. PMID:25817634

  2. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.

  3. Defining a Possible Low LET Bystander Effect

    SciTech Connect

    Charles R. Geard

    2009-05-04

    Current radiation protection guidelines assume a linear response to ionizing radiations down through doses where epidemiological studies provide very limited to no information as to the propriety of such assumptions. The bystander response is a non-targeted effect which might impact such guidelines. These studies while clearly affirming a bystander response for high LET radiations, do not provide such affirmation for environmentally relevant low dose, low LET radiations. Caution and further study are necessary before making judgements that could impact on current standards.

  4. Epigenetic bystander-like effects of stroke in somatic organs

    PubMed Central

    Kovalchuk, Anna; Lowings, Michael; Rodriguez-Juarez, Rocio; Muhammad, Arif; Ilnytskyy, Slava; Kolb, Bryan; Kovalchuk, Olga

    2012-01-01

    Clinical evidence suggests that stroke may lead to damage of somatic organs. This communication of damage is well-established in the case of exposure to genotoxic agents is termed a bystander effect. Genotoxic stress-induced bystander effects are epigenetically mediated. Here we investigated whether stroke causes epigenetic bystander-like effects in the liver, kidney and heart. We found a significant increase in the levels of H3K3 acetylation and H3K4 trimethylation, as well as a decrease in the H3K9 trimethylation in the kidney tissue of stroked rats. Furthermore, here we for the first time show changes in the gene and microRNA expression profile in the kidney tissues of stroked rats, as compared to intact control animals. Interestingly, the observed changes were somewhat similar to those reported earlier in kidney injury, inflammation, and acute renal failure. Our data explain the recent epidemiological evidence for the increased incidence of acute kidney injury post-stroke and provide an important roadmap for the future analysis of the mechanisms and cellular repercussions of the stroke-induced bystander-like effects in distal somatic organs. PMID:22466454

  5. Alternative Medicine Techniques Have Non-Linear Effects on Radiation Response and Can Alter the Expression of Radiation Induced Bystander Effects

    PubMed Central

    Mothersill, Carmel; Smith, Richard; Henry, Matthew; Seymour, Colin; Wong, Raimond

    2013-01-01

    Many so-called “alternative medicine” techniques such as Reiki and acupuncture produce very good outcomes for intractable pain and other chronic illnesses but the efficacy is often dismissed as being psychosomatic. However a plausible mechanism does exist i.e. that the treatments alter the electromagnetic fields in living organisms and thereby prevent or reduce activity of neurons which lead to the pain. Low doses of ionising radiation have similar effects on electromagnetic fields and are known to induce signaling cascades in tissues due to ion gradients. To test this hypothesis cell cultures were exposed to Reiki – like and to acupuncture – like treatments, both performed by qualified practitioners. The cells were exposed either before or after the treatment to x-rays and were monitored for production of direct damage or bystander signals. The data suggest that the alternative techniques altered the response of cells to direct irradiation and altered bystander signal mechanisms. We conclude that alternative medicine techniques involving electromagnetic perturbations may modify the response of cells to ionizing radiation. In addition to the obvious implications for mechanistic studies of low dose effects, this could provide a novel target to exploit in radiation protection and in optimizing therapeutic gain during radiotherapy. PMID:23550268

  6. Genomic Instability in Liver Cells Caused by an LPS-Induced Bystander-Like Effect

    PubMed Central

    Kovalchuk, Igor; Walz, Paul; Thomas, James; Kovalchuk, Olga

    2013-01-01

    Bacterial infection has been linked to carcinogenesis, however, there is lack of knowledge of molecular mechanisms that associate infection with the development of cancer. We analyzed possible effects of the consumption of heat-killed E. coli O157:H7 cells or its cellular components, DNA, RNA, protein or lipopolysaccharides (LPS) on gene expression in naïve liver cells. Four week old mice were provided water supplemented with whole heat-killed bacteria or bacterial components for a two week period. One group of animals was sacrificed immediately, whereas another group was allowed to consume uncontaminated tap water for an additional two weeks, and liver samples were collected, post mortem. Liver cells responded to exposure of whole heat-killed bacteria and LPS with alteration in γH2AX levels and levels of proteins involved in proliferation, DNA methylation (MeCP2, DNMT1, DNMT3A and 3B) or DNA repair (APE1 and KU70) as well as with changes in the expression of genes involved in stress response, cell cycle control and bile acid biosynthesis. Other bacterial components analysed in this study did not lead to any significant changes in the tested molecular parameters. This study suggests that lipopolysaccharides are a major component of Gram-negative bacteria that induce molecular changes within naïve cells of the host. PMID:23874414

  7. Long-term consequences of radiation-induced bystander effects depend on radiation quality and dose and correlate with oxidative stress.

    PubMed

    Buonanno, Manuela; de Toledo, Sonia M; Pain, Debkumar; Azzam, Edouard I

    2011-04-01

    Widespread evidence indicates that exposure of cell populations to ionizing radiation results in significant biological changes in both the irradiated and nonirradiated bystander cells in the population. We investigated the role of radiation quality, or linear energy transfer (LET), and radiation dose in the propagation of stressful effects in the progeny of bystander cells. Confluent normal human cell cultures were exposed to low or high doses of 1GeV/u iron ions (LET ∼ 151 keV/µm), 600 MeV/u silicon ions (LET ∼ 51 keV/µm), or 1 GeV protons (LET ∼ 0.2 keV/µm). Within minutes after irradiation, the cells were trypsinized and co-cultured with nonirradiated cells for 5 h. During this time, irradiated and nonirradiated cells were grown on either side of an insert with 3-µm pores. Nonirradiated cells were then harvested and allowed to grow for 20 generations. Relative to controls, the progeny of bystander cells that were co-cultured with cells irradiated with iron or silicon ions, but not protons, exhibited reduced cloning efficiency and harbored higher levels of chromosomal damage, protein oxidation and lipid peroxidation. This correlated with decreased activity of antioxidant enzymes, inactivation of the redox-sensitive metabolic enzyme aconitase, and altered translation of proteins encoded by mitochondrial DNA. Together, the results demonstrate that the long-term consequences of the induced nontargeted effects greatly depend on the quality and dose of the radiation and involve persistent oxidative stress due to induced perturbations in oxidative metabolism. They are relevant to estimates of health risks from exposures to space radiation and the emergence of second malignancies after radiotherapy. PMID:21319986

  8. Long-Term Consequences of Radiation-Induced Bystander Effects Depend on Radiation Quality and Dose and Correlate with Oxidative Stress

    PubMed Central

    Buonanno, Manuela; de Toledo, Sonia M.; Pain, Debkumar; Azzam, Edouard I.

    2011-01-01

    Widespread evidence indicates that exposure of cell populations to ionizing radiation results in significant biological changes in both the irradiated and nonirradiated bystander cells in the population. We investigated the role of radiation quality, or linear energy transfer (LET), and radiation dose in the propagation of stressful effects in the progeny of bystander cells. Confluent normal human cell cultures were exposed to low or high doses of 1GeV/u iron ions (LET ~ 151 keV/μm), 600 MeV/u silicon ions (LET ~ 51 keV/μm), or 1 GeV protons (LET ~ 0.2 keV/μm). Within minutes after irradiation, the cells were trypsinized and co-cultured with nonirradiated cells for 5 h. During this time, irradiated and nonirradiated cells were grown on either side of an insert with 3-μm pores. Nonirradiated cells were then harvested and allowed to grow for 20 generations. Relative to controls, the progeny of bystander cells that were co-cultured with cells irradiated with iron or silicon ions, but not protons, exhibited reduced cloning efficiency and harbored higher levels of chromosomal damage, protein oxidation and lipid peroxidation. This correlated with decreased activity of antioxidant enzymes, inactivation of the redox-sensitive metabolic enzyme aconitase, and altered translation of proteins encoded by mitochondrial DNA. Together, the results demonstrate that the long-term consequences of the induced nontargeted effects greatly depend on the quality and dose of the radiation and involve persistent oxidative stress due to induced perturbations in oxidative metabolism. They are relevant to estimates of health risks from exposures to space radiation and the emergence of second malignancies after radiotherapy. PMID:21319986

  9. Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions.

    PubMed

    Buonanno, Manuela; De Toledo, Sonia M; Howell, Roger W; Azzam, Edouard I

    2015-05-01

    During interplanetary missions, astronauts are exposed to mixed types of ionizing radiation. The low 'flux' of the high atomic number and high energy (HZE) radiations relative to the higher 'flux' of low linear energy transfer (LET) protons makes it highly probable that for any given cell in the body, proton events will precede any HZE event. Whereas progress has been made in our understanding of the biological effects of low-LET protons and high-LET HZE particles, the interplay between the biochemical processes modulated by these radiations is unclear. Here we show that exposure of normal human fibroblasts to a low mean absorbed dose of 20 cGy of 0.05 or 1-GeV protons (LET ∼ 1.25 or 0.2 keV/μm, respectively) protects the irradiated cells (P < 0.0001) against chromosomal damage induced by a subsequent exposure to a mean absorbed dose of 50 cGy from 1 GeV/u iron ions (LET ∼ 151 keV/μm). Surprisingly, unirradiated (i.e. bystander) cells with which the proton-irradiated cells were co-cultured were also significantly protected from the DNA-damaging effects of the challenge dose. The mitigating effect persisted for at least 24 h. These results highlight the interactions of biological effects due to direct cellular traversal by radiation with those due to bystander effects in cell populations exposed to mixed radiation fields. They show that protective adaptive responses can spread from cells targeted by low-LET space radiation to bystander cells in their vicinity. The findings are relevant to understanding the health hazards of space travel. PMID:25805407

  10. Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions

    PubMed Central

    Buonanno, Manuela; De Toledo, Sonia M.; Howell, Roger W.; Azzam, Edouard I.

    2015-01-01

    During interplanetary missions, astronauts are exposed to mixed types of ionizing radiation. The low ‘flux’ of the high atomic number and high energy (HZE) radiations relative to the higher ‘flux’ of low linear energy transfer (LET) protons makes it highly probable that for any given cell in the body, proton events will precede any HZE event. Whereas progress has been made in our understanding of the biological effects of low-LET protons and high-LET HZE particles, the interplay between the biochemical processes modulated by these radiations is unclear. Here we show that exposure of normal human fibroblasts to a low mean absorbed dose of 20 cGy of 0.05 or 1-GeV protons (LET ∼ 1.25 or 0.2 keV/μm, respectively) protects the irradiated cells (P < 0.0001) against chromosomal damage induced by a subsequent exposure to a mean absorbed dose of 50 cGy from 1 GeV/u iron ions (LET ∼ 151 keV/μm). Surprisingly, unirradiated (i.e. bystander) cells with which the proton-irradiated cells were co-cultured were also significantly protected from the DNA-damaging effects of the challenge dose. The mitigating effect persisted for at least 24 h. These results highlight the interactions of biological effects due to direct cellular traversal by radiation with those due to bystander effects in cell populations exposed to mixed radiation fields. They show that protective adaptive responses can spread from cells targeted by low-LET space radiation to bystander cells in their vicinity. The findings are relevant to understanding the health hazards of space travel. PMID:25805407

  11. Brief report: The bystander effect in cyberbullying incidents.

    PubMed

    Machackova, Hana; Dedkova, Lenka; Mezulanikova, Katerina

    2015-08-01

    This study examined the bystander effect in cyberbullying. Using self-reported data from 257 Czech respondents who had witnessed a cyberbullying attack, we tested whether provided help decreased with increased number of other bystanders. We controlled for several individual and contextual factors, including empathy, social self-efficacy, empathic response to victimization, and relationship to the victim. Results showed that participants tend to help the victims more in incidents with only one or two other bystanders. We also found that, as in the "offline" realm, bystander effect is not linear: no significant differences were found between incidents with a moderate number (3-10) and a larger number of total bystanders. Our findings, thus, provide support for the presence of the bystander effect in cyberbullying. PMID:26070168

  12. A Role for Bioelectric Effects in the Induction of Bystander Signals by Ionizing Radiation?

    PubMed Central

    Mothersill, C.; Moran, G.; McNeill, F.; Gow, M.D.; Denbeigh, J.; Prestwich, W.; Seymour, C.B.

    2007-01-01

    The induction of “bystander effects” i.e. effects in cells which have not received an ionizing radiation track, is now accepted but the mechanisms are not completely clear. Bystander effects following high and low LET radiation exposure are accepted but mechanisms are still not understood. There is some evidence for a physical component to the signal. This paper tests the hypothesis that bioelectric or biomagnetic phenomena are involved. Human immortalized skin keratinocytes and primary explants of mouse bladder and fish skin, were exposed directly to ionizing radiation or treated in a variety of bystander protocols. Exposure of cells was conducted by shielding one group of flasks using lead, to reduce the dose below the threshold of 2mGy 60Cobalt gamma rays established for the bystander effect. The endpoint for the bystander effect in the reporter system used was reduction in cloning efficiency (RCE). The magnitude of the RCE was similar in shielded and unshielded flasks. When cells were placed in a Faraday cage the magnitude of the RCE was less but not eliminated. The results suggest that liquid media or cell-cell contact transmission of bystander factors may be only part of the bystander mechanism. Bioelectric or bio magnetic fields may have a role to play. To test this further, cells were placed in a Magnetic Resonance Imaging (MRI) machine for 10min using a typical head scan protocol. This treatment also induced a bystander response. Apart from the obvious clinical relevance, the MRI results further suggest that bystander effects may be produced by non-ionizing exposures. It is concluded that bioelectric or magnetic effects may be involved in producing bystander signaling cascades commonly seen following ionizing radiation exposure. PMID:18648606

  13. Bystander effects and their implications for clinical radiation therapy: Insights from multiscale in silico experiments.

    PubMed

    Powathil, Gibin G; Munro, Alastair J; Chaplain, Mark A J; Swat, Maciej

    2016-07-21

    Radiotherapy is a commonly used treatment for cancer and is usually given in varying doses. At low radiation doses relatively few cells die as a direct response to radiation but secondary radiation effects, such as DNA mutation or bystander phenomena, may affect many cells. Consequently it is at low radiation levels where an understanding of bystander effects is essential in designing novel therapies with superior clinical outcomes. In this paper, we use a hybrid multiscale mathematical model to study the direct effects of radiation as well as radiation-induced bystander effects on both tumour cells and normal cells. We show that bystander responses play a major role in mediating radiation damage to cells at low-doses of radiotherapy, doing more damage than that due to direct radiation. The survival curves derived from our computational simulations showed an area of hyper-radiosensitivity at low-doses that are not obtained using a traditional radiobiological model. PMID:27084360

  14. Lack of Bystander Effects From High LET Radiation For Early Cytogenetic Endpoints.

    SciTech Connect

    Groesser, Torsten; Cooper, Brian; Rydberg, Bjorn

    2008-05-07

    The aim of this work was to study radiation-induced bystander effects for early cytogenetic end points in various cell lines using the medium transfer technique after exposure to high- and low-LET radiation. Cells were exposed to 20 MeV/ nucleon nitrogen ions, 968 MeV/nucleon iron ions, or 575 MeV/nucleon iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, {gamma}-H2AX focus formation, induction of chromatid breaks in prematurely condensed chromosomes, and micronucleus formation using DNA repair-proficient and -deficient hamster and human cell lines (xrs6, V79, SW48, MO59K and MO59J). Cell survival was also measured in SW48 bystander cells using X rays. Although it was occasionally possible to detect an increase in chromatid break levels using nitrogen ions and to see a higher number of {gamma}-H2AX foci using nitrogen and iron ions in xrs6 bystander cells in single experiments, the results were not reproducible. After we pooled all the data, we could not verify a significant bystander effect for any of these end points. Also, we did not detect a significant bystander effect for DSB induction or micronucleus formation in these cell lines or for clonogenic survival in SW48 cells. The data suggest that DNA damage and cytogenetic changes are not induced in bystander cells. In contrast, data in the literature show pronounced bystander effects in a variety of cell lines, including clonogenic survival in SW48 cells and induction of chromatid breaks and micronuclei in hamster cells. To reconcile these conflicting data, it is possible that the epigenetic status of the specific cell line or the precise culture conditions and medium supplements, such as serum, may be critical for inducing bystander effects.

  15. A Mouse Ear Model for Bystander Studies Induced by Microbeam Irradiation

    PubMed Central

    Buonanno, M.; Randers-Pehrson, G.; Smilenov, L. B.; Kleiman, N. J.; Young, E.; Ponnayia, B.; Brenner, D. J.

    2015-01-01

    Radiation-induced bystander effects have been observed in vitro and in cell and tissue culture models, however, there are few reported studies showing these effects in vivo. To our knowledge, this is the first reported study on bystander effects induced by microbeam irradiation in an intact living mammal. The mouse ear was used to investigate radiation-induced bystander effects in keratinocytes, utilizing a 3 MeV proton microbeam (LET 13.1 keV/µm) with a range in skin of about 135 µm. Using a custom-designed holder, the ear of an anesthetized C57BL/6J mouse was flattened by gentle suction and placed over the microbeam port to irradiate cells along a 35 µm wide, 6 mm long path. Immunohistochemical analysis of γ-H2AX foci formation in tissue sections revealed, compared to control tissue, proton-induced γ-H2AX foci formation in one of the two epidermal layers of the mouse ear. Strikingly, a higher number of cells than expected showed foci from direct irradiation effects. Although the proton-irradiated line was ~35 µm wide, the average width spanned by γ-H2AX-positive cells exceeded 150 µm. Cells adjacent to or in the epidermal layer opposite the γ-H2AX-positive region did not exhibit foci. These findings validate this mammalian model as a viable system for investigating radiation-induced bystander effects in an intact living organism. PMID:26207682

  16. The influence of smoking on radiation-induced bystander signal production in esophageal cancer patients.

    PubMed

    Hanu, C; Timotin, E; Wong, R; Sur, R K; Hayward, J E; Seymour, C B; Mothersill, C E

    2016-05-01

    The relevance of radiation-induced bystander effects in humans is unclear. Much of the existing data relate to cell lines but the effect of bystander signals in complex human tissues is unclear. A phase II clinical study was untaken, where blood sera from 60 patients along with 15 cancer-free volunteers were used to detect whether measurable bystander factor(s) could be found in the blood following high dose rate (HDR) brachytherapy. Overall, there was no significant change in bystander signal production (measured in a human keratinocyte reporter system) before and after one treatment fraction of HDR brachytherapy (p>0.05). Further assessment of patient characteristics and environmental modifiable factors including smoking were also analyzed. Similar to previously published data, samples taken from smokers produced weaker signals compared to non-smokers (p<0.05). Although the number of non-smoking subjects was low, there was a clear decrease in cloning efficiency observed in keratinocyte cultures for these patients that requires further study. This study found that samples taken from smokers do not produce bystander signals, whereas samples taken from non-smokers can produce such signals following HDR brachytherapy. These findings highlight the importance of studying the interactions of multiple stressors including environmental modifiers with radiation, since some factors such as smoking may elicit protection in tumor cells which could counteract the effectiveness of radiation therapy. PMID:26750714

  17. Lack of evidence for low-LET radiation induced bystander response in normal human fibroblasts and colon carcinoma cells

    SciTech Connect

    Marianne B. Sowa; Wilfried Goetz; Janet E. Baulch; Dinah N. Pyles; Jaroslaw Dziegielewski; Susannah Yovino; Andrew R. Snyder; Sonia M. de Toledo; Edouard I. Azzam; William F. Morgan

    2008-06-30

    Purpose: To investigate radiation induced bystander responses and to determine the role of gap junction intercellular communication and the radiation environment in propagating this response. Materials and Methods: We use medium transfer and targeted irradiation to examine radiation induced bystander effects in primary human fibroblast (AG1522) and human colon carcinoma (RKO36) cells. We examined the effect of variables such as gap junction intercellular communication, linear energy transfer (LET), and the role of the radiation environment in non-targeted responses. Endpoints included clonogenic survival, micronucleus formation and foci formation at histone 2AX over doses ranging from 10 to 100 cGy. Results: The results show no evidence of a low-LET radiation induced bystander response for the endpoints of clonogenic survival and induction of DNA damage. Nor do we see evidence of a high-LET, Fe ion radiation (1 GeV/n) induced bystander effect. However, direct comparison for 3.2 MeV α-particle exposures showed a statistically significant medium transfer bystander effect for this high-LET radiation. Conclusions: From our results, it is evident that there are many confounding factors influencing bystander responses as reported in the literature. Our observations reflect the inherent variability in biological systems and the difficulties in extrapolating from in vitro models to radiation risks in humans.

  18. Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

    PubMed Central

    Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  19. Rescue effects: irradiated cells helped by unirradiated bystander cells.

    PubMed

    Lam, R K K; Fung, Y K; Han, W; Yu, K N

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  20. Genomic instability and bystander effects: a paradigm shift in radiation biology?

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2002-01-01

    A basic paradigm in radiobiology is that, following exposure to ionizing radiation, the deposition of energy in the cell nucleus and the resulting damage to DNA, the principal target, are responsible for the radiation's deleterious biological effects. Findings in two rapidly expanding fields of research--radiation-induced genomic instability and bystander effects--have caused us to reevaluate these central tenets. In this article, the potential influence of induced genomic instability and bystander effects on cellular injury after exposure to low-level radiation will be reviewed.

  1. A Variable-Energy Soft X-Ray Microprobe to Investigate Mechanisms of the Radiation-Induced Bystander Effect.

    SciTech Connect

    Folkard, Melvyn; Vojnovic, Borivoj; Schettino, Giuseppe; Atkinson, Kirk; Prise, Kevin, M.; Michael, Barry, D.

    2007-01-23

    The Gray Cancer Institute has pioneered the use of X ray focussing techniques to develop systems for micro irradiating individual cells and sub cellular targets in vitro. Cellular micro irradiation is now recognised as a highly versatile technique for understanding how ionising radiation interacts with living cells and tissues. The strength of the technique lies in its ability to deliver precise doses of radiation to selected individual cells (or sub cellular targets). The application of this technique in the field of radiation biology continues to be of great interest for investigating a number of phenomena currently of concern to the radiobiological community. One important phenomenon is the so called ‘bystander effect’ where it is observed that unirradiated cells can also respond to signals transmitted by irradiated neighbours. Clearly, the ability of a microbeam to irradiate just a single cell or selected cells within a population is well suited to studying this effect. Our prototype ‘tabletop’ X-ray microprobe was optimised for focusing 278 eV C-K X rays and has been used successfully for a number of years. However, we have sought to develop a new variable energy soft X-ray microprobe capable of delivering focused CK (0.28 keV), Al-K (1.48 keV) and notably, Ti-K (4.5 keV) X rays. Ti-K X rays are capable of penetrating several cell layers and are therefore much better suited to studies involving tissues and multi cellular layers. In our new design, X-rays are generated by the focussed electron bombardment of a material whose characteristic-K radiation is required. The source is mounted on a 1.5 x 1.0 metre optical table. Electrons are generated by a custom built gun, designed to operate up to 15 kV. The electrons are focused using a permanent neodymium iron boron magnet assembly. Focusing is achieved by adjusting the accelerating voltage and by fine tuning the target position via a vacuum position feedthrough. To analyze the electron beam properties, a

  2. Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

    PubMed

    Temelie, Mihaela; Stroe, Daniela; Petcu, Ileana; Mustaciosu, Cosmin; Moisoi, Nicoleta; Savu, Diana

    2016-08-01

    Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling. PMID:27025606

  3. Neutron Exposures in Human Cells: Bystander Effect and Relative Biological Effectiveness

    PubMed Central

    Seth, Isheeta; Schwartz, Jeffrey L.; Stewart, Robert D.; Emery, Robert; Joiner, Michael C.; Tucker, James D.

    2014-01-01

    Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001). These data indicate that neutrons do not induce a bystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0±0.13 for micronuclei and 5.8±2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety. PMID:24896095

  4. Caspase-3-independent pathways proceeding in bystander effect of HSV-tk/GCV system

    NASA Astrophysics Data System (ADS)

    Lin, Juqiang; Ma, Yan; Zeng, Shaoqun; Zhang, Zhihong

    2008-02-01

    HSV-tk/GCV system, which is the virus-directed enzyme/prodrug therapy of herpes simplex virus (HSV) thymidine kinase (tk) gene / the anti-viral reagent ganciclovir (GCV), is one of the promising approaches in the rapidly growing area of gene therapy. As gene therapy of cancer such as suicide gene therapy has entered the clinic, another therapy effect which is called 'bystander effect' was reported. Bystander effect can lead to killing of non-transduced tumor cells in the immediate vicinity of GCV-treated HSV-TK-positive cells. Now the magnitude of 'bystander effect' is an essential factor for this anti-tumor approach in vivo. However, the mechanism which HSV-tk/ACV brings "bystander effect" is poorly understood. In this study, we monitor the activation of caspase-3 in HSV-tk/GCV system by a FRET probe CD3, a FRET-based indicator for activity of caspase3, which is composed of an enhanced cyan fluorescent protein, a caspase-sensitive linker, and a red fluorescent protein from Discosoma with efficient maturation property. Through application of CD3 we have visualized the activation of caspase-3 in tk gene positive human adenoid cystic carcinoma (ACC-M) cells but not in bystander effect of HSV-tk/GCV system induced by GCV. This finding provides needed information for understanding the mechanisms by which suicide gene approaches actually kill cancer cells, and may prove to be helpful for the clinical treatment of cancers.

  5. Radiation quality dependence of signal transmission and bystander induced cell killing

    NASA Astrophysics Data System (ADS)

    Esposito, Giuseppe; Bertolotti, Alessia; Facoetti, Angelica; Grande, Sveva; Mariotti, Luca; Ottolenghi, Andrea; Ranza, Elena; Simone, Giustina; Sorrentino, Eugenio; Antonella Tabocchini, Maria

    Low dose radiobiological studies have shown effects, observable in cells that are in the vicinity of irradiated cells, which are due to the release by irradiated cells of several cellular mediators among which Reactive Oxygen and Nitrogen Species (ROS, NRS), and cytokines are likely to play a key role. Despite the large number in the literature of studies on bystander effects induced by ionizing radiation the results are still conflicting, and further studies are therefore needed on the possible underlying mechanisms. The dependence on radiation quality deserve particular attention because bystander mechanisms are probably more important with high-LET irradi-ations, where many cells are not hit (bystander). Moreover, due to the different patterns of energy deposition, the cellular response to low LET and high LET radiation can be different. Understanding whether these cells can contribute to the adverse effects of low radiation doses in a radiation quality-dependent fashion might have important implications in risk estimates for both cancer induction and non-cancer diseases. In this context, we addressed to the study of the bystander induced cell killing after incubation with "conditioned medium" from primary human fibroblasts irradiated with 0.1 and 0.5 Gy of α-particles or γ-rays. Medium transfer was performed after 1h incubation from irradiation. The results have confirmed a reduction in clonogenic survival after incubation with medium from α-irradiated cells, independently of the dose; similar results were obtained after γ-irradiation, although in this case a slight dose depen-dence could be envisaged. Interleukin-6 (IL-6) and Interleukin-8 (IL-8) levels were measured in the conditioned medium collected up to 20 hours after irradiation with α-particles and γ-rays in the dose-range of 0.1-1.0 Gy, in parallel with evaluation of their receptor expression in irradi-ated and bystander cells. Concerning IL-6, we observed the strongest modulation of its release

  6. A Mouse Ear Model for Bystander Studies Induced by Microbeam Irradiation.

    PubMed

    Buonanno, M; Randers-Pehrson, G; Smilenov, L B; Kleiman, N J; Young, E; Ponnayia, B; Brenner, D J

    2015-08-01

    Radiation-induced bystander effects have been observed in vitro and in cell and tissue culture models, however, there are few reported studies showing these effects in vivo. To our knowledge, this is the first reported study on bystander effects induced by microbeam irradiation in an intact living mammal. The mouse ear was used to investigate radiation-induced bystander effects in keratinocytes, utilizing a 3 MeV proton microbeam (LET 13.1 keV/μm) with a range in skin of about 135 μm. Using a custom-designed holder, the ear of an anesthetized C57BL/6J mouse was flattened by gentle suction and placed over the microbeam port to irradiate cells along a 35 μm wide, 6 mm long path. Immunohistochemical analysis of γ-H2AX foci formation in tissue sections revealed, compared to control tissue, proton-induced γ-H2AX foci formation in one of the two epidermal layers of the mouse ear. Strikingly, a higher number of cells than expected showed foci from direct irradiation effects. Although the proton-irradiated line was ~35 μm wide, the average width spanned by γ-H2AX-positive cells exceeded 150 μm. Cells adjacent to or in the epidermal layer opposite the γ-H2AX-positive region did not exhibit foci. These findings validate this mammalian model as a viable system for investigating radiation-induced bystander effects in an intact living organism. PMID:26207682

  7. Bystander Effects During Synchrotron Imaging Procedures?

    SciTech Connect

    Schueltke, Elisabeth; Nikkhah, Guido; Bewer, Brian; Wysokinski, Tomasz; Chapman, Dean

    2010-07-23

    Using monochromatic beam and synchrotron phase-contrast technique at the biomedical beamline of the Italian synchrotron facility Elettra (SYRMEP), we have shown in a small animal model of malignant brain tumor that it is possible to obtain high-resolution images of very small tumors when they have developed from implanted tumor cells loaded with colloidal gold nanoparticles (GNP). All previous experiments were conducted in post-mortem samples. We have now designed a cell culture experiment to investigate the effects of synchrotron radiation with an energy and dose profile similar to that expected in our first in vivo imaging studies according to the protocol developed at SYRMEP.Materials and Methods: Culture flasks containing either gold-loaded or naieve C6 glioma cells were exposed to a dose of 0.5 Gy at 24 keV. The irradiated medium was aspirated and replaced with fresh growth medium. Twenty-four hours later this non-irradiated medium exposed to irradiated cells was aspirated, then added to non-irradiated C6 cells in order to investigate whether bystander effects are seen under the conditions of our image acquisition protocol. The irradiated medium was added to a number of other non-irradiated cell cultures. Cell counts were followed until 72 hrs after irradiation. Western blots were conducted with H2AX antibodies. This experiment was one of the first biomedical experiments conducted at BMIT, the new biomedical imaging and therapy beamline of the Canadian Light Source.Results: No significant differences in proliferation were seen between cells that were directly irradiated, exposed to irradiated medium or exposed to the non-irradiated 24-hr-medium from the irradiated cells. However, there was a tendency towards a higher number of double strand breaks in previously irradiated cells when they were exposed to non-irradiated medium that had been in contact with irradiated cells for 24 hrs.

  8. Bystander Effects During Synchrotron Imaging Procedures?

    NASA Astrophysics Data System (ADS)

    Schültke, Elisabeth; Bewer, Brian; Wysokinski, Tomasz; Chapman, Dean; Nikkhah, Guido

    2010-07-01

    Using monochromatic beam and synchrotron phase-contrast technique at the biomedical beamline of the Italian synchrotron facility Elettra (SYRMEP), we have shown in a small animal model of malignant brain tumor that it is possible to obtain high-resolution images of very small tumors when they have developed from implanted tumor cells loaded with colloidal gold nanoparticles (GNP). All previous experiments were conducted in post-mortem samples. We have now designed a cell culture experiment to investigate the effects of synchrotron radiation with an energy and dose profile similar to that expected in our first in vivo imaging studies according to the protocol developed at SYRMEP. Materials and Methods: Culture flasks containing either gold-loaded or naïve C6 glioma cells were exposed to a dose of 0.5 Gy at 24 keV. The irradiated medium was aspirated and replaced with fresh growth medium. Twenty-four hours later this non-irradiated medium exposed to irradiated cells was aspirated, then added to non-irradiated C6 cells in order to investigate whether bystander effects are seen under the conditions of our image acquisition protocol. The irradiated medium was added to a number of other non-irradiated cell cultures. Cell counts were followed until 72 hrs after irradiation. Western blots were conducted with H2AX antibodies. This experiment was one of the first biomedical experiments conducted at BMIT, the new biomedical imaging and therapy beamline of the Canadian Light Source. Results: No significant differences in proliferation were seen between cells that were directly irradiated, exposed to irradiated medium or exposed to the non-irradiated 24-hr-medium from the irradiated cells. However, there was a tendency towards a higher number of double strand breaks in previously irradiated cells when they were exposed to non-irradiated medium that had been in contact with irradiated cells for 24 hrs.

  9. Recursive mentalizing and common knowledge in the bystander effect.

    PubMed

    Thomas, Kyle A; De Freitas, Julian; DeScioli, Peter; Pinker, Steven

    2016-05-01

    The more potential helpers there are, the less likely any individual is to help. A traditional explanation for this bystander effect is that responsibility diffuses across the multiple bystanders, diluting the responsibility of each. We investigate an alternative, which combines the volunteer's dilemma (each bystander is best off if another responds) with recursive theory of mind (each infers what the others know about what he knows) to predict that actors will strategically shirk when they think others feel compelled to help. In 3 experiments, participants responded to a (fictional) person who needed help from at least 1 volunteer. Participants were in groups of 2 or 5 and had varying information about whether other group members knew that help was needed. As predicted, people's decision to help zigzagged with the depth of their asymmetric, recursive knowledge (e.g., "John knows that Michael knows that John knows help is needed"), and replicated the classic bystander effect when they had common knowledge (everyone knowing what everyone knows). The results demonstrate that the bystander effect may result not from a mere diffusion of responsibility but specifically from actors' strategic computations. (PsycINFO Database Record PMID:26913616

  10. LET-Dependent Bystander Effects Caused by Irradiation of Human Prostate Carcinoma Cells with X Rays or Alpha Particles

    PubMed Central

    Anzenberg, Vered; Chandiramani, Sarika; Coderre, Jeffrey A.

    2014-01-01

    Radiation-induced bystander effects have been demonstrated in both normal and tumor cells using a variety of different radiation qualities. Literature reports are contradictory, however, on whether there is an LET dependence of the bystander effect. This study investigated the ability of DU-145 human prostate carcinoma cells irradiated with either α particles or 250 kVp X rays to cause medium-mediated bystander effects in unirradiated populations of DU-145 cells or in AG01522 human fibroblasts. The end points measured in both of the bystander cell lines were micronucleus formation, γ-H2AX focus induction, and the surviving fraction. The incidence of micronuclei increased 1.5–2.0-fold in both tumor and fibroblast bystander cells after 4 h of co-culture with DU-145 tumor cells that had been directly irradiated with either α particles or X rays. Only the AG01522 fibroblasts showed bystander effects for the γ-H2AX focus (a 1.5-fold increase) and surviving fraction (a decrease to 0.8) end points when co-cultured with X-irradiated tumor cells. Alpha-particle irradiation of DU-145 tumor cells produced no decrease in the surviving fraction and no increase in γ-H2AX focus induction in co-cultured bystander cells of either cell line. These results indicate that there are LET-dependent differences in the signal released from DU-145 human prostate carcinoma cells and that, for some end points, bystander AG01522 fibroblasts and bystander DU-145 prostate carcinoma cells respond differently to the same medium-mediated signal. PMID:19024654

  11. The induction of bystander mutagenic effects in vivo by alpha-particle irradiation in whole Arabidopsis thaliana plants.

    PubMed

    Li, Fanghua; Liu, Ping; Wang, Ting; Bian, Po; Wu, Yuejin; Wu, Lijun; Yu, Zengliang

    2010-08-01

    Our previous studies demonstrated distant/abscopal bystander effects in A. thaliana seeds and embryos; the postembryonic development of bystander tissues, such as root hair differentiation, primary root elongation, lateral root initiation and survival, were inhibited significantly by localized irradiation with microbeam protons and low-energy ions. In the present study, we further investigated radiation-induced bystander mutagenic effects in vivo in A. thaliana plants using homologous recombination (HR) and the expression level of the HR-related AtRAD54 gene as mutagenic end points. We found that alpha-particle irradiation of distal primary roots of young seedlings resulted in a significant increase in the frequency of HR in the aerial plants; the increased induction of HR occurred in every true leaf over the course of rosette development. Moreover, we also found that localized alpha-particle irradiation of roots induced a short-term up-regulated expression of the HR-related AtRAD54 gene in the nonirradiated aerial plants. These results suggested the existence of bystander mutagenic effects in vivo in plants. Treatment with the ROS scavenger DMSO dramatically reduced the effects of localized root irradiation on the induction of HR and expression of the AtRAD54 gene in bystander tissues, suggesting that ROS play a critical role in mediating the bystander mutagenic effects in plants. PMID:20681789

  12. Bystander effects of ionizing radiation can be modulated by signaling amines

    SciTech Connect

    Poon, R.C.C.; Agnihotri, N.; Seymour, C.; Mothersill, C.

    2007-10-15

    Actual risk and risk management of exposure to ionizing radiation are among the most controversial areas in environmental health protection. Recent developments in radiobiology especially characterization of bystander effects have called into question established dogmas and are thought to cast doubt on the scientific basis of the risk assessment framework, leading to uncertainty for regulators and concern among affected populations. In this paper we test the hypothesis that small signaling molecules widely used throughout the animal kingdom for signaling stress or environmental change, such as 5-Hydroxytryptamine (5-HT, serotonin), L-DOPA, glycine or nicotine are involved in bystander signaling processes following ionizing radiation exposure. We report data which suggest that nano to micromolar concentrations of these agents can modulate bystander-induced cell death. Depletion of 5-HT present in tissue culture medium, occurred following irradiation of cells. This suggested that 5-HT might be bound by membrane receptors after irradiation. Expression of 5-HT type 3 receptors which are Ca{sup 2+} ion channels was confirmed in the cells using immunocytochemistry and receptor expression could be increased using radiation or 5-HT exposure. Zofran and Kitryl, inhibitors of 5-HT type 3 receptors, and reserpine a generic serotonin antagonist block the bystander effect induced by radiation or by serotonin. The results may be important for the mechanistic understanding of how low doses of radiation interact with cells to produce biological effects.

  13. Leverage Between the Buffering Effect and the Bystander Effect in Social Networking.

    PubMed

    Chiu, Yu-Ping; Chang, Shu-Chen

    2015-08-01

    This study examined encouraged and inhibited social feedback behaviors based on the theories of the buffering effect and the bystander effect. A system program was used to collect personal data and social feedback from a Facebook data set to test the research model. The results revealed that the buffering effect induced a positive relationship between social network size and feedback gained from friends when people's social network size was under a certain cognitive constraint. For people with a social network size that exceeds this cognitive constraint, the bystander effect may occur, in which having more friends may inhibit social feedback. In this study, two social psychological theories were applied to explain social feedback behavior on Facebook, and it was determined that social network size and social feedback exhibited no consistent linear relationship. PMID:26196410

  14. Induction of a bystander mutagenic effect of alpha particles in mammalian cells

    NASA Technical Reports Server (NTRS)

    Zhou, H.; Randers-Pehrson, G.; Waldren, C. A.; Vannais, D.; Hall, E. J.; Hei, T. K.; Chatterjee, A. (Principal Investigator)

    2000-01-01

    Ever since the discovery of X-rays was made by Rontgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear/extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A(L) cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 microM dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.

  15. Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation.

    PubMed

    Tomita, Masanori; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

    2015-07-01

    In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time

  16. Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

    NASA Astrophysics Data System (ADS)

    Tomita, Masanori; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

    2015-07-01

    In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time

  17. Effects of Low-Dose Alpha-Particle Irradiation in Human Cells: The Role of Induced Genes and the Bystander Effect. Final Technical Report (9/15/1998-5/31/2005)

    SciTech Connect

    Little, John B.

    2013-09-17

    This grant was designed to examine the cellular and molecular mechanisms for the bystander effect of radiation (initially described in this laboratory) whereby damage signals are passed from irradiated to non-irradiated cells in a population. These signals induce genetic effects including DNA damage, mutations and chromosomal aberrations in the nonirradiated cells. Experiments were carried out in cultured mammalian cells, primarily human diploid cells, irradiated with alpha particles. This research resulted in 17 publications in the refereed literature and is described in the Progress Report where it is keyed to the publication list. This project was initiated at the Harvard School of Public Health (HSPH) and continued in collaboration with students/fellows at Colorado State University (CSU) and the New Jersey Medical School (NJMS).

  18. Studies of Bystander Effects in 3-D Tissue Systems Using a Low-LET Microbeam

    SciTech Connect

    Brenner, David J.

    2009-07-17

    It is now accepted that biological effects may occur in cells that were not themselves traversed by ionizing radiation but are close to those that were. Little is known about the mechanism underlying such a bystander effect, although cell-to-cell communication is thought to be important. Previous work demonstrated a significant bystander effect for clonogenic survival and oncogenic transformation in C3H 10T(1/2) cells. Additional studies were undertaken to assess the importance of the degree of cell-to-cell contact at the time of irradiation on the magnitude of this bystander effect by varying the cell density. When 10% of cells were exposed to a range of 2-12 alpha particles, a significantly greater number of cells were inactivated when cells were irradiated at high density than at low density. In addition, the oncogenic transformation frequency was significantly higher in high-density cultures. These results suggest that when a cell is hit by radiation, the transmission of the bystander signal through cell-to-cell contact is an important mediator of the effect, implicating the involvement of intracellular communication through gap junctions. Additional studies to address the relationship between the bystander effect and the adaptive response were undertaken. A novel apparatus, where targeted and non-targeted cells were grown in close proximity, was used to investigate these. It was further examined whether a bystander effect or an adaptive response could be induced by a factor(s) present in the supernatants of cells exposed to a high or low dose of X-rays, respectively. When non-hit cells were co-cultured for 24 h with cells irradiated with 5 Gy alpha-particles, a significant increase in both cell killing and oncogenic transformation frequency was observed. If these cells were treated with 2 cGy X-rays 5 h before co-culture with irradiated cells, approximately 95% of the bystander effect was cancelled out. A 2.5-fold decrease in the oncogenic transformation

  19. Bystander effect in human hepatoma HepG2 cells caused by medium transfers at different times after high-LET carbon ion irradiation

    NASA Astrophysics Data System (ADS)

    Wu, Qingfeng; Li, Qiang; Jin, Xiaodong; Liu, Xinguo; Dai, Zhongying

    2011-01-01

    Although radiation-induced bystander effects have been well documented in a variety of biological systems, whether irradiated cells have the ability to generate bystander signaling persistently is still unclear and the clinical relevance of bystander effects in radiotherapy remains to be elucidated. This study examines tumor cellular bystander response to autologous medium from cell culture irradiated with high-linear energy transfer (LET) heavy ions at a therapeutically relevant dose in terms of clonogenic cell survival. In vitro experiments were performed using human hepatoma HepG2 cell line exposed to 100 keV/μm carbon ions at a dose of 2 Gy. Two different periods (2 and 12 h) after irradiation, irradiated cell conditioned medium (ICCM) and replenished fresh medium were harvested and then transferred to unirradiated bystander cells. Cellular bystander responses were measured with the different medium transfer protocols. Significant higher survival fractions of unirradiated cells receiving the media from the irradiated cultures at the different times post-irradiation than those of the control were observed. Even replenishing fresh medium for unirradiated cells which had been exposed to the ICCM for 12 h could not prevent the bystander cells from the increased survival fraction. These results suggest that the irradiated cells could release unidentified signal factor(s), which induced the increase in survival fraction for the unirradiated bystander cells, into the media sustainedly and the carbon ions triggered a cascade of signaling events in the irradiated cells rather than secreting the soluble signal factor(s) just at a short period after irradiation. Based on the observations in this study, the importance of bystander effect in clinical radiotherapy was discussed and incorporating the bystander effect into the current radiobiological models, which are applicable to heavy ion radiotherapy, is needed urgently.

  20. Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    A number of nontargeted and delayed effects associated with radiation exposure have now been described. These include radiation-induced genomic instability, death-inducing and bystander effects, clastogenic factors and transgenerational effects. It is unlikely that these nontargeted effects are directly induced by cellular irradiation. Instead, it is proposed that some as yet to be identified secreted factor can be produced by irradiated cells that can stimulate effects in nonirradiated cells (death-inducing and bystander effects, clastogenic factors) and perpetuate genomic instability in the clonally expanded progeny of an irradiated cell. The proposed factor must be soluble and capable of being transported between cells by cell-to-cell gap junction communication channels. Furthermore, it must have the potential to stimulate cellular cytokines and/or reactive oxygen species. While it is difficult to imagine a role for such a secreted factor in contributing to transgenerational effects, the other nontargeted effects of radiation may all share a common mechanism.

  1. Lack of evidence for low-LET radiation induced bystander response in normal human fibroblasts and colon carcinoma cells

    SciTech Connect

    Sowa, Marianne B.; Goetz, Wilfried; Baulch, Janet E.; Pyles, Dinah N.; Dziegielewski, J.; Yovino, Susannah; Snyder, Andrew R.; de Toledo, S. M.; Azzam, Edouard I.; Morgan, William F.

    2010-02-01

    The conventional paradigm in radiation biology has been that DNA is the primary target for energy deposition following exposure to ionizing radiation. However, studies focusing on the non-target effects of radiation, i.e. effects occurring in cells not directly exposed to radiation, imply that the target of exposure is larger than what has traditionally been assumed and could have significant implications for radiation health risks. We have conducted an extensive study of the low-LET bystander effect including multiple cell lines and endpoints and various radiation sources and exposure scenarios. In no instance do we see evidence of a low-LET induced bystander effect. However, direct comparison for alpha particle exposure showed a statistically significant media transfer bystander effect for high-LET but not for low-LET radiation. From our results it is evident that there are many confounding factors mitigating bystander responses as reported in the literature and for the cell lines we studied that there is a LET dependence for the observed responses. Our observations reflect the inherent variability in biological systems and the difficulties in extrapolating from in vitro models to radiation risks in humans.

  2. Dependence of the bystander effect for micronucleus formation on dose of heavy-ion radiation in normal human fibroblasts.

    PubMed

    Matsumoto, Yoshitaka; Hamada, Nobuyuki; Aoki-Nakano, Mizuho; Funayama, Tomoo; Sakashita, Tetsuya; Wada, Seiichi; Kakizaki, Takehiko; Kobayashi, Yasuhiko; Furusawa, Yoshiya

    2015-09-01

    Ionising radiation-induced bystander effects are well recognised, but its dependence on dose or linear energy transfer (LET) is still a matter of debate. To test this, 49 sites in confluent cultures of AG01522D normal human fibroblasts were targeted with microbeams of carbon (103 keV µm(-1)), neon (375 keV µm(-1)) and argon ions (1260 keV µm(-1)) and evaluated for the bystander-induced formation of micronucleus that is a kind of a chromosome aberration. Targeted exposure to neon and argon ions significantly increased the micronucleus frequency in bystander cells to the similar extent irrespective of the particle numbers per site of 1-6. In contrast, the bystander micronucleus frequency increased with increasing the number of carbon-ion particles in a range between 1 and 3 particles per site and was similar in a range between 3 and 8 particles per site. These results suggest that the bystander effect of heavy ions for micronucleus formation depends on dose. PMID:26242975

  3. Effects of group status and victim sex on female bystanders' responses to a potential party rape.

    PubMed

    Katz, Jennifer; Colbert, Samuel; Colangelo, Liane

    2015-01-01

    This research examined bystander responses to 1 of 4 potential party rape scenarios. Undergraduate women (N = 249) imagined attending a party either alone or with three friends where a sober man led an intoxicated potential victim (either male or female) into a bedroom. After random assignment to conditions, participants reported on intent to help and barriers to helping the potential victim. In contrast to the classic bystander effect, bystanders in groups intended to offer more help than lone bystanders. Bystanders also intended to offer more help to potential female than male victims and experienced more barriers to helping male victims. Two of these barriers (lack of personal responsibility to help and identifying risk) explained the lower intentions to help potential male victims. Potential male victims were more likely than female victims to be perceived as gay, and bystanders reported the least intentions to help presumably gay men at risk. PMID:25929141

  4. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

    PubMed Central

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-01

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects. We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model. Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males. PMID:26678032

  5. A Bystander Effect Observed in Boron Neutron Capture Therapy: A Study of the Induction of Mutations in the HPRT Locus

    SciTech Connect

    Kinashi, Yuko . E-mail: kinashi@rri.kyoto-u.ac.jp; Masunaga, Shinichiro; Nagata, Kenji; Suzuki, Minoru; Takahashi, Sentaro; Ono, Koji

    2007-06-01

    Purpose: To investigate bystander mutagenic effects induced by {alpha}-particles during boron neutron capture therapy, we mixed cells that were electroporated with borocaptate sodium (BSH), which led to the accumulation of {sup 10}B inside the cells, and cells that did not contain the boron compound. The BSH-containing cells were irradiated with {alpha}-particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction, whereas cells without boron were affected only by the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. Methods and Materials: The lethality and mutagenicity measured by the frequency of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase locus were examined in Chinese hamster ovary cells irradiated with neutrons (Kyoto University Research Reactor: 5 MW). Neutron irradiation of 1:1 mixtures of cells with and without BSH resulted in a survival fraction of 0.1, and the cells that did not contain BSH made up 99.4% of the resulting cell population. The molecular structures of the mutations were determined using multiplex polymerase chain reactions. Results: Because of the bystander effect, the frequency of mutations increased in the cells located nearby the BSH-containing cells compared with control cells. Molecular structural analysis indicated that most of the mutations induced by the bystander effect were point mutations and that the frequencies of total and partial deletions induced by the bystander effect were less than those induced by the original neutron irradiation. Conclusion: These results suggested that in boron neutron capture therapy, the mutations caused by the bystander effect and those caused by the original neutron irradiation are induced by different mechanisms.

  6. SU-D-16A-03: A Radiation Pneumonitis Dose-Response Model Incorporating Non- Local Radiation-Induced Bystander Effect

    SciTech Connect

    Gordon, J; Snyder, K; Zhong, H; Chetty, I

    2014-06-01

    Purpose: Dose-response models that can reliably predict radiation pneumonitis (RP) to guide radiation therapy (RT) for lung cancer presently do not exist. A model is proposed that incorporates non-local radiationinduced bystander effect (RIBE). Methods: A single sigmoid response function, derived from published data for whole lung irradiation, relates RP probability to cumulative lung damage, regardless of fractionation scheme. Lung damage is assumed to be caused by direct local radiation damage, quantified via the linear-quadratic (LQ) model, and RIBE. Based on published data, RIBE is assumed to be activated when per-fraction dose rises above ∼0.6 Gy, but is constant with dose above that threshold. Integral RIBE damage is assumed proportional to lung volume irradiated above ∼0.6 Gy per fraction. Key model parameters include LQ α and β, and two RIBE parameters: the single-fraction probability δ of damage, and a proportionality parameter κ that relates the potential for RIBE damage to irradiated lung volume. All parameters are tentatively fitted from published data, the RIBE parameters from published RP rates for conventionally fractionated RT (CFRT) and stereotactic body RT (SBRT). Results: The model predicts dose-response curves that are consistent with clinical experience. It provides a tentative explanation for why V20 (33 fractions), V13 (20 fractions) and V5 (<10 fractions) are observed to be correlated with RP. It also provides a plausible explanation for the success of SBRT — RIBE damage increases with the number of fractions, so penalizes CFRT relative to SBRT. Conclusion: The proposed model is relatively simple, extrapolates from published data, plausibly explains several clinical observations, and produces dose-response curves that are consistent with clinical experience. While capable of elaboration, its ability to explain doseresponse experience with different fractionation schemes using a small number of assumptions and parameters is an

  7. The Significance of the Bystander Effect: Modeling, Experiments, and More Modeling

    SciTech Connect

    Brenner, David J.

    2009-07-22

    -term models is needed. As an example of this novel approach, we integrated a stochastic short-term initiation/inactivation/repopulation model with a deterministic two-stage long-term model. Within this new formalism, the following assumptions are implemented: radiation initiates, promotes, or kills pre-malignant cells; a pre-malignant cell generates a clone, which, if it survives, quickly reaches a size limitation; the clone subsequently grows more slowly and can eventually generate a malignant cell; the carcinogenic potential of pre-malignant cells decreases with age. The effectiveness of high-LET radiation per unit dose increases as dose rate decreases. This “inverse dose rate effect” is seen in radon-induced lung carcinogenesis. We suggest a biologically-motivated mechanism based on radiation-induced direct and bystander-effect-related risks: During radon exposure, only a fraction of cells are traversed by alpha particles. These irradiated cells have an increased probability of being initiated into a pre-malignant state. They release signals, which convert some nearby unirradiated cells to an activated state. When already pre-malignant cells are activated, their proliferation (promotion) rate increases. If a radiation dose is sufficient to activate most susceptible cells, protracting the exposure does not substantially decrease the number of activated cells, but prolongs the activated state during which pre-malignant cell proliferation is accelerated. This mechanism is implemented in a low-dose-rate extension of our carcinogenesis model, which integrates both short- and long-term modeling approaches, and was applied to radiotherapy-induced second cancer risk estimation. Model predictions adequately describe the data on radon-induced lung carcinogenesis in humans and rats, using few adjustable parameters. Conclusions about the relative importance of promotion vs. initiation for radon carcinogenesis are similar to those reported with the two-stage clonal expansion model

  8. Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors.

    PubMed

    Sharma, Neha; Colangelo, Nicholas W; de Toledo, Sonia M; Azzam, Edouard I

    2016-08-01

    Harmful effects that alter the homeostasis of neural stem or progenitor cells (NSPs) can affect regenerative processes in the central nervous system. We investigated the effect of soluble factors secreted by control or (137)Cs-γ-irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor cells, following 24 h of growth, induced prominent oxidative stress in recipient NSPs as judged by overall increases in mitochondrial superoxide radical levels (p < .001), activation of c-jun N-terminal kinase, and decrease in the active form of FoxO3a. The induced oxidative stress was associated with phosphorylation of p53 on serine 15, a marker of DNA damage, induction of the cyclin-cyclin dependent kinase inhibitors p21(Waf1) and p27(Kip1), and perturbations in cell cycle progression (p < .001). These changes were also associated with increased apoptosis as determined by enhanced annexin V staining (p < .001) and caspase 8 activation (p < .05) and altered expression of critical regulators of self-renewal, proliferation, and differentiation. Exposure of the tumor cells to radiation only slightly altered the induced oxidative changes in the bystander NSPs, except for medium from irradiated medulloblastoma cells that was more potent at inducing apoptosis in the NSPs than medium from nonirradiated cells (p < .001). The elucidation of such stressful bystander effects provides avenues to understand the biochemical events underlying the development or exacerbation of degenerative outcomes associated with brain cancers. It is also relevant to tissue culture protocols whereby growth medium conditioned by tumor cells is often used to support the growth of stem cells. PMID:27511909

  9. Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors

    PubMed Central

    Sharma, Neha; Colangelo, Nicholas W.; de Toledo, Sonia M.

    2016-01-01

    Harmful effects that alter the homeostasis of neural stem or progenitor cells (NSPs) can affect regenerative processes in the central nervous system. We investigated the effect of soluble factors secreted by control or 137Cs-γ-irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor cells, following 24 h of growth, induced prominent oxidative stress in recipient NSPs as judged by overall increases in mitochondrial superoxide radical levels (p < .001), activation of c-jun N-terminal kinase, and decrease in the active form of FoxO3a. The induced oxidative stress was associated with phosphorylation of p53 on serine 15, a marker of DNA damage, induction of the cyclin-cyclin dependent kinase inhibitors p21Waf1 and p27Kip1, and perturbations in cell cycle progression (p < .001). These changes were also associated with increased apoptosis as determined by enhanced annexin V staining (p < .001) and caspase 8 activation (p < .05) and altered expression of critical regulators of self-renewal, proliferation, and differentiation. Exposure of the tumor cells to radiation only slightly altered the induced oxidative changes in the bystander NSPs, except for medium from irradiated medulloblastoma cells that was more potent at inducing apoptosis in the NSPs than medium from nonirradiated cells (p < .001). The elucidation of such stressful bystander effects provides avenues to understand the biochemical events underlying the development or exacerbation of degenerative outcomes associated with brain cancers. It is also relevant to tissue culture protocols whereby growth medium conditioned by tumor cells is often used to support the growth of stem cells. PMID:27511909

  10. [Non-targeted effects (bystander, abscopal) of external beam radiation therapy: an overview for the clinician].

    PubMed

    Sun, R; Sbai, A; Ganem, G; Boudabous, M; Collin, F; Marcy, P-Y; Doglio, A; Thariat, J

    2014-12-01

    Radiotherapy is advocated in the treatment of cancer of over 50 % of patients. It has long been considered as a focal treatment only. However, the observation of effects, such as fatigue and lymphopenia, suggests that systemic effects may also occur. The description of bystander and abscopal effects suggests that irradiated cells may exert an action on nearby or distant unirradiated cells, respectively. A third type of effect that involves feedback interactions between irradiated cells was more recently described (cohort effect). This new field of radiation therapy is yet poorly understood and the definitions suffer from a lack of reproducibility in part due to the variety of experimental models. The bystander effect might induce genomic instability in non-irradiated cells and is thus extensively studied for a potential risk of radiation-induced cancer. From a therapeutic perspective, reproducing an abscopal effect by using a synergy between ionizing radiation and immunomodulatory agents to elicit or boost anticancer immune responses is an interesting area of research. Many applications are being developed in particular in the field of hypofractionated stereotactic irradiation of metastatic disease. PMID:25451674

  11. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    PubMed Central

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  12. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    PubMed

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D; Shetake, Neena; Balla, Murali M S; Kumar, Amit; Ray, Pritha; Ghosh, Anu; Pandey, B N

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  13. Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses.

    PubMed

    Tomita, Masanori; Maeda, Munetoshi

    2015-03-01

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

  14. Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses

    PubMed Central

    Tomita, Masanori; Maeda, Munetoshi

    2015-01-01

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

  15. Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells.

    PubMed

    Song, Man; Wang, Yu; Shang, Zeng-Fu; Liu, Xiao-Dan; Xie, Da-Fei; Wang, Qi; Guan, Hua; Zhou, Ping-Kun

    2016-01-01

    Radiation-induced bystander effect (RIBE) describes a set of biological effects in non-targeted cells that receive bystander signals from the irradiated cells. RIBE brings potential hazards to adjacent normal tissues in radiotherapy, and imparts a higher risk than previously thought. Excessive release of some substances from irradiated cells into extracellular microenvironment has a deleterious effect. For example, cytokines and reactive oxygen species have been confirmed to be involved in RIBE process via extracellular medium or gap junctions. However, RIBE-mediating signals and intercellular communication pathways are incompletely characterized. Here, we first identified a set of differentially expressed miRNAs in the exosomes collected from 2 Gy irradiated human bronchial epithelial BEP2D cells, from which miR-7-5p was found to induce autophagy in recipient cells. This exosome-mediated autophagy was significantly attenuated by miR-7-5p inhibitor. Moreover, our data demonstrated that autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway. Together, our results support the involvement of secretive exosomes in propagation of RIBE signals to bystander cells. The exosomes-containing miR-7-5p is a crucial mediator of bystander autophagy. PMID:27417393

  16. Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells

    PubMed Central

    Song, Man; Wang, Yu; Shang, Zeng-Fu; Liu, Xiao-Dan; Xie, Da-Fei; Wang, Qi; Guan, Hua; Zhou, Ping-Kun

    2016-01-01

    Radiation-induced bystander effect (RIBE) describes a set of biological effects in non-targeted cells that receive bystander signals from the irradiated cells. RIBE brings potential hazards to adjacent normal tissues in radiotherapy, and imparts a higher risk than previously thought. Excessive release of some substances from irradiated cells into extracellular microenvironment has a deleterious effect. For example, cytokines and reactive oxygen species have been confirmed to be involved in RIBE process via extracellular medium or gap junctions. However, RIBE-mediating signals and intercellular communication pathways are incompletely characterized. Here, we first identified a set of differentially expressed miRNAs in the exosomes collected from 2 Gy irradiated human bronchial epithelial BEP2D cells, from which miR-7-5p was found to induce autophagy in recipient cells. This exosome-mediated autophagy was significantly attenuated by miR-7-5p inhibitor. Moreover, our data demonstrated that autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway. Together, our results support the involvement of secretive exosomes in propagation of RIBE signals to bystander cells. The exosomes-containing miR-7-5p is a crucial mediator of bystander autophagy. PMID:27417393

  17. Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells.

    PubMed

    Fu, Jiamei; Wang, Juan; Wang, Xiangdong; Wang, Ping; Xu, Jinping; Zhou, Cuiping; Bai, Yang; Shao, Chunlin

    2016-07-01

    Although radiation induced bystander effects (RIBE) have been investigated for decades for their potential health risk, the underlying gene regulation is still largely unclear, especially the roles of immune system and inflammatory response in RIBE. In the present study, macrophage U937 cells and epithelial Beas-2B cells were co-cultured to disclose the cascades of bystander signaling factors and intercellular communications. After α-particle irradiation, both ERK and p38 pathways were activated in Beas-2B cells and were associated with the autocrine and paracrine signaling of TNF-α and IL-8, resulting in direct damage to the irradiated cells. Similar upregulation of TNF-α and IL-8 was induced in the bystander U937 cells after co-culture with α-irradiated Beas-2B cells. This upregulation was dependent on the activation of NF-κB pathway and was responsible for the enhanced damage of α-irradiated Beas-2B cells. Interestingly, the increased expressions of TNF-α and IL-8 mRNAs in the bystander U937 cells were clearly relayed on the activated ERK and p38 pathways in the irradiated Beas-2B cells, and the upregulation of TNF-α and IL-8 mRNAs in co-cultured Beas-2B cells was also partly due to the activated NF-κB pathway in the bystander U937 cells. With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-κB inhibitor), the aggravated damage in the α-irradiated Beas-2B cells could be largely alleviated. Our results disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-α and IL-8 regulated by MAPK and NF-κB pathways synergistically increased cellular injury after α-particle irradiation. PMID:27155559

  18. Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis, bystander effects, and genomic instability

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Brooks, A. L.; Chatterjee, A. (Principal Investigator)

    2001-01-01

    Cell growth, differentiation and death are directed in large part by extracellular signaling through the interactions of cells with other cells and with the extracellular matrix; these interactions are in turn modulated by cytokines and growth factors, i.e. the microenvironment. Here we discuss the idea that extracellular signaling integrates multicellular damage responses that are important deterrents to the development of cancer through mechanisms that eliminate abnormal cells and inhibit neoplastic behavior. As an example, we discuss the action of transforming growth factor beta (TGFB1) as an extracellular sensor of damage. We propose that radiation-induced bystander effects and genomic instability are, respectively, positive and negative manifestations of this homeostatic process. Bystander effects exhibited predominantly after a low-dose or a nonhomogeneous radiation exposure are extracellular signaling pathways that modulate cellular repair and death programs. Persistent disruption of extracellular signaling after exposure to relatively high doses of ionizing radiation may lead to the accumulation of aberrant cells that are genomically unstable. Understanding radiation effects in terms of coordinated multicellular responses that affect decisions regarding the fate of a cell may necessitate re-evaluation of radiation dose and risk concepts and provide avenues for intervention.

  19. H2AX phosphorylation in response to DNA double-strand break formation during bystander signalling: effect of microRNA knockdown

    PubMed Central

    Dickey, Jennifer S.; Zemp, Franz J.; Altamirano, Alvin; Sedelnikova, Olga A.; Bonner, William M.; Kovalchuk, Olga

    2011-01-01

    Upon DNA double-strand break (DSB) formation, hundreds of H2AX molecules in the chromatin flanking the break site are phosphorylated on serine residue 139, termed gamma-H2AX, so that virtually every DSB site in a nucleus can be visualised within 10 min of its formation using an antibody to gamma-H2AX. One application of this sensitive assay is to examine the induction of DNA double-strand damage in subtle non-targeted cellular effects such as the bystander effect. Here whether microRNA (miRNA) serve as a primary signalling mechanism for bystander effect propagation by comparing matched human colon carcinoma cell lines with wild-type or depleted levels of mature miRNAs was investigated. No major differences were found in the levels of induced gamma-H2AX foci in the tested cell lines, indicating that though miRNAs play a role in bystander effect manifestation, they appear not to be the primary bystander signalling molecules in the formation of bystander effect-induced DSBs. PMID:21183548

  20. The Bystander-Effect: A Meta-Analytic Review on Bystander Intervention in Dangerous and Non-Dangerous Emergencies

    ERIC Educational Resources Information Center

    Fischer, Peter; Krueger, Joachim I.; Greitemeyer, Tobias; Vogrincic, Claudia; Kastenmuller, Andreas; Frey, Dieter; Heene, Moritz; Wicher, Magdalena; Kainbacher, Martina

    2011-01-01

    Research on bystander intervention has produced a great number of studies showing that the presence of other people in a critical situation reduces the likelihood that an individual will help. As the last systematic review of bystander research was published in 1981 and was not a quantitative meta-analysis in the modern sense, the present…

  1. Bystander Activation and Anti-Tumor Effects of CD8+ T Cells Following Interleukin-2 Based Immunotherapy Is Independent of CD4+ T Cell Help

    PubMed Central

    Grossenbacher, Steven K.; Hsiao, Hui-Hua; Zamora, Anthony E.; Mirsoian, Annie; Koehn, Brent; Blazar, Bruce R.; Weiss, Jonathan M.; Wiltrout, Robert H.; Sckisel, Gail D.; Murphy, William J.

    2014-01-01

    We have previously demonstrated that immunotherapy combining agonistic anti-CD40 and IL-2 (IT) results in synergistic anti-tumor effects. IT induces expansion of highly cytolytic, antigen-independent “bystander-activated” (CD8+CD44high) T cells displaying a CD25−NKG2D+ phenotype in a cytokine dependent manner, which were responsible for the anti-tumor effects. While much attention has focused on CD4+ T cell help for antigen-specific CD8+ T cell expansion, little is known regarding the role of CD4+ T cells in antigen-nonspecific bystander-memory CD8+ T cell expansion. Utilizing CD4 deficient mouse models, we observed a significant expansion of bystander-memory T cells following IT which was similar to the non-CD4 depleted mice. Expanded bystander-memory CD8+ T cells upregulated PD-1 in the absence of CD4+ T cells which has been published as a hallmark of exhaustion and dysfunction in helpless CD8+ T cells. Interestingly, compared to CD8+ T cells from CD4 replete hosts, these bystander expanded cells displayed comparable (or enhanced) cytokine production, lytic ability, and in vivo anti-tumor effects suggesting no functional impairment or exhaustion and were enriched in an effector phenotype. There was no acceleration of the post-IT contraction phase of the bystander memory CD8+ response in CD4-depleted mice. The response was independent of IL-21 signaling. These results suggest that, in contrast to antigen-specific CD8+ T cell expansion, CD4+ T cell help is not necessary for expansion and activation of antigen-nonspecific bystander-memory CD8+ T cells following IT, but may play a role in regulating conversion of these cells from a central memory to effector phenotype. Additionally, the expression of PD-1 in this model appears to be a marker of effector function and not exhaustion. PMID:25119341

  2. Stochastic models of the bystander effect and of transmissible genomic instability: implications for mechanisms and low dose risks

    NASA Astrophysics Data System (ADS)

    Little, M. P.

    Bystander effects following exposure to α -particles have been observed in C3H 10T cells and in other experimental systems, and imply that linearly extrapolating low dose risks from high-dose data might materially underestimate risk. In many experimental systems there is evidence of saturation of dose response that would be expected from the bystander effect. The ratio of lung cancer risk among persons exposed to low and high doses of radon daughters is 2.4 -- 4.0, with an upper 95% confidence limit of about 14. Assuming the bystander effect observed in the C3H 10T data applies to human lung cells in vivo, the epidemiological data imply that the number of neighbouring cells that can contribute to the bystander effect is between 0 and 1, with an upper 95% confidence limit of about 7. As a consequence, the bystander effect observed in the C3H 10T system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans. Other experimental data relating to the bystander effect after α -particle exposure are surveyed; some of these data are more compatible with the epidemiological data. Three models of genomic instability recently developed by Little and Wright (Math. Biosci. 2003;183:111-34), with two, three and five stages, are compared with the four-stage model proposed by Luebeck and Moolgavkar (PNAS 2002;99:15095-100) and the two-stage model of Nowak et al. (PNAS 2002;99:16226-31). All models are fitted to SEER colon cancer data. Although the five-stage model of Little and Wright (2003) provides the best fit, it is not much superior to that of the model of Nowak et al. (2002) or the two- and three-stage models of Little and Wright (2003). The fit of the model of Luebeck and Moolgavkar (2002) is somewhat worse than these three, particularly for females under the age of 40. Comparison of the predictions of the two-stage models of Little and Wright (2003) and Nowak (2002) with patterns of excess risk in the Japanese atomic bomb

  3. Bystander effects, genomic instability, adaptive response, and cancer risk assessment for radiation and chemical exposures

    SciTech Connect

    Preston, R. Julian . E-mail: preston.julian@epa.gov

    2005-09-01

    There is an increased interest in utilizing mechanistic data in support of the cancer risk assessment process for ionizing radiation and environmental chemical exposures. In this regard, the use of biologically based dose-response models is particularly advocated. The aim is to provide an enhanced basis for describing the nature of the dose-response curve for induced tumors at low levels of exposure. Cellular responses that might influence the nature of the dose-response curve at low exposures are understandably receiving attention. These responses (bystander effects, genomic instability, and adaptive responses) have been studied most extensively for radiation exposures. The former two could result in an enhancement of the tumor response at low doses and the latter could lead to a reduced response compared to that predicted by a linear extrapolation from high dose responses. Bystander responses, whereby cells other than those directly traversed by radiation tracks are damaged, can alter the concept of target cell population per unit dose. Similarly, induced genomic instability can alter the concept of total response to an exposure. There appears to be a role for oxidative damage and cellular signaling in the etiology of these cellular responses. The adaptive response appears to be inducible at very low doses of radiation or of some chemicals and reduces the cellular response to a larger challenge dose. It is currently unclear how these cellular toxic responses might be involved in tumor formation, if indeed they are. In addition, it is not known how widespread they are as regards inducing agents. Thus, their impact on low dose cancer risk remains to be established.

  4. Bystander effects of PC12 cells treated with Pb²⁺ depend on ROS-mitochondria-dependent apoptotic signaling via gap-junctional intercellular communication.

    PubMed

    Guo, Shu; Zhou, Jin; Chen, Xuemei; Yu, Yunjiang; Ren, Mingzhong; Hu, Guocheng; Liu, Yun; Zou, Fei

    2014-08-17

    The demonstration of bystander effect, which means injured cells propagate damage to neighboring cells, in whole organisms has clear implication of the potential relevance of the non-targeted response to human health. Here we show that 10 μM lead acetate, the optimum concentration for inducing apoptosis confirmed by the expression levels of Bax and Bcl-2, can also induce rat pheochromocytoma (PC12) cells to exert bystander effects to neighboring cells. In a novel co-culture system, GFP-PC12 (Pb(2+)) cells, which were stable transfected with EF1A-eGFP and pre-exposed with lead acetate, were co-cultured with unexposed PC12 cells at a 1:5 ratio. Parachute assays demonstrated the functional gap-junctional intercellular communication (GJIC) formed between Pb(2+)-exposed and unexposed cells. The Pb(2+)-exposed cells induced very similar effects on neighboring unexposed cells to apoptosis coincide with intracellular ROS generation and the collapse of mitochondrial membrane potential (Δψm). Furthermore, carbenoxolone (CBX), a blocker of GJIC, inhibited the bystander effects. The results indicate that the Pb(2+)-induced insults propagate through GJIC between PC12 cells, while inducing the bystander cells to apoptosis via ROS-mitochondria-dependent apoptotic signaling. PMID:24960054

  5. Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype

    PubMed Central

    Akudugu, John M.; Azzam, Edouard I.; Howell, Roger W.

    2013-01-01

    Purpose This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with 125I-labeled 5-iodo-2′-deoxyuridine (125IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. Materials and methods In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix™ carbon scaffold. Cultures were pulse-labeled for 3 h with 125IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2′-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT® EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with 125IdU/EdU. Additional aliquots were used to determine the mean 125I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA-MB-231 cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Results Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. Conclusions These studies demonstrate the capacity of 125IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype. PMID:22489958

  6. SR-FTIR Coupled with Principal Component Analysis Shows Evidence for the Cellular Bystander Effect.

    PubMed

    Lipiec, E; Bambery, K R; Lekki, J; Tobin, M J; Vogel, C; Whelan, D R; Wood, B R; Kwiatek, W M

    2015-07-01

    Synchrotron radiation-Fourier transform infrared (SR-FTIR) microscopy coupled with multivariate data analysis was used as an independent modality to monitor the cellular bystander effect. Single, living prostate cancer PC-3 cells were irradiated with various numbers of protons, ranging from 50-2,000, with an energy of either 1 or 2 MeV using a proton microprobe. SR-FTIR spectra of cells, fixed after exposure to protons and nonirradiated neighboring cells (bystander cells), were recorded. Spectral differences were observed in both the directly targeted and bystander cells and included changes in the DNA backbone and nucleic bases, along with changes in the protein secondary structure. Principal component analysis (PCA) was used to investigate the variance in the entire data set. The percentage of bystander cells relative to the applied number of protons with two different energies was calculated. Of all the applied quantities, the dose of 400 protons at 2 MeV was found to be the most effective for causing significant macromolecular perturbation in bystander PC-3 cells. PMID:26121225

  7. L Particles Transmit Viral Proteins from Herpes Simplex Virus 1-Infected Mature Dendritic Cells to Uninfected Bystander Cells, Inducing CD83 Downmodulation

    PubMed Central

    Kummer, Mirko; Mühl-Zürbes, Petra; Drassner, Christina; Daniel, Christoph; Klewer, Monika; Steinkasserer, Alexander

    2015-01-01

    ABSTRACT Mature dendritic cells (mDCs) are known as the most potent antigen-presenting cells (APCs) since they are also able to prime/induce naive T cells. Thus, mDCs play a pivotal role during the induction of antiviral immune responses. Remarkably, the cell surface molecule CD83, which was shown to have costimulatory properties, is targeted by herpes simplex virus 1 (HSV-1) for viral immune escape. Infection of mDCs with HSV-1 results in downmodulation of CD83, resulting in reduced T cell stimulation. In this study, we report that not only infected mDCs but also uninfected bystander cells in an infected culture show a significant CD83 reduction. We demonstrate that this effect is independent of phagocytosis and transmissible from infected to uninfected mDCs. The presence of specific viral proteins found in these uninfected bystander cells led to the hypothesis that viral proteins are transferred from infected to uninfected cells via L particles. These L particles are generated during lytic replication in parallel with full virions, called H particles. L particles contain viral proteins but lack the viral capsid and DNA. Therefore, these particles are not infectious but are able to transfer several viral proteins. Incubation of mDCs with L particles indeed reduced CD83 expression on uninfected bystander DCs, providing for the first time evidence that functional viral proteins are transmitted via L particles from infected mDCs to uninfected bystander cells, thereby inducing CD83 downmodulation. IMPORTANCE HSV-1 has evolved a number of strategies to evade the host's immune system. Among others, HSV-1 infection of mDCs results in an inhibited T cell activation caused by degradation of CD83. Interestingly, CD83 is lost not only from HSV-1-infected mDCs but also from uninfected bystander cells. The release of so-called L particles, which contain several viral proteins but lack capsid and DNA, during infection is a common phenomenon observed among several viruses, such

  8. I know what you did: The effects of interpersonal deviance on bystanders.

    PubMed

    Ferguson, Merideth; Barry, Bruce

    2011-01-01

    Using social information processing theory, we explore how interpersonally directed deviance affects work group members who observe or are aware of these insidious behaviors. In a field study, we find that indirect knowledge of work group member interpersonal deviance leads to subsequent interpersonal deviance of a focal individual. We also find that when work group cohesion is high, direct observation of deviance is more likely to result in subsequent bystander deviance. These findings add concretely to theory and research on the bystander effects of workplace deviance. PMID:21280946

  9. Irradiation of rainbow trout at early life stages results in trans-generational effects including the induction of a bystander effect in non-irradiated fish.

    PubMed

    Smith, Richard W; Seymour, Colin B; Moccia, Richard D; Mothersill, Carmel E

    2016-02-01

    The bystander effect, a non-targeted effect (NTE) of radiation, which describes the response by non-irradiated organisms to signals emitted by irradiated organisms, has been documented in a number of fish species. However transgenerational effects of radiation (including NTE) have yet to be studied in fish. Therefore rainbow trout, which were irradiated as eggs at 48h after fertilisation, eyed eggs, yolk sac larvae or first feeders, were bred to generate a F1 generation and these F1 fish were bred to generate a F2 generation. F1 and F2 fish were swam with non-irradiated bystander fish. Media from explants of F1 eyed eggs, F1 one year old fish gill and F1 two year old fish gill and spleen samples, and F2 two year old gill and spleen samples, as well as from bystander eggs/fish, was used to treat a reporter cell line, which was then assayed for changes in cellular survival/growth. The results were complex and dependent on irradiation history, age (in the case of the F1 generation), and were tissue specific. For example, irradiation of one parent often resulted in effects not seen with irradiation of both parents. This suggests that, unlike mammals, in certain circumstances maternal and paternal irradiation may be equally important. This study also showed that trout can induce a bystander effect 2 generations after irradiation, which further emphasises the importance of the bystander effect in aquatic radiobiology. Given the complex community structure in aquatic ecosystems, these results may have significant implications for environmental radiological protection. PMID:26618503

  10. Influence of Exercise on Inflammation in Cancer: Direct Effect or Innocent Bystander?

    PubMed

    Murphy, E Angela; Enos, Reilly T; Velázquez, Kandy T

    2015-07-01

    We propose the hypothesis that the benefits of exercise on inflammation in cancer are a result of a direct effect on inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein 1, that are critical for cancer growth as well as a bystander effect of the established relationship between exercise and cancer. PMID:25906430

  11. Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma.

    PubMed

    Shareef, Mohammed M; Cui, Nuan; Burikhanov, Ravshan; Gupta, Seema; Satishkumar, Sabapathi; Shajahan, Shahin; Mohiuddin, Mohammed; Rangnekar, Vivek M; Ahmed, Mansoor M

    2007-12-15

    In the present study, ionizing radiation (IR)-induced bystander effects were investigated in two lung cancer cell lines. A549 cells were found to be more resistant to radiation-conditioned medium (RCM) obtained from A549 cells when compared with the H460 exposed to RCM procured from H460 cells. Significant release of tumor necrosis factor-alpha (TNF-alpha) was observed in A549 cells after IR/RCM exposure, and the survival was reversed with neutralizing antibody against TNF-alpha. In H460 cells, significant release of TNF-related apoptosis-inducing ligand (TRAIL), but not TNF-alpha, was observed in response to IR, RCM exposure, or RCM + 2Gy, and neutralizing antibody against TRAIL diminished clonogenic inhibition. Mechanistically, TNF-alpha present in RCM of A549 was found to mediate nuclear factor-kappaB (NF-kappaB) translocation to nucleus, whereas the soluble TRAIL present in RCM of H460 cells mobilized the nuclear translocation of PAR-4 (a proapoptotic protein). Analysis of IR-inducible early growth response-1 (EGR-1) function showed that EGR-1 was functional in A549 cells but not in H460 cells. A significant decrease in RCM-mediated apoptosis was observed in both A549 cells stably expressing small interfering RNA EGR-1 and EGR-1(-/-) mouse embryonic fibroblast cells. Thus, the high-dose IR-induced bystander responses in A549 may be dependent on the EGR-1 function and its target gene TNF-alpha. These findings show that the reduced bystander response in A549 cells is due to activation of NF-kappaB signaling by TNF-alpha, whereas enhanced response to IR-induced bystander signaling in H460 cells was due to release of TRAIL associated with nuclear translocation of PAR-4. PMID:18089811

  12. “Protective Bystander Effects Simulated with the State-Vector Model”—HeLa x Skin Exposure to 137Cs Not Protective Bystander Response But Mammogram and Diagnostic X-Rays Are

    PubMed Central

    Leonard, Bobby E.

    2008-01-01

    The recent Dose Response journal article “Protective Bystander Effects Simulated with the State-Vector Model” (Schollnberger and Eckl 2007) identified the suppressive (below natural occurring, zero primer dose, spontaneous level) dose response for HeLa x skin exposure to 137Cs gamma rays (Redpath et al 2001) as a protective Bystander Effect (BE) behavior. I had previously analyzed the Redpath et al (2001) data with a Microdose Model and conclusively showed that the suppressive response was from Adaptive Response (AR) radio-protection (Leonard 2005, 2007a). The significance of my microdose analysis has been that low LET radiation induced single (i.e. only one) charged particle traversals through a cell can initiate a Poisson distributed activation of AR radio-protection. The purpose of this correspondence is to clarify the distinctions relative to the BE and the AR behaviors for the Redpath groups 137Cs data, show conversely however that the Redpath group data for mammography (Ko et al 2004) and diagnostic (Redpath et al 2003) X-rays do conclusively reflect protective bystander behavior and also herein emphasize the need for radio-biologist to apply microdosimetry in planning and analyzing their experiments for BE and AR. Whether we are adamantly pro-LNT, adamantly anti-LNT or, like most of us, just simple scientists searching for the truth in radio-biology, it is important that we accurately identify our results, especially when related to the LNT hypothesis controversy. PMID:18846260

  13. A Meta-Analysis of School-Based Bullying Prevention Programs' Effects on Bystander Intervention Behavior

    ERIC Educational Resources Information Center

    Polanin, Joshua R.; Espelage, Dorothy L.; Pigott, Therese D.

    2012-01-01

    This meta-analysis synthesized bullying prevention programs' effectiveness at increasing bystander intervention in bullying situations. Evidence from 12 school-based programs, involving 12,874 students, indicated that overall the programs were successful (Hedges's g = 0.20, 95% confidence interval [CI] = 0.11 to 0.29, p = 0.001), with larger…

  14. BYSTANDER EFFECTS GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIAION AND CHEMICAL EXPOSURES

    EPA Science Inventory

    BYSTANDER EFFECTS, GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIATION AND CHEMICAL EXPOSURES

    R. Julian Preston
    Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, N.C. 27711, USA

    There ...

  15. Induction of DNA Double-Strand Breaks and Cellular Migration Through Bystander Effects in Cells Irradiated With the Slit-Type Microplanar Beam of the Spring-8 Synchrotron

    SciTech Connect

    Kashino, Genro Kondoh, Takeshi; Nariyama, Nobuteru; Umetani, Keiji; Ohigashi, Takuji; Shinohara, Kunio; Kurihara, Ai; Fukumoto, Manabu; Tanaka, Hiroki; Maruhashi, Akira; Suzuki, Minoru; Kinashi, Yuko; Liu Yong; Masunaga, Shin-ichiro; Watanabe, Masami; Ono, Koji

    2009-05-01

    Purpose: To determine whether glioma cells irradiated with a microplanar X-ray beam exert bystander effects. Methods and Materials: Microplanar beam irradiation of glioma cells in vitro was done using the SPring-8 synchrotron radiation facility. The amount of DNA double-strand breaks (dsbs) was measured by the fluorescence intensity of phosphorylated H2AX or the number of 53BP1 foci. The dose distribution in a cell population exposed to a single microplanar beam was determined by the amount of phosphorylated H2AX-positive cells. Bystander effects were determined by counting the number of 53BP1 foci in nonirradiated cells treated with conditioned medium from cultures of irradiated cells. Results: More DNA dsbs were detected in cells adjacent to an area irradiated by the single beam than in cells in distant, nonirradiated areas as a result of bystander effects caused by scattered X-rays and DNA dsbs. In support of this, more 53BP1 foci were observed in nonirradiated, conditioned medium-treated cells than in control cells (i.e., cells not treated with irradiation or conditioned medium). These results suggest that DNA dsbs were induced in nonirradiated cells by soluble factors in the culture medium. In addition, we observed cellular migration into areas irradiated with peak doses, suggesting that irradiated cells send signals that cause nonirradiated cells to migrate toward damaged cells. Conclusions: Bystander effects are produced by factors secreted as a result of slit-type microplanar X-ray beam irradiation.

  16. The potential impact of bystander effects on radiation risks in a Mars mission

    NASA Technical Reports Server (NTRS)

    Brenner, D. J.; Elliston, C. D.; Hall, E. I. (Principal Investigator)

    2001-01-01

    Densely ionizing (high-LET) galactic cosmic rays (GCR) contribute a significant component of the radiation risk in free space. Over a period of a few months-sufficient for the early stages of radiation carcinogenesis to occur-a significant proportion of cell nuclei will not be traversed. There is convincing evidence, at least in vitro, that irradiated cells can send out signals that can result in damage to nearby unirradiated cells. This observation can hold even when the unirradiated cells have been exposed to low doses of low-LET radiation. We discuss here a quantitative model based on the a formalism, an approach that incorporates radiobiological damage both from a bystander response to signals emitted by irradiated cells, and also from direct traversal of high-LET radiations through cell nuclei. The model produces results that are consistent with those of a series of studies of the bystander phenomenon using a high-LET microbeam, with the end point of in vitro oncogenic transformation. According to this picture, for exposure to high-LET particles such as galactic cosmic rays other than protons, the bystander effect is significant primarily at low fluences, i.e., exposures where there are significant numbers of untraversed cells. If the mechanisms postulated here were applicable in vivo, using a linear extrapolation of risks derived from studies using intermediate doses of high-LET radiation (where the contribution of the bystander effect may be negligible) to estimate risks at very low doses (where the bystander effect may be dominant) could underestimate the true risk from low doses of high-LET radiation. It would be highly premature simply to abandon current risk projections for high-LET, low-dose radiation; however, these considerations would suggest caution in applying results derived from experiments using high-LET radiation at fluences above approximately 1 particle per nucleus to risk estimation for a Mars mission.

  17. The potential impact of bystander effects on radiation risks in a Mars mission.

    PubMed

    Brenner, D J; Elliston, C D

    2001-11-01

    Densely ionizing (high-LET) galactic cosmic rays (GCR) contribute a significant component of the radiation risk in free space. Over a period of a few months-sufficient for the early stages of radiation carcinogenesis to occur-a significant proportion of cell nuclei will not be traversed. There is convincing evidence, at least in vitro, that irradiated cells can send out signals that can result in damage to nearby unirradiated cells. This observation can hold even when the unirradiated cells have been exposed to low doses of low-LET radiation. We discuss here a quantitative model based on the a formalism, an approach that incorporates radiobiological damage both from a bystander response to signals emitted by irradiated cells, and also from direct traversal of high-LET radiations through cell nuclei. The model produces results that are consistent with those of a series of studies of the bystander phenomenon using a high-LET microbeam, with the end point of in vitro oncogenic transformation. According to this picture, for exposure to high-LET particles such as galactic cosmic rays other than protons, the bystander effect is significant primarily at low fluences, i.e., exposures where there are significant numbers of untraversed cells. If the mechanisms postulated here were applicable in vivo, using a linear extrapolation of risks derived from studies using intermediate doses of high-LET radiation (where the contribution of the bystander effect may be negligible) to estimate risks at very low doses (where the bystander effect may be dominant) could underestimate the true risk from low doses of high-LET radiation. It would be highly premature simply to abandon current risk projections for high-LET, low-dose radiation; however, these considerations would suggest caution in applying results derived from experiments using high-LET radiation at fluences above approximately 1 particle per nucleus to risk estimation for a Mars mission. PMID:11604082

  18. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    PubMed

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types. PMID:26653982

  19. Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

    SciTech Connect

    Nagasawa, H; Wilson, P F; Chen, D J; Thompson, L H; Bedford, J S; Little, J B

    2007-10-26

    We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells (Nagasawa et al., Radiat. Res. 164, 141-147, 2005). In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23-0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after {alpha}-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.

  20. Adoptive Transfer of Dying Cells Causes Bystander-Induced Apoptosis

    PubMed Central

    Schwulst, Steven J.; Davis, Christopher G.; Coopersmith, Craig M.; Hotchkiss, Richard S.

    2009-01-01

    The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death from several noxious stimuli. Intriguingly, Bcl-2 overexpression in one cell type has been reported to protect against cell death in neighboring non-Bcl-2 overexpressing cell types. The mechanism of this “trans” protection has been speculated to be secondary to the release of a cytoprotective factor by Bcl-2 overexpressing cells. We employed a series of adoptive transfer experiments in which lymphocytes that overexpress Bcl-2 were administered to either wild type mice or mice lacking mature T and B cells (Rag-1-/-) to detect the presence or absence of the putative protective factor. We were unable to demonstrate “trans” protection. However, adoptive transfer of apoptotic or necrotic cells exacerbated the degree of apoptotic death in neighboring non-Bcl-2 overexpressing cells (p≤0.05). Therefore, this data suggests that dying cells emit signals triggering cell death in neighboring non-Bcl-2 overexpressing cells, i.e. a “trans” destructive effect. PMID:17194455

  1. Adoptive transfer of dying cells causes bystander-induced apoptosis.

    PubMed

    Schwulst, Steven J; Davis, Christopher G; Coopersmith, Craig M; Hotchkiss, Richard S

    2007-02-16

    The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death from several noxious stimuli. Intriguingly, Bcl-2 overexpression in one cell type has been reported to protect against cell death in neighboring non-Bcl-2 overexpressing cell types. The mechanism of this "trans" protection has been speculated to be secondary to the release of a cytoprotective factor by Bcl-2 overexpressing cells. We employed a series of adoptive transfer experiments in which lymphocytes that overexpress Bcl-2 were administered to either wild type mice or mice lacking mature T and B cells (Rag-1-/-) to detect the presence or absence of the putative protective factor. We were unable to demonstrate "trans" protection. However, adoptive transfer of apoptotic or necrotic cells exacerbated the degree of apoptotic death in neighboring non-Bcl-2 overexpressing cells (p < or= 0.05). Therefore, this data suggests that dying cells emit signals triggering cell death in neighboring non-Bcl-2 overexpressing cells, i.e., a "trans" destructive effect. PMID:17194455

  2. Sci—Fri PM: Topics — 04: What if bystander effects influence cell kill within a target volume? Potential consequences of dose heterogeneity on TCP and EUD on intermediate risk prostate patients

    SciTech Connect

    Balderson, M.J.; Kirkby, C.

    2014-08-15

    In vitro evidence has suggested that radiation induced bystander effects may enhance non-local cell killing which may influence radiotherapy treatment planning paradigms. This work applies a bystander effect model, which has been derived from published in vitro data, to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) and compare them with predictions from standard linear quadratic (LQ) models that assume a response due only to local absorbed dose. Comparisons between the models were made under increasing dose heterogeneity scenarios. Dose throughout the CTV was modeled with normal distributions, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. The bystander model suggests a moderate degree of dose heterogeneity yields as good or better outcome compared to a uniform dose in terms of EUD and TCP. Intermediate risk prostate prescriptions of 78 Gy over 39 fractions had maximum EUD and TCP values at SD of around 5Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. The bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV is varies. The results suggest the potential for allowing some degree of dose heterogeneity within a CTV, although further investigations of the assumptions of the bystander model are warranted.

  3. Theoretical models and simulation codes to investigate bystander effects and cellular communication at low doses

    NASA Astrophysics Data System (ADS)

    Ballarini, F.; Alloni, D.; Facoetti, A.; Mairani, A.; Nano, R.; Ottolenghi, A.

    Astronauts in space are continuously exposed to low doses of ionizing radiation from Galactic Cosmic Rays During the last ten years the effects of low radiation doses have been widely re-discussed following a large number of observations on the so-called non targeted effects in particular bystander effects The latter consist of induction of cytogenetic damage in cells not directly traversed by radiation most likely as a response to molecular messengers released by directly irradiated cells Bystander effects which are observed both for lethal endpoints e g clonogenic inactivation and apoptosis and for non-lethal ones e g mutations and neoplastic transformation tend to show non-linear dose responses This might have significant consequences in terms of low-dose risk which is generally calculated on the basis of the Linear No Threshold hypothesis Although the mechanisms underlying bystander effects are still largely unknown it is now clear that two types of cellular communication i e via gap junctions and or release of molecular messengers into the extracellular environment play a fundamental role Theoretical models and simulation codes can be of help in elucidating such mechanisms In the present paper we will review different available modelling approaches including one that is being developed at the University of Pavia The focus will be on the different assumptions adopted by the various authors and on the implications of such assumptions in terms of non-targeted radiobiological damage and more generally low-dose

  4. Injection of Resperpine into Zebrafish, Prevents Fish to Fish Communication of Radiation-Induced Bystander Signals: Confirmation in Vivo of a Role for Serotonin in the Mechanism

    PubMed Central

    Saroya, Rohin; Smith, Richard; Seymour, Colin; Mothersill, Carmel

    2009-01-01

    Serotonin (5-HT) has been implicated as a potential modulator of the bystander effect in cell cultures. To assess the relevance of serotonin in vivo experiments were done with the zebrafish (Danio rerio). This species, when irradiated, transmits bystander signals to non-irradiated fish. The animals were injected with reserpine, an inhibitor of serotonin at a dose of 80mg/kg of body mass. The results show that reserpine treated fish had only 27% of the serotonin in non-treated fish. Skin tissue samples were collected from the fish and assayed for bystander signal production using a reporter bioassay. Reserpine prevented the production and communication of signals between fish. Intracellular calcium flux, identified as a bystander response in the reporter cells confirmed this. Medium harvested from tissues of X-rayed fish and their bystanders, showed an oscillating pattern of calcium flux. Samples from X-rayed fish pretreated with reserpine produced a chaotic pattern of random fluctuations in the reporter cells, while their bystander fish led to increased calcium, but no oscillations. These results suggest that 5-HT is involved in bystander signalling in zebrafish, and by decreasing the amount of available 5-HT the bystander effect can be blocked. PMID:20877486

  5. The use of radiation microbeams to investigate the bystander effect in cells and tissues

    NASA Astrophysics Data System (ADS)

    Folkard, M.; Prise, K. M.; Michette, A. G.; Vojnovic, B.

    2007-09-01

    Microbeams are ideally suited to the study of so-called 'non-targeted' phenomena that are now known to occur when living cells and tissues are irradiated. Non-targeted effects are those where cells are seen to respond to ionising radiation through pathways other than direct damage to the DNA. One such phenomenon is the 'bystander effect'; the observation that unirradiated cells can be damaged through signalling pathways initiated by a nearby irradiated cell. The effect leads to a highly non-linear dose-response at low doses and is forcing a rethink of established models used to estimate low-dose radiation risk, which are largely based on linear extrapolations from epidemiological data at much higher doses. The bystander effect may also provide an opportunity for improvements in the treatment of cancer by radiotherapy, as it may be possible to chemically influence the bystander response in such a way as to enhance cell killing in tumour cells or to protect healthy tissue.

  6. Genomic instability, bystander effect, cytoplasmic irradiation and other phenomena that may achieve fame without fortune

    NASA Technical Reports Server (NTRS)

    Hall, E. J.

    2001-01-01

    The possible risk of induced malignancies in astronauts, as a consequence of the radiation environment in space, is a factor of concern for long term missions. Cancer risk estimates for high doses of low LET radiation are available from the epidemiological studies of the A-bomb survivors. Cancer risks at lower doses cannot be detected in epidemiological studies and must be inferred by extrapolation from the high dose risks. The standard setting bodies, such as the ICRP recommend a linear, no-threshold extrapolation of risks from high to low doses, but this is controversial. A study of mechanisms of carcinogenesis may shed some light on the validity of a linear extrapolation. The multi-step nature of carcinogenesis suggests that the role of radiation may be to induce a mutation leading to a mutator phenotype. High energy Fe ions, such as those encountered in space are highly effective in inducing genomic instability. Experiments involving the single particle microbeam have demonstrated a "bystander effect", ie a biological effect in cells not themselves hit, but in close proximity to those that are, as well as the induction of mutations in cells where only the cytoplasm, and not the nucleus, have been traversed by a charged particle. These recent experiments cast doubt on the validity of a simple linear extrapolation, but the data are so far fragmentary and conflicting. More studies are necessary. While mechanistic studies cannot replace epidemiology as a source of quantitative risk estimates, they may shed some light on the shape of the dose response relationship and therefore on the limitations of a linear extrapolation to low doses.

  7. Genomic instability, bystander effect, cytoplasmic irradiation and other phenomena that may achieve fame without fortune.

    PubMed

    Hall, E J

    2001-01-01

    The possible risk of induced malignancies in astronauts, as a consequence of the radiation environment in space, is a factor of concern for long term missions. Cancer risk estimates for high doses of low LET radiation are available from the epidemiological studies of the A-bomb survivors. Cancer risks at lower doses cannot be detected in epidemiological studies and must be inferred by extrapolation from the high dose risks. The standard setting bodies, such as the ICRP recommend a linear, no-threshold extrapolation of risks from high to low doses, but this is controversial. A study of mechanisms of carcinogenesis may shed some light on the validity of a linear extrapolation. The multi-step nature of carcinogenesis suggests that the role of radiation may be to induce a mutation leading to a mutator phenotype. High energy Fe ions, such as those encountered in space are highly effective in inducing genomic instability. Experiments involving the single particle microbeam have demonstrated a "bystander effect", ie a biological effect in cells not themselves hit, but in close proximity to those that are, as well as the induction of mutations in cells where only the cytoplasm, and not the nucleus, have been traversed by a charged particle. These recent experiments cast doubt on the validity of a simple linear extrapolation, but the data are so far fragmentary and conflicting. More studies are necessary. While mechanistic studies cannot replace epidemiology as a source of quantitative risk estimates, they may shed some light on the shape of the dose response relationship and therefore on the limitations of a linear extrapolation to low doses. PMID:11770531

  8. Irradiated human endothelial progenitor cells induce bystander killing in human non-small cell lung and pancreatic cancer cells.

    PubMed

    Turchan, William T; Shapiro, Ronald H; Sevigny, Garrett V; Chin-Sinex, Helen; Pruden, Benjamin; Mendonca, Marc S

    2016-08-01

    Purpose To investigate whether irradiated human endothelial progenitor cells (hEPC) could induce bystander killing in the A549 non-small cell lung cancer (NSCLC) cells and help explain the improved radiation-induced tumor cures observed in A549 tumor xenografts co-injected with hEPC. Materials and methods We investigated whether co-injection of CBM3 hEPC with A549 NSCLC cells would alter tumor xenograft growth rate or tumor cure after a single dose of 0 or 5 Gy of X-rays. We then utilized dual chamber Transwell dishes, to test whether medium from irradiated CBM3 and CBM4 hEPC would induce bystander cell killing in A549 cells, and as an additional control, in human pancreatic cancer MIA PaCa-2 cells. The CBM3 and CBM4 hEPC were plated into the upper Transwell chamber and the A549 or MIA PaCa-2 cells were plated in the lower Transwell chamber. The top inserts with the CBM3 or CBM4 hEPC cells were subsequently removed, irradiated, and then placed back into the Transwell dish for 3 h to allow for diffusion of any potential bystander factors from the irradiated hEPC in the upper chamber through the permeable membrane to the unirradiated cancer cells in the lower chamber. After the 3 h incubation, the cancer cells were re-plated for clonogenic survival. Results We found that co-injection of CBM3 hEPC with A549 NSCLC cells significantly increased the tumor growth rate compared to A549 cells alone, but paradoxically also increased A549 tumor cure after a single dose of 5 Gy of X-rays (p < 0.05). We hypothesized that irradiated hEPC may be inducing bystander killing in the A549 NSCLC cells in tumor xenografts, thus improving tumor cure. Bystander studies clearly showed that exposure to the medium from irradiated CBM3 and CBM4 hEPC induced significant bystander killing and decreased the surviving fraction of A549 and MIA PaCa-2 cells to 0.46 (46%) ± 0.22 and 0.74 ± 0.07 (74%) respectively (p < 0.005, p < 0.0001). In addition, antibody depletion

  9. [Bystander effect development in human mesenchymal stem cells after exposure to adaptive dose of X-radiation].

    PubMed

    Ermakov, A V; Kon'kova, M S; Kostiuk, S V; Smirnova, T D; Kameneva, L V; Veĭko, R V; Kubasova, I Iu; Liubchenko, L N; Veĭko, N N

    2010-01-01

    Transposition and mutual approaching of pericentromeric loci 1q12 of homological chromosomes from the nuclear membrane towards the nuclear centre as well as activation of the chromosomal nucleolus-forming regions (NFR) are observed in human mesenchymal stem cells (hMSCs) as an initial stages of the adaptive response (AR) after exposure to low doses of X-radiation (10 cGy). All these reactions are also induced after addition of cultivation medium from irradiated cells to intact bystander-cells and this phenomenon called bystander effect (BE). Recently the same AR and BE induction results were obtained for human G0-lymphocytes. All these data indicate the existence of universal reaction of homological chromosome loci transposition which was revealed during AR development in differentiated (lymphocytes) and non-differentiated (hMSCs) and also it shows possibility of radiational BE development in suspension and monolayer cell cultures upon addition of stress-signalization factors in incubation medium. We suppose that these factors are extracellular genome DNA fragments apoptotic cells. PMID:20297680

  10. High dose bystander effects in spatially fractionated radiation therapy

    PubMed Central

    Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.

    2014-01-01

    Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848

  11. Tissue-Sparing Effect of X-ray Microplanar Beams Particulary in the CNS: Is a Bystander Effect Involved?

    SciTech Connect

    Dilmanian,A.; Qu, Y.; Feinendegen, L.; Pena, L.; Bacarian, T.; Henn, F.; Kalef-Ezra, J.; Liu, S.; Zhong, Z.; McDonald, J.

    2007-01-01

    Normal tissues, including the central nervous system, tolerate single exposures to narrow planes of synchrotron-generated x-rays (microplanar beams; microbeams) up to several hundred Gy. The repairs apparently involve the microvasculature and the glial system. We evaluate a hypothesis on the involvement of bystander effects in these repairs.

  12. Human Lung Cancer Risks from Radon – Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis

    PubMed Central

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2012-01-01

    Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m−3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid. PMID:22942874

  13. G(2)-M phase-correlative bystander effects are co-mediated by DNA-PKcs and ATM after carbon ion irradiation.

    PubMed

    Tu, Wenzhi; Dong, Chen; Konishi, Teruaki; Kobayashi, Alisa; Furusawa, Yoshiya; Uchihori, Yukio; Xie, Yuexia; Dang, Bingrong; Li, Wenjian; Shao, Chunlin

    2016-01-01

    Accumulated evidence has shown that radiation-induced bystander effect (RIBE) may have significant implications to the efficiency of radiotherapy. Although cellular radiosensitivity relies on cell cycle status, it is largely unknown how about the relationship between RIBE and cell cycle distribution, much less the underlying mechanism. In the present study, the lung cancer A549 cells were synchronized into different cell cycle phases of G1, S and G2/M and irradiated with high linear energy transfer (LET) carbon ions. By treating nonirradiated cells with the conditioned medium from these irradiated cells, it was found that the G2-M phase cells had the largest contribution to RIBE. Meanwhile, the activity of DNA-PKcs but not ATM was increased in the synchronized G2-M phase cells in spite of both of them were activated in the asynchronous cells after carbon ion irradiation. When the G2-M phased cells were transferred with DNA-PKcs siRNA and ATM siRNA individually or treated with an inhibitor of either DNA-PKcs or ATM before carbon ion irradiation, the RIBE was effectively diminished. These results provide new evidence linking cell cycle to bystander responses and demonstrate that DNA-PKcs and ATM are two associated factors in co-regulating G2-M phase-related bystander effects. PMID:26774662

  14. Activation of caspase-3 noninvolved in the bystander effect of the herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) system.

    PubMed

    Zhang, Zhihong; Lin, Juqiang; Chu, Jun; Ma, Yan; Zeng, Shaoqun; Luo, Qingming

    2008-01-01

    Use of the herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) system is one of the promising approaches in the rapidly growing area of gene therapy. The "bystander effect," a phenomenon in which HSV-tk+ cells exposed to GCV are toxic to adjacent HSV-tk- cells, was reported to play an important role in suicide gene therapy. However, the mechanism by which HSV-tk/GCV induces the bystander effect is poorly understood. We monitored the activation of caspase-3 in living cells induced by the HSV-tk/GCV system using a genetically encoded fluorescence resonance energy transfer (FRET) probe CD3, , a caspase-3 recognition site fused with a cyan fluorescent protien (CFP) and a red fluorescent protein (DsRed) which we reported and named in a previous paper. Fluorescence protein (FP)-based multicolor cellular labeling, combined with the multichannel fluorescence imaging and FRET imaging techniques, provides a novel and improved approach to directly determine whether the activation of caspase-3 involved in the HSV-tk/GCV system induces cell apoptosis in tk gene-expressing cells and their neighboring cells. FRET ratio images of CD3, and fluorescence images of the fusion protein of thymidine kinase linked with green fluorescent protein (TK-GFP), indicated that HSV-tk/GCV system-induced apoptosis in human adenoid cystic carcinoma (ACC-M) cells was via a caspase-3 pathway, and the activation of caspase-3 was not involved in the bystander effect of HSV-tk/GCV system. PMID:18601533

  15. Anti-leukaemia activity as a bystander effect of graft-versus-host reactions.

    PubMed Central

    Johnson, P. R.; Hersey, P.

    1976-01-01

    The production of graft-versus-host (GVH) reactions in (PVGc X Wistar) F1 hybrids by the transfer of PVGc spleen cells resulted in significant resistance of these recipients to a subsequent challenge with the PVGc leukaemia. Protection was markedly dependent on dose and timing of allogeneic cell transfer and was abrogated by irradiation of the cells prior to transfer. GVH activity was shown to be a prerequisite for induction of the protective effect but was equally effective when produced by the transfer of Wistar spleen cells in place of PVGc cells. These points, plus the fact that invitro investigations of possible immune mechanisms failed to demonstrate cytotoxic immunity in treated rats, suggested a nonspecific "bystander" effect as the mechanism of protection. The implications of such a mechanism are discussed. PMID:5100

  16. Effects of a Rape Awareness Program on College Women: Increasing Bystander Efficacy and Willingness to Intervene

    ERIC Educational Resources Information Center

    Foubert, John D.; Langhinrichsen-Rohling, Jennifer; Brasfield, Hope; Hill, Brent

    2010-01-01

    An experimental study evaluated the efficacy of a sexual assault risk-reduction program on 279 college women that focused on learning characteristics of male perpetrators and teaching bystander intervention techniques. After seeing The Women's Program, participants reported significantly greater bystander efficacy and significantly greater…

  17. Membrane-Dependent Bystander Effect Contributes to Amplification of the Response to Alpha-Particle Irradiation in Targeted and Nontargeted Cells

    SciTech Connect

    Hanot, Maite; Hoarau, Jim; Carriere, Marie; Angulo, Jaime F.; Khodja, Hicham

    2009-11-15

    Purpose: Free radicals are believed to play an active role in the bystander response. This study investigated their origin as well as their temporal and spatial impacts in the bystander effect. Methods and Materials: We employed a precise alpha-particle microbeam to target a small fraction of subconfluent osteoblastic cells (MC3T3-E1). gammaH2AX-53BP1 foci, oxidative metabolism changes, and micronuclei induction in targeted and bystander cells were assessed. Results: Cellular membranes and mitochondria were identified as two distinct reactive oxygen species producers. The global oxidative stress observed after irradiation was significantly attenuated after cells were treated with filipin, evidence for the primal role of membrane in the bystander effect. To determine the membrane's impact at a cellular level, micronuclei yield was measured when various fractions of the cell population were individually targeted while the dose per cell remained constant. Induction of micronuclei increased in bystander cells as well as in targeted cells and was attenuated by filipin treatment, demonstrating a role for bystander signals between irradiated cells in an autocrine/paracrine manner. Conclusions: A complex interaction of direct irradiation and bystander signals leads to a membrane-dependent amplification of cell responses that could influence therapeutic outcomes in tissues exposed to low doses or to environmental exposure.

  18. Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect

    PubMed Central

    Wang, Xingmin; Yang, Yonghong; Huycke, Mark M

    2015-01-01

    Objective Commensal bacteria and innate immunity play a major role in the development of colorectal cancer (CRC). We propose that selected commensals polarise colon macrophages to produce endogenous mutagens that initiate chromosomal instability (CIN), lead to expression of progenitor and tumour stem cell markers, and drive CRC through a bystander effect. Design Primary murine colon epithelial cells were repetitively exposed to Enterococcus faecalis-infected macrophages, or purified trans-4-hydroxy-2-nonenal (4-HNE)—an endogenous mutagen and spindle poison produced by macrophages. CIN, gene expression, growth as allografts in immunodeficient mice were examined for clones and expression of markers confirmed using interleukin (IL) 10 knockout mice colonised by E. faecalis. Results Primary colon epithelial cells exposed to polarised macrophages or 4-hydroxy-2-nonenal developed CIN and were transformed after 10 weekly treatments. In immunodeficient mice, 8 of 25 transformed clones grew as poorly differentiated carcinomas with 3 tumours invading skin and/or muscle. All tumours stained for cytokeratins confirming their epithelial cell origin. Gene expression profiling of clones showed alterations in 3 to 7 cancer driver genes per clone. Clones also strongly expressed stem/progenitor cell markers Ly6A and Ly6E. Although not differentially expressed in clones, murine allografts positively stained for the tumour stem cell marker doublecortin-like kinase 1. Doublecortin-like kinase 1 and Ly6A/E were expressed by epithelial cells in colon biopsies for areas of inflamed and dysplastic tissue from E. faecalis-colonised IL-10 knockout mice. Conclusions These results validate a novel mechanism for CRC that involves endogenous CIN and cellular transformation arising through a microbiome-driven bystander effect. PMID:24906974

  19. Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation.

    PubMed

    Fernandez-Palomo, Cristian; Schültke, Elisabeth; Bräuer-Krisch, Elke; Laissue, Jean Albert; Blattmann, Hans; Seymour, Colin; Mothersill, Carmel

    2016-08-01

    Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 mice after irradiating their brains using Pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Athymic nude mice injected with F98 glioma cells into their right cerebral hemisphere 7 d earlier were treated with either MRT or PB. After recovery times of 2, 12, and 48 h, the urinary bladders were extracted and cultured as tissue explants for 24 h. The growth medium containing the potential signaling factors was harvested, filtered, and transferred to HaCaT reporter cells to assess their clonogenic survival and calcium signaling potential. The results show that in the tumor-free mice, both treatment modalities produce strong bystander/abscopal signals using the clonogenic reporter assay; however, the calcium data do not support a calcium channel mediated mechanism. The presence of a tumor reduces or reverses the effect. PB produced significantly stronger effects in the bladders of tumor-bearing animals. The authors conclude that immunocompromised mice produce signals, which can alter the response of unirradiated reporter cells; however, a novel mechanism appears to be involved. PMID:27356059

  20. The highly attenuated vaccinia virus strain modified virus Ankara induces apoptosis in melanoma cells and allows bystander dendritic cells to generate a potent anti-tumoral immunity

    PubMed Central

    Greiner, S; Humrich, J Y; Thuman, P; Sauter, B; Schuler, G; Jenne, L

    2006-01-01

    Vaccinia virus (VV) has been tested as oncolytic virus against malignant melanoma in clinical trials for more than 40 years. Until now, mainly strains comparable to viral strains used for smallpox vaccination have been probed for anti-tumoral therapy. We have shown recently that the wild-type strain Western Reserve (WR) can interfere with crucial functions of monocyte-derived dendritic cells (DCs). Our aim was to examine whether viral immune evasion mechanisms might be responsible for the ineffectiveness of WR-based vaccination strategies and whether the highly attenuated strain modified virus Ankara (MVA) differs from WR with respect to its possible immunostimulatory capacity after intratumoral injection. Using in vitro experiments, we compared the effect of both strains on melanoma cells and on local bystander DCs. We found that both VV-strains infected melanoma cells efficiently and caused disintegration of the actin cytoskeleton, as shown by fluorescence microscopy. In addition, both VV-strains caused apoptotic cell death in melanoma cells after infection. In contrast to MVA, WR underwent a complete viral replication cycle in melanoma cells. Bystander DCs were consecutively infected by newly generated WR virions and lost their capacity to induce allogeneic T cell proliferation. DCs in contact with MVA-infected melanoma cells retained their capacity to induce T cell proliferation. Immature DCs were capable of phagocytosing MVA-infected melanoma cells. Priming of autologous CD8+ T cells by DCs that had phagocytosed MVA-infected, MelanA positive melanoma cells resulted in the induction of T cell clones specifically reactive against the model antigen MelanA as shown by enzyme-linked immunospot (ELISPOT) analysis. We conclude that the clinical trials with oncolytic wild-type VV failed probably because of suppression of bystander DCs and consecutive suppression of T cell-mediated anti-melanoma immunity. The attenuated VV-strain MVA facilitates the generation of

  1. The Role of Bystander Effects in the Antitumor Activity of the Hypoxia-Activated Prodrug PR-104

    PubMed Central

    Foehrenbacher, Annika; Patel, Kashyap; Abbattista, Maria R.; Guise, Chris P.; Secomb, Timothy W.; Wilson, William R.; Hicks, Kevin O.

    2013-01-01

    Activation of prodrugs in tumors (e.g., by bioreduction in hypoxic zones) has the potential to generate active metabolites that can diffuse within the tumor microenvironment. Such “bystander effects” may offset spatial heterogeneity in prodrug activation but the relative importance of this effect is not understood. Here, we quantify the contribution of bystander effects to antitumor activity for the first time, by developing a spatially resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) model for PR-104, a phosphate ester pre-prodrug that is converted systemically to the hypoxia-activated prodrug PR-104A. Using Green’s function methods we calculated concentrations of oxygen, PR-104A and its active metabolites, and resultant cell killing, at each point of a mapped three-dimensional tumor microregion. Model parameters were determined in vitro, using single cell suspensions to determine relationships between PR-104A metabolism and clonogenic cell killing, and multicellular layer (MCL) cultures to measure tissue diffusion coefficients. LC-MS/MS detection of active metabolites in the extracellular medium following exposure of anoxic single cell suspensions and MCLs to PR-104A confirmed that metabolites can diffuse out of cells and through a tissue-like environment. The SR-PK/PD model estimated that bystander effects contribute 30 and 50% of PR-104 activity in SiHa and HCT116 tumors, respectively. Testing the model by modulating PR-104A-activating reductases and hypoxia in tumor xenografts showed overall clonogenic killing broadly consistent with model predictions. Overall, our data suggest that bystander effects are important in PR-104 antitumor activity, although their reach may be limited by macroregional heterogeneity in hypoxia and reductase expression in tumors. The reported computational and experimental techniques are broadly applicable to all targeted anticancer prodrugs and could be used to identify strategies for rational prodrug optimization. PMID

  2. Cancer Stem Cells Protect Non-Stem Cells From Anoikis: Bystander Effects.

    PubMed

    Kim, Seog-Young; Hong, Se-Hoon; Basse, Per H; Wu, Chuanyue; Bartlett, David L; Kwon, Yong Tae; Lee, Yong J

    2016-10-01

    Cancer stem cells (CSCs) are capable of initiation and metastasis of tumors. Therefore, understanding the biology of CSCs and the interaction between CSCs and their counterpart non-stem cells is crucial for developing a novel cancer therapy. We used CSC-like and non-stem breast cancer MDA-MB-231 and MDA-MB-453 cells to investigate mammosphere formation. We investigated the role of the epithelial cadherin (E-cadherin)-extracellular signal-regulated kinase (Erk) axis in anoikis. Data from E-cadherin small hairpin RNA assay and mitogen-activated protein kinase kinase (MEK) inhibitor study show that activation of Erk, but not modulation of E-cadherin level, may play an important role in anoikis resistance. Next, the two cell subtypes were mixed and the interaction between them during mammosphere culture and xenograft tumor formation was investigated. Unlike CSC-like cells, increased secretion of interleukin-6 (IL-6) and growth-related oncogene (Gro) chemokines was detected during mammosphere culture in non-stem cells. Similar results were observed in mixed cells. Interestingly, CSC-like cells protected non-stem cells from anoikis and promoted tumor growth. Our results suggest bystander effects between CSC-like cells and non-stem cells. J. Cell. Biochem. 117: 2289-2301, 2016. © 2016 Wiley Periodicals, Inc. PMID:26918647

  3. Concise Review: The Bystander Effect: Mesenchymal Stem Cell-Mediated Lung Repair.

    PubMed

    Savukinas, Ulrika Blank; Enes, Sara Rolandsson; Sjöland, Annika Andersson; Westergren-Thorsson, Gunilla

    2016-06-01

    Mesenchymal stem or stromal cells (MSCs), a heterogeneous subset of adult stem/progenitor cells, have surfaced as potential therapeutic units with significant clinical benefit for a wide spectrum of disease conditions, including those affecting the lung. Although MSCs carry both self-renewal and multilineage differentiation abilities, current dogma holds that MSCs mainly contribute to tissue regeneration and repair by modulating the host tissue via secreted cues. Thus, the therapeutic benefit of MSCs is thought to derive from so called bystander effects. The regenerative mechanisms employed by MSCs in the lung include modulation of the immune system as well as promotion of epithelial and endothelial repair. Apart from secreted factors, a number of recent findings suggest that MSCs engage in mitochondrial transfer and shedding of membrane vesicles as a means to enhance tissue repair following injury. Furthermore, it is becoming increasingly clear that MSCs are an integral component of epithelial lung stem cell niches. As such, MSCs play an important role in coupling information from the environment to stem and progenitor populations, such that homeostasis can be ensured even in the face of injury. It is the aim of this review to outline the major mechanisms by which MSCs contribute to lung regeneration, synthesizing recent preclinical findings with data from clinical trials and potential for future therapy. Stem Cells 2016;34:1437-1444. PMID:26991735

  4. Genetic factors influencing bystander signaling in murine bladder epithelium after low-dose irradiation in vivo.

    PubMed

    Mothersill, Carmel; Lyng, Fiona; Seymour, Colin; Maguire, Paula; Lorimore, Sally; Wright, Eric

    2005-04-01

    Radiation-induced bystander effects occur in cells that are not directly hit by radiation tracks but that receive signals from hit cells. They are well-documented in vitro consequences of low-dose exposure, but their relevance to in vivo radiobiology is not established. To investigate the in vivo production of bystander signals, bladder explants were established from two strains of mice known to differ significantly in both short-term and long-term radiation responses. These were investigated for the ability of 0.5 Gy total-body irradiation in vivo to induce production of bystander signals in bladder epithelium. The studies demonstrate that irradiated C57BL/6 mice, but not CBA/Ca mice, produce bystander signals that induce apoptosis and reduce clonogenic survival in reporter HPV-G-transfected keratinocytes. Transfer of medium from explants established from irradiated animals to explants established from unirradiated animals confirmed these differences in bladder epithelium. The responses to the in vivo-generated bystander signal exhibit genotypic differences in calcium signaling and also in signaling pathways indicative of a major role for the balance of pro-apoptosis and anti-apoptosis proteins in determining the overall response. The results clearly demonstrate the in vivo induction of bystander signals that are strongly influenced by genetic factors and have implications for radiation protection, medical imaging, and radiotherapy. PMID:15799694

  5. Systemic mechanisms and effects of ionizing radiation: A new 'old' paradigm of how the bystanders and distant can become the players.

    PubMed

    Nikitaki, Zacharenia; Mavragani, Ifigeneia V; Laskaratou, Danae A; Gika, Violeta; Moskvin, Vadim P; Theofilatos, Konstantinos; Vougas, Konstantinos; Stewart, Robert D; Georgakilas, Alexandros G

    2016-06-01

    Exposure of cells to any form of ionizing radiation (IR) is expected to induce a variety of DNA lesions, including double strand breaks (DSBs), single strand breaks (SSBs) and oxidized bases, as well as loss of bases, i.e., abasic sites. The damaging potential of IR is primarily related to the generation of electrons, which through their interaction with water produce free radicals. In their turn, free radicals attack DNA, proteins and lipids. Damage is induced also through direct deposition of energy. These types of IR interactions with biological materials are collectively called 'targeted effects', since they refer only to the irradiated cells. Earlier and sometimes 'anecdotal' findings were pointing to the possibility of IR actions unrelated to the irradiated cells or area, i.e., a type of systemic response with unknown mechanistic basis. Over the last years, significant experimental evidence has accumulated, showing a variety of radiation effects for 'out-of-field' areas (non-targeted effects-NTE). The NTE involve the release of chemical and biological mediators from the 'in-field' area and thus the communication of the radiation insult via the so called 'danger' signals. The NTE can be separated in two major groups: bystander and distant (systemic). In this review, we have collected a detailed list of proteins implicated in either bystander or systemic effects, including the clinically relevant abscopal phenomenon, using improved text-mining and bioinformatics tools from the literature. We have identified which of these genes belong to the DNA damage response and repair pathway (DDR/R) and made protein-protein interaction (PPi) networks. Our analysis supports that the apoptosis, TLR-like and NOD-like receptor signaling pathways are the main pathways participating in NTE. Based on this analysis, we formulate a biophysical hypothesis for the regulation of NTE, based on DNA damage and apoptosis gradients between the irradiation point and various distances

  6. Vulnerable Children in Varying Classroom Contexts: Bystanders' Behaviors Moderate the Effects of Risk Factors on Victimization

    ERIC Educational Resources Information Center

    Karna, Antti; Voeten, Marinus; Poskiparta, Elisa; Salmivalli, Christina

    2010-01-01

    We examined whether the bystanders' behaviors in bullying situations influence vulnerable students' risk for victimization. The sample consisted of 6,980 primary school children from Grades 3-5, who were nested within 378 classrooms in 77 schools. These students filled out Internet-based questionnaires in their schools' computer labs. The results…

  7. Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells.

    PubMed

    Desai, Sejal; Kumar, Amit; Laskar, S; Pandey, B N

    2013-01-01

    Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2, 6 Gy) and fractionated doses (3×2 Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-α, IL-1β, PDGF-AA, TGF-β1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080>U373MG>HT29>A549>MCF-7), which was correlated with the levels of IL-1β, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent

  8. A Heterotypic Bystander Effect for Tumor Cell Killing after AAVP-mediated Vascular-targeted Suicide Gene Transfer

    PubMed Central

    Trepel, Martin; Stoneham, Charlotte A.; Eleftherohorinou, Hariklia; Mazarakis, Nicholas D.; Pasqualini, Renata; Arap, Wadih; Hajitou, Amin

    2009-01-01

    Suicide gene transfer is the most commonly used cytotoxic approach in cancer gene therapy; however, a successful suicide gene therapy depends on the generation of efficient targeted systemic gene delivery vectors. We recently reported that selective systemic delivery of suicide genes such as the herpes simplex virus thymidine kinase (HSVtk) to tumor endothelial cells via a novel targeted AAVP vector leads to suppression of tumor growth. This marked effect has been postulated to result primarily from the death of cancer cells by hypoxia following the targeted disruption of tumor blood vessels. Here we investigated whether an additional mechanism of action is involved. We show that there is a heterotypic bystander effect between endothelial cells expressing the HSVtk suicide gene and tumor cells. Treatment of co-cultures of HSVtk-transduced endothelial cells and non-HSVtk-transduced tumor cells with ganciclovir results in the death of both endothelial and tumor cells. Blocking of this effect by 18α-glycyrrhetinic acid indicates that gap junctions between endothelial and tumor cells are largely responsible for this phenomenon. Moreover, the observed bystander killing is mediated by connexin (Cx)43 and Cx26, which are expressed in both endothelial and tumor cell types. Finally, this heterotypic bystander effect is accompanied by a suppression of tumor growth in vivo that is independent of primary gene transfer into host-derived tumor vascular endothelium. These findings add an alternative non-mutually exclusive and potentially synergistic cytotoxic mechanism to cancer gene therapy based on targeted AAVP, and further support the promising role of non-malignant tumor stromal cells as therapeutic targets. PMID:19671758

  9. The Effects of Cell Phone Conversations on the Attention and Memory of Bystanders

    PubMed Central

    Galván, Veronica V.; Vessal, Rosa S.; Golley, Matthew T.

    2013-01-01

    The pervasive use of cell phones impacts many people–both cell phone users and bystanders exposed to conversations. This study examined the effects of overhearing a one-sided (cell phone) conversation versus a two-sided conversation on attention and memory. In our realistic design, participants were led to believe they were participating in a study examining the relationship between anagrams and reading comprehension. While the participant was completing an anagram task, the researcher left the room and participants overheard a scripted conversation, either two confederates talking with each other or one confederate talking on a cell phone. Upon the researcher’s return, the participant took a recognition memory task with words from the conversation, and completed a questionnaire measuring the distracting nature of the conversation. Participants who overheard the one-sided conversation rated the conversation as significantly higher in distractibility than those who overheard the two-sided conversation. Also, participants in the one-sided condition scored higher on the recognition task. In particular they were more confident and accurate in their responses to words from the conversation than participants in the two-sided condition. However, participants’ scores on the anagram task were not significantly different between conditions. As in real world situations, individual participants could pay varying amounts of attention to the conversation since they were not explicitly instructed to ignore it. Even though the conversation was irrelevant to the anagram task and contained less words and noise, one-sided conversations still impacted participants’ self-reported distractibility and memory, thus showing people are more attentive to cell phone conversations than two-sided conversations. Cell phone conversations may be a common source of distraction causing negative consequences in workplace environments and other public places. PMID:23516514

  10. The effect of victims' responses to overt bullying on same-sex peer bystander reactions.

    PubMed

    Sokol, Nicole; Bussey, Kay; Rapee, Ronald M

    2015-10-01

    This study investigated the impact of victims' responses to overt bullying on peer bystanders' attitudes and reactions. Fifth- and seventh-grade students (N = 206; M(age) = 11.13 and 13.18 years, respectively) completed online questionnaires about gender-consistent videotaped hypothetical bullying scenarios in which the victims' responses (angry, sad, confident, ignoring) were experimentally manipulated. Victims' responses significantly influenced bystanders' attitudes towards the victim, perceptions of the victimization, emotional reactions, and behavioral intentions. In general, angry victims elicited more negative reactions, sad victims elicited greater intentions to act, while incidents involving confident victims were perceived as less serious. Several variations depending on the bullying type and students' grade, gender, and personal experiences with bullying were evident. Implications for individual-level and peer-level anti-bullying interventions are discussed. PMID:26407835

  11. Coexpressed Catalase Protects Chimeric Antigen Receptor–Redirected T Cells as well as Bystander Cells from Oxidative Stress–Induced Loss of Antitumor Activity

    PubMed Central

    Ligtenberg, Maarten A.; Mougiakakos, Dimitrios; Mukhopadhyay, Madhura; Witt, Kristina; Lladser, Alvaro; Chmielewski, Markus; Riet, Tobias; Abken, Hinrich

    2016-01-01

    Treatment of cancer patients by adoptive T cell therapy has yielded promising results. In solid tumors, however, T cells encounter a hostile environment, in particular with increased inflammatory activity as a hallmark of the tumor milieu that goes along with abundant reactive oxygen species (ROS) that substantially impair antitumor activity. We present a strategy to render antitumor T cells more resilient toward ROS by coexpressing catalase along with a tumor specific chimeric Ag receptor (CAR) to increase their antioxidative capacity by metabolizing H2O2. In fact, T cells engineered with a bicistronic vector that concurrently expresses catalase, along with the CAR coexpressing catalase (CAR-CAT), performed superior over CAR T cells as they showed increased levels of intracellular catalase and had a reduced oxidative state with less ROS accumulation in both the basal state and upon activation while maintaining their antitumor activity despite high H2O2 levels. Moreover, CAR-CAT T cells exerted a substantial bystander protection of nontransfected immune effector cells as measured by CD3ζ chain expression in bystander T cells even in the presence of high H2O2 concentrations. Bystander NK cells, otherwise ROS sensitive, efficiently eliminate their K562 target cells under H2O2-induced oxidative stress when admixed with CAR-CAT T cells. This approach represents a novel means for protecting tumor-infiltrating cells from tumor-associated oxidative stress–mediated repression. PMID:26673145

  12. Real-time Molecular Study of Bystander Effects of Low dose Low LET radiation Using Living Cell Imaging and Nanoparticale Optics

    SciTech Connect

    Natarajan, Mohan; Xu, Nancy R; Mohan, Sumathy

    2013-06-03

    cGy on coverslips will be examined for (a) low LET radiation-induced alterations of cellular function and its physiological relevance in real time; and (b) radiation damage triggered bystander effect on the neighboring unirradiated cells. First, to determine the low LET radiation induced alteration of cellular function we will examine: (i) the real time transformation of single membrane transporters in single living cells; (ii) the pump efficiency of membrane efflux pump of live cells in real time at the molecular level; (iii) the kinetics of single-ligand receptor interaction on single live cell surface (Figure C); and (iv) alteration in chromosome replication in living cell. Second, to study the radiation triggered bystander responses, we will examine one of the key signaling pathway i.e. TNF- alpha/NF-kappa B mediated signaling. TNF-alpha specific nano particle sensors (green) will be developed to detect the releasing dynamics, transport mechanisms and ligand-receptor binding on live cell surface in real time. A second sensor (blue) will be developed to simultaneously monitor the track of NF-kB inside the cell. The proposed nano-particle optics approach would complement our DOE funded study on biochemical mechanisms of TNF-alpha- NF-kappa B-mediated bystander effect.

  13. Virtual bystanders in a language lesson: examining the effect of social evaluation, vicarious experience, cognitive consistency and praising on students' beliefs, self-efficacy and anxiety in a virtual reality environment.

    PubMed

    Qu, Chao; Ling, Yun; Heynderickx, Ingrid; Brinkman, Willem-Paul

    2015-01-01

    Bystanders in a real world's social setting have the ability to influence people's beliefs and behavior. This study examines whether this effect can be recreated in a virtual environment, by exposing people to virtual bystanders in a classroom setting. Participants (n = 26) first witnessed virtual students answering questions from an English teacher, after which they were also asked to answer questions from the teacher as part of a simulated training for spoken English. During the experiment the attitudes of the other virtual students in the classroom was manipulated; they could whisper either positive or negative remarks to each other when a virtual student was talking or when a participant was talking. The results show that the expressed attitude of virtual bystanders towards the participants affected their self-efficacy, and their avoidance behavior. Furthermore, the experience of witnessing bystanders commenting negatively on the performance of other students raised the participants' heart rate when it was their turn to speak. Two-way interaction effects were also found on self-reported anxiety and self-efficacy. After witnessing bystanders' positive attitude towards peer students, participants' self-efficacy when answering questions received a boost when bystanders were also positive towards them, and a blow when bystanders reversed their attitude by being negative towards them. Still, inconsistency, instead of consistency, between the bystanders' attitudes towards virtual peers and the participants was not found to result in a larger change in the participants' beliefs. Finally the results also reveal that virtual flattering or destructive criticizing affected the participants' beliefs not only about the virtual bystanders, but also about the neutral teacher. Together these findings show that virtual bystanders in a classroom can affect people's beliefs, anxiety and behavior. PMID:25884211

  14. No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblasts after alpha particle irradiation

    NASA Astrophysics Data System (ADS)

    Hu, Burong; Zhu, Jiayun; Zhou, Hongning; Hei, Tom K.

    2013-02-01

    A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G2 phase premature chromosome condensation (G2-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. mFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.

  15. Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells.

    PubMed

    Moon, Ho Suck; Yang, Joo-Sung

    2006-02-28

    The major event in human immunodeficiency virus type 1 (HIV-1) infection is the death of many cells related to host immune response. The demise of these cells is normally explained by cell suicide mechanism, apoptosis. Interestingly, the decrease in the number of immune cells, such as non-CD4(+) cells as well as CD4(+) T cells, in HIV infection usually occurs in uninfected bystander cells, not in directly infected cells. It has, therefore, been suggested that several soluble factors, including viral protein R (Vpr), are released from the infected cells and induce the death of bystander cells. Some studies show that Vpr interacts directly with adenine nucleotide translocator (ANT) to induce mitochondrial membrane permeabilization (MMP). The MMP results in release of some apoptogenic factors such as cytochrome-c (cyt-c) and apoptosis-inducing factor (AIF). Vpr also has indirect effect on mitochondria through enhancing the level of caspase-9 transcription and suppressing nuclear factor-kappa B (NF-kB). The involvement of p53 in Vpr-induced apoptosis remains to be studied. On the other hand, low level of Vpr expression has anti-apoptotic effect, whereas it's high level of expression induces apoptosis. Extracellular Vpr also exhibits cytotoxicity to uninfected bystander cells through apoptotic or necrotic mechanism. The facts that Vpr has cytotoxic effect on both infected cells and bystander cells, and that it exhibits both pro- and anti-apoptotic activity may explain its role in viral survival and disease progression. PMID:16511342

  16. Glucocorticoid-induced leucine zipper (GILZ) in immuno suppression: master regulator or bystander?

    PubMed Central

    Hoppstädter, Jessica; Kiemer, Alexandra K.

    2015-01-01

    Induction of glucocorticoid-induced leucine zipper (GILZ) by glucocorticoids has been reported to be essential for their anti-inflammatory actions. At the same time, GILZ is actively downregulated under inflammatory conditions, resulting in an enhanced pro-inflammatory response. Two papers published in the recent past showed elevated GILZ expression in the late stage of an inflammation. Still, the manuscripts suggest seemingly contradictory roles of endogenous GILZ: one of them suggested compensatory actions by elevated corticosterone levels in GILZ knockout mice, while our own manuscript showed a distinct phenotype upon GILZ knockout in vivo. Herein, we discuss the role of GILZ in inflammation with a special focus on the influence of endogenous GILZ on macrophage responses and suggest a cell-type specific action of GILZ as an explanation for the conflicting results as presented in recent reports. PMID:26498359

  17. BYSTANDER RESPONSES IN THREE-DIMENSIONAL CULTURES CONTAINING RADIOLABELLED AND UNLABELLED HUMAN CELLS

    PubMed Central

    Pinto, M.; Azzam, E. I.; Howell, R. W.

    2010-01-01

    Research on the radiation-induced bystander effect has been carried out mainly in 2-D tissue culture systems. This study uses a 3-D model, wherein apparently normal human diploid fibroblasts (AG1522) are grown in a carbon scaffold, to investigate the induction of a G1 checkpoint in bystander cells present alongside radiolabelled cells. Cultures were simultaneously pulse-labelled with 3H-deoxycytidine (3HdC) to selectively irradiate a minor fraction of cells, and bromodeoxyuridine (BrdU) to identify the radiolabelled cells. After thorough washing of cultures, iododeoxyuridine (IdU) was administered to detect proliferating bystander cells. The cultures were harvested at various times thereafter, and cells were reacted with two monoclonal antibodies specific to IdU/BrdU or BrdU, respectively, stained with propidium iodide, and subjected to multi-parameter flow cytometry. Cell-cycle progression was followed in radiolabelled cells (BrdU+) that were chronically irradiated by low energy beta particles emitted by DNA-incorporated 3H, and in unlabelled bystander cells (BrdU−) by a flow cytometry based cumulative labelling index assay. As expected, radiolabelled cells were delayed, in a dose-dependent manner, in G2 and subsequently G1. No delay occurred in progression of bystander cells through G1, when the labelled cells were irradiated at dose rates up to 0.32 Gy h−1. PMID:17185313

  18. Intrachromosomal Changes and Genomic Instability in Site-Specific Microbeam-Irradiated and Bystander Human-Hamster Hybrid Cells

    PubMed Central

    Hu, Burong; Grabham, Peter; Nie, Jing; Balajee, Adayabalam S.; Zhou, Hongning; Hei, Tom K.; Geard, Charles R.

    2012-01-01

    Exposure to ionizing radiation may induce a heritable genomic instability phenotype that results in a persisting and enhanced genetic and functional change among the progeny of irradiated cells. Since radiation-induced bystander effects have been demonstrated with a variety of biological end points under both in vitro and in vivo conditions, this raises the question whether cytoplasmic irradiation or the radiation-induced bystander effect can also lead to delayed genomic instability. In the present study, we used the Radiological Research Accelerator Facility charged-particle microbeam for precise nuclear or cytoplasmic irradiation. The progeny of irradiated and the bystander human hamster hybrid (AL) cells were analyzed using multicolor banding (mBAND) to examine persistent chromosomal changes. Our results showed that the numbers of metaphase cells involving changes of human chromosome 11 (including rearrangement, deletion and duplication) were significantly higher than that of the control in the progeny of both nuclear and cytoplasmic targeted cells. These chromosomal changes could also be detected among the progeny of bystander cells. mBAND analyses of clonal isolates from nuclear and cytoplasm irradiations as well as the bystander cell group showed that chromosomal unstable clones were generated. Analyses of clonal stability after long-term culture indicated no significant change in the number of unstable clones for the duration of culture in each irradiated group. These results suggest that genomic instability that is manifested after ionizing radiation exposure is not dependent on direct damage to the cell nucleus. PMID:22077336

  19. Virtual Bystanders in a Language Lesson: Examining the Effect of Social Evaluation, Vicarious Experience, Cognitive Consistency and Praising on Students' Beliefs, Self-Efficacy and Anxiety in a Virtual Reality Environment

    PubMed Central

    Qu, Chao; Ling, Yun; Heynderickx, Ingrid; Brinkman, Willem-Paul

    2015-01-01

    Bystanders in a real world's social setting have the ability to influence people’s beliefs and behavior. This study examines whether this effect can be recreated in a virtual environment, by exposing people to virtual bystanders in a classroom setting. Participants (n = 26) first witnessed virtual students answering questions from an English teacher, after which they were also asked to answer questions from the teacher as part of a simulated training for spoken English. During the experiment the attitudes of the other virtual students in the classroom was manipulated; they could whisper either positive or negative remarks to each other when a virtual student was talking or when a participant was talking. The results show that the expressed attitude of virtual bystanders towards the participants affected their self-efficacy, and their avoidance behavior. Furthermore, the experience of witnessing bystanders commenting negatively on the performance of other students raised the participants’ heart rate when it was their turn to speak. Two-way interaction effects were also found on self-reported anxiety and self-efficacy. After witnessing bystanders’ positive attitude towards peer students, participants’ self-efficacy when answering questions received a boost when bystanders were also positive towards them, and a blow when bystanders reversed their attitude by being negative towards them. Still, inconsistency, instead of consistency, between the bystanders’ attitudes towards virtual peers and the participants was not found to result in a larger change in the participants’ beliefs. Finally the results also reveal that virtual flattering or destructive criticizing affected the participants’ beliefs not only about the virtual bystanders, but also about the neutral teacher. Together these findings show that virtual bystanders in a classroom can affect people’s beliefs, anxiety and behavior. PMID:25884211

  20. Mutations in Succinate Dehydrogenase Subunit C Increase Radiosensitivity and Bystander Responses

    NASA Astrophysics Data System (ADS)

    Zhou, Hongning; Hei, Tom K.

    Although radiation-induced bystander effect is well studied in the past decade, the precise mech-anisms are still unclear. It is likely that a combination of pathways involving both primary and secondary signaling processes is involved in producing a bystander effect. There is recent evidence that mitochondria play a critical role in bystander responses. Recently studies found that a mutation in succinate dehydrogenese subunit C (SDHC), an integral membrane protein in complex II of the electron transport chain, resulted in increased superoxide, oxidative stress, apoptosis, tumorigenesis, and genomic instability, indicating that SDHC play a critical role in maintaining mitochondrial function. In the present study, using Chinese hamster fibroblasts (B1 cells) and the mutants (B9 cells) containing a single base substitution that produced a premature stop codon resulting in a 33-amino acid COOH-terminal truncation of the SDHC protein, we found that B9 cells had an increase in intracellular superoxide content, nitric oxide species, and mitochondrial membrane potential when compared with wild type cells. After irradiated with a grade of doses of gamma rays, B9 cells show an increased radiosensitivity, especially at high doses. The HPRT- mutant yield after gamma-ray irradiation in B9 cells was significantly higher than that of B1 cells. A single, 3Gy dose of gamma-rays increased the background mutant level by more than 4 fold. In contrast, the mutant induction was less than 2 fold in B1 cells. In addition, B9 cells produced a higher bystander mutagenesis after alpha particle irradiation than the B1 cells. Furthermore, pretreated with carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), a nitric oxide scavenger, significantly decreased the bystander effect. Our findings demonstrate that a mutation in SDHC increases radiosensitivity in both directly irradiated cells and in neighboring bystander cells, and mito-chondrial function play an essential role in

  1. Gamma-H2AX as a biomarker of DNA damage induced by ionizing radiation in targeted and bystander human artificial skin models and peripheral blood lymphocytes

    NASA Astrophysics Data System (ADS)

    Redon, Christophe; Dickey, Jennifer; Bonner, William; Sedelnikova, Olga

    30 min after irradiation and then declined at a relatively steady pace as the cell repaired the DNA damage. Radiation effects were still detectable after 48 hrs for doses greater than 1 Gy and remained linear to initial dose. Activated bystander lymphocytes cultured with media from irradiated lymphocytes exhibited a two-fold increased damage response as seen by gamma- H2AX formation. The effect reached a maximum 3 hrs post-exposure and was retained for over 24 hrs. Thus, detection of gamma-H2AX formation to determine DNA damage in a minimally invasive skin test and a non-invasive blood test could be useful and promising tools to analyze direct and indirect effects of radiation exposure.

  2. Evaluation of Bystander Cell Killing Effects in Suicide Gene Therapy of Cancer: Engineered Thymidylate Kinase (TMPK)/AZT Enzyme-Prodrug Axis.

    PubMed

    Sato, Takeya; Neschadim, Anton; Nakagawa, Ryo; Yanagisawa, Teruyuki; Medin, Jeffrey A

    2015-01-01

    Suicide gene therapy of cancer (SGTC) entails the introduction of a cDNA sequence into tumor cells whose polypeptide product is capable of either directly activating apoptotic pathways itself or facilitating the activation of pharmacologic agents that do so. The latter class of SGTC approaches is of the greater utility in cancer therapy owing to the ability of some small, activated cytotoxic compounds to diffuse from their site of activation into neighboring malignant cells, where they can also mediate destruction. This phenomenon, termed "bystander killing", can be highly advantageous in driving significant tumor regression in vivo without the requirement of transduction of each and every tumor cell with the suicide gene. We have developed a robust suicide gene therapy enzyme/prodrug system based on an engineered variant of the human thymidylate kinase (TMPK), which has been endowed with the ability to drive azidothymidine (AZT) activation. Delivery of this suicide gene sequence into tumors by means of recombinant lentivirus-mediated transduction embodies an SGTC strategy that successfully employs bystander cell killing as a mechanism to achieve significant ablation of solid tumors in vivo. Thus, this engineered TMPK/AZT suicide gene therapy axis holds great promise for clinical application in the treatment of inoperable solid tumors in the neoadjuvant setting. Here we present detailed procedures for the preparation of recombinant TMPK-based lentivirus, transduction of target cells, and various approaches for the evaluation of bystander cell killing effects in SGCT in both in vitro and in vivo models. PMID:26072401

  3. Are Synchronized Changes in Connexin-43 and Caveolin-3 a Bystander Effect in a Phoneutria nigriventer Venom Model of Blood-Brain Barrier Breakdown?

    PubMed

    Soares, Edilene Siqueira; Mendonça, Monique Culturato Padilha; Rocha, Thalita; Kalapothakis, Evanguedes; da Cruz-Höfling, Maria Alice

    2016-08-01

    Upregulation of caveolin-3 (Cav-3) or connexin-43 (Cx43) in astrocytes has been associated with important brain pathologies. We used Phoneutria nigriventer spider venom (PNV), which induces blood-brain barrier breakdown in rats, in order to investigate Cav-3 and Cx43 expression in the cerebellum over critical periods of rat envenomation. By immunofluorescence, western blotting (WB), and transmission electron microscopy (TEM), we assessed changes at 1, 2, 5, 24, and 72 h post-venom. WB showed immediate increases in Cav-3 and Cx43 at 1 h (interval of greatest manifestations of envenomation) that persisted at 5 h (when there were signs of recovery) and peaked at 24 h when no signs of envenomation were detectable. At 2 and 72 h, Cav-3 was downregulated and Cx43 had returned to baseline. PNV markedly intensified Cx43 in molecular, Purkinje and granular layers and Cav-3 in astrocytes whose colocalization to increased GFAP suggests interaction between reactive astrogliosis and Cav-3 upregulation. TEM showed swollen perivascular astrocytic end-feet and synaptic contact alterations that had generally resolved by 72 h. It is uncertain whether such PNV-induced synchronized changes are an interactive effect between Cav-3 and Cx43, or a bystander effect. Evidences indicate that Cav-3 downregulation coupled to Cx43 return to baseline at 72 h when no signs of envenomation were visible, suggesting homeostasis reestablishment. This experimental model is relevant to studying mechanisms involved in neurological disorders associated with Cav-3 overexpression. PMID:27067308

  4. Evaluation of a bystander education program.

    PubMed

    Amar, Angela Frederick; Sutherland, Melissa; Kesler, Erin

    2012-12-01

    Sexual and partner violence are widespread problems on college campuses. By changing attitudes, beliefs, and behavior, bystander education programs have been found to prevent sexual and partner violence and improve the responses of peers to survivors. The purpose of this study is to evaluate the effectiveness and feasibility of a bystander education program that was adapted to a specific university setting. A convenience sample of 202, full-time undergraduate students aged 18-22 years participated in the bystander education program and completed pre- and post-test measures of attitudes related to sexual and partner violence and willingness to help. Paired sample t-tests were used to examine changes in scores between pre- and post-test conditions. After the program, participants' reported decreased rape myth acceptance and denial of interpersonal violence, and increased intention to act as a bystander and an increased sense of responsibility to intervene. Mental health nurses can use principles of bystander education in violence prevention programs and in providing support to survivors. PMID:23215986

  5. Predicting Improvement After a Bystander Program for the Prevention of Sexual and Dating Violence.

    PubMed

    Hines, Denise A; Palm Reed, Kathleen M

    2015-07-01

    Although evidence suggests that bystander prevention programs are promising interventions for decreasing sexual violence and dating violence on college campuses, there have been no studies to date evaluating moderators of bystander program effectiveness. The current study evaluates whether different demographic characteristics, attitudes, knowledge, and behaviors at pretest predict change over a 6-month follow-up for students who participated in a bystander prevention program. Participants in the three assessments (pretest, posttest, 6-month follow-up) included 296 college students who were mandated to attend a bystander program during their first year orientation. Analyses showed that with few exceptions, the bystander program worked best for students who were most at risk given their pretest demographics and levels of attitudes condoning dating violence and sexual violence, bystander efficacy, and bystander behaviors. Results are discussed in terms of suggestions for future research. PMID:25380846

  6. A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

    PubMed Central

    Leonard, Bobby E.

    2008-01-01

    primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1.) Single Specific Energy Hits initiate Adaptive Response, 2.) Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3.) For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4.) The dose range of the AR protection depends on the value of the Specific Energy per Hit, . 5.) Alpha particle induced deleterious Bystander damage is modulated by low LET radiation. PMID:18648579

  7. Student Voices: What Can Bystanders Do to Prevent Bullying of Students Who Are Different (or Perceived as Different) from Others?

    ERIC Educational Resources Information Center

    Nordseth, Anna; Vepachedu, Vikas; Shipman, Grant; Alayachew, David

    2012-01-01

    In this article, four students share their ideas on what bystanders can do to prevent bullying of students who are different or perceived as different from others. Anna Nordseth says what bystanders need to realize is how to recognize bullying and what a lasting effect it can have on the individuals involved. One bold, compassionate bystander can…

  8. Site Specific Microbeam Irradiation: Defining a Bystander Effect. Final Technical Report

    SciTech Connect

    Brenner, David J.

    2003-10-22

    There is evidence that low-energy x-rays as used in mammography have an increased biological effectiveness relative to higher-energy photons. However, the RBE values are not large, probably less than 2. Thus it is unlikely that the radiation risk alone could prove to be a ''show stopper'' regarding screening mammography because, for older women, the benefit is likely to considerably outweigh the radiation risk. Nevertheless, the RBE for low-energy x-rays might reasonably be taken into account when assessing the recommended age to commence such annual screening.

  9. Bystanders Are the Key to Stopping Bullying

    ERIC Educational Resources Information Center

    Padgett, Sharon; Notar, Charles E.

    2013-01-01

    Bullying is the dominance over another. Bullying occurs when there is an audience. Peer bystanders provide an audience 85% of instances of bullying. If you remove the audience bullying should stop. The article is a review of literature (2002-2013) on the role of bystanders; importance of bystanders; why bystanders behave as they do; resources to…

  10. The Effect of Cognitive Behavioral Therapy and Cognitive Behavioral Therapy Plus Media on the Reduction of Bullying and Victimization and the Increase of Empathy and Bystander Response in a Bully Prevention Program for Urban Sixth-Grade Students

    ERIC Educational Resources Information Center

    McLaughlin, Laura Pierce

    2009-01-01

    The purpose of this study was to investigate the effect of cognitive behavioral therapy and cognitive behavioral therapy plus media on the reduction of bullying and victimization and the increase in empathy and bystander response in a bully prevention program for urban sixth-graders. Sixty-eight students participated. Because one of the…

  11. Bystander and Adaptive Responses in Tissue Models exposed to Low Radiation Doses

    SciTech Connect

    Kevin M. Prise

    2007-01-02

    The overall goal is characterization of 3D tissue models that can be used for investigation of the mechanisms underlying radiation-induced bystander effect at low doses (20 cGy or less) of low LET ionizing radiation, using a unique focused soft X-ray microprobe that had been upgraded to provide a range of focused soft X-ray energies, some sufficient to penetrate 3D models (Ref DE-FG02-01ER63236). The proposed studies will include an examination of whether the passage of a single electron track can trigger bystander responses in the 3D tissue models and, if so, whether the response is altered by increased or decreased levels of oxidative stress. Our existing multi-photon/confocal in-depth microscopy techniques will be used to develop assays for damage induced within intact 3D tissue models. The working hypothesis is that organization of cells into tissues, particularly involving more than one cell type, alters expression of the radiation-induced bystander effect compared to that seen in isolated single cell types in monolayer.

  12. Litomosoides sigmodontis induces TGF-β receptor responsive, IL-10-producing T cells that suppress bystander T-cell proliferation in mice.

    PubMed

    Hartmann, Wiebke; Schramm, Christoph; Breloer, Minka

    2015-09-01

    Helminth parasites suppress immune responses to prolong their survival within the mammalian host. Thereby not only helminth-specific but also nonhelminth-specific bystander immune responses are suppressed. Here, we use the murine model of Litomosoides sigmodontis infection to elucidate the underlying mechanisms leading to this bystander T-cell suppression. When OT-II T cells specific for the third-party antigen ovalbumin are transferred into helminth-infected mice, these cells respond to antigen-specific stimulation with reduced proliferation compared to activation within non-infected mice. Thus, the presence of parasitic worms in the thoracic cavity translates to suppression of T cells with a different specificity at a different site. By eliminating regulatory receptors, cytokines, and cell populations from this system, we provide evidence for a two-staged process. Parasite products first engage the TGF-β receptor on host-derived T cells that are central to suppression. In a second step, host-derived T cells produce IL-10 and subsequently suppress the adoptively transferred OT-II T cells. Terminal suppression was IL-10-dependant but independent of intrinsic TGF-β receptor- or PD-1-mediated signaling in the suppressed OT-II T cells. Blockade of the same key suppression mediators, i.e. TGF-β- and IL-10 receptor, also ameliorated the suppression of IgG response to bystander antigen vaccination in L. sigmodontis-infected mice. PMID:26138667

  13. Action Research Evaluation of Bystander Intervention Training Created by Munche, Stern, and O'Brien

    ERIC Educational Resources Information Center

    Shiflet, Jacqueline H.

    2013-01-01

    This qualitative, appreciative inquiry study was an examination of bystander intervention as related to sexual assault in the military. The purpose of the study was to examine how military personnel and Department of Defense civilian employees reflecting diverse backgrounds perceived the effectiveness of bystander intervention training and sexual…

  14. microRNAome changes in bystander three-dimensional human tissue models suggest priming of apoptotic pathways

    PubMed Central

    Kovalchuk, Olga; Zemp, Franz J.; Filkowski, Jody N.; Altamirano, Alvin M.; Dickey, Jennifer S.; Jenkins-Baker, Gloria; Marino, Stephen A.; Brenner, David J.; Bonner, William M.; Sedelnikova, Olga A.

    2010-01-01

    The radiation-induced bystander effect (RIBE) is a phenomenon whereby unexposed cells exhibit molecular symptoms of stress exposure when adjacent or nearby cells are traversed by ionizing radiation (IR). Recent data suggest that RIBE may be epigenetically mediated by microRNAs (miRNAs), which are small regulatory molecules that target messenger RNA transcripts for translational inhibition. Here, we analyzed microRNAome changes in bystander tissues after α-particle microbeam irradiation of three-dimensional artificial human tissues using miRNA microarrays. Our results indicate that IR leads to a deregulation of miRNA expression in bystander tissues. We report that major bystander end points, including apoptosis, cell cycle deregulation and DNA hypomethylation, may be mediated by altered expression of miRNAs. Specifically, c-MYC-mediated upregulation of the miR-17 family was associated with decreased levels of E2F1 and RB1, suggesting a switch to a proliferative state in bystander tissues, while priming these cells for impending death signals. Upregulation of the miR-29 family resulted in decreased levels of its targets DNMT3a and MCL1, consequently affecting DNA methylation and apoptosis. Altered expression of miR-16 led to changes in expression of BCL2, suggesting modulation of apoptosis. Thus, our data clearly show that miRNAs play a profound role in the manifestation of late RIBE end points. In summary, this study creates a roadmap for understanding the role of microRNAome in RIBE and for developing novel RIBE biomarkers. PMID:20643754

  15. Personal distress and the influence of bystanders on responding to an emergency.

    PubMed

    Hortensius, Ruud; Schutter, Dennis J L G; de Gelder, Beatrice

    2016-08-01

    Spontaneous helping behavior during an emergency is influenced by the personality of the onlooker and by social situational factors such as the presence of bystanders. Here, we sought to determine the influences of sympathy, an other-oriented response, and personal distress, a self-oriented response, on the effect of bystanders during an emergency. In four experiments, we investigated whether trait levels of sympathy and personal distress predicted responses to an emergency in the presence of bystanders by using behavioral measures and single-pulse transcranial magnetic stimulation. Sympathy and personal distress were expected to be associated with faster responses to an emergency without bystanders present, but only personal distress would predict slower responses to an emergency with bystanders present. The results of a cued reaction time task showed that people who reported higher levels of personal distress and sympathy responded faster to an emergency without bystanders (Exp. 1). In contrast to our predictions, perspective taking but not personal distress was associated with slower reaction times as the number of bystanders increased during an emergency (Exp. 2). However, the decrease in motor corticospinal excitability, a direct physiological measure of action preparation, with the increase in the number of bystanders was solely predicted by personal distress (Exp. 3). Incorporating cognitive load manipulations during the observation of an emergency suggested that personal distress is linked to an effect of bystanders on reflexive responding to an emergency (Exp. 4). Taken together, these results indicate that the presence of bystanders during an emergency reduces action preparation in people with a disposition to experience personal distress. PMID:27126708

  16. Bystander's willingness to report theft, physical assault, and sexual assault: the impact of gender, anonymity, and relationship with the offender.

    PubMed

    Nicksa, Sarah C

    2014-01-01

    This research examines bystander willingness to report three different crimes to the police or campus authorities among a college student sample (n = 295). Twelve original vignettes varied anonymity when reporting, bystander's relationship with the offender (friend or stranger), and crime type. A factorial analysis of variance showed that main effects were found for crime type, bystander's gender, and bystander's relationship with the offender; anonymity was not significant. The physical assault was the most likely to be reported (4.47), followed by theft (3.26), and sexual assault (2.36). Women were more likely than men to report each crime type, and bystanders who were good friends of the offender were less likely to report than strangers. No two- or three-way interactions were significant, but a significant four-way interaction indicated that anonymity, relationship with the offender, and bystander's gender predicted willingness to report for the sexual assault scenario. PMID:24142441

  17. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury.

    PubMed

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H R; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo; Molon, Barbara; Mammano, Fabio

    2015-04-30

    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding "bystander" cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca(2+)-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy. PMID:25868859

  18. Characteristics and mechanisms of the bystander response in monolayer cell cultures exposed to very low fluences of alpha particles

    NASA Astrophysics Data System (ADS)

    Little, John B.; Azzam, Edouard I.; de Toledo, Sonia M.; Nagasawa, Hatsumi

    2005-02-01

    When confluent cultures of mammalian cells are irradiated with very low fluences of alpha particles whereby only occasional cells receive any radiation exposure, genetic changes are observed in the non-irradiated ("bystander") cells. Upregulation of the p53 damage-response pathway as well as activation of proteins in the MAPK family occurred in bystander cells; p53 was phosphorylated on the serine 15 residue suggesting that the upregulation of p53 was a consequence of DNA damage. Damage signals were transmitted to bystander cells through gap junctions, as confirmed by the use of genetically manipulated cells including connexin43 knockouts. Expression of connexin43 was markedly enhanced by irradiation. A moderate bystander effect was observed for specific gene mutations and chromosomal aberrations. This effect was markedly enhanced in cells defective in the non-homologous end joining DNA repair pathway. Finally, an upregulation of oxidative metabolism occurred in bystander cells; the increased levels of reactive oxygen species appeared to be derived from flavine-containing oxidase enzymes. We hypothesize that genetic effects observed in non-irradiated bystander cells are a consequence of oxidative base damage; >90% of mutations in bystander cells were point mutations. When bystander cells cannot repair DNA double strand breaks, they become much more sensitive to the induction of chromosomal aberrations and mutations, the latter consisting primarily of deletion mutants. While we propose that the genetic effects occurring in bystander cells are a consequence of oxidative stress, the nature of the signal that initiates this process remains to be determined.

  19. A novel regulatory pathway for autoimmune disease: Binding of partial MHC class II constructs to monocytes reduces CD74 expression and induces both specific and bystander T-cell tolerance

    PubMed Central

    Andrew, Shayne; Huan, Jianya; Chou, Yuan K.; Buenafe, Abigail C.; Dahan, Rony; Reiter, Yoram; Mooney, Jeffery L.; Offner, Halina; Burrows, Gregory G.

    2012-01-01

    Treatment with partial (p)MHC class II-β1α1 constructs (also referred to as recombinant T-cell receptor ligands – RTL) linked to antigenic peptides can induce T-cell tolerance, inhibit recruitment of inflammatory cells and reverse autoimmune diseases. Here we demonstrate a novel regulatory pathway that involves RTL binding to CD11b+ mononuclear cells through a receptor comprised of MHC class II invariant chain (CD74), cell-surface histones and MHC class II itself for treatment of experimental autoimmune encephalomyelitis (EAE). Binding of RTL constructs with CD74 involved a previously unrecognized MHC class II-α1/CD74 interaction that inhibited CD74 expression, blocked activity of its ligand, macrophage migration inhibitory factor, and reduced EAE severity. These findings implicate binding of RTL constructs to CD74 as a key step in both antigen-driven and bystander T-cell tolerance important in treatment of inflammatory diseases. PMID:23026773

  20. The Men's Program: does it impact college men's self-reported bystander efficacy and willingness to intervene?

    PubMed

    Langhinrichsen-Rohling, Jennifer; Foubert, John D; Brasfield, Hope M; Hill, Brent; Shelley-Tremblay, Shannon

    2011-06-01

    This study considered whether a rape prevention program could reduce men's rape myth acceptance, enhance the perceived effectiveness of college men's bystander behavior, and increase men's willingness to intervene as bystanders in potentially dangerous situations. As predicted, college men who experienced The Men's Program significantly increased their self-reported willingness to help as a bystander and their perceived bystander efficacy in comparison to college men who experienced the comparison condition. Men's Program participants also significantly decreased their self-reported rape myth acceptance in comparison with comparison condition participants. The college policy and rape prevention program planning implications of these findings are discussed. PMID:21571743

  1. Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance

    PubMed Central

    Singh, Vikas; Gera, Ruchi; Kushwaha, Rajesh; Sharma, Anuj Kumar; Patnaik, Satyakam; Ghosh, Debabrata

    2016-01-01

    Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc- (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons. PMID:27477106

  2. Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance.

    PubMed

    Singh, Vikas; Gera, Ruchi; Kushwaha, Rajesh; Sharma, Anuj Kumar; Patnaik, Satyakam; Ghosh, Debabrata

    2016-01-01

    Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc(-) (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons. PMID:27477106

  3. Bystander Macrophage Apoptosis after Mycobacterium tuberculosis H37Ra Infection▿

    PubMed Central

    Kelly, Deirdre M.; ten Bokum, Annemieke M. C.; O'Leary, Seonadh M.; O'Sullivan, Mary P.; Keane, Joseph

    2008-01-01

    Human macrophages infected with Mycobacterium tuberculosis may undergo apoptosis. Macrophage apoptosis contributes to the innate immune response against M. tuberculosis by containing and limiting the growth of mycobacteria and also by depriving the bacillus of its niche cell. Apoptosis of infected macrophages is well documented; however, bystander apoptosis of uninfected macrophages has not been described in the setting of M. tuberculosis. We observed that uninfected human macrophages underwent significant bystander apoptosis 48 and 96 h after they came into contact with macrophages infected with avirulent M. tuberculosis. The bystander apoptosis was significantly greater than the background apoptosis observed in uninfected control cells cultured for the same length of time. There was no evidence of the involvement of tumor necrosis factor alpha, Fas, tumor necrosis factor-related apoptosis-inducing ligand, transforming growth factor β, Toll-like receptor 2, or MyD88 in contact-mediated bystander apoptosis. This newly described phenomenon may further limit the spread of M. tuberculosis by eliminating the niche cells on which the bacillus relies. PMID:17954721

  4. Cytotoxic T Lymphocytes Derived from Patients with Chronic Hepatitis C Virus Infection Kill Bystander Cells via Fas-FasL Interaction

    PubMed Central

    Gremion, Christel; Grabscheid, Benno; Wölk, Benno; Moradpour, Darius; Reichen, Jürg; Pichler, Werner; Cerny, Andreas

    2004-01-01

    The role of Fas-mediated lysis of hepatocytes in hepatitis C virus (HCV)-induced injury is frequently discussed. We therefore analyzed the effect of the number of HCV antigen-expressing cells, the mode of antigen presentation, and the number of cytotoxic T lymphocytes in a coculture system mimicking cellular components of the liver. Here, we show that endogenously processed HCV proteins are capable of inducing bystander killing. We further demonstrate that 0.8 to 1.5% of cells presenting HCV antigens suffice to induce lysis of 10 to 29% of bystander cells, suggesting that the mechanism may be operative at low fractions of infected versus uninfected hepatocytes in vivo. Our data underscore the role of the Fas pathway in HCV-related liver injury and support the exploration of Fas-based treatment strategies for patients with chronic hepatitis C virus infection. PMID:14747581

  5. Long-term biological effects induced by ionizing radiation--implications for dose mediated risk.

    PubMed

    Miron, S D; Astărăstoae, V

    2014-01-01

    Ionizing radiations are considered to be risk agents that are responsible for the effects on interaction with living matter. The occurring biological effects are due to various factors such as: dose, type of radiation, exposure time, type of biological tissue, health condition and the age of the person exposed. The mechanisms involved in the direct modifications of nuclear DNA and mitochondrial DNA are reviewed. Classical target theory of energy deposition in the nucleus that causes DNA damages, in particular DNA double-strand breaks and that explanation of the biological consequences of ionizing radiation exposure is a paradigm in radiobiology. Recent experimental evidences have demonstrated the existence of a molecular mechanism that explains the non-targeted effects of ionizing radiation exposure. Among these novel data, genomic instability and a variety of bystander effects are discussed here. Those bystander effects of ionizing radiation are fulfilled by cellular communication systems that give rise to non-targeted effects in the neighboring non irradiated cells. This paper provides also a commentary on the synergistic effects induced by the co-exposures to ionizing radiation and various physical agents such as electromagnetic fields and the co-exposures to ionizing radiation and chemical environmental contaminants such as metals. The biological effects of multiple stressors on genomic instability and bystander effects are also discussed. Moreover, a brief presentation of the methods used to characterize cyto- and genotoxic damages is offered. PMID:25341291

  6. Investigating the influence of respiratory motion on the radiation induced bystander effect in modulated radiotherapy

    NASA Astrophysics Data System (ADS)

    Cole, Aidan J.; McGarry, Conor K.; Butterworth, Karl T.; McMahon, Stephen J.; Hounsell, Alan R.; Prise, Kevin M.; O'Sullivan, Joe M.

    2013-12-01

    Respiratory motion introduces complex spatio-temporal variations in the dosimetry of radiotherapy and may contribute towards uncertainties in radiotherapy planning. This study investigates the potential radiobiological implications occurring due to tumour motion in areas of geometric miss in lung cancer radiotherapy. A bespoke phantom and motor-driven platform to replicate respiratory motion and study the consequences on tumour cell survival in vitro was constructed. Human non-small-cell lung cancer cell lines H460 and H1299 were irradiated in modulated radiotherapy configurations in the presence and absence of respiratory motion. Clonogenic survival was calculated for irradiated and shielded regions. Direction of motion, replication of dosimetry by multi-leaf collimator (MLC) manipulation and oscillating lead shielding were investigated to confirm differences in cell survival. Respiratory motion was shown to significantly increase survival for out-of-field regions for H460/H1299 cell lines when compared with static irradiation (p < 0.001). Significantly higher survival was found in the in-field region for the H460 cell line (p < 0.030). Oscillating lead shielding also produced these significant differences. Respiratory motion and oscillatory delivery of radiation dose to human tumour cells has a significant impact on in- and out-of-field survival in the presence of non-uniform irradiation in this in vitro set-up. This may have important radiobiological consequences for modulated radiotherapy in lung cancer.

  7. Moral Disengagement among Bystanders to School Bullying

    ERIC Educational Resources Information Center

    Obermann, Marie-Louise

    2011-01-01

    This study examined the use of moral disengagement among children indirectly involved in bullying (bystanders). A sample of Danish adolescents (N = 660, M age 12.6 years) were divided into four groups depending on their bystander status: (a) outsiders, who did not experience bullying among their peers; (b) defenders, who were likely to help the…

  8. Bystander chronic infection negatively impacts development of CD8+ T cell memory

    PubMed Central

    Stelekati, Erietta; Shin, Haina; Doering, Travis A.; Dolfi, Douglas V.; Ziegler, Carly G.; Beiting, Daniel P.; Dawson, Lucas; Liboon, Jennifer; Wolski, David; Ali, Mohammed-Alkhatim A.; Katsikis, Peter D.; Shen, Hao; Roos, David S.; Haining, W. Nicholas; Lauer, Georg M.; Wherry, E. John

    2014-01-01

    Summary Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8+ T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8+ T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8+ T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation. PMID:24837104

  9. Non-targeted effects induced by high LET charged particles

    NASA Astrophysics Data System (ADS)

    Hei, Tom K.; Chai, Yunfei; Hamada, Nobuyuki; Kakinuma, Shizuko; Uchihori, Yukio

    Radiation-induced non-targeted response represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the final biological consequences of exposure to low doses of radiation. Using the gpt delta transgenic mouse model, there is evidence that irradiation of a small area (1 cm by 1 cm) of the lower abdominal area of animals with a 5 Gy dose of X-rays induced cyclooxygenase-2 as well as deletion mutations in the out-of-field lung tissues of the animals. The mutation correlated with an increase in prostaglandin levels in the bystander lung tissues and with an increase in the level of 8-hydroxydeoxyguanosine (8-OHdG), an oxidative DNA damage marker. An increase in COX-2 level was also detected in the out-of-field lung tissues of animals similarly exposed to high LET argon and carbon ions accelerated at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences in Japan. These results provide the first evidence that the COX-2 -related pathway, which is essential in mediating cellular inflammatory response, is the critical signaling link for the non-targeted, bystander phenomenon. A better understanding of the cellular and molecular mechanisms of the non-targeted, out of field phenomenon together with evidence of their occurrence in vivo will allow us to formulate a more accurate assessment of radiation risk.

  10. Morbidity among bystanders of bullying behavior at school: concepts, concerns, and clinical/research issues.

    PubMed

    Rivers, Ian

    2012-01-01

    The role of the bystander is not one that is easily understood in the anti-bullying literature. Roles within the unofficial hierarchy of the school-yard and playground overlap considerably, and each role has its own social dynamic that brings with it a shifting behavioral landscape that affects every student. In this article, the mental health correlates of three categories of bystander are explored: the co-victim, the isolate, and the confederate. Each category of bystander has its own characterizations and mental health correlates. Reports of post-traumatic stress, internalized hostility, substance use, and suicide ideation are discussed with reference to studies involving witnesses of family abuse, community and school violence as well as bullying. It is argued that bystanders are the key to challenging bullying in schools, and their mental health and well-being is pivotal to the effectiveness of anti-bullying interventions. PMID:22909907

  11. Speculations about Bystander and Biophotons.

    PubMed

    Sanders, Charles L

    2014-12-01

    Mothersill and many others during the last hundred years have shown that cells and now whole animals may communicate with each other by electromagnetic waves called biophotons. This would explain the source of the bystander phenomena. These ultra-weak photons are coherent, appear to originate and concentrate in DNA of the cell nucleus and rapidly carry large amounts of data to each cell and to the trillions of other cells in the human body. The implications of such a possibility can be wonderfully important. PMID:25552952

  12. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury

    PubMed Central

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H.R.; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo

    2015-01-01

    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding “bystander” cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca2+-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy. PMID:25868859

  13. An Online Bystander Intervention Program for the Prevention of Sexual Violence

    PubMed Central

    Kleinsasser, Anne; Jouriles, Ernest N.; McDonald, Renee; Rosenfield, David

    2014-01-01

    Objective Because of its high prevalence and serious consequences for victims, sexual violence is a significant problem on college campuses. Sexual assault prevention programs based on the bystander intervention model have been shown to be effective; however, current programs are limited in terms of ease of distribution. To address this issue, we developed and evaluated “Take Care,” an online bystander intervention program. To our knowledge, this is the first empirical evaluation of an online bystander intervention program designed to prevent sexual violence. Method Ninety-three participants (80.6% female, 19.4% male) recruited from social psychology classes at a mid-size university were randomly assigned to view one of two online programs: Take Care or a control program on study skills. Before viewing the programs, participants completed measures of bystander behaviors and feelings of efficacy for performing such behaviors. Measures were administered again post-intervention and at a two-month follow-up assessment. Results Participants who viewed Take Care reported greater efficacy for engaging in bystander behaviors at post-treatment and two months following treatment, compared to those who viewed the control program. In addition, participants who viewed Take Care reported performing relatively more bystander behaviors for friends at the two-month follow-up assessment, compared to participants who viewed the control program. Conclusions These results suggest that sexual violence prevention programs may be effectively adapted to an online format. PMID:26240776

  14. Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV Nef

    SciTech Connect

    Bouzar, Baya Amel; Rea, Angela; Hoc-Villet, Stephanie; Garnier, Celine; Guiguen, Francois; Jin Yuhuai; Narayan, Opendra; Chebloune, Yahia . E-mail: ychebloune@kumc.edu

    2007-08-01

    Caprine arthritis encephalitis virus (CAEV) is the natural lentivirus of goats, well known for its tropism for macrophages and its inability to cause infection in lymphocytes. The viral genome lacks nef, tat, vpu and vpx coding sequences. To test the hypothesis that when nef is expressed by the viral genome, the virus became toxic for lymphocytes during replication in macrophages, we inserted the SIVsmm PBj14 nef coding sequences into the genome of CAEV thereby generating CAEV-nef. This recombinant virus is not infectious for lymphocytes but is fully replication competent in goat macrophages in which it constitutively expresses the SIV Nef. We found that goat lymphocytes cocultured with CAEV-nef-infected macrophages became activated, showing increased expression of the interleukin-2 receptor (IL-2R). Activation correlated with increased proliferation of the cells. Interestingly, a dual effect in terms of apoptosis regulation was observed in exposed goat lymphocytes. Nef was found first to induce a protection of lymphocytes from apoptosis during the first few days following exposure to infected macrophages, but later it induced increased apoptosis in the activated lymphocytes. This new recombinant virus provides a model to study the functions of Nef in the context of infection of macrophages, but in absence of infection of T lymphocytes and brings new insights into the biological effects of Nef on lymphocytes.

  15. Do Sexual Assault Bystander Interventions Change Men's Intentions? Applying the Theory of Normative Social Behavior to Predicting Bystander Outcomes.

    PubMed

    Mabry, Amanda; Turner, Monique Mitchell

    2016-01-01

    The high prevalence of sexual assault on college campuses has led to the implementation of health communication programs to prevent sexual assault. A few novel programs focus on primary prevention by targeting social norms related to gender and masculinity among men through bystander intervention. Guided by the theory of normative social behavior, this study sought to examine the relative effect of campaigns communicating positive versus negative injunctive norms and the interaction between exposure to such campaign messages and perceived descriptive norms and relevant cognitive moderators (e.g., outcome expectations, injunctive norms, group identity, ego involvement) among men. A 2 (high/low descriptive norms) × 2 (high/low moderator) × 3 (public service announcement) independent groups quasi-experimental design (N = 332) was used. Results indicated that messages communicating positive injunctive norms were most effective among men who were least likely to engage in bystander intervention. Furthermore, descriptive norms played a significant role in behavioral intentions, such that those with stronger norms were more likely to report intentions to engage in bystander behaviors in the future. Similarly, the moderators of aspiration, injunctive norms, social approval, and ego involvement had a significant positive effect on behavioral intentions. These findings have important implications for future message design strategy and audience segmentation. PMID:26716826

  16. Sex differences in bystander intervention in a theft.

    PubMed

    Austin, W

    1979-11-01

    A series of studies demonstrated a strong relationship among the situation-defining variable of degree of harm to victim, sexual configuration among participants, and bystanders' willingness to intervene to stop a theft. A pretest showed that a prior verbal commitment was absolutely necessary for intervention. The remaining data showed that high harm to a victim produced a high rate of intervention and showed strong sex differences in helping behavior in low-harm conditions. A high percentage of female bystanders helped in both low- and high-harm situations, whereas frequent helping by males was observed only when harm to the victim was high. Female victims elicited a significantly greater amount of helping, and sex of thief had no effect. A significant sex of bystander, sex of victim, and harm to victim interaction best describes the data. Results are interpreted in terms of different motivational sets held by males and females when they are responsible for the fate of others. Results also support the utility of an interactionist approach to the question of how individual and situational variables influence prosocial action. PMID:521904

  17. Booze, Bars, and Bystander Behavior: People Who Consumed Alcohol Help Faster in the Presence of Others

    PubMed Central

    van Bommel, Marco; van Prooijen, Jan-Willem; Elffers, Henk; Van Lange, Paul A. M.

    2016-01-01

    People help each other less often and less quickly when bystanders are present. In this paper, we propose that alcohol consumption could attenuate or reverse this so-called bystander effect. Alcohol impairs people cognitively and perceptually, leading them to think less about the presence of others and behave less inhibited. Moreover, alcohol makes people more prone to see the benefits of helping and not the costs. To provide an initial test of these lines of reasoning, we invited visitors of bars in Amsterdam to join our study at a secluded spot at the bar. We manipulated bystander presence, and at the end of the study, we measured alcohol consumption. When participants took their seats, the experimenter dropped some items. We measured how many items were picked up and how quickly participants engaged in helping. Results revealed that alcohol did not influence the bystander effect in terms of the amount of help given. But importantly, it did influence the bystander effect in terms of response times: people who consumed alcohol actually came to aid faster in the presence of others. PMID:26903929

  18. Radiation Induced Non-targeted Response: Mechanism and Potential Clinical Implications

    PubMed Central

    Hei, Tom K.; Zhou, Hongning; Chai, Yunfei; Ponnaiya, Brian; Ivanov, Vladimir N.

    2012-01-01

    Generations of students in radiation biology have been taught that heritable biological effects require direct damage to DNA. Radiation-induced non-targeted/bystander effects represent a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the biological consequences of exposure to low doses of radiation. Although radiation induced bystander effects have been well documented in a variety of biological systems, including 3D human tissue samples and whole organisms, the mechanism is not known. There is recent evidence that the NF-κB-dependent gene expression of interleukin 8, interleukin 6, cyclooxygenase-2, tumor necrosis factor and interleukin 33 in directly irradiated cells produced the cytokines and prostaglandin E2 with autocrine/paracrine functions, which further activated signaling pathways and induced NF-κB-dependent gene expression in bystander cells. The observations that heritable DNA alterations can be propagated to cells many generations after radiation exposure and that bystander cells exhibit genomic instability in ways similar to directly hit cells indicate that the low dose radiation response is a complex interplay of various modulating factors. The potential implication of the non-targeted response in radiation induced secondary cancer is discussed. A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy. PMID:21143185

  19. Predicting Bystander Behavior to Prevent Sexual Assault on College Campuses: The Role of Self-Efficacy and Intent.

    PubMed

    McMahon, Sarah; Peterson, N Andrew; Winter, Samantha C; Palmer, Jane E; Postmus, Judy L; Koenick, Ruth Anne

    2015-09-01

    Bystander intervention has been increasingly applied to prevent sexual violence on college campuses. Its underlying theory assumes unidirectional relationships between variables, predicting that bystander behaviors (i.e., actions taken to intervene in sexual violence situations) will be influenced by bystander intentions (BI; i.e., likelihood to intervene in the future), which in turn will be affected by bystander efficacy (BE; i.e., confidence to intervene). One question for theory is whether a reciprocal relationship exists between BI and BE. We used structural equation modeling (SEM) with longitudinal data to test unidirectional and reciprocal causal relations between BI and BE. Participants (n = 1390) were students at a northeastern US university. Four models were examined using SEM: (1) a baseline model with autoregressive paths; (2) a model with autoregressive effects and BI predicting future BE; (3) a model with autoregressive effects and BE predicting future BI; and, (4) a fully cross-lagged model. Results indicated that reciprocal causality was found to occur between BI and BE. In addition, a final model demonstrated indirect effects of a bystander intervention program on bystander behaviors through both BI and BE at different time points. Implications for theory and practice are described, and directions for future research discussed. PMID:26194588

  20. Rethinking the bystander role in school violence prevention.

    PubMed

    Stueve, Ann; Dash, Kimberly; O'Donnell, Lydia; Tehranifar, Parisa; Wilson-Simmons, Renée; Slaby, Ronald G; Link, Bruce G

    2006-01-01

    Public concerns about school shootings and safety draw attention to the role bystanders can play in preventing school violence. Although school violence prevention plans are often required, there is little guidance about whether these should address the roles of bystanders and what actions bystanders should take in different circumstances, from more common instances of bullying and fighting to rare, but potentially lethal, threats and use of weapons. Literature pertaining to bystanders is reviewed and applied to the school setting. The definition of bystander is expanded, including parents, teachers, and other school staff as well as youths and those who have information about potential violence as well as those who witness its occurrence. Barriers preventing bystanders from taking positive actions are discussed. The authors call on health promotion researchers and practitioners to work with school communities to identify norms, attitudes, and outcome expectancies that shape bystander behaviors to inform prevention efforts. PMID:16410428

  1. Assessing Bystander Behavior Intentions Toward Friends to Prevent Dating Violence: Development of the Bystander Behavior Intentions-Friends Scale Through Concept Mapping and Exploratory Factor Analysis.

    PubMed

    Borsky, Amanda E; McDonnell, Karen; Rimal, Rajiv N; Turner, Monique

    2016-01-01

    Bystander behavior interventions aim to reduce violence by encouraging individuals to intervene in a safe and effective manner when they hear or see circumstances that could lead to violence. This study used a participatory-based approach to develop a 9-item scale to measure bystander behaviors to prevent dating violence among friends. Predominantly, female students (N = 37) on a college campus in the Mid-Atlantic region of the United States were asked to define bystander behaviors. Responses were thematically sorted and ranked according to importance in preventing dating violence and feasibility by 12 participants. Psychometric testing of intentions to perform the behavior was done based on responses from an additional 288 respondents. Exploratory factor analysis was used to examine whether bystander behaviors directed at friends to prevent dating violence was a uni- or multidimensional construct, which has not been done to date in the available literature. Results demonstrated a unidimensional factor structure with strong factor loadings (above .71) and internal consistency (Cronbach's alpha .92); items focused on primary and secondary prevention behaviors toward friends. These findings provide a reliable and single construct scale to assess college-age women's response to witnessing the victimization of a friend. These findings can facilitate future program evaluations. PMID:26822267

  2. Bystander signalling: exploring clinical relevance through new approaches and new models.

    PubMed

    Butterworth, K T; McMahon, S J; Hounsell, A R; O'Sullivan, J M; Prise, K M

    2013-10-01

    Classical radiation biology research has centred on nuclear DNA as the main target of radiation-induced damage. Over the past two decades, this has been challenged by a significant amount of scientific evidence clearly showing radiation-induced cell signalling effects to have important roles in mediating overall radiobiological response. These effects, generally termed radiation-induced bystander effects (RIBEs) have challenged the traditional DNA targeted theory in radiation biology and highlighted an important role for cells not directly traversed by radiation. The multiplicity of experimental systems and exposure conditions in which RIBEs have been observed has hindered precise definitions of these effects. However, RIBEs have recently been classified for different relevant human radiation exposure scenarios in an attempt to clarify their role in vivo. Despite significant research efforts in this area, there is little direct evidence for their role in clinically relevant exposure scenarios. In this review, we explore the clinical relevance of RIBEs from classical experimental approaches through to novel models that have been used to further determine their potential implications in the clinic. PMID:23849503

  3. Exogenous Nitric Oxide Suppresses in Vivo X-ray-Induced Targeted and Non-Targeted Effects in Zebrafish Embryos

    PubMed Central

    Kong, E.Y.; Yeung, W.K.; Chan, T.K.Y.; Cheng, S.H.; Yu, K.N.

    2016-01-01

    The present paper studied the X-ray-induced targeted effect in irradiated zebrafish embryos (Danio rerio), as well as a non-targeted effect in bystander naïve embryos partnered with irradiated embryos, and examined the influence of exogenous nitric oxide (NO) on these targeted and non-targeted effects. The exogenous NO was generated using an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). The targeted and non-targeted effects, as well as the toxicity of the SNAP, were assessed using the number of apoptotic events in the zebrafish embryos at 24 h post fertilization (hpf) revealed through acridine orange (AO) staining. SNAP with concentrations of 20 and 100 µM were first confirmed to have no significant toxicity on zebrafish embryos. The targeted effect was mitigated in zebrafish embryos if they were pretreated with 100 µM SNAP prior to irradiation with an X-ray dose of 75 mGy but was not alleviated in zebrafish embryos if they were pretreated with 20 µM SNAP. On the other hand, the non-targeted effect was eliminated in the bystander naïve zebrafish embryos if they were pretreated with 20 or 100 µM SNAP prior to partnering with zebrafish embryos having been subjected to irradiation with an X-ray dose of 75 mGy. These findings revealed the importance of NO in the protection against damages induced by ionizing radiations or by radiation-induced bystander signals, and could have important impacts on development of advanced cancer treatment strategies. PMID:27529238

  4. Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects

    PubMed Central

    Sprung, Carl N.; Ivashkevich, Alesia; Forrester, Helen B.; Redon, Christophe E.; Georgakilas, Alexandros; Martin, Olga A.

    2013-01-01

    A spectrum of radiation-induced non-targeted effects has been reported during the last two decades since Nagasawa and Little first described a phenomenon in cultured cells that was later called the “bystander effect”. These non-targeted effects include radiotherapy-related abscopal effects, where changes in organs or tissues occur distant from the irradiated region. The spectrum of non-targeted effects continue to broaden over time and now embrace many types of exogenous and endogenous stressors that induce a systemic genotoxic response including a widely studied tumor microenvironment. Here we discuss processes and factors leading to DNA damage induction in non-targeted cells and tissues and highlight similarities in the regulation of systemic effects caused by different stressors. PMID:24041866

  5. Bystanders, parcelling, and an absence of trust in the grooming interactions of wild male chimpanzees

    PubMed Central

    Kaburu, Stefano S. K.; Newton-Fisher, Nicholas E.

    2016-01-01

    The evolution of cooperation remains a central issue in socio-biology with the fundamental problem of how individuals minimize the risks of being short-changed (‘cheated’) should their behavioural investment in another not be returned. Economic decisions that individuals make during interactions may depend upon the presence of potential partners nearby, which offers co operators a temptation to defect from the current partner. The parcelling model posits that donors subdivide services into parcels to force cooperation, and that this is contingent on opportunities for defection; that is, the presence of bystanders. Here we test this model and the effect of bystander presence using grooming interactions of wild chimpanzees. We found that with more bystanders, initiators gave less grooming at the beginning of the bout and were more likely to abandon a grooming bout, while bouts were less likely to be reciprocated. We also found that the groomer’s initial investment was not higher among frequent groomers or stronger reciprocators, suggesting that contrary to current assumptions, grooming decisions are not based on trust, or bonds, within dyads. Our work highlights the importance of considering immediate social context and the influence of bystanders for understanding the evolution of the behavioural strategies that produce cooperation. PMID:26856371

  6. Peer bystanders to bullying: who wants to play with the victim?

    PubMed

    Howard, Anne M; Landau, Steven; Pryor, John B

    2014-02-01

    Given widespread concern associated with school-based bullying, researchers have looked beyond a dyadic perspective (i.e., bullies and victims only), and now consider the broader social ecology of the peer group. In this research, we examined how the behaviors of peer bystanders influence subsequent reactions to bullies and their victims. Two hundred and six 10- to 15-year-old boys (Mage = 12.46) were invited to play a computer game with three other boys allegedly located at another school. Before the start of the game, participants "met the other players" apparently sitting in a waiting room. These child actors depicted an escalating bullying episode in which the behavior of the bystander was manipulated: aide to the bully, defender of the victim, or passive outsider. Immediately after exposure to the bullying, each participant played a ball toss game (Cyberball) with the three other boys in the video. Individual differences among participants were examined as moderators of the effect of bystander behavior on participants' willingness to include the "victim" in the game. Results indicated that, when exposed to a passive bystander, boys' normative beliefs about aggression, as well as their tendency to morally disengage from observed egregious acts, decreased their willingness to include the victim in the game. PMID:23801432

  7. Participation in High School Sports and Bystander Intentions, Efficacy to Intervene, and Rape Myth Beliefs.

    PubMed

    McMahon, Sarah

    2015-10-01

    Debate exists as to whether male athletes are more prone to commit acts of sexual violence and maintain problematic attitudes about sexual assault. To contribute to the literature on this relationship, this study posed the following research questions: (1) Do those students who participated in high school sports and those who did not differ significantly in their attitudes about sexual violence and willingness to intervene as a bystander? Do these differ among types of rape myths and bystander intervention situations? (2) Within a group of athletes, are there significant differences by gender or type of sport (contact sport vs. non-contact?) To answer these questions, surveys were analyzed with a sample of recent high school graduates the summer before entering college (N = 3,588). Results indicate that there were only minor differences between those students who participated in high school varsity sports and those who did not. Students who participated in sports had greater acceptance of three out of five types of rape myths, and less willingness to intervene with perpetrators after an assault; however, the effect sizes were small. There were no significant differences for bystander efficacy. The interaction between sport and gender was significant, but contact sport was not. The findings suggest that there may be aspects of male athletic participation in sports that needs to be addressed, yet there also exists the potential for engaging athletes as leaders who can act as prosocial bystanders. PMID:25392384

  8. Conditioning of naive CD4(+) T cells for enhanced peripheral Foxp3 induction by nonspecific bystander inflammation.

    PubMed

    Thompson, Lucas J; Lai, Jen-Feng; Valladao, Andrea C; Thelen, Tennille D; Urry, Zoe L; Ziegler, Steven F

    2016-03-01

    Inflammation induced during infection can both promote and suppress immunity. This contradiction suggests that inflammatory cytokines affect the immune system in a context-dependent manner. Here we show that nonspecific bystander inflammation conditions naive CD4(+) T cells for enhanced peripheral Foxp3 induction and reduced effector differentiation. This results in inhibition of immune responses in vivo via a Foxp3-dependent effect on antigen-specific naive CD4(+) T cell precursors. Such conditioning may have evolved to allow immunity to infection while limiting subsequent autoimmunity caused by release of self-antigens in the wake of infection. Furthermore, this phenomenon suggests a mechanistic explanation for the idea that early tuning of the immune system by infection affects the long-term quality of immune regulation. PMID:26752376

  9. Measuring Bystander Attitudes and Behavior to Prevent Sexual Violence

    ERIC Educational Resources Information Center

    McMahon, Sarah; Allen, Christopher T.; Postmus, Judy L.; McMahon, Sheila M.; Peterson, N. Andrew; Lowe Hoffman, Melanie

    2014-01-01

    Objective: The purpose of this study is to further investigate the factor structure and strength of the Bystander Attitude Scale-Revised and Bystander Behavior Scale-Revised (BAS-R and BBS-R). Participants: First-year students (N = 4,054) at a large public university in the Northeast completed a survey in 2010 as part of a larger longitudinal…

  10. Implications for Sexual Assault Prevention: College Students as Prosocial Bystanders

    ERIC Educational Resources Information Center

    Exner, Deinera; Cummings, Nina

    2011-01-01

    Prosocial bystander interventions are promising approaches to sexual assault prevention on college campuses. Objective: To assess bystander attitudes among undergraduate students at a northeastern university. Participants: A convenience sample of 188 students from 4 undergraduate classes was surveyed during regularly scheduled class sessions.…

  11. Rape Myth Beliefs and Bystander Attitudes among Incoming College Students

    ERIC Educational Resources Information Center

    McMahon, Sarah

    2010-01-01

    Objective: The bystander approach to rape prevention is gaining popularity on college campuses, although research is limited. This study explored bystander attitudes and their relationship with rape myths in a sample of college students. Participants: Surveys from 2,338 incoming undergraduate students at a large, northeastern university were…

  12. Identification of Key Proteins in Human Epithelial Cells Responding to Bystander Signals From Irradiated Trout Skin

    PubMed Central

    Smith, Richard; Wang, Jiaxi; Seymour, Colin; Mothersill, Carmel; Howe, Orla

    2015-01-01

    Radiation-induced bystander signaling has been found to occur in live rainbow trout fish (Oncorhynchus mykiss). This article reports identification of key proteomic changes in a bystander reporter cell line (HaCaT) grown in low-dose irradiated tissue-conditioned media (ITCM) from rainbow trout fish. In vitro explant cultures were generated from the skin of fish previously exposed to low doses (0.1 and 0.5 Gy) of X-ray radiation in vivo. The ITCM was harvested from all donor explant cultures and placed on recipient HaCaT cells to observe any change in protein expression caused by the bystander signals. Proteomic methods using 2-dimensional (2D) gel electrophoresis and mass spectroscopy were employed to screen for novel proteins expressed. The proteomic changes measured in HaCaT cells receiving the ITCM revealed that exposure to 0.5 Gy induced an upregulation of annexin A2 and cingulin and a downregulation of Rho-GDI2, F-actin-capping protein subunit beta, microtubule-associated protein RP/EB family member, and 14-3-3 proteins. The 0.1 Gy dose also induced a downregulation of Rho-GDI2, hMMS19, F-actin-capping protein subunit beta, and microtubule-associated protein RP/EB family member proteins. The proteins reported may influence apoptotic signaling, as the results were suggestive of an induction of cell communication, repair mechanisms, and dysregulation of growth signals. PMID:26673684

  13. Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes.

    PubMed

    Cheung, Wing Yee; Fritton, J Christopher; Morgan, Stacy Ann; Seref-Ferlengez, Zeynep; Basta-Pljakic, Jelena; Thi, Mia M; Suadicani, Sylvia O; Spray, David C; Majeska, Robert J; Schaffler, Mitchell B

    2016-04-01

    Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring "bystander" cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin-1 (Panx1) channels to release adenosine diphosphate (ATP) as a "find-me" signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue-loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF-κB ligand (RANKL) expression and osteoclastic bone resorption in wild-type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X7 R in ATP release; thus, we examined P2X7 R-deficient mice and WT mice treated with P2X7 R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find-me signal. P2X7 RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1KO and P2X7 RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X7 R are required for apoptotic osteocytes

  14. Characterization of a novel epigenetic effect of ionizing radiation: the death-inducing effect

    NASA Technical Reports Server (NTRS)

    Nagar, Shruti; Smith, Leslie E.; Morgan, William F.

    2003-01-01

    The detrimental effects associated with exposure to ionizing radiation have long been thought to result from the direct targeting of the nucleus leading to DNA damage; however, the emergence of concepts such as radiation-induced genomic instability and bystander effects have challenged this dogma. After cellular exposure to ionizing radiation, we have isolated a number of clones of Chinese hamster-human hybrid GM10115 cells that demonstrate genomic instability as measured by chromosomal destabilization. These clones show dynamic and persistent generation of chromosomal rearrangements multiple generations after the original insult. We hypothesize that these unstable clones maintain this delayed instability phenotype by secreting factors into the culture medium. To test this hypothesis we transferred filtered medium from unstable cells to unirradiated GM10115 cells. No GM10115 cells were able to survive this medium. This phenomenon by which GM10115 cells die when cultured in medium from chromosomally unstable GM10115 clones is the death-inducing effect. Medium transfer experiments indicate that a factor or factors is/are secreted by unstable cells within 8 h of growth in fresh medium and result in cell killing within 24 h. These factors are stable at ambient temperature but do not survive heating or freezing, and are biologically active when diluted with fresh medium. We present the initial description and characterization of the death-inducing effect. This novel epigenetic effect of radiation has implications for radiation risk assessment and for health risks associated with radiation exposure.

  15. Unique aspects of mda-7/IL-24 antitumor bystander activity: establishing a role for secretion of MDA-7/IL-24 protein by normal cells.

    PubMed

    Su, Zhaozhong; Emdad, Luni; Sauane, Moira; Lebedeva, Irina V; Sarkar, Devanand; Gupta, Pankaj; James, C David; Randolph, Aaron; Valerie, Kirstoffer; Walter, Mark R; Dent, Paul; Fisher, Paul B

    2005-11-17

    Melanoma differentiation associated gene-7 (mda-7) was cloned using subtraction hybridization from terminally differentiated human melanoma cells. Based on structural and functional properties, mda-7 is now recognized as interleukin-24 (IL-24), a new member of the expanding IL-10 gene family. Unique properties of mda-7/IL-24 include its ability to selectively induce growth suppression, apoptosis and radiosensitization in diverse human cancer cells, without causing similar effects in normal cells. The utility of mda-7/IL-24, administered by means of a replication-incompetent adenovirus, as a gene therapy for cancer has recently received validation in patients, highlighting an important phenomenon initially observed in pancreatic tumor cells, namely a 'potent bystander apoptosis-inducing effect' in adjacent tumor cells not initially receiving this gene product. We presently investigated the contribution of mda-7/IL-24 secreted by normal cells in mediating this 'bystander effect', and document that normal cells induced to produce mda-7/IL-24 following infection with recombinant adenoviruses expressing this cytokine secrete mda-7/IL-24, which modifies the anchorage-independent growth, invasiveness, survival and sensitivity to radiation of cancer cells that contain functional IL-20/IL-22 receptors, but not in cancer cells that lack a complete set of receptors. Moreover, the combination of secreted mda-7/IL-24 and radiation engenders a 'bystander antitumor effect' not only in inherently mda-7/IL-24 or radiation-sensitive cancer cells, but also in tumor cells overexpressing the antiapoptotic proteins bcl-2 or bcl-x(L) and displaying resistance to either treatment alone. The present studies provide definitive evidence that secreted mda-7/IL-24 from normal cells can induce direct antitumor and radiation-enhancing effects that are dependent on the presence of canonical receptors for this cytokine on tumor cells. Moreover, we now describe a novel means of enhancing mda-7/IL

  16. Mechanistic and quantitative studies of bystander response in 3D tissues for low-dose radiation risk estimations

    SciTech Connect

    Amundson, Sally A.

    2013-06-12

    We have used the MatTek 3-dimensional human skin model to study the gene expression response of a 3D model to low and high dose low LET radiation, and to study the radiation bystander effect as a function of distance from the site of irradiation with either alpha particles or low LET protons. We have found response pathways that appear to be specific for low dose exposures, that could not have been predicted from high dose studies. We also report the time and distance dependent expression of a large number of genes in bystander tissue. the bystander response in 3D tissues showed many similarities to that described previously in 2D cultured cells, but also showed some differences.

  17. Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis

    PubMed Central

    Shim, Grace; Ricoul, Michelle; Hempel, William M.; Azzam, Edouard I.; Sabatier, Laure

    2014-01-01

    It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked to telomeric proteins and telomere maintenance. Long-term propagation of this radiation-induced chromosomal damage during cell proliferation results in chromosomal instability. Many studies have shown the link between radiation exposure and radiation-induced changes in oxidative stress and DNA damage repair in both targeted and non-targeted cells. However, the effect of these factors on telomeres, long established as guardians of the genome, still remains to be clarified. In this review, we will focus on what is known about how telomeres are affected by exposure to low- and high-LET ionizing radiation and during proliferation, and will discuss how telomeres may be a key player in the process of radiation-induced carcinogenesis. PMID:24486376

  18. Cell Cycle Checkpoint Proteins p21 and Hus1 Regulating Intercellular Signaling Induced By Alpha Particle Irradiation

    NASA Astrophysics Data System (ADS)

    Wu, Lijun; Zhao, Ye; Wang, Jun; Hang, Haiying

    In recent years, the attentions for radiation induced bystander effects (RIBE) have been paid on the intercellular signaling events connecting the irradiated and non-irradiated cells. p21 is a member of the Cip/Kip family and plays essential roles in cell cycle progression arrest after cellular irradiation. DNA damage checkpoint protein Hus1 is a member of the Rad9-Rad1-Hus1 complex and functions as scaffold at the damage sites to facilitate the activation of downstream effectors. Using the medium trasfer method and the cells of MEF, MEF (p21-/-), MEF (p21-/-Hus1-/-) as either medium donor or receptor cells, it was found that with 5cGy alpha particle irradiation, the bystander cells showed a significant induction of -H2AX for normal MEFs (p¡0.05). However, the absence of p21 resulted in deficiency in inducing bystander effects. Further results indicated p21 affected the intercellular DNA damage signaling mainly through disrupting the production or release of the damage signals from irradiated cells. When Hus1 and p21 were both knocked out, an obvious induction of -H2AX recurred in bystander cells and the induction of -H2AX was GJIC (gap junction-mediated intercellular communication) dependent, indicating the interrelationship between p21 and Hus1 regulated the production and relay of DNA damage signals from irradiated cells to non-irradiated bystander cells.

  19. The impact of onlooking and including bystander behaviour on judgments and emotions regarding peer exclusion.

    PubMed

    Malti, Tina; Strohmeier, Dagmar; Killen, Melanie

    2015-09-01

    We investigated judgments and emotions in contexts of social exclusion that varied as a function of bystander behaviour (N = 173, 12- and 16-year-olds). Adolescents responded to film vignettes depicting a target excluded by a group with no bystanders, onlooking bystanders, or bystanders who included the target. Adolescents were asked to judge the behaviour and attribute emotions to the excluding group, the excluded target, and the bystanders. Younger adolescents judged the behaviour of the excluding group as more wrong than older adolescents when there were no bystanders present, indicating that the presence of bystanders was viewed as lessening the negative outcome of exclusion by the younger group. Yet, bystanders play a positive role only when they are includers, not when they are silent observers. This distinction was revealed by the findings that adolescents rated the behaviour of onlooking bystanders as more wrong compared with the behaviour of including bystanders. Moreover, all adolescents justified the inclusive behaviour more frequently with empathy than the onlooking behaviour. Adolescents also anticipated more empathy to including bystanders than to onlooking bystanders, as well as anticipated more guilt to onlooking bystanders than including bystanders. The findings are discussed in light of the role of group norms and group processes regarding bystanders' roles in social exclusion peer encounters. PMID:25953459

  20. Blame Conformity: Innocent Bystanders Can Be Blamed for a Crime as a Result of Misinformation from a Young, but Not Elderly, Adult Co-Witness

    PubMed Central

    Thorley, Craig

    2015-01-01

    This study examined whether or not exposing an eyewitness to a co-witness statement that incorrectly blames an innocent bystander for a crime can increase the likelihood of the eyewitness subsequently blaming the innocent bystander for the crime. It also examined whether or not the perceived age of the co-witness influences this effect. Participant eyewitnesses first watched a video of a crime featuring a perpetrator and an innocent bystander. They then read one of six bogus co-witness statements about the crime. All were presented as having been written by a female co-witness and they differed in terms of her age (young adult or elderly) and who she blamed for the crime (the perpetrator, the innocent bystander, or nobody). One week later the participants were asked who committed the crime. When the young adult co-witness had blamed the innocent bystander just over 40% of participants subsequently did the same. Few participants (less than 8%) in the other conditions subsequently blamed the innocent bystander. The elderly co-witness was also rated as less credible, less competent, and less accurate than the younger co-witness suggesting eyewitnesses were less likely to be influenced by her incorrect statement as they perceived her to be a less reliable source of information. The applied implications of these findings are discussed. PMID:26230523

  1. Blame Conformity: Innocent Bystanders Can Be Blamed for a Crime as a Result of Misinformation from a Young, but Not Elderly, Adult Co-Witness.

    PubMed

    Thorley, Craig

    2015-01-01

    This study examined whether or not exposing an eyewitness to a co-witness statement that incorrectly blames an innocent bystander for a crime can increase the likelihood of the eyewitness subsequently blaming the innocent bystander for the crime. It also examined whether or not the perceived age of the co-witness influences this effect. Participant eyewitnesses first watched a video of a crime featuring a perpetrator and an innocent bystander. They then read one of six bogus co-witness statements about the crime. All were presented as having been written by a female co-witness and they differed in terms of her age (young adult or elderly) and who she blamed for the crime (the perpetrator, the innocent bystander, or nobody). One week later the participants were asked who committed the crime. When the young adult co-witness had blamed the innocent bystander just over 40% of participants subsequently did the same. Few participants (less than 8%) in the other conditions subsequently blamed the innocent bystander. The elderly co-witness was also rated as less credible, less competent, and less accurate than the younger co-witness suggesting eyewitnesses were less likely to be influenced by her incorrect statement as they perceived her to be a less reliable source of information. The applied implications of these findings are discussed. PMID:26230523

  2. Commitment and the responsive bystander: a field evaluation with a less problematic request.

    PubMed

    Guéguen, Nicolas

    2014-10-01

    Prior research on the effect of commitment on bystander intervention has focused on situations involving crime (e.g., robbery). However, the effect of commitment on less problematic situations has never been examined. In this field study, a female confederate asked (commitment condition) or did not ask (no-commitment condition) a customer to keep an eye on her grocery cart on the pretext that she had forgotten something in the store. Several seconds later, a male confederate arrived behind the first confederate's cart and began to move it in order to take her place. It was found that participants (N = 40) intervened to stop the second confederate more frequently in the commitment condition. The results support the assumption that bystander commitment influences behavior even in a non-crime situation. PMID:25153842

  3. Effects of Induced Astigmatism.

    ERIC Educational Resources Information Center

    Schubert, Delwyn G.; Walton, Howard N.

    1968-01-01

    The relationship of astigmatism to reading and the possible detrimental effects it might have on reading were investigated. The greatest incidence of astigmatism was for the with-the-rule type ranging from .50 to 1.00 diopter. This type of astigmatism was induced in 35 seniors from the Los Angeles College of Optometry by placing cylindrical lenses…

  4. Heavy ion microprobes: a unique tool for bystander research and other radiobiological applications

    NASA Astrophysics Data System (ADS)

    Voss, K. O.; Fournier, C.; Taucher-Scholz, G.

    2008-07-01

    The risk assessment for low doses of high linear energy transfer (LET) radiation has been challenged by a growing body of experimental evidence showing that non-irradiated bystander cells can receive signals from irradiated cells to elicit a variety of cellular responses. These may be significant for radiation protection but also for radiation therapy using heavy ions. Charged particle microbeams for radiobiological application provide a unique means to address these issues by allowing the precise irradiation of single cells with a counted numbers of ions. Here, we focus specifically on heavy ion microbeam facilities currently in use for biological purposes, describing their technical features and biological results. Typically, ion species up to argon are used for targeted biological irradiation at the vertically collimated microbeam at JAEA (Takasaki, Japan). At the SNAKE microprobe in Munich, mostly oxygen ions have been used in a horizontal focused beam line for cell targeting. At GSI (Darmstadt), a horizontal microprobe with a focused beam for defined targeting using ion species up to uranium is operational. The visualization of DNA damage response proteins relocalizing to defined sites of ion traversal has been accomplished at the three heavy ion microbeam facilities described above and is used to study mechanistic aspects of heavy ion effects. However, bystander studies have constituted the main focus of biological applications. While for cell inactivation and effects on cell cycle progression a response of non-targeted cells has been described at JAEA and GSI, respectively, in part controversial results have been obtained for the induction of DNA damage measured by double-strand formation or at the cytogenetic level. The results emphasize the influence of the cellular environment, and standardization of experimental conditions for cellular studies at different facilities as well as the investigation of bystander effects in tissue will be the aims of future

  5. Immune checkpoint blockade in cancer treatment: a double-edged sword cross-targeting the host as an "innocent bystander".

    PubMed

    Gelao, Lucia; Criscitiello, Carmen; Esposito, Angela; Goldhirsch, Aron; Curigliano, Giuseppe

    2014-03-01

    Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific "immune-related adverse events" (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique "innocent bystander" effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. What do we need going forward to limit immune checkpoint blockade-induced toxicity? Most importantly, we need a better understanding of the roles played by these agents in normal tissues, so that we can begin to predict potentially problematic side effects on the basis of their selectivity profile. Second, we need to focus on the predictive factors of the response and toxicity of the host rather than serially focusing on individual agents. Third, rigorous biomarker-driven clinical trials are needed to further elucidate the mechanisms of both the benefit and toxicity. We will summarize the double-edged sword effect of immunotherapeutics in cancer treatment. PMID:24594636

  6. Standing Up for the Victim, Siding with the Bully or Standing By? Bystander Responses in Bullying Situations

    ERIC Educational Resources Information Center

    Poyhonen, Virpi; Juvonen, Jaana; Salmivalli, Christina

    2012-01-01

    In this study we examined children's self-efficacy, outcome expectations, and outcome values in relation to bystander responses in bullying situations. We proposed that beyond the effect of self-efficacy, the decision to defend the victim of bullying vs. remain passive vs. reinforce the bully depends on outcomes children expect from defending, and…

  7. Gender differences in attitudes and beliefs associated with bystander behavior and sexual assault.

    PubMed

    Amar, Angela F; Sutherland, Melissa; Laughon, Kathryn

    2014-01-01

    Sexual violence is a significant problem on many college campuses. Bystander education programs have been found to train individuals to act to prevent sexual and partner violence and improve the responses of peers to survivors. Limited evidence suggests that gender differences exist between males and females regarding both attitudes toward, and use of, bystander behavior, with females reporting more supportive attitudes and greater use of bystander behavior. The purpose of this study is to compare male and female college students on attitudes toward date rape, bystander efficacy, intention to act as a bystander, and actual use of bystander behaviors. A secondary aim explored gender differences in theoretically driven bystander behaviors and barriers to acting as a bystander. A convenience sample of 157 full-time undergraduate students aged 18-24 years completed survey measures of attitudes related to sexual and partner violence and willingness to help. Analysis of variance and chi-square were used to compare gender differences in scores. Significant gender differences were found for date rape attitudes, efficacy, and intention to act as a positive bystander. Men reported more rape-supportive attitudes and greater intention to act as a bystander than women, whereas women reported greater levels of bystander efficacy than men. The findings can be used in tailoring gender-specific components of bystander education programs for sexual assault prevention and intervention. PMID:24762431

  8. A Randomized Controlled Trial of a Multi-Dose Bystander Intervention Program Using Peer Education Theater

    ERIC Educational Resources Information Center

    McMahon, Sarah; Winter, Samantha C.; Palmer, Jane E.; Postmus, Judy L.; Peterson, N. Andrew; Zucker, Sharon; Koenick, RuthAnne

    2015-01-01

    This article reports findings from a longitudinal, experimental evaluation of a peer education theater program, Students Challenging Realities and Educating Against Myths (SCREAM) Theater. This study examines the impact of SCREAM Theater on a range of bystander-related outcomes (i.e. bystander intentions, bystander efficacy, perception of friend…

  9. [Potential laser hazards to bystanders during photocoagulation].

    PubMed

    Okamoto, N; Harino, S; Saito, Y; Ogawa, K

    1993-02-01

    The authors measured reflected laser beams delivered by slit-lamp photocoagulator and binocular indirect ophthalmoscope laser delivery systems, to evaluate potential hazards to the eyes of bystanders. 514 nm laser beams were used; reflected laser beams were measured by a light power meter (Advantest: TQ8210). Reflected lasers were found to be hazardous at 1 meter from whitish tile when a 0.75 Watt laser beam was delivered by the binocular ophthalmoscope laser system, as in an operating room. At 1 meter from a wall in a photo-coagulating room for out-patients, the reflected laser beam was found to be well below hazardous levels. Reflections at 40 cm from a non-laser-coated Goldmann 3-mirror contact lens were 2.66 mW/cm2, which exceeds the exposure limits, when 0.3 W laser was delivered by the slit-lamp photocoagulator. This decreased 85-90% when the laser was reflected from a laser-coated lens. From the point of view of safety, it is recommended that laser surgeons replace non-laser-coated lenses with laser-coated ones. PMID:8475831

  10. Radioimmunotherapy of Cryptococcus neoformans spares bystander mammalian cells

    PubMed Central

    Bryan, Ruth A; Jiang, Zewei; Morgenstern, Alfred; Bruchertseifer, Frank; Casadevall, Arturo; Dadachova, Ekaterina

    2013-01-01

    Aim Previously, we showed that radioimmunotherapy (RIT) for cryptococcal infections using radioactively labeled antibodies recognizing the cryptococcal capsule reduced fungal burden and prolonged survival of mice infected with Cryptococcus neoformans. Here, we investigate the effects of RIT on bystander mammalian cells. Materials & methods Heat-killed C. neoformans bound to anticapsular antibodies, unlabeled or labeled with the β-emitter rhenium-188 (16.9-h half-life) or the α-emitter bismuth-213 (46-min half-life), was incubated with macrophage-like J774.16 cells or epithelial-like Chinese hamster ovary cells. Lactate dehydrogenase activity, crystal violet uptake, reduction of tetrazolium dye (2,3)-bis-(2-methoxy-4-nitro-5-sulfenyl)-(2H)-terazolium-5-carboxanilide and nitric oxide production were measured. Results The J774.16 and Chinese hamster ovary cells maintained membrane integrity, viability and metabolic activity following exposure to radiolabeled C. neoformans. Conclusion RIT of C. neoformans is a selective therapy with minimal effects on host cells and these results are consistent with observations that RIT-treated mice with cryptococcal infection lacked RIT-related pathological changes in lungs and brain tissues. PMID:24020737

  11. Time-series clustering of gene expression in irradiated and bystander fibroblasts: an application of FBPA clustering

    PubMed Central

    2011-01-01

    Background The radiation bystander effect is an important component of the overall biological response of tissues and organisms to ionizing radiation, but the signaling mechanisms between irradiated and non-irradiated bystander cells are not fully understood. In this study, we measured a time-series of gene expression after α-particle irradiation and applied the Feature Based Partitioning around medoids Algorithm (FBPA), a new clustering method suitable for sparse time series, to identify signaling modules that act in concert in the response to direct irradiation and bystander signaling. We compared our results with those of an alternate clustering method, Short Time series Expression Miner (STEM). Results While computational evaluations of both clustering results were similar, FBPA provided more biological insight. After irradiation, gene clusters were enriched for signal transduction, cell cycle/cell death and inflammation/immunity processes; but only FBPA separated clusters by function. In bystanders, gene clusters were enriched for cell communication/motility, signal transduction and inflammation processes; but biological functions did not separate as clearly with either clustering method as they did in irradiated samples. Network analysis confirmed p53 and NF-κB transcription factor-regulated gene clusters in irradiated and bystander cells and suggested novel regulators, such as KDM5B/JARID1B (lysine (K)-specific demethylase 5B) and HDACs (histone deacetylases), which could epigenetically coordinate gene expression after irradiation. Conclusions In this study, we have shown that a new time series clustering method, FBPA, can provide new leads to the mechanisms regulating the dynamic cellular response to radiation. The findings implicate epigenetic control of gene expression in addition to transcription factor networks. PMID:21205307

  12. Who intervenes against homophobic behavior? Attributes that distinguish active bystanders.

    PubMed

    Poteat, V Paul; Vecho, Olivier

    2016-02-01

    Research on homophobic behavior has focused on students engaging in this behavior or students toward whom this behavior is directed. There has been little attention to the large segment of students who observe this behavior, including active bystanders who defend or support students when homophobic behavior occurs. Among 722 high school students (55% female, 87% white, 86% heterosexual), 66.8% had observed at least one instance of homophobic behavior in the past 30 days. Gender (in this case, girls more so than boys), leadership, courage, altruism, justice sensitivity, and number of LGBT friends were associated with engagement in more active bystander behavior in response to observing homophobic behavior. Further, gender, courage, altruism, and number of LGBT friends each made unique contributions in accounting for variability in students' defending behavior in a comprehensive regression model. Findings highlight qualities that interventionists should cultivate in students that could lead to more active bystander engagement against homophobic behavior. PMID:26790700

  13. Why are bystanders friendly to recipients of aggression?

    PubMed Central

    Koski, Sonja E; Wittig, Roman M; Aureli, Filippo

    2009-01-01

    The escalation of conflicts of interest into aggressive conflict can be costly in terms of increased post-conflict stress and damage to the opponents' relationship. Some costs may be mitigated through post-conflict interactions. One such type of interaction is affiliative contact from a bystander to the recipient of aggression. This type of interaction has been suggested to have a number of functions, including stress reduction and opponent relationship repair. It may also protect bystanders from redirected aggression from the original recipient of aggression. Here we review the evidence for such functions and propose a framework within which the function and occurrence of post-conflict affiliation directed from a bystander to the recipient of aggression is related to the quality of the relationships between the individuals involved and the patterns of behavior expressed. PMID:19641753

  14. Why are bystanders friendly to recipients of aggression?

    PubMed

    Fraser, Orlaith N; Koski, Sonja E; Wittig, Roman M; Aureli, Filippo

    2009-05-01

    The escalation of conflicts of interest into aggressive conflict can be costly in terms of increased post-conflict stress and damage to the opponents' relationship. Some costs may be mitigated through post-conflict interactions. One such type of interaction is affiliative contact from a bystander to the recipient of aggression. This type of interaction has been suggested to have a number of functions, including stress reduction and opponent relationship repair. It may also protect bystanders from redirected aggression from the original recipient of aggression. Here we review the evidence for such functions and propose a framework within which the function and occurrence of post-conflict affiliation directed from a bystander to the recipient of aggression is related to the quality of the relationships between the individuals involved and the patterns of behavior expressed. PMID:19641753

  15. The Engineered Thymidylate Kinase (TMPK)/AZT Enzyme-Prodrug Axis Offers Efficient Bystander Cell Killing for Suicide Gene Therapy of Cancer

    PubMed Central

    Lavie, Arnon; Yanagisawa, Teruyuki; Medin, Jeffrey A.

    2013-01-01

    We previously described a novel suicide (or ‘cell fate control’) gene therapy enzyme/prodrug system based on an engineered variant of human thymidylate kinase (TMPK) that potentiates azidothymidine (AZT) activation. Delivery of a suicide gene sequence into tumors by lentiviral transduction embodies a cancer gene therapy that could employ bystander cell killing as a mechanism driving significant tumor regression in vivo. Here we present evidence of a significant bystander cell killing in vitro and in vivo mediated by the TMPK/AZT suicide gene axis that is reliant on the formation of functional gap-junctional intercellular communications (GJICs). Potentiation of AZT activation by the engineered TMPK expressed in the human prostate cancer cell line, PC-3, resulted in effective bystander killing of PC-3 cells lacking TMPK expression – an effect that could be blocked by the GJIC inhibitor, carbenoxolone. Although GJICs are mainly formed by connexins, a new family of GJIC molecules designated pannexins has been recently identified. PC-3 cells expressed both connexin43 (Cx43) and Pannexin1 (Panx1), but Panx1 expression predominated at the plasma membrane, whereas Cx43 expression was primarily localized to the cytosol. The contribution of bystander effects to the reduction of solid tumor xenografts established by the PC-3 cell line was evaluated in an animal model. We demonstrate the contribution of bystander cell killing to tumor regression in a xenograft model relying on the delivery of expression of the TMPK suicide gene into tumors via direct intratumoral injection of recombinant therapeutic lentivirus. Taken together, our data underscore that the TMPK/AZT enzyme-prodrug axis can be effectively utilized in suicide gene therapy of solid tumors, wherein significant tumor regression can be achieved via bystander effects mediated by GJICs. PMID:24194950

  16. The engineered thymidylate kinase (TMPK)/AZT enzyme-prodrug axis offers efficient bystander cell killing for suicide gene therapy of cancer.

    PubMed

    Sato, Takeya; Neschadim, Anton; Lavie, Arnon; Yanagisawa, Teruyuki; Medin, Jeffrey A

    2013-01-01

    We previously described a novel suicide (or 'cell fate control') gene therapy enzyme/prodrug system based on an engineered variant of human thymidylate kinase (TMPK) that potentiates azidothymidine (AZT) activation. Delivery of a suicide gene sequence into tumors by lentiviral transduction embodies a cancer gene therapy that could employ bystander cell killing as a mechanism driving significant tumor regression in vivo. Here we present evidence of a significant bystander cell killing in vitro and in vivo mediated by the TMPK/AZT suicide gene axis that is reliant on the formation of functional gap-junctional intercellular communications (GJICs). Potentiation of AZT activation by the engineered TMPK expressed in the human prostate cancer cell line, PC-3, resulted in effective bystander killing of PC-3 cells lacking TMPK expression--an effect that could be blocked by the GJIC inhibitor, carbenoxolone. Although GJICs are mainly formed by connexins, a new family of GJIC molecules designated pannexins has been recently identified. PC-3 cells expressed both connexin43 (Cx43) and Pannexin1 (Panx1), but Panx1 expression predominated at the plasma membrane, whereas Cx43 expression was primarily localized to the cytosol. The contribution of bystander effects to the reduction of solid tumor xenografts established by the PC-3 cell line was evaluated in an animal model. We demonstrate the contribution of bystander cell killing to tumor regression in a xenograft model relying on the delivery of expression of the TMPK suicide gene into tumors via direct intratumoral injection of recombinant therapeutic lentivirus. Taken together, our data underscore that the TMPK/AZT enzyme-prodrug axis can be effectively utilized in suicide gene therapy of solid tumors, wherein significant tumor regression can be achieved via bystander effects mediated by GJICs. PMID:24194950

  17. Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects

    SciTech Connect

    Chen, Xian

    2013-10-23

    The goal of our project is to apply our unique systems investigation strategy to reveal the molecular mechanisms underlying the radiation induction and transmission of oxidative damage, adaptive response, and bystander effect at low-doses. Beginning with simple in vitro systems such as fibroblast or epithelial pure culture, our amino acid-coded mass tagging (AACT) comparative proteomic platform will be used to measure quantitatively proteomic changes at high- or low-dose level with respect to their endogenous damage levels respectively, in which a broad range of unique regulated proteins sensitive to low-dose IR will be distinguished. To zoom in how these regulated proteins interact with other in the form of networks in induction/transmission pathways, these regulated proteins will be selected as baits for making a series of fibroblast cell lines that stably express each of them. Using our newly developed method of ?dual-tagging? quantitative proteomics that integrate the capabilities of natural complex expression/formation, simple epitope affinity isolation (not through tandem affinity purification or TAP), and ?in-spectra? AACT quantitative measurements using mass spectrometry (MS), we will be able to distinguish systematically interacting proteins with each bait in real time. Further, in addition to both proteome-wide (global differentially expressed proteins) and pathway-scale (bait-specific) profiling information, we will perform a computational network analysis to elucidate a global pathway/mechanisms underlying cellular responses to real-time low-dose IR. Similarly, we will extend our scheme to investigate systematically those induction/transmission pathways occurring in a fibroblast-epithelial interacting model in which the bystander cell (fibroblast) monitor the IR damage to the target cell (epithelial cell). The results will provide the proteome base (molecular mechanisms/pathways for signaling) for the low dose radiation-induced essential tissue

  18. Mechanism of bystander-blaming: defensive attribution, counterfactual thinking, and gender.

    PubMed

    Levy, Inna; Ben-David, Sarah

    2015-01-01

    Contemporary victimology recognizes that an understanding of the mechanism of blaming requires a comprehensive approach that includes the victim, the offender, and the bystander. However, most of the existing research on blaming focuses on the victim and the offender, ignoring the issue of bystander-blaming. This study highlights the bystander and investigates bystander-blaming by exploring some theoretical explanations, including counterfactual thinking, defensive attribution, and gender differences. The study included 363 young male and female participants, who read vignettes describing the behavior of the victim and the bystander in a rape scenario and answered questions regarding bystander-blaming. The results show that both counterfactual thinking and defensive attribution play a role in bystander-blaming. This article addresses the theoretical and practical implications of these findings. PMID:24052599

  19. Bullying victimization and the social and emotional maladjustment of bystanders: A propensity score analysis.

    PubMed

    Werth, Jilynn M; Nickerson, Amanda B; Aloe, Ariel M; Swearer, Susan M

    2015-08-01

    This study investigated how bystanders, who have and have not been bullied, perceive their social and emotional maladjustment depending on the form of bullying (physical or verbal) they witness. Using propensity score matching, equivalent groups of 270 victimized and 270 non-victimized bystander groups were created based on middle school students' responses on the Bully Survey-Student Version (BYS-S; Swearer, 2001). Victimized bystanders experienced higher social maladjustment than non-victimized bystanders. Path analysis results suggest that social and emotional maladjustment as a bystander is related not only to social-emotional maladjustment as victim, but to gender and the form of bullying witnessed. The way in which bystanders are influenced by their personal victimization may be a critical factor in predicting, understanding, and increasing active bystander intervention. PMID:26270274

  20. Changing attitudes about being a bystander to violence: translating an in-person sexual violence prevention program to a new campus.

    PubMed

    Cares, Alison C; Banyard, Victoria L; Moynihan, Mary M; Williams, Linda M; Potter, Sharyn J; Stapleton, Jane G

    2015-02-01

    Bystander approaches to reducing sexual violence train community members in prosocial roles to interrupt situations with risk of sexual violence and be supportive community allies after an assault. This study employs a true experimental design to evaluate the effectiveness of Bringing in the Bystander™ through 1-year post-implementation with first-year students from two universities (one rural, primarily residential; one urban, heavily commuter). We found significant change in bystander attitudes for male and female student program participants compared with the control group on both campuses, although the pattern of change depended on the combination of gender and campus. PMID:25540255

  1. Rehearsing for real life: the impact of the InterACT Sexual Assault Prevention Program on self-reported likelihood of engaging in bystander interventions.

    PubMed

    Ahrens, Courtney E; Rich, Marc D; Ullman, Jodie B

    2011-06-01

    The interACT Sexual Assault Prevention Program is an interactive, skill-building performance based on the pedagogy of Augusto Boal's Theatre of the Oppressed. A longitudinal evaluation of this program compared pretest, posttest, and 3-month follow-up data from 509 university student participants. Results suggested that the interACT performance was successful in increasing participants' beliefs about the effectiveness of bystander interventions and the self-rated likelihood that participants would engage in bystander interventions in the future. Differences in both overall ratings and rates of change were noted. Implications of these results for research and practice are discussed. PMID:21628338

  2. Preventing sexual aggression among college men: an evaluation of a social norms and bystander intervention program.

    PubMed

    Gidycz, Christine A; Orchowski, Lindsay M; Berkowitz, Alan D

    2011-06-01

    Men and women living in randomly selected 1st-year dormitories participated in tailored single-sex sexual assault prevention or risk-reduction programs, respectively. An evaluation of the men's project is presented (N = 635). The program incorporated social norms and bystander intervention education and had an impact on self-reported sexual aggression and an effect on men's perceptions that their peers would intervene when they encountered inappropriate behavior in others. Relative to the control group, participants also reported less reinforcement for engaging in sexually aggressive behavior, reported fewer associations with sexually aggressive peers, and indicated less exposure to sexually explicit media. PMID:21571742

  3. A Qualitative Exploration of Cyber-Bystanders and Moral Engagement

    ERIC Educational Resources Information Center

    Price, Deborah; Green, Deborah; Spears, Barbara; Scrimgeour, Margaret; Barnes, Alan; Geer, Ruth; Johnson, Bruce

    2014-01-01

    Studies have found that moral disengagement plays a significant role in the continuation of bullying situations (Bonanno, 2005); however, the moral stance of cyber-bystanders--those who witness online bullying--is not yet clear. While research into traditional face-to-face bullying reported that peers would probably or certainly intervene to…

  4. Incoming College Students' Bystander Behaviors to Prevent Sexual Violence

    ERIC Educational Resources Information Center

    McMahon, Sarah; Banyard, Victoria L.; McMahon, Sheila M.

    2015-01-01

    Evaluations of bystander intervention education programs demonstrate that this approach results in students' increased willingness to intervene in prosocial ways to prevent sexual violence (e.g., Moynihan, Banyard, Arnold, Eckstein, & Stapleton, 2010). These programs often focus on first-year college students, though theories and research on…

  5. Bystander Reaction to Women Fighting: Developing a Theory of Intervention

    ERIC Educational Resources Information Center

    Lowe, Robert D.; Levine, Mark; Best, Rachel M.; Heim, Derek

    2012-01-01

    This article explores accounts of bystanders to female-on-female public violence. Group interviews with participants in the night-time economy are carried out. Whereas men tend to respond to the discussion topic of female-on-female violence with laughter, this laughter reveals ambivalence and discomfort as much as amusement. Men seem to negotiate…

  6. AutoTutor Passes the Bystander Turing Test.

    ERIC Educational Resources Information Center

    Person, Natalie; Erkel, Mary; Graesser, Arthur C.

    In this study, the Bystander Turing Test (BTT) paradigm is used to determine whether participants rate particular dialog moves in tutoring transcripts to be generated by a computer tutor, AutoTutor, or by a skilled human tutor. Currently, AutoTutor initiates a conversation with the learner by posing a question or presenting a problem for the…

  7. Complement-mediated 'bystander' damage initiates host NLRP3 inflammasome activation.

    PubMed

    Suresh, Rahul; Chandrasekaran, Prabha; Sutterwala, Fayyaz S; Mosser, David M

    2016-05-01

    Complement activation has long been associated with inflammation, primarily due to the elaboration of the complement anaphylotoxins C5a and C3a. In this work, we demonstrate that the phagocytosis of complement-opsonized particles promotes host inflammatory responses by a new mechanism that depends on the terminal complement components (C5b-C9). We demonstrate that during the phagocytosis of complement-opsonized particles, the membrane attack complex (MAC) of complement can be transferred from the activating particle to the macrophage plasma membrane by a 'bystander' mechanism. This MAC-mediated bystander damage initiates NLRP3 inflammasome activation, resulting in caspase-1 activation and IL-1β and IL-18 secretion. Inflammasome activation is not induced when macrophages phagocytize unopsonized particles or particles opsonized with serum deficient in one of the terminal complement components. The secretion of IL-1β and IL-18 by macrophages depends on NLRP3, ASC (also known as PYCARD) and caspase-1, as macrophages deficient in any one of these components fail to secrete these cytokines following phagocytosis. The phagocytosis of complement-opsonized particles increases leukocyte recruitment and promotes T helper 17 cell (TH17) biasing. These findings reveal a new mechanism by which complement promotes inflammation and regulates innate and adaptive immunity. PMID:27006116

  8. Evaluation of Green Dot: an active bystander intervention to reduce sexual violence on college campuses.

    PubMed

    Coker, Ann L; Cook-Craig, Patricia G; Williams, Corrine M; Fisher, Bonnie S; Clear, Emily R; Garcia, Lisandra S; Hegge, Lea M

    2011-06-01

    Using a cross-sectional survey of a random sample of 7,945 college undergraduates, we report on the association between having received Green Dot active bystander behavior training and the frequency of actual and observed self-reported active bystander behaviors as well as violence acceptance norms. Of 2,504 students aged 18 to 26 who completed the survey, 46% had heard a Green Dot speech on campus, and 14% had received active bystander training during the past 2 years. Trained students had significantly lower rape myth acceptance scores than did students with no training. Trained students also reported engaging in significantly more bystander behaviors and observing more self-reported active bystander behaviors when compared with nontrained students. When comparing self-reported active bystander behavior scores of students trained with students hearing a Green Dot speech alone, the training was associated with significantly higher active bystander behavior scores. Those receiving bystander training appeared to report more active bystander behaviors than those simply hearing a Green Dot speech, and both intervention groups reported more observed and active bystander behaviors than nonexposed students. PMID:21642269

  9. Workplace mobbing and bystanders' helping behaviour towards victims: the role of gender, perceived responsibility and anticipated stigma by association.

    PubMed

    Mulder, Roelie; Pouwelse, Mieneke; Lodewijkx, Hein; Bolman, Catherine

    2014-08-01

    We examined victims' perceived responsibility and bystanders' anticipated risk of being victimized themselves when others associate them with the victim (stigma by association, SBA) as possible antecedents of bystanders' helping behaviour towards a victim of workplace mobbing, and explored the effects of gender. Guided by the attribution model of social conduct (Weiner, 2006), a 2 × 2 vignette experiment was conducted. Participants were Dutch regional government employees (N = 161). Path analyses generally supported the hypotheses, but showed different results for women and men. In the strong (Vs. weak) responsibility condition, women reported less sympathy and more anger and men only more anger, which resulted in lower helping intention. Additionally, for men the results showed an unexpected direct positive effect of responsibility on helping intention. Furthermore, in the strong SBA condition, women and men reported more fear and men, unexpectedly, more anger. Consequently, helping intention decreased. The findings on gender are discussed in the context of social role theory, gender and emotion. Our findings suggest that to prevent and tackle mobbing, organizations and professionals should be aware of the attributional and emotional processes and gender differences in bystanders' helping behaviour. PMID:24990642

  10. Self-Protective Function of Post-Conflict Bystander Affiliation in Mandrills

    PubMed Central

    Schino, Gabriele; Marini, Claudia

    2012-01-01

    Background Affiliative interactions exchanged between victims of aggression and individuals not involved in the original aggression (bystanders) have been observed in various species. Three hypothetical functions have been proposed for these interactions: consolation, self-protection and substitute reconciliation, but data to test them are scanty. Methodology/Principal Findings We conducted post-conflict and matched control observations on a captive group of mandrills (Mandrillus sphinx). We found that victims often redirected aggression to bystanders, that they received most affiliation from those bystanders that were frequently the target of redirection, and that bystander affiliation reduced the likelihood of redirection. Bystander affiliation did not reduce the victim's distress (as measured by its scratching rates) and was not received primarily from kin/friends. Finally, bystander affiliation did not reduce the likelihood of renewed aggression from the original aggressor. Conclusions/Significance These results provide support for the self-protection hypothesis but not for the consolation and substitute reconciliation hypotheses. PMID:22715420

  11. Electronic cigarettes and indoor air quality: a simple approach to modeling potential bystander exposures to nicotine.

    PubMed

    Colard, Stéphane; O'Connell, Grant; Verron, Thomas; Cahours, Xavier; Pritchard, John D

    2015-01-01

    There has been rapid growth in the use of electronic cigarettes ("vaping") in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably accurately based on empirical emissions data and using some basic assumptions. Here, we present a simplified model, based on physical principles, which considers aerosol propagation, dilution and extraction to determine the potential contribution of a single puff from an e-cigarette to indoor air. From this, it was then possible to simulate the cumulative effect of vaping over time. The model was applied to a virtual, but plausible, scenario considering an e-cigarette user and a non-user working in the same office space. The model was also used to reproduce published experimental studies and showed good agreement with the published values of indoor air nicotine concentration. With some additional refinements, such an approach may be a cost-effective and rapid way of assessing the potential exposure of bystanders to exhaled e-cigarette aerosol constituents. PMID:25547398

  12. Electronic Cigarettes and Indoor Air Quality: A Simple Approach to Modeling Potential Bystander Exposures to Nicotine

    PubMed Central

    Colard, Stéphane; O’Connell, Grant; Verron, Thomas; Cahours, Xavier; Pritchard, John D.

    2014-01-01

    There has been rapid growth in the use of electronic cigarettes (“vaping”) in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably accurately based on empirical emissions data and using some basic assumptions. Here, we present a simplified model, based on physical principles, which considers aerosol propagation, dilution and extraction to determine the potential contribution of a single puff from an e-cigarette to indoor air. From this, it was then possible to simulate the cumulative effect of vaping over time. The model was applied to a virtual, but plausible, scenario considering an e-cigarette user and a non-user working in the same office space. The model was also used to reproduce published experimental studies and showed good agreement with the published values of indoor air nicotine concentration. With some additional refinements, such an approach may be a cost-effective and rapid way of assessing the potential exposure of bystanders to exhaled e-cigarette aerosol constituents. PMID:25547398

  13. Increased Frequency of Spontaneous Neoplastic Transformation in Progeny of Bystander Cells from Cultures Exposed to Densely Ionizing Radiation

    PubMed Central

    Buonanno, Manuela; de Toledo, Sonia M.; Azzam, Edouard I.

    2011-01-01

    An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs), modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons. PMID:21738697

  14. Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation.

    PubMed

    Buonanno, Manuela; de Toledo, Sonia M; Azzam, Edouard I

    2011-01-01

    An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs), modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons. PMID:21738697

  15. Low Dose Studies with Focused X-Rays in cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    SciTech Connect

    Kathy Held; Kevin Prise; Barry Michael; Melvyn Folkard

    2002-12-14

    the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in low-dose radiation risk. This project therefore also examines how cells are damaged by treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and therefore it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  16. Low Dose Studies with Focused X-rays in Cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    SciTech Connect

    Barry D. Michael; Kathryn Held; Kevin Prise

    2002-12-19

    of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and there it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  17. Conceptualizing the Engaging Bystander Approach to Sexual Violence Prevention on College Campuses

    ERIC Educational Resources Information Center

    McMahon, Sarah; Postmus, Judy L.; Koenick, Ruth Anne

    2011-01-01

    Bystander intervention offers promise as a sexual violence prevention tool for student affairs administrators on college campuses, but the conceptualization and definition of the approach is in its infancy and needs further development. In an effort to emphasize the potential role of bystanders in the primary prevention of sexual violence, we put…

  18. Why Do Bystanders of Bullying Help or Not? A Multidimensional Model

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Gini, Gianluca

    2013-01-01

    The authors employed Latane and Darley's model about bystanders' behavior to explain children's active defending and passive bystanding behavior in school bullying. The three central steps of the model were operationalized by measuring provictim attitudes, personal responsibility for intervention, and coping strategies. Moreover,…

  19. Contributions of Personal and Situational Factors to Bystanders' Reactions to School Bullying

    ERIC Educational Resources Information Center

    Oh, Insoo; Hazler, Richard J.

    2009-01-01

    The intent of this study was to explore bystanders' personal and situational variables predicting their behavioural reactions to school bullying by investigating a sample of 298 college students who had witnessed bullying during middle or high school. Results indicated that the bystander personal variables, gender and past experience as a bully or…

  20. Roles of Fatalism and Parental Support in the Relationship between Bullying Victimization and Bystander Behaviors

    ERIC Educational Resources Information Center

    Li, Yiqiong; Chen, Peter Y.; Chen, Fu-Li; Wu, Wen-Chi

    2015-01-01

    This article examines how past bullied victims engage two types of bystander behaviors (defender and outsider) when they witness bullying situations.We also investigate if fatalism mediates the relationship between past victimization and two bystander behaviors. Finally, we test if parental support moderates the relationship between fatalism and…

  1. Individual Motivations and Characteristics Associated with Bystander Intervention during Bullying Episodes among Children and Youth

    ERIC Educational Resources Information Center

    Cappadocia, M. Catherine; Pepler, Debra; Cummings, Joanne G.; Craig, Wendy

    2012-01-01

    The aim of the current study was to explore bystander experiences during bullying episodes among children and youth attending a residential summer camp by investigating rates of witnessing and intervention, as well as individual motivations and characteristics associated with bystander intervention. The majority of children had witnessed bullying…

  2. What Would You Do? Strategies for Bystander Intervention to Prevent Sexual Violence by College Students

    ERIC Educational Resources Information Center

    McMahon, Sarah; Hoffman, Melanie Lowe; McMahon, Sheila M.; Zucker, Sharon; Koenick, Ruth Anne

    2013-01-01

    Bystander education is an increasingly utilized strategy for addressing sexual assault prevention and intervention on U.S. college campuses. Given the paramount importance of peers among college students, what types of pro-social bystander interventions do students themselves deem feasible in the campus context? Drawing on self-reports from…

  3. On Standby? A Comparison of Online and Offline Witnesses to Bullying and Their Bystander Behaviour

    ERIC Educational Resources Information Center

    Quirk, Roslynn; Campbell, Marilyn

    2015-01-01

    Given their ubiquitous presence as witnesses to school-yard bullying, the role of the "bystander" has been studied extensively. The prevalence and behaviour of bystanders to "cyberbullying," however, is less understood. In an anonymous, school-based questionnaire, 716 secondary school students from South-East Queensland…

  4. Adolescent bystanders' perspectives of aggression in the online versus school environments.

    PubMed

    Patterson, Lisa J; Allan, Alfred; Cross, Donna

    2016-06-01

    Researchers' understanding of bystanders' perspectives in the cyber-environment fails to take young people's perceptions into account and remains imperfect. Interventions encouraging adolescents to help targets of cyber-aggression are therefore typically based upon traditional school-based aggression research. Twenty-four in-depth interviews with Australian 13-16 year-olds revealed two themes that reflect how young bystanders perceive differences between aggression online and at school. The physical presence theme suggests that young bystanders struggle to determine online intentions in the absence of body language, leading to hesitancy in reactions and furthermore make it easier for them to ignore online transgressions and avoid becoming involved. The authority theme indicates young bystanders perceive that, compared to the school environment, the online environment lacks clearly established rules, authority figures and formal reporting mechanisms. These differences indicate that unique strategies should be developed to encourage young bystanders to intervene in cyber-aggression situations. PMID:27007497

  5. Measurement of the bystander intervention model for bullying and sexual harassment.

    PubMed

    Nickerson, Amanda B; Aloe, Ariel M; Livingston, Jennifer A; Feeley, Thomas Hugh

    2014-06-01

    Although peer bystanders can exacerbate or prevent bullying and sexual harassment, research has been hindered by the absence of a validated assessment tool to measure the process and sequential steps of the bystander intervention model. A measure was developed based on the five steps of Latané and Darley's (1970) bystander intervention model applied to bullying and sexual harassment. Confirmatory factor analysis with a sample of 562 secondary school students confirmed the five-factor structure of the measure. Structural equation modeling revealed that all the steps were influenced by the previous step in the model, as the theory proposed. In addition, the bystander intervention measure was positively correlated with empathy, attitudes toward bullying and sexual harassment, and awareness of bullying and sexual harassment facts. This measure can be used for future research and to inform intervention efforts related to the process of bystander intervention for bullying and sexual harassment. PMID:24793386

  6. Action of methotrexate and tofacitinib on directly stimulated and bystander-activated lymphocytes.

    PubMed

    Piscianz, Elisa; Candilera, Vanessa; Valencic, Erica; Loganes, Claudia; Paron, Greta; De Iudicibus, Sara; Decorti, Giuliana; Tommasini, Alberto

    2016-07-01

    Chronic inflammation associated with autoimmune activation is characteristic of rheumatic diseases from childhood to adulthood. In recent decades, significant improvements in the treatment of these types of disease have been achieved using disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and, more recently, using biologic inhibitors. The recent introduction of kinase inhibitors (for example, tofacitinib; Tofa) further increases the available ARDs. However, there are patients that do not respond to any treatment strategies, for whom combination therapies are proposed. The data regarding the combined action of different drugs is lacking and the knowledge of the mechanisms of ARDs and their actions upon pathogenic lymphocytes, which are hypothesized to sustain disease, is poor. An in vitro model of inflammation was developed in the current study, in which stimulated and unstimulated lymphocytes were cultured together, but tracked separately, to investigate the action of MTX and Tofa on the two populations. By analysing lymphocyte proliferation and activation, and cytokine secretion in the culture supernatants, it was established that, due to the presence of activated cells, unstimulated cells underwent a bystander activation that was modulated by the ARDs. Additionally, varying administration schedules were demonstrated to affect lymphocytes differently in vitro, either directly or via bystander activation. Furthermore, MTX and Tofa exerted different effects; while MTX showed an antiproliferative effect, Tofa marginally effected activation, although only a slight antiproliferative action, which could be potentiated by sequential treatment with MTX. Thus, it was hypothesized that these differences may be exploited in sequential therapeutic strategies, to maximize the anti‑rheumatic effect. These findings are notable and must be accounted for, as bystander‑activated cells in vivo could contribute to the spread of autoimmune activation

  7. Propulsion Induced Effects Test Program

    NASA Technical Reports Server (NTRS)

    Cappuccio, Gelsomina; Won, Mark; Bencze, Dan

    1999-01-01

    The objective of this milestone is to assess the propulsion/airframe integration characteristics of the Technology Concept Airplane and design variations through computational analysis and experimental subsonic through supersonic wind tunnel testing. The Milestone will generate a comprehensive CFD and wind tunnel data base of the baseline, and design variations. Emphasis will be placed on establishing the propulsion induced effects on the flight performance of the Technology Concept Airplane with all appropriate wind tunnel corrections.

  8. A Web-Based Sexual Violence Bystander Intervention for Male College Students: Randomized Controlled Trial

    PubMed Central

    Vivolo-Kantor, Alana; Hardin, James; Berkowitz, Alan

    2014-01-01

    Background Bystander intervention approaches offer promise for reducing rates of sexual violence on college campuses. Most interventions are in-person small-group formats, which limit their reach and reduce their overall public health impact. Objective This study evaluated the efficacy of RealConsent, a Web-based bystander approach to sexual violence prevention, in enhancing prosocial intervening behaviors and preventing sexual violence perpetration. Methods A random probability sample of 743 male undergraduate students (aged 18 to 24 years) attending a large, urban university located in the southeastern United States was recruited online and randomized to either RealConsent (n=376) or a Web-based general health promotion program (n=367). Participants were surveyed online at baseline, postintervention, and 6-months postintervention. RealConsent was delivered via a password-protected Web portal that contained six 30-minute media-based and interactive modules covering knowledge of informed consent, communication skills regarding sex, the role of alcohol and male socialization in sexual violence, empathy for rape victims, and bystander education. Primary outcomes were self-reported prosocial intervening behaviors and sexual violence perpetration. Secondary outcomes were theoretical mediators (eg, knowledge, attitudes). Results At 6-month follow-up RealConsent participants intervened more often (P=.04) and engaged in less sexual violence perpetration (P=.04) compared to controls. In addition, RealConsent participants reported greater legal knowledge of sexual assault (P<.001), greater knowledge of effective consent (P<.001), less rape myths (P<.001), greater empathy for rape victims (P<.001), less negative date rape attitudes (P<.001), less hostility toward women (P=.01), greater intentions to intervene (P=.04), less hyper-gender ideology (P<.001), less positive outcome expectancies for nonconsensual sex (P=.03), more positive outcome expectancies for intervening (P

  9. Low-LET Bystander Responses in Gap Junction Null Human Colon Carcinoma Cells (RK036)

    SciTech Connect

    Sowa, Marianne B.; Goetz, Wilfried; Baulch, Janet E.; Morgan, William F.

    2006-10-01

    Combined with sensitive molecular techniques, the microbeam has proven extremely useful in studying radiation biology. This technology allows individual cells, or selected groups of cells, to be irradiated at specific doses and dose rates. Such capabilities lend themselves well to studies of low dose responses, delayed and non-targeted bystander effects of radiation. High-linear energy transfer (LET) microbeams mimic heavy energetic particles such as the ?-particles associated with radon exposure and have been used in numerous biological studies. Several low-LET microbeams have also been developed. One such low-LET microbeam, developed at the Pacific Northwest National Laboratory and currently located at the University of Maryland Radiation Oncology Research Laboratory, uses a variable energy electron source to mimic low-LET radiation and allows observation of how x-rays and ?-rays affect mammalian cells.

  10. In Vivo Space Radiation-Induced Non-Targeted Responses: Late Effects On Molecular Signaling In Mitochondria

    PubMed Central

    Jain, Mohit R.; Li, Min; Chen, Wei; Liu, Tong; de Toledo, Sonia M.; Pandey, Badri N.; Li, Hong; Rabin, Bernard M.; Azzam, Edouard I.

    2012-01-01

    The lack of clear knowledge about space radiation-induced biological effects has been singled out as the most important factor limiting the prediction of radiation risk associated with human space exploration. The expression of space radiation-induced non-targeted effects is thought to impact our understanding of the health risks associated with exposure to low fluences of particulate radiation encountered by astronauts during prolonged space travel. Following a brief review of radiation-induced bystander effects and the growing literature for the involvement of oxidative metabolism in their expression, we show novel data on the induction of in vivo non-targeted effects following exposure to 1100 MeV/nucleon titanium ions. Analyses of proteins by two-dimensional gel electrophoresis in non-targeted liver of cranially-irradiated Sprague Dawley rats revealed that the levels of key proteins involved in mitochondrial fatty acid metabolism are decreased. In contrast, those of proteins involved in various cellular defense mechanisms, including antioxidation, were increased. These data contribute to our understanding of the mechanisms underlying the biological responses to space radiation, and support the involvement of mitochondrial processes in the expression of radiation induced non-targeted effects. Significantly, they reveal the cross-talk between propagated stressful effects and induced adaptive responses. Together, with the accumulating data in the field, our results may help reduce the uncertainty in the assessment of the health risks to astronauts. They further demonstrate that ‘network analyses’ is an effective tool towards characterizing the signaling pathways that mediate the long-term biological effects of space radiation. PMID:21166651

  11. Electromagnetically induced angular Talbot effect

    NASA Astrophysics Data System (ADS)

    Qiu, Tianhui; Yang, Guojian

    2015-12-01

    The discrete angular spectrum (angular Talbot effect) of a periodic grating illuminated by a suitable spherical wave front has been observed recently (Azaña and Chatellus 2104 Phys. Rev. Lett. 112 213902). In this paper we study the possibility of such a phenomenon being realized with a medium that has no macroperiodic structure itself. Tunable electromagnetically induced grating (EIG) could be such a kind of medium. We obtain an EIG based on the periodically modulated strong susceptibility due to the third-order nonlinear effect generated in a double Λ-type four-level atomic system, and show the angular Talbot effect of an amplitude EIG, as well as a hybrid EIG, as the condition of the discrete phase-modulation shift of the illumination light front is satisfied. EIG parameters are tunable and the EIG-based angular Talbot effect may have the same potential applications as its periodic grating counterpart has.

  12. Prosocial Bystander Behavior in Bullying Dynamics: Assessing the Impact of Social Capital.

    PubMed

    Evans, Caroline B R; Smokowski, Paul R

    2015-12-01

    Individuals who observe a bullying event, but are not directly involved as a bully or victim, are referred to as bystanders. Prosocial bystanders are those individuals who actively intervene in bullying dynamics to support the victim and this prosocial behavior often ends the bullying. The current study examines how social capital in the form of social support, community engagement, mental health functioning, and positive school experiences and characteristics is associated with the likelihood of engaging in prosocial bystander behavior in a large sample (N = 5752; 51.03% female) of racially/ethnically diverse rural youth. It was hypothesized that social capital would be associated with an increased likelihood of engaging in prosocial bystander behavior. Following multiple imputation, an ordered logistic regression with robust standard errors was run. The hypothesis was partially supported and results indicated that social capital in the form of friend and teacher support, ethnic identity, religious orientation, and future optimism were significantly associated with an increased likelihood of engaging in prosocial bystander behavior. Contrary to the hypothesis, a decreased rate of self-esteem was significantly associated with an increased likelihood of engaging in prosocial bystander behavior. The findings highlight the importance of positive social relationships and community engagement in increasing prosocial bystander behavior and ultimately decreasing school bullying. Implications were discussed. PMID:26251101

  13. Risk Factors Associated with Peer Victimization and Bystander Behaviors among Adolescent Students.

    PubMed

    Huang, Zepeng; Liu, Zhenni; Liu, Xiangxiang; Lv, Laiwen; Zhang, Yan; Ou, Limin; Li, Liping

    2016-01-01

    Despite the prevalence of the phenomena of peer victimization and bystander behaviors, little data has generated to describe their relationships and risk factors. In this paper, a self-administered survey using a cross-sectional cluster-random sampling method in a sample of 5450 participants (2734 girls and 2716 boys) between 4th and 11th grades was conducted at six schools (two primary schools and four middle schools) located in Shantou, China. Self-reported peer victimization, bystander behaviors and information regarding parents' risky behaviors and individual behavioral factors were collected. Multinomial logistic regression analysis was applied to evaluate risk factors affecting peer victimization and bystander behaviors. The results indicated that urban participants were more likely to become bullying victims but less likely to become passive bystanders. Contrarily, bullying victimization was related to the increasing of passive bystander behaviors. Father drinking and mother smoking as independent factors were risk factors for peer victimization. Participants who were smoking or drinking had a tendency to be involved in both peer victimization and passive bystander behaviors. This study suggested that bystander behaviors, victims' and parents' educations play a more important role in peer victimization than previously thought. PMID:27472354

  14. Risk Factors Associated with Peer Victimization and Bystander Behaviors among Adolescent Students

    PubMed Central

    Huang, Zepeng; Liu, Zhenni; Liu, Xiangxiang; Lv, Laiwen; Zhang, Yan; Ou, Limin; Li, Liping

    2016-01-01

    Despite the prevalence of the phenomena of peer victimization and bystander behaviors, little data has generated to describe their relationships and risk factors. In this paper, a self-administered survey using a cross-sectional cluster-random sampling method in a sample of 5450 participants (2734 girls and 2716 boys) between 4th and 11th grades was conducted at six schools (two primary schools and four middle schools) located in Shantou, China. Self-reported peer victimization, bystander behaviors and information regarding parents’ risky behaviors and individual behavioral factors were collected. Multinomial logistic regression analysis was applied to evaluate risk factors affecting peer victimization and bystander behaviors. The results indicated that urban participants were more likely to become bullying victims but less likely to become passive bystanders. Contrarily, bullying victimization was related to the increasing of passive bystander behaviors. Father drinking and mother smoking as independent factors were risk factors for peer victimization. Participants who were smoking or drinking had a tendency to be involved in both peer victimization and passive bystander behaviors. This study suggested that bystander behaviors, victims’ and parents’ educations play a more important role in peer victimization than previously thought. PMID:27472354

  15. Predictors of Sexual Assault-Specific Prosocial Bystander Behavior and Intentions: A Prospective Analysis.

    PubMed

    Austin, Megan J Murphy; Dardis, Christina M; Wilson, Milo S; Gidycz, Christine A; Berkowitz, Alan D

    2016-01-01

    This study prospectively examined the impact of men's own attitudes and behaviors and perceptions of peer attitudes and behaviors on intentions and engagement in prosocial bystander behavior. Undergraduate men completed surveys at baseline and 4- and 7-month follow-ups. Men's perceptions of peer attitudes and behaviors and their own attitudes and behaviors were both important predictors of intentions. However, men's own attitudes and behaviors appeared to be more robustly predictive of behavior. Intentions to engage in bystander behavior were not predictive of behavior. Results support two specific areas of bystander intervention programming addressing misperceptions of social norms and personal attitudes and behaviors. PMID:26303402

  16. Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes.

    PubMed

    Pane, Jessica A; Coulson, Barbara S

    2015-06-01

    Viruses are considered to be potential key modulators of type 1 diabetes mellitus, with several possible mechanisms proposed for their modes of action. Here we discuss the evidence for virus involvement, including pancreatic infection and the induction of T cell-mediated molecular mimicry. A particular focus of this review is the further possibility that virus infection triggers bystander activation of pre-existing autoreactive lymphocytes. In this scenario, the virus triggers dendritic cell maturation and proinflammatory cytokine secretion by engaging pattern recognition receptors. These proinflammatory cytokines provoke bystander autoreactive lymphocyte activation in the presence of cognate autoantigen, which leads to enhanced beta cell destruction. Importantly, this mechanism does not necessarily involve pancreatic virus infection, and its virally non-specific nature suggests that it might represent a means commonly employed by multiple viruses. The ability of viruses specifically associated with type 1 diabetes, including group B coxsackievirus, rotavirus and influenza A virus, to induce these responses is also examined. The elucidation of a mechanism shared amongst several viruses for accelerating progression to type 1 diabetes would facilitate the identification of important targets for disease intervention. PMID:25794781

  17. Radiation-induced cardiovascular effects

    NASA Astrophysics Data System (ADS)

    Tapio, Soile

    Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in the radiation-response of the endothelium and myocardium, respectively. We have recently started co-operation with GSI in Darmstadt to study the effect of heavy ions on the endothelium. Our research will facilitate the identification of biomarkers associated with adverse cardiac effects of ionising radiation and may lead to the development of countermeasures against radiation-induced cardiac damage.

  18. When can I help? A conceptual framework for the prevention of sexual violence through bystander intervention.

    PubMed

    McMahon, Sarah; Banyard, Victoria L

    2012-01-01

    The bystander intervention approach is gaining popularity as a means for engaging communities in sexual assault prevention, especially on college campuses. Many bystander programs are teaching community members how to intervene without first assisting them to identify the full range of opportunities when they can intervene. In this article, the authors review the literature on sexual violence bystander intervention and present a conceptual framework that lays out a continuum of bystander opportunities ranging from reactive situations after an assault has occurred, to situations before an assault has occurred (posing high to low risk to victims), as well as proactive situations where no risk to the victim is present. The implications of this typology are discussed in the context of program development, evaluation, and further research. PMID:22096017

  19. Being a Positive Bystander: Male Antiviolence Allies’ Experiences of “Stepping Up”

    PubMed Central

    Casey, Erin A.; Ohler, Kristin

    2014-01-01

    As bystander approaches become increasingly prevalent elements of sexual and domestic violence prevention efforts, it is necessary to better understand the factors that support or impede individuals in taking positive action in the face of aggressive or disrespectful behavior from others. This study presents descriptive findings about the bystander experiences of 27 men who recently became involved in antiviolence against women work. More specifically, we describe the consistency with which respondents actively intervene in the speech or behavior of others, the strategies they use, and the factors they weigh as they deliberate taking action. Respondents report a complex and interrelated set of individual and contextual influences on their choices within bystander opportunities, which hold implications for both violence-specific models of bystander behavior and for prevention intervention development. PMID:21859757

  20. Translating sexual assault prevention from a college campus to a United States military installation: piloting the know-your-power bystander social marketing campaign.

    PubMed

    Potter, Sharyn J; Stapleton, Jane G

    2012-05-01

    One population that shares both similar and different characteristics with traditional college-age students is the U.S. Military. Similarities include a high concentration of 18- to 26-year-olds dealing with new found independence, peer pressure, and the presence of social norms that support violence and hypermasculinity. Sexual violence is a major public health problem in the United States, and because of the similarities in the age group of college and military populations, the problems regarding sexual violence in both constituencies have been well-documented. In the current pilot study we seek to add to both current knowledge about and promising practices of translating prevention strategies from one target audience to another. We describe how we translated, administered, and evaluated a bystander intervention social marketing campaign focused on sexual assault prevention that had been found to significantly affect attitude change on a college campus for a U.S. Army installation in Europe. In addition to demonstrating the process of translating prevention strategies across target audiences, findings from this pilot study contribute to the evaluation data on the effectiveness of sexual violence prevention strategies implemented with members of the U.S. Military. From our analysis, we see that research participants indicate that the degree to which the images resonate with them and the familiarity of the context (i.e., social self-identification) significantly effect the participants' personal responsibility for reducing sexual assault, confidence in acting as a bystander, and reported engagement as a bystander. PMID:22080576

  1. Determinants of self-reported bystander behavior in cyberbullying incidents amongst adolescents.

    PubMed

    DeSmet, Ann; Veldeman, Charlene; Poels, Karolien; Bastiaensens, Sara; Van Cleemput, Katrien; Vandebosch, Heidi; De Bourdeaudhuij, Ilse

    2014-04-01

    This study explores behavioral determinants of self-reported cyberbullying bystander behavior from a behavioral change theoretical perspective, to provide levers for interventions. Nine focus groups were conducted with 61 young adolescents (aged 12-16 years, 52% girls). Assertive defending, reporting to others, providing advice, and seeking support were the most mentioned behaviors. Self-reported bystander behavior heavily depended on contextual factors, and should not be considered a fixed participant role. Bystanders preferred to handle cyberbullying offline and in person, and comforting the victim was considered more feasible than facing the bully. Most prevailing behavioral determinants to defend or support the victim were low moral disengagement, that the victim is an ingroup member, and that the bystander is popular. Youngsters felt they received little encouragement from their environment to perform positive bystanding behavior, since peers have a high acceptance for not defending and perceived parental support for defending behavior is largely lacking. These results suggest multilevel models for cyberbullying research, and interventions are needed. With much previous research into cyberbullying insufficiently founded in theoretical models, the employed framework of the Integrative Model and Social Cognitive Theory may inspire future studies into bystander behavior. PMID:24359305

  2. Bystanders' responses to offline bullying and cyberbullying: The role of empathy and normative beliefs about aggression.

    PubMed

    Machackova, Hana; Pfetsch, Jan

    2016-04-01

    Cyberbullying often takes place with the virtual presence or knowledge of bystanders. While we have some evidence about the determinants of bystanders' responses to offline bullying, we lack empirical studies concerning the variables that influence bystanders' responses to cyberbullying. The current study examines bystanders' responses to offline bullying and cyberbullying incidents. Two types of responses were captured: support toward the victims and the reinforcement of bullies' actions. Using data from 321 German adolescents (ages 12-18; M = 14.99; 44% girls), the association between bystanders' responses and normative beliefs about verbal aggression and cyberaggression, and affective and cognitive empathy, were tested in a path model. Both types of normative beliefs positively predicted the reinforcement of bullies, and normative belief about verbal aggression also predicted support for the victims of offline bullying. Both types of empathy predicted support in offline bullying, but only affective empathy predicted support in cyberbullying. There was no link between affective or cognitive empathy to the reinforcement of bullies. Moreover, bystanders' tendencies to respond supportively to the victim or to reinforce the bully were rather consistent in both cyber- and offline bullying, but there was no link between support and reinforcement. The findings are discussed with regard to implications for prevention and intervention efforts. PMID:26946454

  3. Call for research on bystander intervention to prevent sexual violence: the role of campus environments.

    PubMed

    McMahon, Sarah

    2015-06-01

    An important next step for the field is to determine what setting-level factors beyond the individual are critical to fostering campus environments that support pro-social, helpful bystander intervention action to prevent sexual violence. Therefore, the purpose of this paper is to provide a research agenda to investigate key areas of the campus environment and their potential influence on bystander intervention. To create the research agenda, a number of steps were followed including: (1) systematically reviewing the larger bystander literature to identify key environmental areas, (2) assessing what research is available specific to college campuses and sexual assault in each of these areas, and (3) outlining future research to address each of these areas on college campuses and determine their applicability to sexual violence situations. Five main groups of factors were found to influence bystander intervention beyond the individual, group and situational levels, including: social norms, sense of community, pro-social modeling, policies, and the physical environment. Certain areas of research on environmental influences on bystander intervention are more developed such as social norms, with little research on areas such as policies and the physical environment. However, further research is needed in each of the identified five areas to help identify how college campuses can support bystander intervention. PMID:25896230

  4. The Role of Alcohol Consumption Patterns and Pro-Social Bystander Interventions in Contexts of Gender Violence.

    PubMed

    Fleming, Wm Michael; Wiersma-Mosley, Jacquelyn D

    2015-10-01

    Studies have shown that people differ in their likelihood of intervening as a bystander in situations of violence, but it is unclear how these actions relate to the use of alcohol. Two studies (N = 1,525) examined the relationship between alcohol use and pro-social bystander interventions in situations of physical and sexual coercion. Studies 1 and 2 provided cross-sectional evidence that alcohol use, along with alcohol expectancies, predicted patterns of bystander interventions, depending on gender. Discussion centers on the importance of including alcohol as another facet in understanding the role of pro-social bystander interventions. PMID:26175516

  5. Non-targeted radiation effects in vertebrate cell lines

    NASA Astrophysics Data System (ADS)

    Ryan, Lorna

    Radiation effects, such as bystander effects, hyper radiosensitivity/induced radioresistance (HRS/IRR) and adaptive response that are not related to direct DNA damage are now accepted. However the inter-relationship between them and the possible impact on the scientific basis for radiation protection are highly controversial. This thesis attempts to elucidate the mechanisms of some of these well known but little understood effects. Each paper examines some aspect of bystander effects, adaptive responses and HRS/IRR in an effort to understand how they vary with cell type, dose and time of exposure to single or multiple doses. All the effects involve non-linear dose effect curves and are mainly evident following low doses. Overall findings of the thesis include (1) A clear difference was observed between radioresistant, tumorigenic cell lines with mutant p53 gene expression, and radiosensitive, more normal, cell lines with wild type p53. In general death inducing bystander responses are induced in normal cell populations exposed to low doses of radiation while survival inducing IRR and adaptive responses are seen in the radioresistant tumorigenic cell lines. (2) A cohort of fish cell lines which demonstrated survival promoting bystander effects, also did not show a protective adaptive responses. (3) Adaptive responses traditionally occur when a large challenge dose is given 4--6hrs following low (10--100mGy) priming doses but this thesis shows that for the epithelial cell lines tested, the size of the priming dose (range 0.1--2Gy) does not appear to alter the size of the recovery response. Additionally increased survival could be detected in some cases when the challenge dose was given within one hour of the priming dose. The overall conclusion is that cell lines induce either a bystander response or a protective/adaptive response depending on genetic background and other factors. Care is needed in the interpretation of data generated from only one or two cell lines

  6. Vibrational spectroscopy in sensing radiobiological effects: analyses of targeted and non-targeted effects in human keratinocytes.

    PubMed

    Meade, Aidan D; Howe, Orla; Unterreiner, Valérie; Sockalingum, Ganesh D; Byrne, Hugh J; Lyng, Fiona M

    2016-06-23

    Modern models of radiobiological effects include mechanisms of damage initiation, sensing and repair, for those cells that directly absorb ionizing radiation as well as those that experience molecular signals from directly irradiated cells. In the former case, the effects are termed targeted effects while, in the latter, non-targeted effects. It has emerged that phenomena occur at low doses below 1 Gy in directly irradiated cells that are associated with cell-cycle-dependent mechanisms of DNA damage sensing and repair. Likewise in non-targeted bystander-irradiated cells the effect saturates at 0.5 Gy. Both effects at these doses challenge the limits of detection of vibrational spectroscopy. In this paper, a study of the sensing of both targeted and non-targeted effects in HaCaT human keratinocytes irradiated with gamma ray photons is conducted with vibrational spectroscopy. In the case of directly irradiated cells, it is shown that the HaCaT cell line does exhibit both hyperradiosensitivity and increased radioresistance at low doses, a transition between the two effects occurring at a dose of 200 mGy, and that cell survival and other physiological effects as a function of dose follow the induced repair model. Both Raman and FTIR signatures are shown to follow a similar model, suggesting that the spectra include signatures of DNA damage sensing and repair. In bystander-irradiated cells, pro- and anti-apoptotic signalling and mechanisms of ROS damage were inhibited in the mitogen-activated protein kinase (MAPK) transduction pathway. It is shown that Raman spectral profiles of bystander-irradiated cells are correlated with markers of bystander signalling and molecular transduction. This work demonstrates for the first time that both targeted and non-targeted effects of ionizing radiation damage are detected by vibrational spectroscopy in vitro. PMID:27043923

  7. Analysis of the common deletions in the mitochondrial DNA is a sensitive biomarker detecting direct and non-targeted cellular effects of low dose ionizing radiation.

    PubMed

    Schilling-Tóth, Boglárka; Sándor, Nikolett; Kis, Eniko; Kadhim, Munira; Sáfrány, Géza; Hegyesi, Hargita

    2011-11-01

    One of the key issues of current radiation research is the biological effect of low doses. Unfortunately, low dose science is hampered by the unavailability of easily performable, reliable and sensitive quantitative biomarkers suitable detecting low frequency alterations in irradiated cells. We applied a quantitative real time polymerase chain reaction (qRT-PCR) based protocol detecting common deletions (CD) in the mitochondrial genome to assess direct and non-targeted effects of radiation in human fibroblasts. In directly irradiated (IR) cells CD increased with dose and was higher in radiosensitive cells. Investigating conditioned medium-mediated bystander effects we demonstrated that low and high (0.1 and 2Gy) doses induced similar levels of bystander responses and found individual differences in human fibroblasts. The bystander response was not related to the radiosensitivity of the cells. The importance of signal sending donor and signal receiving target cells was investigated by placing conditioned medium from a bystander response positive cell line (F11-hTERT) to bystander negative cells (S1-hTERT) and vice versa. The data indicated that signal sending cells are more important in the medium-mediated bystander effect than recipients. Finally, we followed long term effects in immortalized radiation sensitive (S1-hTERT) and normal (F11-hTERT) fibroblasts up to 63 days after IR. In F11-hTERT cells CD level was increased until 35 days after IR then reduced back to control level by day 49. In S1-hTERT cells the increased CD level was also normalized by day 42, however a second wave of increased CD incidence appeared by day 49 which was maintained up to day 63 after IR. This second CD wave might be the indication of radiation-induced instability in the mitochondrial genome of S1-hTERT cells. The data demonstrated that measuring CD in mtDNA by qRT-PCR is a reliable and sensitive biomarker to estimate radiation-induced direct and non-targeted effects. PMID:21843534

  8. To act or not to act, that is the question? Barriers and facilitators of bystander intervention.

    PubMed

    Bennett, Sidney; Banyard, Victoria L; Garnhart, Lydia

    2014-02-01

    A promising line of inquiry in sexual violence prevention involves training potential bystanders to intervene in situations where there is risk for violence. Theories of bystander intervention often discuss barriers to helping behavior, but there has been little empirical inquiry into this question. We will present findings of a study of both barriers and facilitators of helping behavior in the context of sexual violence among first-semester college students. Two hundred and forty-two first year college students completed surveys during their first year of college. Measures included assessment of bystander behavior, perceived barriers to helping, as well as a variety of other variables identified in the literature as key correlates of helping. Quantitative and qualitative analyses were used to (a) describe barriers and facilitators of helping, (b) examine the relationship between barriers and self-reports of helping, and (c) model individual differences in helping behavior. In quantitative analyses, barriers, as assessed in this study, were better predictors of helping behavior directed at strangers than helping of friends. Results suggested that open-ended responses about the facilitators and barriers to helping for sexual violence map well onto social-psychological models of bystander behavior, and that greater prosocial tendencies, an intrapersonal variable, increase actual helping behavior. A more specific understanding of what promotes and hinders helping can be used to enhance prevention education efforts focused on increasing helpful bystander actions. PMID:24097909

  9. A randomized controlled trial of a multi-dose bystander intervention program using peer education theater.

    PubMed

    McMahon, Sarah; Winter, Samantha C; Palmer, Jane E; Postmus, Judy L; Peterson, N Andrew; Zucker, Sharon; Koenick, RuthAnne

    2015-08-01

    This article reports findings from a longitudinal, experimental evaluation of a peer education theater program, Students Challenging Realities and Educating Against Myths (SCREAM) Theater. This study examines the impact of SCREAM Theater on a range of bystander-related outcomes (i.e. bystander intentions, bystander efficacy, perception of friend norms and bystander behaviors) in situations involving sexual violence and whether there was a differential impact of the program by participant sex. First-year college students completed three waves of surveys (pretest, first post-test and second post-test). All participants received one dose of the intervention during summer orientation after the pretest. After the first post-test, participants were randomly assigned to receive two additional doses, or to a control condition, in which they received no additional doses. Students in both one- and three-dose groups reported a number of positive increases. Overall, an intent-to-treat analysis (n = 1390) indicated three doses of the intervention during the first semester of college resulted in better outcomes than the one-time intervention during summer orientation alone. Although both male and female students' scores increased during the study period, female students consistently scored higher than male students on each outcome. The findings suggest that peer education theater holds promise for bystander intervention education on college campuses. PMID:26135957

  10. Disparities in Survival with Bystander CPR following Cardiopulmonary Arrest Based on Neighborhood Characteristics

    PubMed Central

    Kumar, Shari L.; Bhandari, Rohit K.; Kumar, Sunil D.

    2016-01-01

    The American Heart Association reports the annual incidence of out-of-hospital cardiopulmonary arrests (OHCA) is greater than 300,000 with a survival rate of 9.5%. Bystander cardiopulmonary resuscitation (CPR) saves one life for every 30, with a 10% decrease in survival associated with every minute of delay in CPR initiation. Bystander CPR and training vary widely by region. We conducted a retrospective study of 320 persons who suffered OHCA in South Florida over 25 months. Increased survival, overall and with bystander CPR, was seen with increasing income (p = 0.05), with a stronger disparity between low- and high-income neighborhoods (p = 0.01 and p = 0.03, resp.). Survival with bystander CPR was statistically greater in white- versus black-predominant neighborhoods (p = 0.04). Increased survival, overall and with bystander CPR, was seen with high- versus low-education neighborhoods (p = 0.03). Neighborhoods with more high school age persons displayed the lowest survival. We discovered a significant disparity in OHCA survival within neighborhoods of low-income, black-predominance, and low-education. Reduced survival was seen in neighborhoods with larger populations of high school students. This group is a potential target for training, and instruction can conceivably change survival outcomes in these neighborhoods, closing the gap, thus improving survival for all. PMID:27379186

  11. Non-targeted effects of ionising radiation and radiotherapy.

    PubMed

    Sjostedt, Svetlana; Bezak, Eva

    2010-09-01

    Modern radiobiology is undergoing rapid change due to new discoveries contradicting the target concept which is currently used to predict dose-response relationships. Thus relatively recently discovered radiation-induced bystander effects (RIBEs), that include additional death, mutation and radio-adaptation in non-irradiated cells, change our understanding of the target concept and broadens its boundaries. This can be significant from a radioprotection point of view and also has the potential to reassess radiation damage models currently used in radiotherapy. This article reviews briefly the general concepts of RIBEs such as the proposed underlying mechanisms of signal induction and propagation, experimental approaches and biological end points used to investigate these phenomena. It also summarises several mathematical models currently proposed in an attempt to quantify RIBE. The main emphasis of this article is to review and highlight the potential impact of the bystander phenomena in radiotherapy. PMID:20857259

  12. Innocent Bystanders and Smoking Guns: Dwarf Carbon Stars

    NASA Astrophysics Data System (ADS)

    Green, Paul J.

    2014-01-01

    As far as we know, most carbon throughout the Universe is created and dispersed by AGB stars. So it was at first surprising to find that the carbon stars most prevalent in the Galaxy are in fact dwarfs. We suspect that dC stars are most likely innocent bystanders in post-mass transfer binaries, and may be predominantly metal-poor. Among 1200 C stars found in the SDSS (Green 2013), we confirm 724 dCs, of which a dozen are DA/dC stars in composite spectrum binaries, quadrupling the total sample of these "smoking guns" for AGB binary mass transfer. The dCs likely span absolute magnitudes M_i from about 6.5 to 10.5. G-type dC stars with weak CN and relatively blue colors are probably the most massive dCs still cool enough to show C_2 bands. Eleven very red C stars with strong red CN bands appear to be N-type AGB stars at large Galactocentric distances, one likely a new discovery in the dIrr galaxy Le A. Two such stars within 30arcmin of each other may trace a previously unidentified dwarf galaxy or tidal stream at ~40 kpc. We describe follow-up projects to study the spatial, kinematic, and binary properties of these C-enriched dwarfs.

  13. Fungi in the cystic fibrosis lung: bystanders or pathogens?

    PubMed

    Chotirmall, Sanjay H; McElvaney, Noel G

    2014-07-01

    Improvement to the life expectancy of people with cystic fibrosis (PWCF) brings about novel challenges including the need for evaluation of the role of fungi in the cystic fibrosis (CF) lung. To determine if such organisms represent bystanders or pathogens affecting clinical outcomes we review the existing knowledge from a clinical, biochemical, inflammatory and immunological perspective. The prevalence and importance of fungi in the CF airway has likely been underestimated with the most frequently isolated filamentous fungi being Aspergillus fumigatus and Scedosporium apiospermum and the major yeast Candida albicans. Developing non-culture based microbiological methods for fungal detection has improved both our classification and understanding of their clinical consequences including localized, allergic and systemic infections. Cross-kingdom interaction between bacteria and fungi are discussed as is the role of biofilms further affecting clinical outcome. A combination of host and pathogen-derived factors determines if a particular fungus represents a commensal, colonizer or pathogen in the setting of CF. The underlying immune state, disease severity and treatment burden represent key host variables whilst fungal type, form, chronicity and virulence including the ability to evade immune recognition determines the pathogenic potential of a specific fungus at a particular point in time. Further research in this emerging field is warranted to fully elucidate the spectrum of disease conferred by the presence of fungi in the CF airway and the indications for therapeutic interventions. PMID:24625547

  14. A Longitudinal Study of the Associations between Moral Disengagement and Active Defending versus Passive Bystanding during Bullying Situations

    ERIC Educational Resources Information Center

    Doramajian, Caroline; Bukowski, William M.

    2015-01-01

    This study investigated the prospective association between moral disengagement and bystander behaviors in bullying situations, including both defending and passive bystanding. A diverse sample of Canadian school children (N = 130; 68 boys and 62 girls; mean age = 11.36 years) participated in a three-wave longitudinal study over a 4-month period.…

  15. Sorority Women's and Fraternity Men's Rape Myth Acceptance and Bystander Intervention Attitudes

    ERIC Educational Resources Information Center

    Bannon, R. Sean; Brosi, Matthew W.; Foubert, John D.

    2013-01-01

    Sorority women and fraternity men are more likely than other students to be survivors and perpetrators of sexual assault, respectively. The present study examined sorority and fraternity members' rape myth acceptance, bystander efficacy, and bystander willingness to help in potential sexual assault situations. Sorority women were more…

  16. Electromagnetically induced classical and quantum Lau effect

    NASA Astrophysics Data System (ADS)

    Qiu, Tianhui; Yang, Guojian; Xiong, Jun; Xu, Deqin

    2016-07-01

    We present two schemes of Lau effect for an object, an electromagnetically induced grating generated based on the electromagnetically induced effect. The Lau interference pattern is detected either directly in the way of the traditional Lau effect measurement with a classical thermal light being the imaging light, or indirectly and nonlocally in the way of two-photon coincidence measurement with a pair of entangled photons being the imaging light.

  17. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  18. Dynamically Induced Zeeman Effect in Massless QED

    SciTech Connect

    Ferrer, Efrain J.; Incera, Vivian de la

    2009-02-06

    It is shown that in nonperturbative massless QED an anomalous magnetic moment is dynamically induced by an applied magnetic field. The induced magnetic moment produces a Zeeman splitting for electrons in Landau levels higher than l=0. The expressions for the nonperturbative Lande g factor and Bohr magneton are obtained. Possible applications of this effect are outlined.

  19. The fluctuation induced Hall effect

    SciTech Connect

    Shen, W.; Prager, S.C.

    1993-02-01

    The fluctuation induced Hall term, [le][approximately][ovr J] [times] [approximately][ovr B][ge], has been measured in the MST reversed field pinch. The term is of interest as a possible source of current self-generation (dynamo). It is found to be non-negligible, but small in that it can account for less than 25% of the dynamo driven current.

  20. The fluctuation induced Hall effect

    SciTech Connect

    Shen, W.; Prager, S.C.

    1993-02-01

    The fluctuation induced Hall term, {le}{approximately}{ovr J} {times} {approximately}{ovr B}{ge}, has been measured in the MST reversed field pinch. The term is of interest as a possible source of current self-generation (dynamo). It is found to be non-negligible, but small in that it can account for less than 25% of the dynamo driven current.

  1. The Influence of Social Norms on Advancement Through Bystander Stages for Preventing Interpersonal Violence.

    PubMed

    Deitch-Stackhouse, Jacqueline; Kenneavy, Kristin; Thayer, Richard; Berkowitz, Alan; Mascari, Janine

    2015-10-01

    This research evaluates the impact of social norms on the advancement through the bystander stages toward prosocial (active) intervention in interpersonal violence (IPV): emotional abuse, physical violence, controlling behavior, sexual violence, and stalking. The influence of social norms on bystander behavior across stages and types of violence varies. Accurate social norms perceptions are associated with routine intervention, although social norms misperceptions are not always a strong deterrent to intervention. Interpretation of a violent situation as problematic predicts increased willingness to intervene. Implications for the development of social norms antiviolence campaigns and strategies for reducing barriers to prosocial intervention are discussed. PMID:26175519

  2. Phase modulation induced by cooperative effects in electromagnetically induced transparency

    SciTech Connect

    Fleischhaker, Robert; Evers, Joerg; Dey, Tarak N.

    2010-07-15

    We analyze the influence of dipole-dipole interactions in an electromagnetically induced transparency set up for a density at the onset of cooperative effects. To this end, we include mean-field models for the influence of local-field corrections and radiation trapping into our calculation. We show both analytically and numerically that the polarization contribution to the local field strongly modulates the phase of a weak pulse. We give an intuitive explanation for this local-field-induced phase modulation and demonstrate that it distinctively differs from the nonlinear self-phase-modulation that a strong pulse experiences in a Kerr medium.

  3. Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single recombinant T-cell receptor ligand.

    PubMed

    Sinha, Sushmita; Subramanian, Sandhya; Miller, Lisa; Proctor, Thomas M; Roberts, Chris; Burrows, Gregory G; Vandenbark, Arthur A; Offner, Halina

    2009-03-25

    Recombinant T-cell receptor ligands (RTLs) can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner, and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). Antigen specificity of RTL raises the question as to whether this treatment would be successful in MS patients where target antigens are unknown. Using spinal cord homogenate or combinations of two different peptides to induce disease, we found that treatment with single RTL could reverse EAE as long as targeted T-cells were present. Therapy with three different RTLs each caused a significant reduction in IL-17 and increases in IL-10 and IL-13 in peptide-activated splenocytes, reduced proliferation of both cognate and bystander specificities of lymph node cells, and reduced inflammatory lesions and secreted IL-17 and IL-2 from peptide-activated spinal cord cells. These results show that treatment with single RTLs can induce a cytokine switch in cognate T-cells that inhibits both the target and bystander T-cells, providing new evidence for the potential applicability of RTL therapy in MS. PMID:19321778

  4. Cytokine Switch and Bystander Suppression of Autoimmune Responses to Multiple Antigens in Experimental Autoimmune Encephalomyelitis by a Single Recombinant T-Cell Receptor Ligand

    PubMed Central

    Sinha, Sushmita; Subramanian, Sandhya; Miller, Lisa; Proctor, Thomas M.; Roberts, Chris; Burrows, Gregory G.; Vandenbark, Arthur A.; Offner, Halina

    2009-01-01

    Recombinant T-cell receptor ligands (RTLs) can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner, and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). Antigen specificity of RTL raises the question as to whether this treatment would be successful in MS patients where target antigens are unknown. Using spinal cord homogenate or combinations of two different peptides to induce disease,we found that treatment with single RTL could reverse EAE as long as targeted T-cells were present. Therapy with three different RTLs each caused a significant reduction in IL-17 and increases in IL-10 and IL-13 in peptide-activated splenocytes, reduced proliferation of both cognate and bystander specificities of lymph node cells, and reduced inflammatory lesions and secreted IL-17 and IL-2 from peptide-activated spinal cord cells. These results show that treatment with single RTLs can induce a cytokine switch in cognate T-cells that inhibits both the target and bystander T-cells, providing new evidence for the potential applicability of RTL therapy in MS. PMID:19321778

  5. New risk indicator approach for Operators, Workers, Bystanders and Residents for a sustainable use of plant protection products.

    PubMed

    Sacchettini, Gabriele; Calliera, Maura; Marchis, Alexandru; Glass, Richard; Ellis, Clare Butler; Machera, Kyriaki; Gerritsen-Ebben, Rianda; Spanoghe, Pieter; Capri, Ettore

    2015-11-01

    In 2009, the European Union adopted the Directive on Sustainable Use of pesticides (SUD, Directive 2009/128/EC) establishing a framework for achieving a sustainable use of Plant Protection Products (PPPs) through reducing the risks and impacts of PPP use on human health and the environment, promoting integrated pest management and stimulating effective non-chemical alternatives. The core idea of the SUD is that it is necessary to monitor the use of PPPs through the implementation of an appropriate set of risk indicators to monitor progress and trends in risk reduction within the Member States. To contribute to this direction, following a comprehensive analysis of the risk (including procedures of risk assessment and risk management) and involving stakeholders in the decision process, specific toolboxes of practical indirect risk indicators of exposure of Operators, Workers, Bystanders and Residents were developed and are now available to be used by Member States (MSs) based on their specific context. PMID:26143544

  6. Reticle processing induced proximity effects

    NASA Astrophysics Data System (ADS)

    Janssen, Maurice; de Kruif, Robert; Kiers, Ton

    2002-08-01

    Minimising Across Retical Line width Variation is a continuous challenge for each resolution node. Having tight critical dimension (CD) uniformity for a large variety of pitches is even more challenging. The causes of the reticle errors originate mainly from writing reticles at the edge of the write-tool's capabilities, and from manufacturing at the edge of etching and processing capabilities. These various reticle errors will subsequently lead to non-uniformity effects on wafer level. The reticle errors can be compensated for using technologies similar to those used to correct for optical proximity effects at wafer level. The errors can be small effects in the nanometer range like write noise or larger effects of 10 nm to 100 nm on reticle level from etching. Many effects that we see on reticle will be made visible on the wafer after exposure on a Step & Scan system. To visualise system performance one can use specific techniques such as selection of lines that are on target. In addition, with extensive measurement these reticle errors can be subtracted and thus removed from the final wafer result. For the investigation use is made of a reticle, which has a variation of 35 pitches for four line widths of 100 nm, 130 nm, 150 nm, and 170 nm at 1X. The reticle underwent extensive measurements, and its characteristics are described from these measurements. In addition, some wafer results are shown.

  7. Reducing Sexual Violence on Campus: The Role of Student Leaders as Empowered Bystanders

    ERIC Educational Resources Information Center

    Banyard, Victoria L.; Moynihan, Mary M.; Crossman, Maria T.

    2009-01-01

    Sexual violence is a widespread problem for college communities. Students, faculty, and staff are increasingly involved in prevention efforts. To date, however, evaluation of sexual violence prevention programs has shown mixed results. One promising new practice teaches segments of college communities to be engaged, positive bystanders. It aims to…

  8. Using a Multimedia Social Marketing Campaign to Increase Active Bystanders on the College Campus

    ERIC Educational Resources Information Center

    Potter, Sharyn J.

    2012-01-01

    Objective: To evaluate the campus-wide administration of the Know Your Power bystander-oriented social marketing campaign. Participants: Undergraduate students at a public college were invited to participate in a public awareness survey before and after the 6-week campaign administration in February and March 2009. Methods: Pretest and posttests…

  9. Bystander Behavior in Bullying Situations: Basic Moral Sensitivity, Moral Disengagement and Defender Self-Efficacy

    ERIC Educational Resources Information Center

    Thornberg, Robert; Jungert, Tomas

    2013-01-01

    The aim of the present study was to investigate how basic moral sensitivity in bullying, moral disengagement in bullying and defender self-efficacy were related to different bystander behaviors in bullying. Therefore, we examined pathways that linked students' basic moral sensitivity, moral disengagement, and defender self-efficacy to different…

  10. Bystanders Matter: Associations between Reinforcing, Defending, and the Frequency of Bullying Behavior in Classrooms

    ERIC Educational Resources Information Center

    Salmivalli, Christina; Voeten, Marinus; Poskiparta, Elisa

    2011-01-01

    This study investigated whether the bystanders' behaviors (reinforcing the bully vs. defending the victim) in bullying situations are related to the frequency of bullying in a classroom. The sample consisted of 6,764 primary school children from Grades 3 to 5 (9-11 years of age), who were nested within 385 classrooms in 77 schools. The students…

  11. Determinants of Adolescents' Active Defending and Passive Bystanding Behavior in Bullying

    ERIC Educational Resources Information Center

    Gini, Gianluca; Albiero, Paolo; Benelli, Beatrice; Altoe, Gianmarco

    2008-01-01

    The literature on participant roles in bullying lacks empirical studies that seek to explain what differentiates defenders from outsiders (or passive bystanders). The present study tested a conceptual model in which two personal characteristics of early adolescent students (empathy and perceived social self-efficacy) were considered as possible…

  12. Being a Positive Bystander: Male Antiviolence Allies' Experiences of "Stepping up"

    ERIC Educational Resources Information Center

    Casey, Erin A.; Ohler, Kristin

    2012-01-01

    As bystander approaches become increasingly prevalent elements of sexual and domestic violence prevention efforts, it is necessary to better understand the factors that support or impede individuals in taking positive action in the face of aggressive or disrespectful behavior from others. This study presents descriptive findings about the…

  13. Participant Roles in Bullying: How Can Peer Bystanders Be Utilized in Interventions?

    ERIC Educational Resources Information Center

    Salmivalli, Christina

    2014-01-01

    This article provides a view of school bullying as a group phenomenon and practical implications stemming from this approach. The motivation for bullying perpetration often relates to one's social standing in the group. Peer bystanders are typically present when bullying takes place, often providing the perpetrators with social rewards. The…

  14. Bystander Responses to School Bullying: A Cross-Sectional Investigation of Grade and Sex Differences

    ERIC Educational Resources Information Center

    Trach, Jessica; Hymel, Shelley; Waterhouse, Terry; Neale, Ken

    2010-01-01

    Addressing the impact of peer bystanders on school bullying, this cross-sectional study examined whether student responses to bullying that they witnessed varied as a function of sex and grade. In a school-based survey regarding social experiences at school, Grade 4 to 11 students (N = 9397, 51% male) who reported witnessing bullying (68%) rated…

  15. Counseling and the Bystander-Equity Model of Supervisory Helping Behavior: Directions for EAP Research.

    ERIC Educational Resources Information Center

    Gerstein, Lawrence H.; Bayer, Gregory A.

    1991-01-01

    Discusses contribution of Bystander-Equity Model of Supervisory Helping Behavior to pursuit of employee assistance program (EAP) research based on traditions of field of counseling. Offers structure for pursuing empirical and applied activities in EAP settings. Encourages counseling researchers and practitioners to respond to challenge of working…

  16. The Role of Bystanders in Students' Perception of Bullying and Sense of Safety

    ERIC Educational Resources Information Center

    Gini, Gianluca; Pozzoli, Tiziana; Borghi, Francesco; Franzoni, Lara

    2008-01-01

    Two studies employing a mixed experimental design were conducted to determine if perceptions of bullying, attitudes towards victims, and students' sense of safety at school were influenced by bystanders' reactions to different types of bullying. In Study 1, 217 middle-school children were randomly assigned to read a hypothetical scenario…

  17. Bystanders to Bullying: Fourth-to Seventh-Grade Students' Perspectives on Their Reactions

    ERIC Educational Resources Information Center

    Forsberg, Camilla; Thornberg, Robert; Samuelsson, Marcus

    2014-01-01

    The aim with the present study was to investigate bystander actions in bullying situations as well as reasons behind these actions as they are articulated by Swedish students from fourth to seventh grade. Forty-three semi-structured individual interviews were conducted with students. Qualitative analysis of data was performed by methods from…

  18. R.U. Ready?: Peer Education and Bystander Intervention Sexual Assault Programming

    ERIC Educational Resources Information Center

    Schweer, Jen Luettel; Heather, Katie; Kay, Kathryn; Stewart, K. Leigh; Kovach, Laura

    2012-01-01

    R.U. Ready? at Georgetown University is an annual sexual assault awareness event that incorporates peer education and resources with opportunities for students, staff, and faculty to dialogue about providing bystander intervention throughout the campus community. Beyond dialogue, participants learn about student activism and the resources and…

  19. Bystander Intervention, Bullying, and Victimization: A Multilevel Analysis of New Zealand High Schools

    ERIC Educational Resources Information Center

    Denny, Simon; Peterson, Elizabeth R.; Stuart, Jaimee; Utter, Jennifer; Bullen, Pat; Fleming, Theresa; Ameratunga, Shanthi; Clark, Terryann; Milfont, Taciano

    2015-01-01

    This study examines the association between schools and student bullying behaviors and victimization among a nationally representative sample (N = 9,107) of New Zealand high school students. In particular, the study sought to explore the role of characteristics of schools and school culture with respect to bystander behavior, while controlling for…

  20. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    EPA Science Inventory

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
    Cancer Responses
    .
    There has been a concerted effort in the field of radiation biology to better understand cellular
    responses that could have an impact on the estin1ation of cancer...

  1. Validity for an integrated laboratory analogue of sexual aggression and bystander intervention.

    PubMed

    Parrott, Dominic J; Tharp, Andra Teten; Swartout, Kevin M; Miller, Cameron A; Hall, Gordon C Nagayama; George, William H

    2012-01-01

    This study sought to develop and validate an integrated laboratory paradigm of sexual aggression and bystander intervention. Participants were a diverse community sample (54% African American) of heterosexual males (N = 156) between 21 and 35 years of age who were recruited to complete the study with a male friend and an ostensibly single, heterosexual female who reported a strong dislike of sexual content in the media. Participants viewed a sexually explicit or nonsexually explicit film clip as part of contrived media rating task and made individual choices of which film clip to show the female confederate. Immediately thereafter, participants were required to reach consensus on a group decision of which film clip to show the female confederate. Subjecting a target to an unwanted experience with a sexual connotation was operationalized as selection of the sexually explicit video, whereas successful bystander intervention was operationalized as the event of one partner individually selecting the sexually explicit video but then selecting the nonsexually explicit video for the group choice. Results demonstrated that a 1-year history of sexual aggression and endorsement of pertinent misogynistic attitudes significantly predicted selection of the sexually-explicit video. In addition, bystander efficacy significantly predicted men's successful prevention of their male peer's intent to show the female confederate a sexually explicit video. Discussion focused on how these data inform future research and bystander intervention programming for sexual aggression. PMID:22549741

  2. Emergency dispatch process and patient outcome in bystander-witnessed out-of-hospital cardiac arrest with a shockable rhythm

    PubMed Central

    Silfvast, Tom O.; Jäntti, T. Helena; Kuisma, Markku J.; Kurola, Jouni O.

    2015-01-01

    Objective To describe the dispatch process for out-of-hospital cardiac arrest (OHCA) in bystander-witnessed patients with initial shockable rhythm, and to evaluate whether recognition of OHCA by the emergency medical dispatcher (EMD) has an effect on the outcome. Methods This study was part of the FINNRESUSCI study focusing on the epidemiology and outcome of OHCA in Finland. Witnessed [not by Emergency Medical Service (EMS)] OHCA patients with initial shockable rhythm in the southern and the eastern parts of Finland during a 6-month period from March 1 to August 31 2010, were electronically collected from eight dispatch centres and from paper case reports filled out by EMS crews. Results Of the 164 patients, 82.3% (n=135) were correctly recognized by the EMD as cardiac arrests. The majority of all calls (90.7%) were dispatched within 2 min. Patients were more likely to survive and be discharged from the hospital if the EMS response time was within 8 min (P<0.001). Telephone-guided cardiopulmonary resuscitation (T-CPR) was given in 53 cases (32.3%). Overall survival to hospital discharge was 43.4% (n=71). Survival to hospital discharge was 44.4% (n=60) when the EMD recognized OHCA and 37.9% (n=11) when OHCA was not recognized. The difference was not statistically significant (P=0.521). Conclusion The rate of recognition of cardiac arrest by EMD was high, but EMD recognition did not affect the outcome. The survival rate was high in both groups. Recognized cardiac arrest patients received bystander CPR more frequently than those for whom OHCA remained unrecognized. PMID:24809817

  3. Challenge and opportunity in evaluating a diffusion-based active bystanding prevention program: Green Dot in high schools.

    PubMed

    Cook-Craig, Patricia G; Coker, Ann L; Clear, Emily R; Garcia, Lisandra S; Bush, Heather M; Brancato, Candace J; Williams, Corrine M; Fisher, Bonnie S

    2014-10-01

    Increasing attention has recently been paid to the development of prevention programs designed to actively engage bystanders in prevention efforts to reduce the risk of sexual and dating violence; yet, few evaluations have been conducted. Our proposed plan to rigorously evaluate a randomized intervention trial of the Green Dot bystander program as it is implemented in high schools across Kentucky is presented. We highlight the value of measuring violence victimization and perpetration outcomes, capturing actual and observed student bystander behaviors, and testing the diffusion of Green Dot training through students' social networks. PMID:25255794

  4. Bystander T cells participate in specific response to cockroach antigen (CR) in vitro.

    PubMed

    Walters, C S; Tackey, R N; Reece, E; Paluvoi, S

    2003-02-01

    Allergic reactions due to whole body, body parts and fecal products of cockroach (CR) are characterized by inflammatory reaction that may lead to symptoms of rhinitis or asthma in atopic individuals. Although the majority of T cells at the site of CR hypersensitivity are not antigen specific, the cellular subset and cytokine receptors that participate and control the outcome of the reaction have not been fully studied. In this study, we have used fluorescent activated cell sorter (FACS) analysis to characterize the activation marker and cytokine profile of antigen specific and bystander T cells after in vitro stimulation of peripheral blood lymphocytes with whole body extract of CR antigen. There was significant enhancement of CD69 on blast and bystander T cells in all atopic subjects compared to non-atopics. Both antigen specific and bystander T cells showed increased expression of HLA-DR, CD25 and CD71 in 9 of 11 atopic patients compared to control. There was also an increase in CD45RA+ and a decrease in CD45RO+ cells following antigen stimulation. These results correlated with the increase in the early apoptotic cells observed in patients as measured by Annexin V stain. Our data revealed that there was no difference in the expression of CD95 in both stimulated and bystander T cells. However, there was enhancement of FasL by CR antigen, suggesting that the increased apoptosis that was observed was probably due to the Fas/FasL interaction. Positive intracellular IL2, IL-4 and IFN-gamma in T cells were observed in only the antigen specific blast cells in 83% of patients studied. These results suggest interplay of memory T cell response, apoptosis, and activated bystander T cells activities in maintaining cellular homeostasis during allergic reaction in cockroach sensitive atopic subjects. PMID:12722946

  5. Dendritic cells and NK cells stimulate bystander T cell activation in response to TLR agonists through secretion of IFN-alpha beta and IFN-gamma.

    PubMed

    Kamath, Arun T; Sheasby, Christopher E; Tough, David F

    2005-01-15

    Recognition of conserved features of infectious agents by innate pathogen receptors plays an important role in initiating the adaptive immune response. We have investigated early changes occurring among T cells after injection of TLR agonists into mice. Widespread, transient phenotypic activation of both naive and memory T cells was observed rapidly after injection of molecules acting through TLR3, -4, -7, and -9, but not TLR2. T cell activation was shown to be mediated by a combination of IFN-alphabeta, secreted by dendritic cells (DCs), and IFN-gamma, secreted by NK cells; notably, IFN-gamma-secreting NK cells expressed CD11c and copurified with DCs. Production of IFN-gamma by NK cells could be stimulated by DCs from TLR agonist-injected mice, and although soluble factors secreted by LPS-stimulated DCs were sufficient to induce IFN-gamma, maximal IFN-gamma production required both direct contact of NK cells with DCs and DC-secreted cytokines. In vitro, IFN-alphabeta, IL-18, and IL-12 all contributed to DC stimulation of NK cell IFN-gamma, whereas IFN-alphabeta was shown to be important for induction of T cell bystander activation and NK cell IFN-gamma production in vivo. The results delineate a pathway involving innate immune mediators through which TLR agonists trigger bystander activation of T cells. PMID:15634897

  6. Nonspreading Rift Valley Fever Virus Infection of Human Dendritic Cells Results in Downregulation of CD83 and Full Maturation of Bystander Cells

    PubMed Central

    Oreshkova, Nadia; Wichgers Schreur, Paul J.; Spel, Lotte; Vloet, Rianka P. M.; Moormann, Rob J. M.; Boes, Marianne; Kortekaas, Jeroen

    2015-01-01

    Vaccines based on nonspreading Rift Valley fever virus (NSR) induce strong humoral and robust cellular immune responses with pronounced Th1 polarisation. The present work was aimed to gain insight into the molecular basis of NSR-mediated immunity. Recent studies have demonstrated that wild-type Rift Valley fever virus efficiently targets and replicates in dendritic cells (DCs). We found that NSR infection of cultured human DCs results in maturation of DCs, characterized by surface upregulation of CD40, CD80, CD86, MHC-I and MHC-II and secretion of the proinflammatory cytokines IFN-β, IL-6 and TNF. Interestingly, expression of the most prominent marker of DC maturation, CD83, was consistently downregulated at 24 hours post infection. Remarkably, NSR infection also completely abrogated CD83 upregulation by LPS. Downregulation of CD83 was not associated with reduced mRNA levels or impaired CD83 mRNA transport from the nucleus and could not be prevented by inhibition of the proteasome or endocytic degradation pathways, suggesting that suppression occurs at the translational level. In contrast to infected cells, bystander DCs displayed full maturation as evidenced by upregulation of CD83. Our results indicate that bystander DCs play an important role in NSR-mediated immunity. PMID:26575844

  7. Effects of high-dose microbeam irradiation on tumor microvascular function and angiogenesis.

    PubMed

    Fontanella, Andrew N; Boss, Mary-Keara; Hadsell, Michael; Zhang, Jian; Schroeder, Thies; Berman, Katherine G; Dewhirst, Mark W; Chang, Sha; Palmer, Gregory M

    2015-02-01

    Microbeam radiation therapy (MRT) is a form of cancer treatment in which a single large dose of radiation is spatially fractionated in-line or grid-like patterns. Preclinical studies have demonstrated that MRT is capable of eliciting high levels of tumor response while sparing normal tissue that is exposed to the same radiation field. Since a large fraction of the MRT-treated tumor is in the dose valley region that is not directly irradiated, tumor response may be driven by radiation bystander effects, which in turn elicit a microvascular response. Differential alterations in hemodynamics between the tumor and normal tissue may explain the therapeutic advantages of MRT. Direct observation of these dynamic responses presents a challenge for conventional ex vivo analysis. Furthermore, knowledge gleaned from in vitro studies of radiation bystander response has not been widely incorporated into in vivo models of tumor radiotherapy, and the biological contribution of the bystander effect within the tumor microenvironment is unknown. In this study, we employed noninvasive, serial observations of the tumor microenvironment to address the question of how tumor vasculature and HIF-1 expression are affected by microbeam radiotherapy. Tumors (approximately 4 mm in diameter) grown in a dorsal window chamber were irradiated in a single fraction using either a single, microplanar beam (300 micron wide swath) or a wide-field setup (whole-window chamber) to a total dose of 50 Gy. The tumors were optically observed daily for seven days postirradiation. Microvascular changes in the tumor and surrounding normal tissue differed greatly between the wide-field and microbeam treatments. We present evidence that these changes may be due to dissimilar spatial and temporal patterns of HIF-1 expression induced through radiation bystander effects. PMID:25574586

  8. Effects of High-Dose Microbeam Irradiation on Tumor Microvascular Function and Angiogenesis

    PubMed Central

    Fontanella, Andrew N.; Boss, Mary-Keara; Hadsell, Michael; Zhang, Jian; Schroeder, Thies; Berman, Katherine G.; Dewhirst, Mark W.; Chang, Sha; Palmer, Gregory M.

    2015-01-01

    Microbeam radiation therapy (MRT) is a form of cancer treatment in which a single large dose of radiation is spatially fractionated in-line or grid-like patterns. Preclinical studies have demonstrated that MRT is capable of eliciting high levels of tumor response while sparing normal tissue that is exposed to the same radiation field. Since a large fraction of the MRT-treated tumor is in the dose valley region that is not directly irradiated, tumor response may be driven by radiation bystander effects, which in turn elicit a microvascular response. Differential alterations in hemodynamics between the tumor and normal tissue may explain the therapeutic advantages of MRT. Direct observation of these dynamic responses presents a challenge for conventional ex vivo analysis. Furthermore, knowledge gleaned from in vitro studies of radiation bystander response has not been widely incorporated into in vivo models of tumor radiotherapy, and the biological contribution of the bystander effect within the tumor microenvironment is unknown. In this study, we employed noninvasive, serial observations of the tumor microenvironment to address the question of how tumor vasculature and HIF-1 expression are affected by microbeam radiotherapy. Tumors (approximately 4 mm in diameter) grown in a dorsal window chamber were irradiated in a single fraction using either a single, microplanar beam (300 micron wide swath) or a wide-field setup (whole-window chamber) to a total dose of 50 Gy. The tumors were optically observed daily for seven days postirradiation. Microvascular changes in the tumor and surrounding normal tissue differed greatly between the wide-field and microbeam treatments. We present evidence that these changes may be due to dissimilar spatial and temporal patterns of HIF-1 expression induced through radiation bystander effects. PMID:25574586

  9. Zeeman effect induced by intense laser light.

    PubMed

    Stambulchik, E; Maron, Y

    2014-08-22

    We analyze spectral line shapes of hydrogenlike species subjected to fields of electromagnetic waves. It is shown that the magnetic component of an electromagnetic wave may significantly influence the spectra. In particular, the Zeeman effect induced by a visible or infrared light can be experimentally observed using present-day powerful lasers. In addition, the effect may be used for diagnostics of focused beam intensities achieved at existing and newly built laser facilities. PMID:25192094

  10. Current heating induced spin Seebeck effect

    SciTech Connect

    Schreier, Michael Roschewsky, Niklas; Dobler, Erich; Meyer, Sibylle; Huebl, Hans; Goennenwein, Sebastian T. B.; Gross, Rudolf

    2013-12-09

    A measurement technique for the spin Seebeck effect is presented, wherein the normal metal layer used for its detection is exploited simultaneously as a resistive heater and thermometer. We show how the various contributions to the measured total signal can be disentangled, allowing to extract the voltage signal solely caused by the spin Seebeck effect. To this end, we performed measurements as a function of the external magnetic field strength and its orientation. We find that the effect scales linearly with the induced rise in temperature, as expected for the spin Seebeck effect.

  11. That's What Friends Are For: Bystander Responses to Friends or Strangers at Risk for Party Rape Victimization.

    PubMed

    Katz, Jennifer; Pazienza, Rena; Olin, Rachel; Rich, Hillary

    2015-10-01

    The present research examined bystander responses to potential party rape scenarios involving either a friend or a stranger at risk. Undergraduate students (N = 151) imagined attending a party and seeing a man lead an intoxicated woman (friend or stranger) into a bedroom. After random assignment to conditions, participants reported on intentions to help, barriers to helping, victim blame, and empathic concern. As expected, based on their shared social group membership, bystanders intended to offer more help to friends than to strangers. Bystanders also reported more personal responsibility to help and more empathic concern when the potential victim was a friend rather than stranger. Observing a friend versus stranger at risk did not affect audience inhibition or perceived victim blame. Compared with women, men reported more blame and less empathic concern for potential victims. However, there were no gender differences in bystander intent to help or barriers to helping. In multivariate analyses, both responsibility to help and empathic concern for the potential victim uniquely predicted bystanders' intent to help a woman at risk for party rape. Results suggest that promoting social identification with peers at risk could increase bystander intervention. PMID:25349015

  12. Victim Reports of Bystander Reactions to In-Person and Online Peer Harassment: A National Survey of Adolescents.

    PubMed

    Jones, Lisa M; Mitchell, Kimberly J; Turner, Heather A

    2015-12-01

    Bullying prevention is increasingly targeting education to bystanders, but more information is needed on the complexities of bystander actions across a wide variety of incidents, including both online and in-person peer harassment. The current study analyzes victim report data from a nationally representative survey of youth ages 10-20 (n = 791; 51% female). Bystander presence was common across all harassment incident types (80% of incidents). In contrast to previous research, our study found that supportive bystander behaviors occurred at relatively high rates. Unfortunately, antagonistic bystander behaviors, although less common, were predictive of higher negative impact for the victim. A large percentage of victims (76%) also disclosed the harassment to confidants, who play an important role as secondary bystanders. While friends were the most common confidant, incidents were also disclosed to adults at high rates (60%) and with mostly positive results. The findings suggest that prevention programs could increase their impact by targeting education to both direct witnesses and confidants, and considering a wider variety of peer victimization incident types. PMID:26316304

  13. Efficacy of Bystander Programs to Prevent Dating Abuse Among Youth and Young Adults: A Review of the Literature.

    PubMed

    Storer, Heather L; Casey, Erin; Herrenkohl, Todd

    2016-07-01

    Estimates suggest that between 10% and 25% of adolescents have experienced some form of physical violence within a dating relationship, and one in four college-age women experiences attempted or completed sexual violence on campus. Bystander programs focus on equipping young adults with the skills to safely intervene when they witness behaviors that can result in dating abuse. This approach is promoted for its capacity both to transform community norms that contribute to dating abuse and to foster more positive social interactions among youth, however, there has been limited review of the literature on the outcomes of bystander programs. Therefore, this article provides an in-depth systematic literature review, which describes the content and program components of bystander programs and summarizes what is currently known about the impact of bystander interventions on participants' behaviors and attitudes. Results indicate that bystander programs are promising from the standpoint of increasing young adults' willingness to intervene and confidence in their ability to intervene when they witness dating or sexual violence, however, the utilization of actual bystander behaviors was less straightforward. Implications for prevention practice and for future research are presented. PMID:25951840

  14. Absent bystanders and cognitive dissonance: a comment on Timmins & de Vries.

    PubMed

    Paley, John

    2015-04-01

    Timmins & de Vries are more sympathetic to my editorial than other critics, but they take issue with the details. They doubt whether the bystander phenomenon applies to Mid Staffs nurses; they believe that cognitive dissonance is a better explanation of why nurses fail to behave compassionately; and they think that I am 'perhaps a bit rash' to conclude that 'teaching compassion may be fruitless'. In this comment, I discuss all three points. I suggest that the bystander phenomenon is irrelevant; that Timmins & de Vries give an incomplete account of cognitive dissonance; and that it isn't rash to propose that educating nurses 'for compassion' is a red herring. Additionally, I comment on the idea that I wish to mount a 'defence of healthcare staff'. PMID:25549986

  15. Chimpanzees' Bystander Reactions to Infanticide: An Evolutionary Precursor of Social Norms?

    PubMed

    von Rohr, Claudia Rudolf; van Schaik, Carel P; Kissling, Alexandra; Burkart, Judith M

    2015-06-01

    Social norms-generalized expectations about how others should behave in a given context-implicitly guide human social life. However, their existence becomes explicit when they are violated because norm violations provoke negative reactions, even from personally uninvolved bystanders. To explore the evolutionary origin of human social norms, we presented chimpanzees with videos depicting a putative norm violation: unfamiliar conspecifics engaging in infanticidal attacks on an infant chimpanzee. The chimpanzees looked far longer at infanticide scenes than at control videos showing nut cracking, hunting a colobus monkey, or displays and aggression among adult males. Furthermore, several alternative explanations for this looking pattern could be ruled out. However, infanticide scenes did not generally elicit higher arousal. We propose that chimpanzees as uninvolved bystanders may detect norm violations but may restrict emotional reactions to such situations to in-group contexts. We discuss the implications for the evolution of human morality. PMID:26108616

  16. Video calls from lay bystanders to dispatch centers - risk assessment of information security

    PubMed Central

    2011-01-01

    Background Video calls from mobile phones can improve communication during medical emergencies. Lay bystanders can be instructed and supervised by health professionals at Emergency Medical Communication Centers. Before implementation of video mobile calls in emergencies, issues of information security should be addressed. Methods Information security was assessed for risk, based on the information security standard ISO/IEC 27005:2008. A multi-professional team used structured brainstorming to find threats to the information security aspects confidentiality, quality, integrity, and availability. Results Twenty security threats of different risk levels were identified and analyzed. Solutions were proposed to reduce the risk level. Conclusions Given proper implementation, we found no risks to information security that would advocate against the use of video calls between lay bystanders and Emergency Medical Communication Centers. The identified threats should be used as input to formal requirements when planning and implementing video calls from mobile phones for these call centers. PMID:21958387

  17. Outcomes of a Bystander Intervention Community Health Service-Learning Project.

    PubMed

    Decker, Kim; Hensel, Desiree; Fasone, Leslie

    2016-01-01

    The purpose of this article is to describe the integration of a college bystander intervention service-learning project into an entry-level community clinical course in a prelicensure program and its outcomes. Two years of data from 118 students showed that students helped improve campus safety while growing as professionals and gaining leadership and health promotion skills. Approximately one-third of the students described a specific incident in which they intervened in an ambiguous situation. PMID:26633150

  18. Environmental effects of blast induced immissions

    SciTech Connect

    Schillinger, R.R.

    1996-12-01

    The subject of the paper is blasting vibrations as sources of environmental molestations including acceptance level, complaint level and damage level, as well. In addition, the paper shows a comparison of international regulations and their problematical aspects. In consideration of blast induced immissions the subject shows that human annoyance has become an important place in blasting works. It provides a solution proposal how to minimize environmental effects of blasting works.

  19. Induced effects of advanced oxidation processes

    NASA Astrophysics Data System (ADS)

    Liu, Peng; Li, Chaolin; Zhao, Zhuanjun; Lu, Gang; Cui, Haibo; Zhang, Wenfang

    2014-02-01

    Hazardous organic wastes from industrial, military, and commercial activities represent one of the greatest challenges to human beings. Advanced oxidation processes (AOPs) are alternatives to the degradation of those organic wastes. However, the knowledge about the exact mechanisms of AOPs is still incomplete. Here we report a phenomenon in the AOPs: induced effects, which is a common property of combustion reaction. Through analysis EDTA oxidation processes by Fenton and UV-Fenton system, the results indicate that, just like combustion, AOPs are typical induction reactions. One most compelling example is that pre-feeding easily oxidizable organic matter can promote the oxidation of refractory organic compound when it was treated by AOPs. Connecting AOPs to combustion, it is possible to achieve some helpful enlightenment from combustion to analyze, predict and understand AOPs. In addition, we assume that maybe other oxidation reactions also have induced effects, such as corrosion, aging and passivation. Muchmore research is necessary to reveal the possibilities of induced effects in those fields.

  20. Induced effects of advanced oxidation processes

    PubMed Central

    Liu, Peng; Li, Chaolin; Zhao, Zhuanjun; Lu, Gang; Cui, Haibo; Zhang, Wenfang

    2014-01-01

    Hazardous organic wastes from industrial, military, and commercial activities represent one of the greatest challenges to human beings. Advanced oxidation processes (AOPs) are alternatives to the degradation of those organic wastes. However, the knowledge about the exact mechanisms of AOPs is still incomplete. Here we report a phenomenon in the AOPs: induced effects, which is a common property of combustion reaction. Through analysis EDTA oxidation processes by Fenton and UV-Fenton system, the results indicate that, just like combustion, AOPs are typical induction reactions. One most compelling example is that pre-feeding easily oxidizable organic matter can promote the oxidation of refractory organic compound when it was treated by AOPs. Connecting AOPs to combustion, it is possible to achieve some helpful enlightenment from combustion to analyze, predict and understand AOPs. In addition, we assume that maybe other oxidation reactions also have induced effects, such as corrosion, aging and passivation. Muchmore research is necessary to reveal the possibilities of induced effects in those fields. PMID:24503715

  1. Bystanding an abused child: testing the applicability of the stages of change construct.

    PubMed

    Mudde, Aart N; Hoefnagels, Cees J; Van Wijnen, Lisa G C; Kremers, Stef P J

    2007-02-01

    A minority of child abuse cases is recognized by professionals, making the role of non-professional bystanders essential. The stages of change construct, as proposed by the Transtheoretical Model, may provide a useful approach to explain non-professional helping behavior. The objective of this study was to test the applicability of the stages of change construct by (i) assessing whether cognitive determinants distinguish between the stages, (ii) testing the predictive value of the stages for future helping behavior and (iii) examining the mediating role of the stages in the relation between previous and future helping behavior. Data of 126 adult non-professional bystanders were analyzed. Respondents were questioned by telephone or via an Internet questionnaire, at baseline and after a follow-up of about two months later. Attitude toward helping was significantly less positive in pre-contemplation than in the other stages, and self-efficacy expectations were significantly higher in preparation compared with the other stages. Moreover, baseline preparators were more likely to conduct future helping behavior than those in the two earlier stages. Finally, the stages of change mediated the relation between previous and future helping behavior. Initial support was found for the applicability of the stages of change construct for helping behavior by non-professional bystanders. PMID:16849390

  2. Cytomegalovirus generates long-lived antigen-specific NK cells with diminished bystander activation to heterologous infection

    PubMed Central

    Min-Oo, Gundula

    2014-01-01

    Natural killer (NK) cells play a key role in the host response to cytomegalovirus (CMV) and can mediate an enhanced response to secondary challenge with CMV. We assessed the ability of mouse CMV (MCMV)–induced memory Ly49H+ NK cells to respond to challenges with influenza, an acute viral infection localized to the lung, and Listeria monocytogenes, a systemic bacterial infection. MCMV-memory NK cells did not display enhanced activation or proliferation after infection with influenza or Listeria, as compared with naive Ly49H+ or Ly49H− NK cells. Memory NK cells also showed impaired activation compared with naive cells when challenged with a mutant MCMV lacking m157, highlighting their antigen-specific response. Ex vivo, MCMV-memory NK cells displayed reduced phosphorylation of STAT4 and STAT1 in response to stimulation by IL-12 and type I interferon (IFN), respectively, and IFN-γ production was reduced in response to IL-12 + IL-18 compared with naive NK cells. However, costimulation of MCMV-memory NK cells with IL-12 and m157 antigen rescues their impaired response compared with cytokines alone. These findings reveal that MCMV-primed memory NK cells are diminished in their response to cytokine-driven bystander responses to heterologous infections as they become specialized and antigen-specific for the control of MCMV upon rechallenge. PMID:25422494

  3. Non-targeted radiation effects in vivo: a critical glance of the future in radiobiology.

    PubMed

    Hatzi, Vasiliki I; Laskaratou, Danae A; Mavragani, Ifigeneia V; Nikitaki, Zacharenia; Mangelis, Anastasios; Panayiotidis, Mihalis I; Pantelias, Gabriel E; Terzoudi, Georgia I; Georgakilas, Alexandros G

    2015-01-01

    Radiation-induced bystander effects (RIBE), demonstrate the induction of biological non-targeted effects in cells which have not directly hit by radiation or by free radicals produced by ionization events. Although RIBE have been demonstrated using a variety of biological endpoints the mechanism(s) of this phenomenon still remain unclear. The controversial results of the in vitro RIBE and the evidence of non-targeted effects in various in vivo systems are discussed. The experimental evidence on RIBE, indicate that a more analytical and mechanistic in depth approach is needed to secure an answer to one of the most intriguing questions in radiobiology. PMID:24333869

  4. Bystander position taking in school bullying: the role of positive identity, self-efficacy, and self-determination.

    PubMed

    Tsang, Sandra K M; Hui, Eadaoin K P; Law, Bella C M

    2011-01-01

    School bullying has become an explicit, burgeoning problem challenging the healthy development of children and adolescents in Hong Kong. Many bullying prevention and intervention programs focus on victims and bullies, with bystanders treated as either nonexistent or irrelevant. This paper asserts that bystanders actually play pivotal roles in deciding whether the bullying process and dynamics are benign or adversarial. Bystanders' own abilities and characteristics often influence how they respond to victims and bullies. "P.A.T.H.S. to Adulthood: A Jockey Club Youth Enhancement Scheme" (P.A.T.H.S. = Positive Adolescent Training through Holistic Social Programmes) is an evidence-based positive youth development program which shows that primary intervention programs have constructive impacts on junior secondary school students' beliefs and behavior. This paper asserts that intrapsychic qualities, namely identity, self-efficacy, and self-determination, greatly influence how bystanders react in school bullying situations. The paper also explains how classroom-based educational programs based on the P.A.T.H.S. model have been designed to help junior secondary school students strengthen these characteristics, so that they can be constructive bystanders when they encounter school bullying. PMID:22194663

  5. Educating for Justice: Creating a Mission-Driven Model of Bystander Intervention to Address Sexual Violence at U.S. Catholic Colleges and Universities

    ERIC Educational Resources Information Center

    Galarneau, Joy; O'Neill, Shannon

    2015-01-01

    This article presents bystander intervention education as a best-practice approach to sexual violence prevention in college settings. It draws out a connection between mission-specific resources that can be used to advance the prevention agenda, while examining how bystander intervention education can deepen community engagement in collegiate…

  6. Overlapped optics induced perfect coherent effects.

    PubMed

    Li, Jian Jie; Zang, Xiao Fei; Mao, Jun Fa; Tang, Min; Zhu, Yi Ming; Zhuang, Song Lin

    2013-01-01

    For traditional coherent effects, two separated identical point sources can be interfered with each other only when the optical path difference is integer number of wavelengths, leading to alternate dark and bright fringes for different optical path difference. For hundreds of years, such a perfect coherent condition seems insurmountable. However, in this paper, based on transformation optics, two separated in-phase identical point sources can induce perfect interference with each other without satisfying the traditional coherent condition. This shifting illusion media is realized by inductor-capacitor transmission line network. Theoretical analysis, numerical simulations and experimental results are performed to confirm such a kind of perfect coherent effect and it is found that the total radiation power of multiple elements system can be greatly enhanced. Our investigation may be applicable to National Ignition Facility (NIF), Inertial Confined Fusion (ICF) of China, LED lighting technology, terahertz communication, and so on. PMID:24356577

  7. Torsion-induced effects in magnetic nanowires

    NASA Astrophysics Data System (ADS)

    Sheka, Denis D.; Kravchuk, Volodymyr P.; Yershov, Kostiantyn V.; Gaididei, Yuri

    2015-08-01

    A magnetic helix wire is one of the simplest magnetic systems which manifests properties of both curvature and torsion. Possible equilibrium magnetization states in the helix wire with different anisotropy directions are studied theoretically. There exist two equilibrium states in the helix wire with easy-tangential anisotropy: a quasitangential magnetization distribution in the case of relatively small curvatures and torsions, and an onion state in the opposite case. The curvature and torsion also essentially influence the spin-wave dynamics in the helix wire, acting as an effective magnetic field. Originated from a geometry-induced effective Dzyaloshinskii interaction, this magnetic field leads to a coupling between the helix chirality and the magnetochirality and breaks mirror symmetry in the spin-wave spectrum: the modification of magnon dispersion relation is linear with respect to the torsion and quadratic with respect to the curvature. All analytical predictions on magnetization statics and dynamics are well confirmed by direct spin-lattice simulations.

  8. Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro.

    PubMed

    Jasiulewicz, Aleksandra; Lisowska, Katarzyna A; Pietruczuk, Krzysztof; Frąckowiak, Joanna; Fulop, Tamas; Witkowski, Jacek M

    2015-11-01

    The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re)stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these Th-derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge. PMID:25995267

  9. Nitrogen isotope effects induced by anammox bacteria

    PubMed Central

    Brunner, Benjamin; Contreras, Sergio; Lehmann, Moritz F.; Matantseva, Olga; Rollog, Mark; Kalvelage, Tim; Klockgether, Gabriele; Lavik, Gaute; Jetten, Mike S. M.; Kartal, Boran; Kuypers, Marcel M. M.

    2013-01-01

    Nitrogen (N) isotope ratios (15N/14N) provide integrative constraints on the N inventory of the modern ocean. Anaerobic ammonium oxidation (anammox), which converts ammonium and nitrite to dinitrogen gas (N2) and nitrate, is an important fixed N sink in marine ecosystems. We studied the so far unknown N isotope effects of anammox in batch culture experiments. Anammox preferentially removes 14N from the ammonium pool with an isotope effect of +23.5‰ to +29.1‰, depending on factors controlling reversibility. The N isotope effects during the conversion of nitrite to N2 and nitrate are (i) inverse kinetic N isotope fractionation associated with the oxidation of nitrite to nitrate (−31.1 ± 3.9‰), (ii) normal kinetic N isotope fractionation during the reduction of nitrite to N2 (+16.0 ± 4.5‰), and (iii) an equilibrium N isotope effect between nitrate and nitrite (−60.5 ± 1.0‰), induced when anammox is exposed to environmental stress, leading to the superposition of N isotope exchange effects upon kinetic N isotope fractionation. Our findings indicate that anammox may be responsible for the unresolved large N isotope offsets between nitrate and nitrite in oceanic oxygen minimum zones. Irrespective of the extent of N isotope exchange between nitrate and nitrite, N removed from the combined nitrite and nitrate (NOx) pool is depleted in 15N relative to NOx. This net N isotope effect by anammox is superimposed on the N isotope fractionation by the co-occurring reduction of nitrate to nitrite in suboxic waters, possibly enhancing the overall N isotope effect for N loss from oxygen minimum zones. PMID:24191043

  10. Tubulointerstitial Nephritis and Uveitis Syndrome: Are Drugs Offenders or Bystanders?

    PubMed Central

    Kawamata, Mutsumi; Akimoto, Tetsu; Sugase, Taro; Otani-Takei, Naoko; Miki, Takuya; Masuda, Takahiro; Kobayashi, Takahisa; Takeda, Shin-ichi; Muto, Shigeaki; Nagata, Daisuke

    2016-01-01

    A 16-year-old female patient was admitted to our hospital due to progressive renal dysfunction with an increased serum creatinine (sCr) level of 1.7 mg/dL. Her clinical course without any ocular manifestations and results of drug-induced, lymphocyte-stimulating tests, in addition to a renal histological assessment, initially encouraged us to ascribe the patient’s renal abnormalities to drug-induced acute interstitial nephritis (AIN). Four months later, she started to complain about reduced visual acuity when she was found to have anterior bilateral uveitis despite the recovered renal function with almost constant sCr levels around 0.7 mg/dL. Thus, a diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was finally made. Our case illustrates the difficulties in distinguishing late-onset uveitis TINU syndrome from drug-induced AIN at the time of the renal biopsy, thereby suggesting the importance of a longitudinal follow-up to overcome the potential underdiagnosis of the disease. Several diagnostic conundrums that emerged in this case are also discussed. PMID:26997878

  11. Bystander responses to a violent incident in an immersive virtual environment.

    PubMed

    Slater, Mel; Rovira, Aitor; Southern, Richard; Swapp, David; Zhang, Jian J; Campbell, Claire; Levine, Mark

    2013-01-01

    Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the in-group condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation. PMID:23300991

  12. Bystander Responses to a Violent Incident in an Immersive Virtual Environment

    PubMed Central

    Slater, Mel; Rovira, Aitor; Southern, Richard; Swapp, David; Zhang, Jian J.; Campbell, Claire; Levine, Mark

    2013-01-01

    Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the in-group condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation. PMID:23300991

  13. Bringing in the target audience in bystander social marketing materials for communities: suggestions for practitioners.

    PubMed

    Potter, Sharyn J; Stapleton, Jane G

    2011-06-01

    The Know Your Power™ social marketing campaign images model active bystander behaviors that target audience members can use in situations where sexual and relationship violence and stalking are occurring, have occurred, or have the potential to occur. In this practitioner note, we describe strategies that we have used to engage target audience members in the development of the social marketing campaign that we hope can be used by practitioners. We give examples from the development and evaluation of the Know Your Power(TM) social marketing campaign that used focus group and other types of feedback from the target audience to inform the direction of the campaign. PMID:21727157

  14. Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

    NASA Astrophysics Data System (ADS)

    Azzam, Edouard

    Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial

  15. A tale of two cities: The role of neighborhood socioeconomic status in spatial clustering of bystander CPR in Austin and Houston☆

    PubMed Central

    Root, Elisabeth Dowling; Gonzales, Louis; Persse, David E.; Hinchey, Paul R.; McNally, Bryan; Sasson, Comilla

    2013-01-01

    Background Despite evidence to suggest significant spatial variation in out-of-hospital cardiac arrest (OHCA) and bystander cardiopulmonary resuscitation (BCPR) rates, geographic information systems (GIS) and spatial analysis have not been widely used to understand the reasons behind this variation. This study employs spatial statistics to identify the location and extent of clusters of bystander CPR in Houston and Travis County, TX. Methods Data were extracted from the Cardiac Arrest Registry to Enhance Survival for two U.S. sites –Austin-Travis County EMS and the Houston Fire Department – between October 1, 2006 and December 31, 2009. Hierarchical logistic regression models were used to assess the relationship between income and racial/ethnic composition of a neighborhood and BCPR for OHCA and to adjust expected counts of BCPR for spatial cluster analysis. The spatial scan statistic was used to find the geographic extent of clusters of high and low BCPR. Results Results indicate spatial clusters of lower than expected BCPR rates in Houston. Compared to BCPR rates in the rest of the community, there was a circular area of 4.2 km radius where BCPR rates were lower than expected (RR = 0.62; p < 0.0001 and RR = 0.55; p = 0.037) which persist when adjusted for individual-level patient characteristics (RR = 0.34; p = 0.027) and neighborhood-level race (RR = 0.34; p = 0.034) and household income (RR = 0.34; p = 0.046). We also find a spatial cluster of higher than expected BCPR in Austin. Compared to the rest of the community, there was a 23.8 km radius area where BCPR rates were higher than expected (RR = 1.75; p = 0.07) which disappears after controlling for individual-level characteristics. Conclusions A geographically targeted CPR training strategy which is tailored to individual and neighborhood population characteristics may be effective in reducing existing disparities in the provision of bystander CPR for out-of-hospital cardiac arrest. PMID:23318916

  16. Complement-induced regulatory T cells suppress T-cell responses but allow for dendritic-cell maturation

    PubMed Central

    Barchet, Winfried; Price, Jeffrey D.; Cella, Marina; Colonna, Marco; MacMillan, Sandra K.; Cobb, J. Perren; Thompson, Paul A.; Murphy, Kenneth M.; Atkinson, John P.; Kemper, Claudia

    2006-01-01

    Concurrent activation of the T-cell receptor (TCR) and complement regulator CD46 on human CD4+ T lymphocytes induces Tr1-like regulatory T cells that suppress through IL-10 secretion bystander T-cell proliferation. Here we show that, despite their IL-10 production, CD46-induced T-regulatory T cells (Tregs) do not suppress the activation/maturation of dendritic cells (DCs). DC maturation by complement/CD46-induced Tregs is mediated through simultaneous secretion of GM-CSF and soluble CD40L, factors favoring DC differentiation and reversing inhibitory effects of IL-10. Thus, CD46-induced Tregs produce a distinct cytokine profile that inhibits T-cell responses but leaves DC activation unimpaired. Such “DC-sparing” Tregs could be desirable at host/environment interfaces such as the gastrointestinal tract where their specific cytokine profile provides a mechanism that ensures unresponsiveness to commensal bacteria while maintaining reactivity to invading pathogens. PMID:16239430

  17. Acute phase glycoproteins: bystanders or participants in carcinogenesis?

    PubMed

    Dempsey, Eugene; Rudd, Pauline M

    2012-04-01

    Acute phase proteins (APPs) are a group of serum proteins that undergo dramatic changes in concentration during times of inflammation. Many APPs are heavily glycosylated, and their sugar content and complexity change in the presence of cancer-induced chronic inflammation. These changes in glycosylation are currently being exploited in the search for novel biomarkers of cancer. Like other posttranslational modifications, such as phosphorylation, changes in glycosylation can profoundly alter the function of a protein. We hypothesize that besides being a rich source of potential biomarkers APPs may also play an active role in tumorigenesis. The glycan content of the APPs haptoglobin and kininogen, for example, is altered in many types of cancer. These APPs can interact with a number of receptors on macrophages in the tumor microenvironment, potentially modulating macrophage activity and thereby contributing to tumor cell survival, growth, and metastasis. PMID:22352780

  18. The relative biological effectiveness of out-of-field dose

    NASA Astrophysics Data System (ADS)

    Balderson, Michael; Koger, Brandon; Kirkby, Charles

    2016-01-01

    Purpose: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. Materials and methods: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. Results: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. Conclusions: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions.

  19. Achalasia and chronic opiate use: innocent bystanders or associated conditions?

    PubMed

    Ravi, K; Murray, J A; Geno, D M; Katzka, D A

    2016-01-01

    High-resolution manometry identifies three subtypes of achalasia. However, type 3 differs from classic achalasia. Although opiates affect esophageal motility, opiate use and achalasia have not been studied. Patients with a new diagnosis of achalasia at Mayo Clinic Rochester between June 1, 2012 and January 3, 2014 were identified. Clinical records were reviewed to assess symptoms, opiate use, and therapy. Fifty-six patients with achalasia were identified, 14 (25%) were on opiates. Opiate prescription was unrelated to achalasia in all cases, with chronic back and joint pain constituting the majority. Of patients on opiates, five (36%) had type 3 achalasia compared with four (10%) not on opiates (P = 0.02). No patients on opiates had type 1 achalasia. Clinical presentation did not differ with opiates, although those on opiates were more likely to report chest pain (39 vs. 14%, P = 0.05) and less likely to have esophageal dilation (62 vs. 82%, P = 0.13), none with greater than 5-cm diameter. Contractile vigor was greater with opiate use, with distal contractile integral of 7149 versus 2615.5 mmHg/cm/second (P = 0.08). Treatment response was inferior on opiates, with persistent symptoms in 22% compared with 3% without opiates (P = 0.06). Opiate use is common in type 3 achalasia, with the majority of patients on opiates. No patients on opiates were diagnosed with type 1 achalasia. Manometric findings of type 3 achalasia mimic those induced by opiates, suggesting a physiologic mechanism for opiate induced type 3 achalasia. Treatment outcome is inferior with opiates, with opiate cessation perhaps preferable. Further studies assessing opiate use and achalasia are needed. PMID:25604060

  20. The role of gender, values, and culture in adolescent bystanders' strategies.

    PubMed

    Tamm, Anni; Tulviste, Tiia

    2015-02-01

    We examined the relationship between adolescent bystanders' strategies for intervening in the bullying-like situation and their gender, values, and cultural origin. The sample consisted of 682 Estonian and Russian-Estonian adolescents (M age = 13.02 years). They were shown a video of a bullying-like situation with a non-intervening adult bystander and asked to describe what they would do if they, instead of the adult, witnessed that situation. Only 10% said that they would not intervene. Girls were more likely than boys to suggest multiple actions. Adolescents who valued conformity were less likely to propose using physical aggression. Doing nothing was less likely suggested by those who placed more importance on conformity and less on power. Estonian adolescents were more likely than their Russian-Estonian peers to suggest finding out what is going on, and less likely to say that they would do nothing. The findings suggest that although most adolescents express willingness to help the victim, they might not actually know how to intervene. PMID:24919991

  1. Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner.

    PubMed

    White, Jason T; Cross, Eric W; Burchill, Matthew A; Danhorn, Thomas; McCarter, Martin D; Rosen, Hugo R; O'Connor, Brian; Kedl, Ross M

    2016-01-01

    Virtual memory cells (VM) are an antigen-specific, memory phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM cells were the result of homeostatic proliferation (HP) resembling the proliferation observed in a lymphopenic environment. Here we demonstrate that HP is ongoing in lymphoreplete mice, the degree of which is dictated by the number of naive CD8 T cells with a sufficiently high affinity for self-antigen interacting with peripheral IL-15. VM cell transcriptional profiles suggest a capacity to mediate protective immunity via antigen non-specific bystander killing, a function we show is dependent on IL-15. Finally, we show a VM-like population of human cells that accumulate with age and traffic to the liver, displaying phenotypic and functional attributes consistent with the bystander protective functions of VM cells identified in the mouse. These data identify developmental and functional attributes of VM cells, including their likely role in protective immunity. PMID:27097762

  2. Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner

    PubMed Central

    White, Jason T.; Cross, Eric W.; Burchill, Matthew A.; Danhorn, Thomas; McCarter, Martin D.; Rosen, Hugo R.; O'Connor, Brian; Kedl, Ross M.

    2016-01-01

    Virtual memory cells (VM) are an antigen-specific, memory phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM cells were the result of homeostatic proliferation (HP) resembling the proliferation observed in a lymphopenic environment. Here we demonstrate that HP is ongoing in lymphoreplete mice, the degree of which is dictated by the number of naive CD8 T cells with a sufficiently high affinity for self-antigen interacting with peripheral IL-15. VM cell transcriptional profiles suggest a capacity to mediate protective immunity via antigen non-specific bystander killing, a function we show is dependent on IL-15. Finally, we show a VM-like population of human cells that accumulate with age and traffic to the liver, displaying phenotypic and functional attributes consistent with the bystander protective functions of VM cells identified in the mouse. These data identify developmental and functional attributes of VM cells, including their likely role in protective immunity. PMID:27097762

  3. Bystanders' Reactions to Bullying: A Cross-Cultural Analysis of Personal Correlates among Italian and Singaporean Students

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Ang, Rebecca P.; Gini, Gianluca

    2012-01-01

    This study examined the role of attitudes against bullying and perceived peer pressure for intervention in explaining defending the victim and passive bystanding behavior in bullying. Participants were 1031 school-age children from two culturally diverse settings, namely Italy and Singapore, which are similar on several dimensions (e.g., quality…

  4. The Role of Individual Correlates and Class Norms in Defending and Passive Bystanding Behavior in Bullying: A Multilevel Analysis

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Gini, Gianluca; Vieno, Alessio

    2012-01-01

    This study investigates possible individual and class correlates of defending and passive bystanding behavior in bullying, in a sample of 1,825 Italian primary school (mean age = 10 years 1 month) and middle school (mean age = 13 years 2 months) students. The findings of a series of multilevel regression models show that both individual (e.g.,…

  5. Active Defending and Passive Bystanding Behavior in Bullying: The Role of Personal Characteristics and Perceived Peer Pressure

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Gini, Gianluca

    2010-01-01

    This study examined the role of pro-victim attitudes, personal responsibility, coping responses to observations of bullying, and perceived peer normative pressure in explaining defending the victim and passive bystanding behavior in bullying. A total of 462 Italian early adolescents (mean age = 13.4 years, SD = 9 months) participated in the study.…

  6. How Students' Perceptions of the School Climate Influence Their Choice to Upstand, Bystand, or Join Perpetrators of Bullying

    ERIC Educational Resources Information Center

    Ferráns, Silvia Diazgranados; Selman, Robert L.

    2014-01-01

    The authors of this article, Silvia Diazgranados Ferráns and Robert Selman, use an emergent framework to explore how the rules of the school culture at different perceived school climates affect early adolescents' decisions to upstand, bystand, or join the perpetrators when they witness peer aggression and bullying. Through a grounded theory…

  7. The Emergence of New Paradigms in Student-University Relations: From In Loco Parentis to Bystander to Facilitator.

    ERIC Educational Resources Information Center

    Bickel, Robert D.; Lake, Peter F.

    1997-01-01

    University liability is in transition; its role changing from a parental/custodial "in loco parentis" model (and then a bystander role) to a new model of facilitator. The university enjoys a position of authority and respect, while exercising control more subtly than in the mid-1990s. At the same time, universities may be unable to claim the same…

  8. Sexual Violence Prevention through Bystander Education: An Experimental Evaluation

    ERIC Educational Resources Information Center

    Banyard, Victoria L.; Moynihan, Mary M.; Plante, Elizabethe G.

    2007-01-01

    The current study used an experimental design to evaluate a sexual violence prevention program based on a community of responsibility model that teaches women and men how to intervene safely and effectively in cases of sexual violence before, during, and after incidents with strangers, acquaintances, or friends. It approaches both women and men as…

  9. From Bystander to Ally: Transforming the District Human Resources Department

    ERIC Educational Resources Information Center

    Campbell, Christine; DeArmond, Michael; Schumwinger, Abigail

    2004-01-01

    Although policymakers and academics tend to overlook the behind-the-scenes role that district human resources (HR) departments play in education, the HR office's effect is far from small. HR departments determine whether qualified teacher candidates make it to the classroom, or slip through the cracks. They can help principals find teachers who…

  10. Vaccination Expands Antigen-Specific CD4+ Memory T Cells and Mobilizes Bystander Central Memory T Cells

    PubMed Central

    Li Causi, Eleonora; Parikh, Suraj C.; Chudley, Lindsey; Layfield, David M.; Ottensmeier, Christian H.; Stevenson, Freda K.; Di Genova, Gianfranco

    2015-01-01

    CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7RαLow and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7Rα and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines. PMID:26332995

  11. Bioelectromagnetic effects measurements - SAR and induced current.

    PubMed

    Dlugosz, Tomasz

    2015-01-01

    The paper discusses several theoretical and practical aspects of the application of currents flowing through the body of a radiotelephone operator and Specific Absorption Rate (SAR). SAR is known as the physical quantity which is a perfect solution for biological experiments. Unfortunately, SAR cannot be measured directly. Contrary to SAR, which is limited to the penetration depth, a current induced in a point of a body is measurable in any other point of the body. The main objective of this paper is to show that the current induced in a human body when using a radiotelephone or mobile phone is significant and should be analyzed as widely as SAR is. Computer simulations of a human's hand with a radiotelephone were made. Experiments were also conducted. The results of the experiments show that induced current is also as important as SAR and it cannot be omitted in bioelectromagnetic experiments. In biomedical studies both parameters: induced current and SAR play a major role. PMID:25585976

  12. Non-targeted effects of radiation exposure: recent advances and implications.

    PubMed

    Kadhim, M A; Hill, M A

    2015-09-01

    The target theory of radiation-induced effects has been challenged by numerous studies, which indicate that in addition to biological effects resulting from direct DNA damage within the cell, a variety of non-DNA targeted effects (NTE) may make important contributions to the overall outcome. Ionising radiation induces complex, global cellular responses, such as genomic instability (GI) in both irradiated and never-irradiated 'bystander' cells that receive molecular signals produced by irradiated cells. GI is a well-known feature of many cancers, increasing the probability of cells to acquire the 'hallmarks of cancer' during the development of tumours. Although epidemiological data include contributions of both direct and NTE, they lack (i) statistical power at low dose where differences in dose response for NTE and direct effects are likely to be more important and (ii) heterogeneity of non-targeted responses due to genetic variability between individuals. In this article, NTE focussing on GI and bystander effects were critically examined, the specific principles of NTE were discussed and the potential influence on human health risk assessment from low-dose radiation was considered. PMID:25897137

  13. A patient with commotio cordis successfully resuscitated by bystander cardiopulmonary resuscitation and automated external defibrillator.

    PubMed

    Ngai, K Y; Chan, H Y; Ng, F

    2010-10-01

    Sudden deaths of children and adolescents during competitive sports are usually due to congenital heart diseases. Ventricular fibrillation, however, may also occur in individuals with no underlying cardiac disease who have sustained a low-impact chest wall blow. This phenomenon is described as commotio cordis, and the overall survival rate is poor. Successful resuscitation can be achieved by prompt cardiopulmonary resuscitation and early defibrillation. We report a teenager who sustained a chest wall blow that resulted in a cardiac arrest during a rugby competition. Cardiopulmonary resuscitation was given by bystanders. The ambulance crew arrived with an automated external defibrillator. Ventricular fibrillation was detected and responded to defibrillation. Subsequent investigations including imaging and electrophysiological studies did not reveal any cardiac or brain abnormality, and the patient recovered well neurologically. Accessible cardiopulmonary resuscitation-trained personnel and automated external defibrillators should be present at all organised sporting events. PMID:20890008

  14. The bone marrow stroma in hematological neoplasms—a guilty bystander

    PubMed Central

    Tripodo, Claudio; Sangaletti, Sabina; Piccaluga, Pier P.; Prakash, Sonam; Franco, Giovanni; Borrello, Ivan; Orazi, Attilio; Colombo, Mario P.; Pileri, Stefano A.

    2013-01-01

    In the setting of hematological neoplasms, changes in the bone marrow (BM) stroma might arise from pressure exerted by the neoplastic clone in shaping a supportive microenvironment, or from chronic perturbation of the BM homeostasis. Under such conditions, alterations in the composition of the BM stroma can be profound, and could emerge as relevant prognostic factors. In this Review, we delineate the multifaceted contribution of the BM stroma to the pathobiology of several hematological neoplasms, and discuss the impact of stromal modifications on the natural course of these diseases. Specifically, we highlight the involvement of BM stromal components in lymphoid and myeloid malignancies, and present the most relevant processes responsible for remodeling the BM stroma. The role of bystander BM stromal elements in the setting of hematological neoplasms is discussed, strengthening the rationale for treatment strategies that target the BM stroma. PMID:21448151

  15. Re-Evaluating Sexual Violence Prevention Through Bystander Education: A Latent Growth Curve Approach.

    PubMed

    Shaw, Jessica; Janulis, Patrick

    2016-10-01

    Recently, there has been a call for more advanced analytic techniques in violence against women research, particularly in community interventions that use longitudinal designs. The current study re-evaluates experimental evaluation data from a sexual violence bystander intervention program. Using an exploratory latent growth curve approach, we were able to model the longitudinal growth trajectories of individual participants over the course of the entire study. Although the results largely confirm the original evaluation findings, the latent growth curve approach better fits the demands of "messy" data (e.g., missing data, varying number of time points per participant, and unequal time spacing within and between participants) that are frequently obtained during a community-based intervention. The benefits of modern statistical techniques to practitioners and researchers in the field of sexual violence prevention, and violence against women more generally, are further discussed. PMID:25888503

  16. The role of individual and collective moral disengagement in peer aggression and bystanding: a multilevel analysis.

    PubMed

    Gini, Gianluca; Pozzoli, Tiziana; Bussey, Kay

    2015-04-01

    This study investigates the relationships between individual and collective moral disengagement and aggression-related behaviors (peer aggression, defending, and passive bystanding) among 918 adolescents (55.8% boys; M age = 14.1 years, SD = 1.1). Hierarchical linear modeling showed that, at the individual level, aggressive behavior was significantly explained by both individual moral disengagement and student perceived collective moral disengagement, which was also positively associated with defending. Student perceived collective moral disengagement moderated the link between individual moral disengagement and peer aggression. At the class level, classroom collective moral disengagement explained between-class variability in all the three aggression-related behaviors. These results extend previous research by demonstrating the role of collective moral disengagement at the individual and the class levels and have potential implications for interventions. PMID:25123080

  17. Exercise-related sudden cardiac arrest in London: incidence, survival and bystander response

    PubMed Central

    Edwards, Melanie J; Fothergill, Rachael T

    2015-01-01

    Objective The study aimed to (1) establish the incidence of exercise-related sudden cardiac arrest (SCA) in London, (2) investigate survival from exercise-related SCA and (3) examine factors related to survival. Method This retrospective observational study examined 2 years’ data from the London Ambulance Service (LAS) cardiac arrest registry for patients in whom resuscitation was attempted following an out-of-hospital cardiac arrest (OHCA), a cardiac cause was presumed and the arrest occurred during or within 1 h of exercise. Results The incidence of exercise-related SCA in London was estimated to be 0.6 per 100 000 person-years which equated to 0.5% of all OHCA, and 1.5% of all OHCA with presumed cardiac aetiology and resuscitation attempted. The majority of cases were male and the incidence increased from age 40 years. Just under one-third of patients survived to hospital discharge. Survival in the Utstein comparator group (cases with presumed cardiac aetiology, resuscitation attempted, bystander witnessed and a presenting cardiac rhythm of ventricular fibrillation or tachycardia) was higher at 42%. Survival was significantly associated with initial cardiac rhythm (χ2=17.5, df=2, p<0.001) and bystander defibrillation (Fisher's exact test, p<0.05). Conclusions Incidence of exercise-related SCA in the general population in London is rare. Survival following exercise-related SCA was considerably higher than survival for all OHCA with presumed cardiac aetiology and resuscitation attempted attended by the LAS during the same period. The major limitation of the study is the likely under identification of cases of exercise-related SCA. PMID:26468401

  18. Radiation Induced Genomic Instability

    SciTech Connect

    Morgan, William F.

    2011-03-01

    themselves to prolonged study, many tend to eliminate or rearrange the target chromosome until it is too small for further rearrangement. The observed frequency of induced instability by low and high linear-energy-transfer radiations greatly exceeds that observed for nuclear gene mutations at similar doses; hence, mutation of a gene or gene family is unlikely to be the initiating mechanism. Once initiated however, there is evidence in the GM10115 model system that it can be perpetuated over time by dicentric chromosome formation followed by bridge breakage fusion cycles (Marder and Morgan 1993), as well as recombinational events involving interstitial telomere like repeat sequences (Day et al. 1998). There is also increasing evidence that inflammatory type reactions (Lorimore et al. 2001, Lorimore and Wright 2003), presumably involving reactive oxygen and nitrogen species as well as cytokines and chemokines might be involved in driving the ustable phenotype (Liaikis et al. 2007, Hei et al. 2008). To this end there is very convincing evidence for such reactions being involved in another non-targeted effect associated with ionizing radiation, the bystander effect (Hei et al. 2008). Clearly the link between induced instability and bystander effects suggests common processes and inflammatory type reactions will likely be the subject of future investigation.

  19. Bullying Bystanders

    ERIC Educational Resources Information Center

    Jeffrey, Linda R.

    2004-01-01

    Bullies like an audience, and bullying is often a public interaction in which there are perceived winners and losers. While some victims are targeted because of a perceived vulnerability or difference, it is also the case that anyone can become a victim of bullying. As such, students intuitively weigh their own chances of becoming victims and…

  20. The study on space-flight induced DNA damage in Arabidopsis thaliana using the related homologous recombination reporter system

    NASA Astrophysics Data System (ADS)

    Sun, Qiao; Nechitailo, Galina S.; Lu, Jinying; Liu, Min; Li, Huasheng

    Usually, phenotype changes of plants were used to analayze the responding genetic damages. However, this method is time-consuming, laborious and needs a long period. Here, we developed an Arabidopsis thaliana homologous recombination reporter system, in which HR frequency and HR-related AtRAD54 gene expression level were used as mutagenic end points. Based on the system, effect of DNA damage by space-flight during the Shenzhou-9 mission was investigated. In this study, an Arabidopsis thaliana-line transgenic for GUS recombination substrates (R3L66, AtRAD54promoter:: GFP + GUS) was used to study the mutagenicity of space-flight, and the results showed that 13 days space-flight exposure of seedlings induced a significant increase in HRF compared with its ground-base three-dimensional clinostat (generally called a random positioning machine or RPM, an effective simulator of microgravity) controls and ground 1g controls. We also observed three-dimensional clinostat induced a significant increase in HRF and HR-related AtRAD54 gene expression level compared with ground 1g controls. Treatment with the ROS scavenger DMSO dramatically reduced the effects of simulated microgravity on the induction of HR and expression of the AtRAD54 gene, suggesting that ROS play a critical role in mediating the simulated microgravity mutagenic effects in plants. In order to understand the combined effects of radiation and microgravity (the main factors in space environment) on DNA damage, we further investigated the effects of modeled microgravity on radiation-induced bystander effects (RIBE) n vivo in A. thaliana plants using the expression level of the HR-related AtRAD54 gene as mutagenic end points. The results showed that the modeled microgravity significantly inhibited the up-regulated expression of the AtRAD54 gene in bystander aerial plants after root irradiation, suggesting a repressive effect of microgravity on RIBE.

  1. Effective radii of deuteron-induced reactions

    SciTech Connect

    Hashimoto, Shintaro; Chiba, Satoshi; Yahiro, Masanobu; Ogata, Kazuyuki; Minomo, Kosho

    2011-05-15

    The continuum-discretized coupled-channels method (CDCC) for exclusive reactions and the eikonal reaction theory (ERT) as an extension of CDCC to inclusive reactions are applied to deuteron-induced reactions. The CDCC result reproduces experimental data on the reaction cross section for d+{sup 58}Ni scattering at 200 MeV/nucleon, and ERT provides data on the neutron-stripping cross section for inclusive {sup 7}Li(d,n) reaction at 40 MeV. For deuteron-induced reactions at 200 MeV/nucleon, target-dependence of the reaction, elastic-breakup, nucleon-stripping, nucleon-removal, and complete- and incomplete-fusion cross sections is clearly explained by simple formulas. Accuracy of the Glauber model is also investigated.

  2. Engaging Active Bystanders in Mass Casualty Events and Other Life-Threatening Emergencies: A Pilot Training Course Demonstration.

    PubMed

    Smith, Tracey O; Baker, Susan D; Roberts, Kathryn; Payne, Skip A

    2016-04-01

    Emerging research indicates the critical role members of the public can play in saving lives and reducing morbidity at the scene in the immediate aftermath of a disaster. It is anticipated that with training, more members of the public will be ready and able to assist should they be present at mass casualty events or other circumstances in which there are serious injuries or potential loss of life. This article describes a training course developed by multiple federal and nonfederal partners aimed at preparing the public to become "active bystanders" followed by a pilot demonstration project conducted by Medical Reserve Corps Units. The outcomes of the project indicated that the training was comprehensive and appropriate for members of the public with little or no first aid knowledge. National availability of the "Becoming an Active Bystander" training course is currently being planned. PMID:26841861

  3. The role of individual correlates and class norms in defending and passive bystanding behavior in bullying: a multilevel analysis.

    PubMed

    Pozzoli, Tiziana; Gini, Gianluca; Vieno, Alessio

    2012-11-01

    This study investigates possible individual and class correlates of defending and passive bystanding behavior in bullying, in a sample of 1,825 Italian primary school (mean age=10 years 1 month) and middle school (mean age=13 years 2 months) students. The findings of a series of multilevel regression models show that both individual (e.g., provictim attitudes and perceived peer pressure for intervention) and class characteristics (e.g., class provictim attitudes, peer injunctive norms, and descriptive norms) help explain defending and passive bystanding behavior in bullying. These results significantly expand previous findings in this field, by demonstrating the need for a social-ecological approach to the study of the different aspects of bullying. Implications for antibullying programs are discussed. PMID:22880944

  4. Arsenic exposure induces the Warburg effect in cultured human cells

    SciTech Connect

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T.

    2013-08-15

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

  5. Active defending and passive bystanding behavior in bullying: the role of personal characteristics and perceived peer pressure.

    PubMed

    Pozzoli, Tiziana; Gini, Gianluca

    2010-08-01

    This study examined the role of pro-victim attitudes, personal responsibility, coping responses to observations of bullying, and perceived peer normative pressure in explaining defending the victim and passive bystanding behavior in bullying. A total of 462 Italian early adolescents (mean age = 13.4 years, SD = 9 months) participated in the study. The behaviors were measured through two informants: each individual student and the teachers. The findings of a series of hierarchical regressions showed that, regardless of the informant, problem solving coping strategies and perceived peer normative pressure for intervention were positively associated with active help towards a bullied peer and negatively related to passivity. In contrast, distancing strategies were positively associated with passive bystanding, whereas they were negatively associated with teacher-reported defending behavior. Moreover, self-reported defending behavior was positively associated with personal responsibility for intervention, but only under conditions of low perceived peer pressure. Finally, the perception of peer pressure for intervention buffered the negative influence of distancing on passive bystanding tendencies. Future directions are discussed. PMID:20228996

  6. DECOHERENCE EFFECTS OF MOTION-INDUCED RADIATION

    SciTech Connect

    P. NETO; D. DALVIT

    2000-12-01

    The radiation pressure coupling with vacuum fluctuations gives rise to energy damping and decoherence of an oscillating particle. Both effects result from the emission of pairs of photons, a quantum effect related to the fluctuations of the Casimir force. We discuss different alternative methods for the computation of the decoherence time scale. We take the example of a spherical perfectly-reflecting particle, and consider the zero and high temperature limits. We also present short general reviews on decoherence and dynamical Casimir effect.

  7. Wavelength mismatch effect in electromagnetically induced absorption

    NASA Astrophysics Data System (ADS)

    Bharti, Vineet; Wasan, Ajay; Natarajan, Vasant

    2016-07-01

    We present a theoretical investigation of the phenomenon of electromagnetically induced absorption (EIA) in a 4-level system consisting of vee and ladder subsystems. The four levels are coupled using one weak probe field, and two strong control fields. We consider an experimental realization using energy levels of Rb. This necessitates dealing with different conditions of wavelength mismatch-near-perfect match where all three wavelengths are approximately equal; partial mismatch where the wavelength of one control field is less than the other fields; and complete mismatch where all three wavelengths are unequal. We present probe absorption profiles with Doppler averaging at room temperature to account for experiments in a room temperature Rb vapor cell. Our analysis shows that EIA resonances can be studied using Rydberg states excited with diode lasers.

  8. Effects of inhaled thiazinamium chloride on histamine-induced and exercise-induced bronchoconstriction.

    PubMed

    Gong, H; Brik, A; Tashkin, D P; Dauphinee, B

    1989-03-01

    The protective efficacy of aerosolized thiazinamium chloride (TC) against histamine-induced and exercise-induced bronchoconstriction was evaluated in 15 subjects with stable, mild asthma. Following reproducible bronchoprovocation with these stimuli, each subject underwent randomized, double-blind, crossover pretreatment with single doses of nebulized TC (300, 600, and 900 micrograms), placebo, and an active control drug (metaproterenol or cromolyn), followed by histamine or exercise challenge (two separate protocols). The results indicated that all doses of TC significantly blocked histamine-induced bronchoconstriction as compared with placebo. Overall, aerosolized TC was ineffective in blocking exercise-induced bronchoconstriction, although 900 micrograms TC tended to be more effective than placebo. Thiazinamium (900 micrograms) produced a modest bronchodilator effect. No clinically significant adverse effects related to TC occurred. We conclude that aerosolized TC is effective in attenuating histamine-induced but not exercise-induced bronchoconstriction in the doses studied. Further studies are warranted to evaluate the role of TC in asthma therapy. PMID:2564267

  9. PAS-1, a protein affinity purified from Ascaris suum worms, maintains the ability to modulate the immune response to a bystander antigen.

    PubMed

    Oshiro, Telma M; Enobe, Cristina S; Araújo, Cláudia A; Macedo, Mahasti S; Macedo-Soares, Maria Fernanda

    2006-04-01

    Helminth infections and parasite components have potent immunomodulatory effects on a host's immune system. In the present study, we investigated the effect of PAS-1, a protein component of Ascaris suum adult worms recognized by a monoclonal antibody (MAIP-1), on humoral and cell-mediated responses to a bystander antigen (ovalbumin [OVA]). MAIP-1 recognized only one of the three polypeptide chains of PAS-1, but neutralized the suppressive effect of the whole worm extract on OVA-specific antibody production. PAS-1 inhibited antibody production against a T-cell-dependent, but not a T-cell-independent, antigen in a dose-dependent way. IgM, IgG1, IgG2b, and also IgE and anaphylactic IgG1 levels were downregulated. In addition, PAS-1 inhibited OVA-specific delayed type hypersensitivity reactions in the footpad of mice, showing a potent immunosuppressive activity on both Th1 and Th2 responses that seems to be mediated by the induction of large amounts of IL-10 and IL-4. Indeed, PAS-1-specific spleen cells secreted sevenfold more IL-10 and threefold more IL-4 than OVA-specific cells in response to in vitro restimulation with the respective antigens. In conclusion, we showed that PAS-1, a single protein component from A. suum, maintains all its immunosuppressive properties. PMID:16519731

  10. ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO

    EPA Science Inventory

    Antioxidant amelioration of arsenical-induced effects in vivo. ES Hunter and EH Rogers. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC.

    Antioxidants have been reported to ameliorate the effects of many developmental toxicants. We tested the hypothesis that oxi...

  11. Laser tumor thermotherapy: Is there a clinically relevant effect on the immune system?

    NASA Astrophysics Data System (ADS)

    Tranberg, Karl-G.

    2006-02-01

    Laser thermotherapy is interesting from an immunological point of view since it can reduce tumor volume without causing immunosuppression at the same time as it may induce and/or enhance tumor immunity. In a rat liver tumor model, we have demonstrated that laser thermotherapy 1) is superior to surgical resection, 2) gives a strong rejection immunity associated with an immune cellular response of tumor-infiltrating macrophages and CD8 lymphocytes, 3) results in pronounced suppression of the growth of a simultaneous untreated tumor (distant bystander effect), 4) produces an increased anti-tumor lymphocyte proliferative response in tumor-draining and systemic lymph nodes and spleen, and 5) results in increased HSP70 immunoreactivity in tumors and tumor-infiltrating macrophages. Thus, the evidence for a laser-induced immunologic effect in tumor-bearing rats is strong. Some observations suggest that laser thermotherapy may be used for inducing favorable immunologic effects also in patients. Thus, we have shown a laser-induced bystander effect in a patient with malignant melanoma. In patients with breast cancer we have shown that laser thermotherapy induces intratumoral infiltration of immunocompetent cells like CD68 macrophages and CD8 lymphocytes. Laser thermotherapy is likely to be beneficial mainly when tumor burden is small, that is, when treatment is performed with curative intent, either with laser alone or together with surgical resection. For optimal effect, it appears likely that thermotherapy should be combined with other therapies. Most likely, a clinically meaningful effect can only be proven in prospective randomized studies comparing thermotherapy with other methods, particularly surgical resection.

  12. Photo-Induced Effect on Bacterial Cells

    NASA Astrophysics Data System (ADS)

    El Batanouny, M. H.; Amin, Rehab M.; Naga, M. I.; Ibrahim, M. K.

    2010-04-01

    Bacterial resistance against antibiotics is an increasing problem in medicine. This stimulates study of other bactericidal regimens, one of which is photodynamic therapy (PDT), which involves the killing of bacterial species by low power laser light (LLL) in the presence of photosensitizing agent. It has already been shown that, various gram- negative and gram-positive bacteria can be killed by photodynamic therapy in vitro, using exogenous sensitizers. The mechanisms of laser action on bacteria are not adequately understood. Here, PDT on H. pylori, as an example of gram negative bacteria was studied. The ultra structure changes of the organism after PDT were examined under electron microscope. Neither Irradiation with laser without sensitizer nor sensitizing without laser has any lethal effect on bacterial cells. However, the successful lethal photosensitization was achieved by applying certain laser dose with the corresponding concentration of the photosensitizer. On the other hand, PDT has no significant effect on the genomic DNA of the cells.

  13. Generic superweak chaos induced by Hall effect.

    PubMed

    Ben-Harush, Moti; Dana, Itzhack

    2016-05-01

    We introduce and study the "kicked Hall system" (KHS), i.e., charged particles periodically kicked in the presence of uniform magnetic (B) and electric (E) fields that are perpendicular to each other and to the kicking direction. We show that for resonant values of B and E and in the weak-chaos regime of sufficiently small nonintegrability parameter κ (the kicking strength), there exists a generic family of periodic kicking potentials for which the Hall effect from B and E significantly suppresses the weak chaos, replacing it by "superweak" chaos (SWC). This means that the system behaves as if the kicking strength were κ^{2} rather than κ. For E=0, SWC is known to be a classical fingerprint of quantum antiresonance, but it occurs under much less generic conditions, in particular only for very special kicking potentials. Manifestations of SWC are a decrease in the instability of periodic orbits and a narrowing of the chaotic layers, relative to the ordinary weak-chaos case. Also, for global SWC, taking place on an infinite "stochastic web" in phase space, the chaotic diffusion on the web is much slower than the weak-chaos one. Thus, the Hall effect can be relatively stabilizing for small κ. In some special cases, the effect is shown to cause ballistic motion for almost all parameter values. The generic global SWC on stochastic webs in the KHS appears to be the two-dimensional closest analog to the Arnol'd web in higher dimensional systems. PMID:27300880

  14. Generic superweak chaos induced by Hall effect

    NASA Astrophysics Data System (ADS)

    Ben-Harush, Moti; Dana, Itzhack

    2016-05-01

    We introduce and study the "kicked Hall system" (KHS), i.e., charged particles periodically kicked in the presence of uniform magnetic (B ) and electric (E ) fields that are perpendicular to each other and to the kicking direction. We show that for resonant values of B and E and in the weak-chaos regime of sufficiently small nonintegrability parameter κ (the kicking strength), there exists a generic family of periodic kicking potentials for which the Hall effect from B and E significantly suppresses the weak chaos, replacing it by "superweak" chaos (SWC). This means that the system behaves as if the kicking strength were κ2 rather than κ . For E =0 , SWC is known to be a classical fingerprint of quantum antiresonance, but it occurs under much less generic conditions, in particular only for very special kicking potentials. Manifestations of SWC are a decrease in the instability of periodic orbits and a narrowing of the chaotic layers, relative to the ordinary weak-chaos case. Also, for global SWC, taking place on an infinite "stochastic web" in phase space, the chaotic diffusion on the web is much slower than the weak-chaos one. Thus, the Hall effect can be relatively stabilizing for small κ . In some special cases, the effect is shown to cause ballistic motion for almost all parameter values. The generic global SWC on stochastic webs in the KHS appears to be the two-dimensional closest analog to the Arnol'd web in higher dimensional systems.

  15. Immediate effects of chocolate on experimentally induced mood states.

    PubMed

    Macht, Michael; Mueller, Jochen

    2007-11-01

    In this work two hypotheses were tested: (1) that eating a piece of chocolate immediately affects negative, but not positive or neutral mood, and (2) that this effect is due to palatability. Experiment 1 (48 normal-weight and healthy women and men) examined the effects of eating a piece of chocolate and drinking water on negative, positive and neutral mood states induced by film clips. Eating chocolate reduced negative mood compared to drinking water, whereas no or only marginal effects were found on neutral and positive moods. Experiment 2 (113 normal-weight and healthy women and men) compared effects of eating palatable and unpalatable chocolate on negative mood, and examined the duration of chocolate-induced mood change. Negative mood was improved after eating palatable chocolate as compared to unpalatable chocolate or nothing. This effect was short lived, i.e., it disappeared after 3 min. In both experiments, chocolate-induced mood improvement was associated with emotional eating. The present studies demonstrate that eating a small amount of sweet food improves an experimentally induced negative mood state immediately and selectively and that this effect of chocolate is due to palatability. It is hypothesized that immediate mood effects of palatable food contribute to the habit of eating to cope with stress. PMID:17597253

  16. Vortex induced strain effects in anisotropic superconductors

    SciTech Connect

    Miranovic, P.; Dobrosavljevic-Grujic, L.; Kogan, V.G.

    1996-12-31

    Strain in a superconductor, produced by the normal vortex core, can affect both static and dynamic properties of vortices. It causes an additional vortex-vortex interaction which is long-ranged ({approximately} 1/r{sup 2}) as compared with finite but much stronger London interaction in the fields far below H{sub c2}. The energy of this magneto-elastic interaction is calculated within London model. The role of strain effects in forming vortex lattice structure is demonstrated for YBa{sub 2}Cu{sub 3}O{sub 7}.

  17. Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells.

    PubMed

    Jones, Anna J; Gokhale, Paul J; Allison, Thomas F; Sampson, Barry; Athwal, Sharan; Grant, Simon; Andrews, Peter W; Allen, Nicholas D; Case, C Patrick

    2015-01-01

    Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular 'bystander signalling' both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development. PMID:26170169

  18. Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells

    PubMed Central

    Jones, Anna J; Gokhale, Paul J; Allison, Thomas F; Sampson, Barry; Athwal, Sharan; Grant, Simon; Andrews, Peter W; Allen, Nicholas D; Patrick Case, C

    2015-01-01

    Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular ‘bystander signalling’ both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development. PMID:26170169

  19. The not-so innocent bystander: The microenvironment as a therapeutic target in cancer

    SciTech Connect

    Erickson, Anna C.; Barcellos-Hoff, Mary Helen

    2003-06-19

    The microenvironment in which cancer arises is often regarded as a bystander to the clonal expansion and acquisition of malignant characteristics of the tumour. However, a major function of the microenvironment is to suppress cancer, and its disruption is required for the establishment of cancer. In addition, tumour cells can further distort the microenvironment to promote growth, recruit non-malignant cells that provide physiological resources, and facilitate invasion. In this review, the authors discuss the contribution of the microenvironment, i.e., the stroma and its resident vasculature, inflammatory cells, growth factors and the extracellular matrix (ECM), in the development of cancer, and focus on two components as potential therapeutic targets in breast cancer. First, the ECM, which imparts crucial signaling via integrins and other receptors, is a first-line barrier to invasion, modulates aggressive behavior and may be manipulated to provide novel impediments to tumour growth. Second, the authors discuss the involvement of TGF-beta1 as an example of one of many growth factors that can regulate ECM composition and degradation and that play complex roles in cancer. Compared to the variable routes taken by cells to become cancers, the response of tissues to cancer is relatively consistent. Therefore, controlling and eliminating cancer may be more readily achieved indirectly via the tissue microenvironment.

  20. Acting in solidarity: Testing an extended dual pathway model of collective action by bystander group members.

    PubMed

    Saab, Rim; Tausch, Nicole; Spears, Russell; Cheung, Wing-Yee

    2015-09-01

    We examined predictors of collective action among bystander group members in solidarity with a disadvantaged group by extending the dual pathway model of collective action, which proposes one efficacy-based and one emotion-based path to collective action (Van Zomeren, Spears, Fischer, & Leach, 2004). Based on two proposed functions of social identity performance (Klein, Spears, & Reicher, 2007), we distinguished between the efficacy of collective action at consolidating the identity of a protest movement and its efficacy at achieving social change (political efficacy). We expected identity consolidation efficacy to positively predict collective action tendencies directly and indirectly via political efficacy. We also expected collective action tendencies to be positively predicted by moral outrage and by sympathy in response to disadvantaged outgroup's suffering. These hypotheses were supported in two surveys examining intentions to protest for Palestine in Britain (Study 1), and intentions to attend the June 4th vigil in Hong Kong to commemorate the Tiananmen massacre among a sample of Hong Kong citizens (Study 2). The contributions of these findings to research on the dual pathway model of collective action and the different functions of collective action are discussed. PMID:25406712

  1. Teens’ Self-Efficacy to Deal with Dating Violence as Victim, Perpetrator or Bystander

    PubMed Central

    Van Camp, Tinneke; Hébert, Martine; Guidi, Elisa; Lavoie, Francine; Blais, Martin

    2015-01-01

    Multiple studies have demonstrated that adolescent dating violence is highly prevalent and associated with internalizing and externalizing problems. A number of prevention initiatives are being implemented in North-American high schools. Such initiatives do not only aim to raise awareness among potential victims and offenders but also among peer bystanders. Since teenagers mainly reach out to their peers when experiencing adversity, it is important to address adolescents’ efficiency to deal with witnessing dating violence or with friends disclosing dating abuse, in addition to increasing ability to deal with experienced dating violence victimization or perpetration. The aim of this study is to explore adolescents’ self-efficacy to deal with dating violence victimization and perpetration in their relationships and those of their peers. A paper-and-pencil questionnaire was completed by 259 14–18 years olds in Quebec, Canada. The data allows building insight into adolescents’ confidence to reach out for help or to help others in a situation of dating violence victimization and perpetration. We also considered the impact of gender and dating victimization history. Results suggest that dating violence prevention can build on teens’ self-efficacy to deal with dating violence and offer them tools to do so efficiently. PMID:26807554

  2. Heart rate modulation in bystanding geese watching social and non-social events

    PubMed Central

    Wascher, Claudia A.F; Scheiber, Isabella B.R; Kotrschal, Kurt

    2008-01-01

    Simply observing other individuals interacting has been shown to affect subsequent behaviour and also hormones in ‘bystander’ individuals. However, immediate physiological responses of an observer have been hardly investigated. Here we present results on individuals' heart rate (HR) responses during various situations, which occur regularly in a flock of greylag geese (Anser anser, e.g. agonistic encounters, vehicles passing by). We recorded simultaneously HR and behaviour of 21 semi-tame free-roaming geese, equipped with fully implanted transmitters. We considered 304 social and 81 non-social events during which the focal individuals did not respond behaviourally. Independent of the spatial distance to the event, these HR responses were significantly greater in social contexts (e.g. departing or landing geese, agonistic interactions) than in non-social situations (e.g. vehicles passing by, thunder). Focal individuals showed a significantly higher maximum HR as well as a greater HR increase in response to agonistic interactions, in which the pair partner or a family member was involved, as compared with a non-affiliated goose. Also, HR was significantly higher when the bystander watched non-affiliated geese interacting, which were higher ranking than the focal. We conclude that these differences are due to different relevance of the recorded events for the focal individual, depending on the individuals involved in the observed interaction. PMID:18430645

  3. The HANDDS Program: A Systematic Approach for Addressing Disparities in the Provision of Bystander Cardiopulmonary Resuscitation

    PubMed Central

    Sasson, Comilla; Haukoos, Jason S.; Eigel, Brian; Magid, David J.

    2015-01-01

    The current paradigm of bystander cardiopulmonary resuscitation (CPR) blankets a community with training. Recently, the authors have found that high-risk neighborhoods can be identified, and CPR training can be targeted in the neighborhoods in which it is most needed. This article presents a novel method and pilot implementation trial for the HANDDS (identifying High Arrest Neighborhoods to Decrease Disparities in Survival) program. The authors also seek to describe example methods in which the HANDDS program is being implemented in Denver, Colorado. The HANDDS program uses a simple three-step approach: identify, implement, and evaluate. This systematic conceptual framework uses qualitative and quantitative methods to 1) identify high-risk neighborhoods, 2) understand common barriers to learning and performing CPR in these neighborhoods, and 3) implement and evaluate a train-the-trainer CPR Anytime intervention designed to improve CPR training in these neighborhoods. The HANDDS program is a systematic approach to implementing a community-based CPR training program. Further research is currently being conducted in four large metropolitan U.S. cities to examine whether the results from the HANDDS program can be successfully replicated in other locations. PMID:25269587

  4. Radiofrequency field-induced thermal cytotoxicity in cancer cells treated with fluorescent nanoparticles

    PubMed Central

    Glazer, Evan S.; Curley, Steven A.

    2010-01-01

    Background Non-ionizing radiation, such as radiofrequency (RF) field and near infrared laser, induces thermal cytotoxicity in cancer cells treated with gold nanoparticles (AuNP). Quantum dots (QD) are fluorescent semiconducting nanoparticles that we hypothesize will induce similar injury following RF field irradiation. Methods AuNP and two types of QD (cadmium-selenide and indium-gallium-phosphide) conjugated to cetuximab (C225), a monoclonal antibody against human epidermal growth factor receptor (EGFR-1), demonstrated concentration-dependent heating in a RF field. We investigated the effect of RF field exposure after targeted nanoparticle treatment in a co-culture of two human cancer cell lines that have differential EGFR-1 expression (a high expressing pancreatic carcinoma, Panc-1, and a low expressing breast carcinoma, Cama-1). Results RF exposed Panc-1 or Cama-1 cells not containing AuNP or QD had a viability greater than 92%. The viability of Panc-1 cells exposed to the RF field after treatment with 50 nM Au-C225 was 39.4% ± 8.3% without injury to bystander Cama-1 cells (viability was 93.7% ± 1.0%, p ~ 0.0006). Panc-1 cells treated with targeted Cd-Se QD were only 47.5% viable after RF field exposure (p < 0.0001 compared to RF only Panc-1 control cells). Targeted InGaP QD decreased Panc-1 viability to 58.2% ± 3.4% after RF field exposure (p ~ 0.0004 compared to Cama-1 and Panc-1 controls). Conclusion We selectively induced RF field cytotoxicity in Panc-1 cells without injury to bystander Cama-1 cells utilizing EGFR-1 targeted nanoparticles, and demonstrated an interesting bifunctionality of fluorescent nanoparticles as agents for both cancer cell imaging and treatment. PMID:20564640

  5. Electromagnetic field induced biological effects in humans.

    PubMed

    Kaszuba-Zwolińska, Jolanta; Gremba, Jerzy; Gałdzińska-Calik, Barbara; Wójcik-Piotrowicz, Karolina; Thor, Piotr J

    2015-01-01

    Exposure to artificial radio frequency electromagnetic fields (EMFs) has increased significantly in recent decades. Therefore, there is a growing scientific and social interest in its influence on health, even upon exposure significantly below the applicable standards. The intensity of electromagnetic radiation in human environment is increasing and currently reaches astronomical levels that had never before experienced on our planet. The most influential process of EMF impact on living organisms, is its direct tissue penetration. The current established standards of exposure to EMFs in Poland and in the rest of the world are based on the thermal effect. It is well known that weak EMF could cause all sorts of dramatic non-thermal effects in body cells, tissues and organs. The observed symptoms are hardly to assign to other environmental factors occurring simultaneously in the human environment. Although, there are still ongoing discussions on non-thermal effects of EMF influence, on May 31, 2011--International Agency for Research on Cancer (IARC)--Agenda of World Health Organization (WHO) has classified radio electromagnetic fields, to a category 2B as potentially carcinogenic. Electromagnetic fields can be dangerous not only because of the risk of cancer, but also other health problems, including electromagnetic hypersensitivity (EHS). Electromagnetic hypersensitivity (EHS) is a phenomenon characterized by the appearance of symptoms after exposure of people to electromagnetic fields, generated by EHS is characterized as a syndrome with a broad spectrum of non-specific multiple organ symptoms including both acute and chronic inflammatory processes located mainly in the skin and nervous systems, as well as in respiratory, cardiovascular systems, and musculoskeletal system. WHO does not consider the EHS as a disease-- defined on the basis of medical diagnosis and symptoms associated with any known syndrome. The symptoms may be associated with a single source of EMF

  6. Noise-induced effects in population dynamics

    NASA Astrophysics Data System (ADS)

    Spagnolo, Bernardo; Cirone, Markus; La Barbera, Antonino; de Pasquale, Ferdinando

    2002-03-01

    We investigate the role of noise in the nonlinear relaxation of two ecosystems described by generalized Lotka-Volterra equations in the presence of multiplicative noise. Specifically we study two cases: (i) an ecosystem with two interacting species in the presence of periodic driving; (ii) an ecosystem with a great number of interacting species with random interaction matrix. We analyse the interplay between noise and periodic modulation for case (i) and the role of the noise in the transient dynamics of the ecosystem in the presence of an absorbing barrier in case (ii). We find that the presence of noise is responsible for the generation of temporal oscillations and for the appearance of spatial patterns in the first case. In the other case we obtain the asymptotic behaviour of the time average of the ith population and discuss the effect of the noise on the probability distributions of the population and of the local field.

  7. Preventive effects of bicarbonate on cerivastatin-induced apoptosis.

    PubMed

    Kobayashi, Masaki; Kaido, Fumie; Kagawa, Toshiki; Itagaki, Shirou; Hirano, Takeshi; Iseki, Ken

    2007-08-16

    Although HMG-CoA reductase inhibitors such as statins are the most widely used cholesterol-lowering agents, there is a risk of myopathy or rhabdmyolysis occurring in patients taking these drugs. It has been reported that a number of lipophilic statins cause apoptosis in various cells, but it is still not clear whether intracellular acidification is involved in statin-induced apoptosis. There have been few studies aimed at identifying compounds that suppress statin-induced myotoxicity. In the present study, we examined the relationship between cerivastatin-induced apoptosis and intracellular acidification and the effect of bicarbonate on cerivastatin-induced apoptosis using an RD cell line as a model of in vitro skeletal muscle. Cerivastatin reduced the number of viable cells and caused dramatic morphological changes and DNA fragmentation in a concentration-dependent manner. Moreover, cerivastatin-induced apoptosis was associated with intracellular acidification and caspase-9 and -3/7 activation. On the other hand, bicarbonate suppressed cerivastatin-induced pH alteration, caspase activation, morphological change and reduction of cell viability. Accordingly, bicarbonate suppressed statin-induced apoptosis. The strategy to combine statins with bicarbonate can lead to reduction in the chance of the severe adverse events including myopathy or rhabdmyolysis. PMID:17553641

  8. Superior neuroprotective effects of cerebrolysin in nanoparticle-induced exacerbation of hyperthermia-induced brain pathology.

    PubMed

    Sharma, Aruna; Muresanu, Dafin Fior; Mössler, Herbert; Sharma, Hari Shanker

    2012-02-01

    In recent years, the incidence of heat stroke and associated brain pathology are increasing Worldwide. More than half of the world's population are living in areas associated with high environmental heat especially during the summer seasons. Thus, new research is needed using novel drug targets to achieve neuroprotection in heat-induced brain pathology. Previous research from our laboratory showed that the pathophysiology of brain injuries following heat stroke are exacerbated by chronic intoxication of engineered nanoparticles of small sizes (50-60 nm) following identical heat exposure in rats. Interestingly, in nanoparticle-intoxicated animals the known neuroprotective agents in standard doses failed to induce effective neuroprotection. This suggests that the dose-response of the drugs either requires modification or new therapeutic agents are needed to provide better neuroprotection in nanoparticle-intoxicated animals after heat stroke. This review is focused on the use of cerebrolysin, a mixture of several neurotrophic factors and active peptide fragments, in relation to other neuroprotective agents normally used to treat ischemic stroke in clinics in nanoparticle-induced exacerbation of brain damage in heat stroke. It appears that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal rats. Interestingly, to induce effective neuroprotection in nanoparticle-induced exacerbation of brain pathology a double dose of cerebrolysin is needed. On the other hand, double doses of the other drugs were quite ineffective in reducing brain damage. These observations suggest that the drug type and doses are important factors in attenuating nanoparticle-induced exacerbation of brain pathology in heat stroke. The functional significance and possible mechanisms of drug-induced neuroprotection in nanoparticle-treated, heat-stressed rats are discussed. PMID:22229316

  9. Doppler effect induced spin relaxation boom.

    PubMed

    Zhao, Xinyu; Huang, Peihao; Hu, Xuedong

    2016-01-01

    We study an electron spin qubit confined in a moving quantum dot (QD), with our attention on both spin relaxation, and the product of spin relaxation, the emitted phonons. We find that Doppler effect leads to several interesting phenomena. In particular, spin relaxation rate peaks when the QD motion is in the transonic regime, which we term a spin relaxation boom in analogy to the classical sonic boom. This peak indicates that a moving spin qubit may have even lower relaxation rate than a static qubit, pointing at the possibility of coherence-preserving transport for a spin qubit. We also find that the emitted phonons become strongly directional and narrow in their frequency range as the qubit reaches the supersonic regime, similar to Cherenkov radiation. In other words, fast moving excited spin qubits can act as a source of non-classical phonons. Compared to classical Cherenkov radiation, we show that quantum dot confinement produces a small but important correction on the Cherenkov angle. Taking together, these results have important implications to both spin-based quantum information processing and coherent phonon dynamics in semiconductor nanostructures. PMID:26996253

  10. Doppler effect induced spin relaxation boom

    PubMed Central

    Zhao, Xinyu; Huang, Peihao; Hu, Xuedong

    2016-01-01

    We study an electron spin qubit confined in a moving quantum dot (QD), with our attention on both spin relaxation, and the product of spin relaxation, the emitted phonons. We find that Doppler effect leads to several interesting phenomena. In particular, spin relaxation rate peaks when the QD motion is in the transonic regime, which we term a spin relaxation boom in analogy to the classical sonic boom. This peak indicates that a moving spin qubit may have even lower relaxation rate than a static qubit, pointing at the possibility of coherence-preserving transport for a spin qubit. We also find that the emitted phonons become strongly directional and narrow in their frequency range as the qubit reaches the supersonic regime, similar to Cherenkov radiation. In other words, fast moving excited spin qubits can act as a source of non-classical phonons. Compared to classical Cherenkov radiation, we show that quantum dot confinement produces a small but important correction on the Cherenkov angle. Taking together, these results have important implications to both spin-based quantum information processing and coherent phonon dynamics in semiconductor nanostructures. PMID:26996253

  11. Doppler effect induced spin relaxation boom

    NASA Astrophysics Data System (ADS)

    Zhao, Xinyu; Huang, Peihao; Hu, Xuedong

    2016-03-01

    We study an electron spin qubit confined in a moving quantum dot (QD), with our attention on both spin relaxation, and the product of spin relaxation, the emitted phonons. We find that Doppler effect leads to several interesting phenomena. In particular, spin relaxation rate peaks when the QD motion is in the transonic regime, which we term a spin relaxation boom in analogy to the classical sonic boom. This peak indicates that a moving spin qubit may have even lower relaxation rate than a static qubit, pointing at the possibility of coherence-preserving transport for a spin qubit. We also find that the emitted phonons become strongly directional and narrow in their frequency range as the qubit reaches the supersonic regime, similar to Cherenkov radiation. In other words, fast moving excited spin qubits can act as a source of non-classical phonons. Compared to classical Cherenkov radiation, we show that quantum dot confinement produces a small but important correction on the Cherenkov angle. Taking together, these results have important implications to both spin-based quantum information processing and coherent phonon dynamics in semiconductor nanostructures.

  12. Differential CD4+ T-Lymphocyte Apoptosis and Bystander T-Cell Activation in Rhesus Macaques and Sooty Mangabeys during Acute Simian Immunodeficiency Virus Infection▿

    PubMed Central

    Meythaler, Mareike; Martinot, Amanda; Wang, Zichun; Pryputniewicz, Sarah; Kasheta, Melissa; Ling, Binhua; Marx, Preston A.; O'Neil, Shawn; Kaur, Amitinder

    2009-01-01

    In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8+ T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8+ T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4+ and CD4−CD8− T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the “excess” activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection. PMID:18987149

  13. Effects of naltrexone on lipopolysaccharide-induced sepsis in rats.

    PubMed

    Lin, Shinn-Long; Lee, Yen-Mei; Chang, Hsin-Yi; Cheng, Yu-Wen; Yen, Mao-Hsiung

    2005-01-01

    Naltrexone, an opioid antagonist, has been reported to possess an anti-inflammatory effect via blockade of opioid receptor. The aim of this study is to evaluate the protective effect of naltrexone on LPS-induced septic shock in rats. Sepsis was induced by administration of LPS (10 mg/kg, i.v.) in anesthetized rats. Results demonstrated that pretreatment with naltrexone (10 mg/kg, i.v.) significantly ameliorated hypotension and bradycardia of rats 6 h after LPS administration. In isolated blood vessel, study showed that pretreatment with naltrexone significantly improved norepinephrine-induced vasoconstriction and ACh-induced vasorelaxation in aorta of endotoxemic animals. Naltrexone significantly reduced the elevation of serum glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase (as index of hepatic function) induced by LPS. The infiltration of polymorphonuclear neutrophils into liver 48 h after LPS treatment in mice was also reduced by naltrexone. On the other hand, naltrexone significantly decreased the levels of plasma TNF-alpha and inhibited overproduction of superoxide anions in aortic rings. However, naltrexone did not suppress the overproduction of NO (measured by its metabolites nitrite/nitrate in plasma) and iNOS expression in lungs induced by LPS. In in vitro study, naltrexone did not attenuate non-enzymatic iron-induced lipid peroxidation in rat brain homogenates. In conclusion, pretreatment with naltrexone significantly improved circulatory failure and hepatic dysfunction in sepsis. These effects were associated with reduction of TNF-alpha levels and superoxide anion formation, which may be attributed to antagonism of opioid receptors. PMID:15917999

  14. A functional genomics approach using radiation-induced changes in gene expression to study low dose radiation effects in vitro and in vivo

    SciTech Connect

    Fornace, Jr, A J

    2007-03-03

    Abstract for final report for project entitled A functional genomics approach using radiation-induced changes in gene expression to study low dose radiation effects in vitro and in vivo which has been supported by the DOE Low Dose Radiation Research Program for approximately 7 years. This project has encompassed two sequential awards, ER62683 and then ER63308, in the Gene Response Section in the Center for Cancer Research at the National Cancer Institute. The project was temporarily suspended during the relocation of the Principal Investigators laboratory to the Dept. of Genetics and Complex Diseases at Harvard School of Public Health at the end of 2004. Remaining support for the final year was transferred to this new site later in 2005 and was assigned the DOE Award Number ER64065. The major aims of this project have been 1) to characterize changes in gene expression in response to low-dose radiation responses; this includes responses in human cells lines, peripheral blood lymphocytes (PBL), and in vivo after human or murine exposures, as well as the effect of dose-rate on gene responses; 2) to characterize changes in gene expression that may be involved in bystander effects, such as may be mediated by cytokines and other intercellular signaling proteins; and 3) to characterize responses in transgenic mouse models with relevance to genomic stability. A variety of approaches have been used to study transcriptional events including microarray hybridization, quantitative single-probe hybridization which was developed in this laboratory, quantitative RT-PCR, and promoter microarray analysis using genomic regulatory motifs. Considering the frequent responsiveness of genes encoding cytokines and related signaling proteins that can affect cellular metabolism, initial efforts were initiated to study radiation responses at the metabolomic level and to correlate with radiation-responsive gene expression. Productivity includes twenty-four published and in press manuscripts

  15. PD-1 Restrains Radiotherapy-Induced Abscopal Effect.

    PubMed

    Park, Sean S; Dong, Haidong; Liu, Xin; Harrington, Susan M; Krco, Christopher J; Grams, Michael P; Mansfield, Aaron S; Furutani, Keith M; Olivier, Kenneth R; Kwon, Eugene D

    2015-06-01

    We investigated the influence of PD-1 expression on the systemic antitumor response (abscopal effect) induced by stereotactic ablative radiotherapy (SABR) in preclinical melanoma and renal cell carcinoma models. We compared the SABR-induced antitumor response in PD-1-expressing wild-type (WT) and PD-1-deficient knockout (KO) mice and found that PD-1 expression compromises the survival of tumor-bearing mice treated with SABR. None of the PD-1 WT mice survived beyond 25 days, whereas 20% of the PD-1 KO mice survived beyond 40 days. Similarly, PD-1-blocking antibody in WT mice was able to recapitulate SABR-induced antitumor responses observed in PD-1 KO mice and led to increased survival. The combination of SABR plus PD-1 blockade induced near complete regression of the irradiated primary tumor (synergistic effect), as opposed to SABR alone or SABR plus control antibody. The combination of SABR plus PD-1 blockade therapy elicited a 66% reduction in size of nonirradiated, secondary tumors outside the SABR radiation field (abscopal effect). The observed abscopal effect was tumor specific and was not dependent on tumor histology or host genetic background. The CD11a(high) CD8(+) T-cell phenotype identifies a tumor-reactive population, which was associated in frequency and function with a SABR-induced antitumor immune response in PD-1 KO mice. We conclude that SABR induces an abscopal tumor-specific immune response in both the irradiated and nonirradiated tumors, which is potentiated by PD-1 blockade. The combination of SABR and PD-1 blockade has the potential to translate into a potent immunotherapy strategy in the management of patients with metastatic cancer. PMID:25701325

  16. Reduction of the Misinformation Effect by Arousal Induced after Learning

    ERIC Educational Resources Information Center

    English, Shaun M.; Nielson, Kristy A.

    2010-01-01

    Misinformation introduced after events have already occurred causes errors in later retrieval. Based on literature showing that arousal induced after learning enhances delayed retrieval, we investigated whether post-learning arousal can reduce the misinformation effect. 251 participants viewed four short film clips, each followed by a retention…

  17. Explosive spread F caused by lightning-induced electromagnetic effects

    NASA Technical Reports Server (NTRS)

    Liao, C. P.; Freidberg, J. P.; Lee, M. C.

    1989-01-01

    Lightning-produced electromagnetic effects may produce significant modifications in the ionospheric plasmas. An outstanding phenomenon investigated in this paper is the so-called explosive spread F, whose close link with lightning has been identified (Woodman and Kudeki, 1984). Parametric instability excited by the lightning-induced whistler waves is proposed as a potential source mechanism causing the explosive spread F.

  18. CARDIAC MOLECULAR EFFECTS INDUCED BY AIR POLLUTION PARTICLES

    EPA Science Inventory

    Abstract Submitted to the American Thoracic Society 98th International Conference, May 17 - 22, 2002, Atlanta, GA

    CARDIAC MOLECULAR EFFECTS INDUCED BY AIR POLLUTION PARTICLES
    K. Dreher1, R. Jaskot1, J. Richards1, and T. Knuckles2. 1U. S. Environmental Protection Agency,...

  19. Effective field theory approach to gravitationally induced decoherence.

    PubMed

    Blencowe, M P

    2013-07-12

    Adopting the viewpoint that the standard perturbative quantization of general relativity provides an effective description of quantum gravity that is valid at ordinary energies, we show that gravity as an environment induces the rapid decoherence of stationary matter superposition states when the energy differences in the superposition exceed the Planck energy scale. PMID:23889383

  20. Effects of diesel exhaust on influenza-induced nasal inflammation

    EPA Science Inventory

    Title: Effects of Diesel Exhaust on Influenza-Induced Nasal Inflammation T L Noah, MD1,2, K Horvath, BS3, C Robinette, RN2, 0 Diaz Sanchez, PhD4 and I Jaspers, PhD1,2. 1UNC Dept. of Pediatrics, United States; 2UNC Center for Environmental Medicine, Asthma and Lung Biology, ...

  1. Perceptions of pesticides exposure risks by operators, workers, residents and bystanders in Greece, Italy and the UK.

    PubMed

    Remoundou, K; Brennan, M; Sacchettini, G; Panzone, L; Butler-Ellis, M C; Capri, E; Charistou, A; Chaideftou, E; Gerritsen-Ebben, M G; Machera, K; Spanoghe, P; Glass, R; Marchis, A; Doanngoc, K; Hart, A; Frewer, L J

    2015-02-01

    The EU Directive on the sustainable use of pesticides (EU128/2009/EC) requires European Member States to develop training activities targeting occupational exposure to pesticides, and communication material aimed at residents and bystanders. Risk perceptions, knowledge and attitudes associated with passive and occupational exposure to pesticide potentially influence the extent to which different stakeholders adopt self-protective behaviour. A methodology for assessing the link between attitudes, adoption of self-protective behaviours and exposure was developed and tested. A survey was implemented in the Greece, Italy and the UK, and targeted stakeholders associated with pesticide exposure linked to orchards, greenhouse crops and arable crops respectively. The results indicated that the adoption of protective measures is low for residents and bystanders, with the exception of residents in Greece, when compared to operators and workers, who tend to follow recommended safety practices. A regression analysis was used to examine the factors affecting the probability of adopting protective measures as well the as the level of exposure in the case of operators and workers where data are available. The results indicate that the likelihood of engaging in self-protective behaviour is not significantly affected by perceptions of own health being affected by pesticides for residents and bystanders. However, operators who perceive that their heath has been negatively affected by the use of pesticides are found to be more likely to adopt self-protective behaviours. Gender and country differences, in perceptions, attitudes and self-protection are also observed. Recommendations for improved communication, in particular for vulnerable groups, are provided. PMID:25461109

  2. Aharonov-Bohm effect induced by circularly polarized light

    NASA Astrophysics Data System (ADS)

    Sigurdsson, H.; Kibis, O. V.; Shelykh, I. A.

    2015-11-01

    We demonstrated theoretically that the strong electron interaction with circularly polarized photons in ring-like nanostructures changes the phase of electron wave. This optically-induced effect is caused by the breaking of time-reversal symmetry and is similar to the Aharonov-Bohm effect. As a consequence of this phenomenon, the conductance of mesoscopic rings irradiated by a circularly polarized electromagnetic wave behaves as an oscillating function of the intensity and frequency of the wave.

  3. Microwave-Induced Resistance Oscillations as a Classical Memory Effect

    NASA Astrophysics Data System (ADS)

    Beltukov, Y. M.; Dyakonov, M. I.

    2016-04-01

    By numerical simulations and analytical studies, we show that the phenomenon of microwave-induced resistance oscillations can be understood as a classical memory effect caused by recollisions of electrons with scattering centers after a cyclotron period. We develop a Drude-like approach to magnetotransport in the presence of a microwave field, taking into account memory effects, and find an excellent agreement between numerical and analytical results, as well as a qualitative agreement with experiment.

  4. Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity.

    PubMed

    Etebari, M; Jafarian-Dehkordi, A; Lame, V

    2015-01-01

    Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentration of DTIC, HepG2 cells were incubated with various DTIC concentrations including 5, 10 and 20 μg/ml for 2 h and the genotoxic effects were evaluated by the comet assay. The result of this part of the study showed that incubation of HepG2 cells with DTIC at 5 μg/ml was sufficient to produce genotoxic effect. In order to determine the protective effects of amifostine on genotoxicity induced by DTIC, HepG2 cells were incubated with different concentrations of amifostine (2, 3 and 5 mg/ml) for 1 h which was followed by incubation with DTIC at 5 μg/ml for 2 h. One hour incubation of cells with different concentrations of amifostine before incubation with DITC indicated that at least 5 mg/ml concentration of amifostine can prevent genotoxic effects induced by DTIC on HepG2 cells under described condition. In conclusion amifostine could prevent DNA damage induced by DTIC on HepG2 cells. PMID:26430459

  5. Bystander suppression to unrelated allergen sensitization through intranasal administration of tolerogenic exosomes in mouse.

    PubMed

    Prado, Noela; Cañamero, Marta; Villalba, Mayte; Rodríguez, Rosalía; Batanero, Eva

    2010-07-01

    Exosomes represent a new family of bioactive nanovesicles (30-100 nm in diameter) secreted by different cell types whose appealing features can be exploited for designing vaccines in the context of several human diseases. We previously reported the potential of bronchoalveolar lavage fluid (BALF)-derived tolerogenic exosomes (Exo(Tol)) to be used as a nasal allergy vaccine in a mouse model of sensitization to Ole e 1, the main allergen of olive pollen. The aim of the study was to investigate whether such nanovesicles specific to Ole e 1 can also prevent the sensitization to other unrelated allergen, as Bet v 1 from birch pollen. Exo(Tol) were isolated from BALF of mice tolerized against Ole e 1 and used in a prophylactic approach. BALB/c mice were intranasally pretreated with Exo(Tol) one week before sensitization/challenge with Bet v 1, and the magnitude of allergen-specific response was analyzed. Intranasal pretreatment with Exo(Tol) resulted in significant inhibition of both specific IgE and IgG1 antibodies levels. Moreover, T cells from mice pretreated with Exo(Tol) showed a reduction in IL-5 and IL-13 (Th2 cytokines) production. Lung inflammatory response triggered by unrelated allergen-challenge was also significantly reduced after pretreatment: perivascular/peribronchial inflammatory cell infiltration, eosinophilia and mucus secretion. In conclusion, Exo(Tol) specific to Ole e 1, in addition to inhibit specific immune response to this allergen, blocked the allergic response to a second unrelated allergen such as Bet v 1. The in vivo "bystander suppression" that we herein describe for Exo(Tol) may have implications for the treatment of allergy based on mucosal tolerance induction. PMID:20478618

  6. Amiodarone-induced hypothyroidism and other adverse effects.

    PubMed

    Mosher, Mary C

    2011-01-01

    Amiodarone is a class III antiarrhythmic agent that is frequently prescribed today for the treatment of ventricular and atrial arrhythmias. Amiodarone has many adverse effects, and one of them is thyroid dysfunction. Advanced practice and staff nurses need to be vigilant, recognizing early signs and symptoms of thyroid dysfunction to prevent adverse drug reactions. Often, the signs and symptoms of amiodarone-induced hypothyroidism are overlooked because of the complexity of the patient's condition. The purpose of this article was to review a case study, present differential diagnoses and testing, discuss risk factors associated with amiodarone-induced hypothyroidism, discuss its pathogenesis, and review clinical management. PMID:21307683

  7. Nearshore bar migration and sediment-induced buoyancy effects

    NASA Astrophysics Data System (ADS)

    Falchetti, Silvia; Conley, Daniel C.; Brocchini, Maurizio; Elgar, Steve

    2010-02-01

    A 1-D General Ocean Turbulence Model that includes the effects of sediment-induced stratification is shown to simulate the observed onshore and offshore migration of a nearshore sandbar. The only two free parameters of the model, the bed reference concentration and the sediment diffusivity, are taken from the literature, rather than tuned to the data used here. The model results suggest that predictions of onshore bar migration, in which wave-induced sediment transport confined to within a few centimeters of the bottom dominates, are not greatly affected by accounting for buoyancy effects. The model results also suggest that both mean flows and waves transport sediment during offshore bar migration, with different components of transport dominating at different cross-shore locations across the bar-trough bathymetry. Neglecting the effects of sediment-induced stratification results in higher model skill during the largest waves, likely because the excess turbulence production simulated by the non-stratified model is counterbalanced by neglected breaking-wave-generated turbulence. Considering both onshore and offshore migration, the model that includes sediment-induced stratification has higher skill than the model without stratification.

  8. Shock induced magnetic effects in fine particle iron dispersions

    NASA Technical Reports Server (NTRS)

    Wasilewski, P. J.

    1979-01-01

    Magnetic effects associated with shock induced transformation of fcc antiferromagnetic iron precipitates in polycrystalline copper disks at levels up to 5 GPa in weak magnetic fields (H not greater than 0.5 Oe) were investigated. The demagnetization and anisotropy associated with second order transition, the effects of plastic deformation in imparting magnetic anisotropy and magnetic hardening, and the influence of post shock thermal transients on magnetization associated with recovery, recrystallization and grain growth were studied. It was found that on the microsecond time scale of the shock induced first order transformation, the field sense is recorded in the transformed iron particles. For a given particle size the degree of transformation of fcc iron depends on the level of the shock. For a given shock level the resultant magnetic properties depend on the particle size distribution, with maximum effects noted in specimens with 400 to 600 A particles.

  9. Quantifying induced effects of subsurface renewable energy storage

    NASA Astrophysics Data System (ADS)

    Bauer, Sebastian; Beyer, Christof; Pfeiffer, Tilmann; Boockmeyer, Anke; Popp, Steffi; Delfs, Jens-Olaf; Wang, Bo; Li, Dedong; Dethlefsen, Frank; Dahmke, Andreas

    2015-04-01

    New methods and technologies for energy storage are required for the transition to renewable energy sources. Subsurface energy storage systems such as salt caverns or porous formations offer the possibility of hosting large amounts of energy or substance. When employing these systems, an adequate system and process understanding is required in order to assess the feasibility of the individual storage option at the respective site and to predict the complex and interacting effects induced. This understanding is the basis for assessing the potential as well as the risks connected with a sustainable usage of these storage options, especially when considering possible mutual influences. For achieving this aim, in this work synthetic scenarios for the use of the geological underground as an energy storage system are developed and parameterized. The scenarios are designed to represent typical conditions in North Germany. The types of subsurface use investigated here include gas storage and heat storage in porous formations. The scenarios are numerically simulated and interpreted with regard to risk analysis and effect forecasting. For this, the numerical simulators Eclipse and OpenGeoSys are used. The latter is enhanced to include the required coupled hydraulic, thermal, geomechanical and geochemical processes. Using the simulated and interpreted scenarios, the induced effects are quantified individually and monitoring concepts for observing these effects are derived. This presentation will detail the general investigation concept used and analyze the parameter availability for this type of model applications. Then the process implementation and numerical methods required and applied for simulating the induced effects of subsurface storage are detailed and explained. Application examples show the developed methods and quantify induced effects and storage sizes for the typical settings parameterized. This work is part of the ANGUS+ project, funded by the German Ministry

  10. Cholera toxin effects on body temperature changes induced by morphine.

    PubMed

    Basilico, L; Parenti, M; Fumagalli, A; Parolaro, D; Giagnoni, G

    1997-03-01

    The present study evaluates the influence of cholera toxin and its B-subunit on thermic responses to morphine in the rats. The holotoxin (1 microg/rat) and the B-subunit (5 microg) were administered ICV and three days later rats were challenged ICV with morphine and tested for changes of body temperature. Cholera toxin, but not its B-subunit, modified the time course of the hyperthermic response induced by a low dose of morphine (2.5 microg), converted the hypothermia due to a higher dose of morphine (18 microg) to a consistent hyperthermia and only partially reduced the greater hypothermia induced by 36 microg of morphine. Cholera toxin-induced modifications of thermic responses to morphine were paralleled with a decreased Gs(alpha) immunoreactivity and a reduced ability for the toxin to catalyse the "in vitro" ADP-ribosylation of Gs(alpha) in hypothalamic membranes. In contrast, at the same time when morphine-induced effects on body temperature were assessed, no changes in pertussis toxin-mediated ADP-ribosylation of Gi(alpha)/Go(alpha), or basal adenylate cyclase activity, or binding of mu-opioid receptor selective ligand [3H]-DAMGO were observed in hypothalamic areas from rats treated with cholera toxin. These findings suggest that adaptative events secondary to prolonged activation of Gs(alpha) play a role in the modifications of thermic responses to morphine induced by CTX. PMID:9077589

  11. Effects of particles on stability of flow-induced precursors

    NASA Astrophysics Data System (ADS)

    Zhu, Peng-Wei; Phillips, Andrew W.; Edward, Graham

    2012-02-01

    The effect of two colorant particles with different surface geometries on the stability of shear-induced precursors in isotactic polypropylene was studied after the cessation of shear flow at 140 °C. In the absence of particles, the shear-induced precursors survived for at least 100 s after the shear flow ended. The presence of particles was found to stabilize lower molecular weight chains assisting in the formation of additional shear-induced precursors. The precursors thus formed in the samples containing particles contained two oriented clusters with different molecular weights. Incorporation of lower molecular weight chains in the precursors led to increased dissolution rates of the shear-induced precursors. Particle surface geometry was found to influence precursor dissolution, with planar particles stabilizing the shear-induced precursors to a much greater extent than curved particles. The particles investigated thus act like structural probes to follow quantitatively the dissolution process of precursors after shear and importantly to infer the formation of precursors during shear.

  12. Spin Hall magnetoresistance induced by a nonequilibrium proximity effect.

    PubMed

    Nakayama, H; Althammer, M; Chen, Y-T; Uchida, K; Kajiwara, Y; Kikuchi, D; Ohtani, T; Geprägs, S; Opel, M; Takahashi, S; Gross, R; Bauer, G E W; Goennenwein, S T B; Saitoh, E

    2013-05-17

    We report anisotropic magnetoresistance in Pt|Y(3)Fe(5)O(12) bilayers. In spite of Y(3)Fe(5)O(12) being a very good electrical insulator, the resistance of the Pt layer reflects its magnetization direction. The effect persists even when a Cu layer is inserted between Pt and Y(3)Fe(5)O(12), excluding the contribution of induced equilibrium magnetization at the interface. Instead, we show that the effect originates from concerted actions of the direct and inverse spin Hall effects and therefore call it "spin Hall magnetoresistance." PMID:25167435

  13. Salubrious effects of oxytocin on social stress-induced deficits

    PubMed Central

    Smith, Adam S.; Wang, Zuoxin

    2012-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

  14. Hormetic effect induced by depleted uranium in zebrafish embryos.

    PubMed

    Ng, C Y P; Cheng, S H; Yu, K N

    2016-06-01

    The present work studied the hormetic effect induced by uranium (U) in embryos of zebrafish (Danio rerio) using apoptosis as the biological endpoint. Hormetic effect is characterized by biphasic dose-response relationships showing a low-dose stimulation and a high-dose inhibition. Embryos were dechorionated at 4h post fertilization (hpf), and were then exposed to 10 or 100μg/l depleted uranium (DU) in uranyl acetate solutions from 5 to 6 hpf. For exposures to 10μg/l DU, the amounts of apoptotic signals in the embryos were significantly increased at 20 hpf but were significantly decreased at 24 hpf, which demonstrated the presence of U-induced hormesis. For exposures to 100μg/l DU, the amounts of apoptotic signals in the embryos were significantly increased at 20, 24 and 30 hpf. Hormetic effect was not shown but its occurrence between 30 and 48 hpf could not be ruled out. In conclusion, hormetic effect could be induced in zebrafish embryos in a concentration- and time-dependent manner. PMID:27060238

  15. CD46-induced human Tregs enhance B cell responses

    PubMed Central

    Fuchs, Anja; Atkinson, John P.; Fremeaux-Bacchi, Veronique; Kemper, Claudia

    2010-01-01

    Summary Regulatory CD4+ T cells (Tregs) are important modulators of the immune response. Different types of Tregs have been identified based on whether they are thymically derived (natural Tregs) or induced in the periphery (adaptive Tregs). We recently reported on an adaptive Treg phenotype that can be induced by the concomitant stimulation of human CD4+ T cells through CD3 and the membrane complement regulator CD46. These complement-induced Treg cells (cTreg) potently inhibit bystander T cell proliferation through high-level secretion of IL-10. In addition, cTreg express granzyme B and exhibit cytotoxic effects towards activated effector T cells. Here we analyzed the effect of cTreg on B cell functions in a co-culture system. We found that cTreg enhance B cell antibody production. This B cell support is dependent on cell/cell contact as well as cTreg-derived IL-10. In addition, we show that T cells from a CD46-deficient patient are not capable of promoting B cell responses, whereas CD46-deficient B cells have no intrinsic defect in Ig production. This finding may relate to a subset of CD46-deficient patients who present with common variable immunodeficiency (CVID). Thus, the lack of cTreg function in optimizing B cell responses could explain why some CD46-deficient patients develop CVID. PMID:19784949

  16. Bystander immunotherapy as a strategy to control allergen-driven airway inflammation.

    PubMed

    Navarro, S; Lazzari, A; Kanda, A; Fleury, S; Dombrowicz, D; Glaichenhaus, N; Julia, V

    2015-07-01

    Allergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), lung infiltration of Th2 cells, and high levels of IgE. To date, allergen-specific immunotherapy (SIT) is the only treatment that effectively alleviates clinical symptoms and has a long-term effect after termination. Unfortunately, SIT is unsuitable for plurisensitized patients, and highly immunogenic allergens cannot be used. To overcome these hurdles, we sought to induce regulatory CD4(+) T cells (Treg) specific to an exogenous antigen that could be later activated as needed in vivo to control allergic responses. We have established an experimental approach in which mice tolerized to ovalbumin (OVA) were sensitized to the Leishmania homolog of receptors for activated c kinase (LACK) antigen, and subsequently challenged with aerosols of LACK alone or LACK and OVA together. Upon OVA administration, AHR and allergic airway responses were strongly reduced. OVA-induced suppression was mediated by CD25(+) Treg, required CTLA-4 and ICOS signaling and resulted in decreased numbers of migrating airway dendritic cells leading to a strong impairment in the proliferation of allergen-specific Th2 cells. Therefore, inducing Treg specific to a therapeutic antigen that could be further activated in vivo may represent a safe and novel curative approach for allergic asthma. PMID:25425267

  17. Gastroprotective effect of kefir on ulcer induced in irradiated rats.

    PubMed

    Fahmy, Hanan A; Ismail, Amel F M

    2015-03-01

    The current study was designed to investigate the protective effect of kefir milk on ethanol-induced gastric ulcers in γ-irradiated rats. The results of the present study revealed that treatment with γ-irradiation and/or ethanol showed a significant increase in ulcers number, total acidity, peptic, H(+)K(+)ATPase, MMP-2 and MMP-9 activities and MDA level, which were accompanied by a significant decrease in the mucus content, the stomach GSH level, the GSH-Px activity and DNA damage. Pre-treatment with kefir milk exert significant improvement in all the tested parameters. Kefir milk exerts comparable effect to that of the antiulcer drug ranitidine. In conclusion, the present study revealed that oral administration of kefir milk prevents ethanol-induced gastric ulcer in γ-irradiated rats that could attribute to its antioxidant, anti-apoptotic and radio-protective activities. PMID:25728227

  18. Birefringence effects of short probe pulses of electromagnetically induced transparency

    NASA Astrophysics Data System (ADS)

    Parshkov, Oleg M.; Kochetkova, Anastasia E.; Budyak, Victoria V.

    2016-04-01

    The numerical simulation results of radiations evolution in the presence of electromagnetically induced transparency for J=0-->J=1-->J=2 scheme of degenerate quantum transitions are presented. The pulse regime of wave interaction with Doppler broadening spectral lines was investigated. It was indicated that when the control field is linear polarized, the input circular polarized probe pulse breaks up in the medium into pulses with mutually perpendicular linear polarizations. Polarization direction of one of these pulses coincides with the polarization direction of control fields. The distance, which probe pulse passes in the medium to its full separation, decreases, when input probe pulse duration or control field intensity decreases. The input probe pulse intensity variation almost does not influence separation distance and speed of the linear polarized probe pulses in the medium. The effects, described above, may be interpreted as the birefringence effects of electromagnetically induced transparency in the case of short probe pulse.

  19. Anomalous transport induced by sheath instability in Hall effect thrusters

    SciTech Connect

    Taccogna, Francesco; Schneider, Ralf

    2009-06-22

    It is well recognized to ascribe the anomalous cross-field conductivity inside Hall-effect thrusters to fluctuation-induced transport due to gradient-driven instabilities (Rayleigh or electron drift) and to electron-wall interaction (near-wall conductivity). In this letter, we have performed numerical experiments showing the possibility of another mechanism inducing azimuthal fluctuations: the lateral sheath instability. It is created by a negative differential resistance of the current-voltage I-V characteristic of the floating wall as a consequence of high secondary electron emission. The contribution from this effect to the anomalous axial current is calculated and it accounts of more than 80% of the experimental value.

  20. Reversibility of cadmium-induced health effects in rabbits

    SciTech Connect

    Nomiyama, K.; Nomiyama, H.

    1984-03-01

    Twenty-one male rabbits were divided into three groups: rabbits of two groups were given pelleted food containing cadmium chloride at a dose level of 300 ..mu..g Cd/g over periods of 44 or 19 weeks. Rabbits of the last group were given ordinary commercial pelleted food and served as controls. Cadmium increased urinary protein and amino acid by week 19 and increased it to a remarkably high level by week 44. After cessation of cadmium exposure, rabbits of the first group (44 weeks exposure group) showed only little recovery from cadmium health effects: proteinuria and aminoaciduria were slightly improved. Depressed hepatic functions were also slightly improved, but did not return to the control level in 24 weeks. Fat and bone metabolism also remained depressed below the control level. Anemia did not also readily recover. On the other hand, rabbits of the second group (19 weeks exposure) recovered from the effects of cadmium: proteinuria and aminoaciduria in most animals disappeared soon after the end of cadmium exposure, plasma GPT fell after 1 week, and hemoglobin and hematocrit returned to normal in 6-11 weeks. The above results show that after cessation of cadmium exposure, mild cadmium-induced health effects were reversible in a short period, while more severe effects were not readily reversible. High performance liquid chromatographic (HPLC) profiles of renal and hepatic cadmium-thionein (Cd-MT) during and after exposure to cadmium showed no correlation to the degree of cadmium health effects, and therefore, did not help to elucidate mechanisms of the recovery from cadmium-induced health effects, probably because cadmium not bound with metallothionein (non-MT-Cd) is responsible for inducing renal effects. 31 references, 4 figures.

  1. Guest-Induced Breathing Effect in a Flexible Molecular Crystal.

    PubMed

    Sheng, Yujie; Chen, Qibin; Yao, Junyao; Lu, Yunxiang; Liu, Honglai; Dai, Sheng

    2016-03-01

    By introducing a flexible component into a molecular building block, we present an unprecedented alkyl-decorated flexible crystalline material with a breathing behavior. Its selective adsorption is derived from the breathing effect induced by a guest triggered alkyl transformation. This feature allows the crystal to take up 2.5 mmol g(-1) of chloroform with high adsorption selectivity (CHCl3 /EA >2000 for example), implying a potential application in sorption separation and chemical sensors. PMID:26836312

  2. Lasing effects in a laser-induced plasma plume

    NASA Astrophysics Data System (ADS)

    Nagli, Lev; Gaft, Michael

    2015-11-01

    We have studied coherent emission from optically pumped preliminarily created laser induced plasma and demonstrate the possibility to create laser sources based on laser plasma as an active medium. The effect was studied in detail with Al plasma, and preliminary but promising results were also obtained with other atoms from the 13th and 14th groups of the periodic table. These lasers may be used as coherent light sources in a variety of optical applications.

  3. HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes▿

    PubMed Central

    Nobile, Cinzia; Rudnicka, Dominika; Hasan, Milena; Aulner, Nathalie; Porrot, Françoise; Machu, Christophe; Renaud, Olivier; Prévost, Marie-Christine; Hivroz, Claire; Schwartz, Olivier; Sol-Foulon, Nathalie

    2010-01-01

    The HIV-1 Nef protein is a pathogenic factor modulating the behavior of infected cells. Nef induces actin cytoskeleton changes and impairs cell migration toward chemokines. We further characterized the morphology, cytoskeleton dynamics, and motility of HIV-1-infected lymphocytes. By using scanning electron microscopy, confocal immunofluorescence microscopy, and ImageStream technology, which combines flow cytometry and automated imaging, we report that HIV-1 induces a characteristic remodeling of the actin cytoskeleton. In infected lymphocytes, ruffle formation is inhibited, whereas long, thin filopodium-like protrusions are induced. Cells infected with HIV with nef deleted display a normal phenotype, and Nef expression alone, in the absence of other viral proteins, induces morphological changes. We also used an innovative imaging system to immobilize and visualize living individual cells in suspension. When combined with confocal “axial tomography,” this technique greatly enhances three-dimensional optical resolution. With this technique, we confirmed the induction of long filopodium-like structures in unfixed Nef-expressing lymphocytes. The cytoskeleton reorganization induced by Nef is associated with an important impairment of cell movements. The adhesion and spreading of infected cells to fibronectin, their spontaneous motility, and their migration toward chemokines (CXCL12, CCL3, and CCL19) were all significantly decreased. Therefore, Nef induces complex effects on the lymphocyte actin cytoskeleton and cellular morphology, which likely impacts the capacity of infected cells to circulate and to encounter and communicate with bystander cells. PMID:20015995

  4. Ameliorative effect of methylthiouracil on TGFBIp-induced septic responses.

    PubMed

    Jung, Byeongjin; Ku, Sae-Kwang; Bae, Jong-Sup

    2015-08-01

    The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-β. TGFBIp is released by human umbilical vein endothelial cells (HUVECs), and functions as a mediator of experimental sepsis. Here, we investigated the anti-septic effects and underlying mechanisms of methylthiouracil (MTU), used as antithyroid drug, against TGFBIp-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of MTU were determined by measuring permeability, human neutrophils adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated HUVECs and mice. According to the results, MTU effectively inhibited lipopolysaccharide-induced release of TGFBIp, and suppressed TGFBIp-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, MTU suppressed CLP-induced sepsis lethality and pulmonary injury. Collectively, these results indicate that MTU could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway. PMID:26043683

  5. Modulatory effect of semelil (ANGIPARS™) on isoproterenol induced cardiac injury

    PubMed Central

    Joukar, Siyavash; Najafipour, Hamid; Mirzaeipour, Fateme; Nasri, Hamidreza; Ahmadi, Mahboubeh Yeganeh Haj; Badinloo, Marziyeh

    2013-01-01

    Administration of semelil (ANGIPARS™) has been successful in the treatment of diabetic foot ulcer. Considering the improvement of blood flow and anti-inflammatory effect that are attributed to this drug, we investigated its effect on cardiovascular performance in rabbits with isoproterenol (ISO) induced myocardial injury. Animal groups included: control group; ISO group, received ISO 50 mg/kg s.c. for two consecutive days; S1+ISO, S5+ISO and S10+ISO groups, received semelil 1, 5, and 10 mg/kg/day i.p. respectively, 30 min before ISO. On the 3rd day, electrocardiogram (ECG) and hemodynamic parameters were recorded; blood samples were taken and hearts were removed for lab investigations. ISO induced heart injury, ECG disturbance, raise of cardiac troponin I and significant decrease in LVSP (p<0.05), +dp/dt max (p<0.01), -dp/dt max (p<0.05) along with increase of LVEDP (p<0.01). Semelil had no significant effects on ECG and plasma cardiac troponin I. Impairment of +dp/dt max and -dp/dt max was significantly improved in S5+ISO and S10+ISO groups (P<0.05 versus ISO). In addition, LVSP and LVEDP was somewhat recovered in these groups, although semelil (1 mg/kg/day) to some extent exacerbated the myocardial lesions induced by ISO (P<0.05). Therefore, in stressful conditions, semelil may improve myocardial contractility; however, it may aggravate the severity of injury. PMID:26417221

  6. Modulatory effect of semelil (ANGIPARS™) on isoproterenol induced cardiac injury.

    PubMed

    Joukar, Siyavash; Najafipour, Hamid; Mirzaeipour, Fateme; Nasri, Hamidreza; Ahmadi, Mahboubeh Yeganeh Haj; Badinloo, Marziyeh

    2013-01-01

    Administration of semelil (ANGIPARS™) has been successful in the treatment of diabetic foot ulcer. Considering the improvement of blood flow and anti-inflammatory effect that are attributed to this drug, we investigated its effect on cardiovascular performance in rabbits with isoproterenol (ISO) induced myocardial injury. Animal groups included: control group; ISO group, received ISO 50 mg/kg s.c. for two consecutive days; S1+ISO, S5+ISO and S10+ISO groups, received semelil 1, 5, and 10 mg/kg/day i.p. respectively, 30 min before ISO. On the 3(rd) day, electrocardiogram (ECG) and hemodynamic parameters were recorded; blood samples were taken and hearts were removed for lab investigations. ISO induced heart injury, ECG disturbance, raise of cardiac troponin I and significant decrease in LVSP (p<0.05), +dp/dt max (p<0.01), -dp/dt max (p<0.05) along with increase of LVEDP (p<0.01). Semelil had no significant effects on ECG and plasma cardiac troponin I. Impairment of +dp/dt max and -dp/dt max was significantly improved in S5+ISO and S10+ISO groups (P<0.05 versus ISO). In addition, LVSP and LVEDP was somewhat recovered in these groups, although semelil (1 mg/kg/day) to some extent exacerbated the myocardial lesions induced by ISO (P<0.05). Therefore, in stressful conditions, semelil may improve myocardial contractility; however, it may aggravate the severity of injury. PMID:26417221

  7. Fundamental Proximity Effects in Focused electron Beam Induced Deposition

    SciTech Connect

    Plank, Harald; Smith, Daryl; Haber, Thomas; Rack, Philip D; Hofer, Ferdinand

    2012-01-01

    Fundamental proximity effects for electron beam induced deposition processes on nonflat surfaces were studied experimentally and via simulation. Two specific effects were elucidated and exploited to considerably increase the volumetric growth rate of this nanoscale direct write method: (1) increasing the scanning electron pitch to the scale of the lateral electron straggle increased the volumetric growth rate by 250% by enhancing the effective forward scattered, backscattered, and secondary electron coefficients as well as by strong recollection effects of adjacent features; and (2) strategic patterning sequences are introduced to reduce precursor depletion effects which increase volumetric growth rates by more than 90%, demonstrating the strong influence of patterning parameters on the final performance of this powerful direct write technique.

  8. Fundamental proximity effects in focused electron beam induced deposition.

    PubMed

    Plank, Harald; Smith, Daryl A; Haber, Thomas; Rack, Philip D; Hofer, Ferdinand

    2012-01-24

    Fundamental proximity effects for electron beam induced deposition processes on nonflat surfaces were studied experimentally and via simulation. Two specific effects were elucidated and exploited to considerably increase the volumetric growth rate of this nanoscale direct write method: (1) increasing the scanning electron pitch to the scale of the lateral electron straggle increased the volumetric growth rate by 250% by enhancing the effective forward scattered, backscattered, and secondary electron coefficients as well as by strong recollection effects of adjacent features; and (2) strategic patterning sequences are introduced to reduce precursor depletion effects which increase volumetric growth rates by more than 90%, demonstrating the strong influence of patterning parameters on the final performance of this powerful direct write technique. PMID:22181556

  9. Noble or Malevolent in a Moment of Dismay: How Postsecondary Students Construe and Characterize Bystander Action in School Violence Shooting Incidents

    ERIC Educational Resources Information Center

    Underhill, Dyan Whitlow

    2012-01-01

    Multiple incidents of postsecondary school shooting violence have occurred in American society--prompting concern about safety on college campuses, administrators' roles in prevention, and proactive and responsible bystander actions. Active shooter plans have become more established in educational environments, with efforts are directed…

  10. Influence of Psychological and Social Factors on Bystanders' Roles in School Bullying among Korean-American Students in the United States

    ERIC Educational Resources Information Center

    Choi, Sumi; Cho, Young Il

    2013-01-01

    This study investigated the associations of psychological and social variables with the likelihood of exhibiting three different behaviors as a bystander in a bullying situation. The sample comprised 238 Korean-American and Korean students, from the 3rd to 12th grades, studying in the USA. Students receiving classmate support showed a lower…

  11. Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity

    PubMed Central

    Richard, Jonathan; Veillette, Maxime; Ding, Shilei; Zoubchenok, Daria; Alsahafi, Nirmin; Coutu, Mathieu; Brassard, Nathalie; Park, Jongwoo; Courter, Joel R.; Melillo, Bruno; Smith, Amos B.; Shaw, George M.; Hahn, Beatrice H.; Sodroski, Joseph; Kaufmann, Daniel E.; Finzi, Andrés

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection causes a progressive depletion of CD4 + T cells. Despite its importance for HIV-1 pathogenesis, the precise mechanisms underlying CD4 + T-cell depletion remain incompletely understood. Here we make the surprising observation that antibody-dependent cell-mediated cytotoxicity (ADCC) mediates the death of uninfected bystander CD4 + T cells in cultures of HIV-1-infected cells. While HIV-1-infected cells are protected from ADCC by the action of the viral Vpu and Nef proteins, uninfected bystander CD4 + T cells bind gp120 shed from productively infected cells and are efficiently recognized by ADCC-mediating antibodies. Thus, gp120 shedding represents a viral mechanism to divert ADCC responses towards uninfected bystander CD4 + T cells. Importantly, CD4-mimetic molecules redirect ADCC responses from uninfected bystander cells to HIV-1-infected cells; therefore, CD4-mimetic compounds might have therapeutic utility in new strategies aimed at specifically eliminating HIV-1-infected cells. PMID:26870823

  12. Rain-induced subsurface airflow and Lisse effect

    USGS Publications Warehouse

    Guo, H.; Jiao, J.J.; Weeks, E.P.

    2008-01-01

    Water-level increase after rainfall is usually indicative of rainfall recharge to groundwater. This, however, may not be true if the Lisse effect occurs. This effect represents the water-level increase in a well driven by airflow induced by an advancing wetting front during highly intensive rains. The rainwater, which may behave like a low-permeability lid, seals the ground surface so that the air pressure beneath the wetting front is increased because of air compression due to downward movement of the wetting front. A rapid and substantial rise of the water level in the well screened below water table, which bears no relationship to groundwater recharge, can be induced when various factors such as soil properties and the rain-runoff condition combine favorably. A transient, three-dimensional and variably saturated flow model was employed to study the air and groundwater flows in the soil under rain conditions. The objectives of this paper are two-fold: to evaluate the reliability of the theory of the Lisse effect presented by Weeks to predict its magnitude in modeled situations that mimic the physical complexity of real aquifers, and to conduct parametric studies on the sensitivity of the water-level rise in the well to soil properties and the rain event. The simulation results reveal that the magnitude of the Lisse effect increases with the ponding depth. Soil permeability plays a key role in generating the Lisse effect. The water-level rise in the well is delayed relative to the air-pressure rise in the unsaturated zone when the soil permeability is low, and the maximum water-level rise is less than the maximum air pressure induced by rain infiltration. The simulation also explores the sensitivity of the Lisse effect to the van Genuchten parameters and the water table depth. Copyright 2008 by the American Geophysical Union.

  13. Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.

    PubMed

    Polzin, Amin; Richter, Stefan; Schrör, Karsten; Rassaf, Tienush; Merx, Marc W; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias

    2015-07-01

    We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. Dipyrone metabolite plasma levels were determined by high-performance-liquid-chromatography (HPLC). In seven healthy individuals, in vitro ASA (30 µM/ 100 µM/ 300 µM/ 1,000 µM) and dipyrone (10 µM) coincubation revealed, that the aspirin and dipyrone interaction can be overcome by increasing doses of aspirin. In 36 aspirin and dipyrone comedicated CAD patients, addition of ASA (30 µM/ 100 µM) in vitro inhibited, but did not completely overcome the dipyrone induced reduction of aspirin antiplatelet effects. Notably, the inhibition of thromboxane formation in aspirin and dipyrone comedicated CAD patients coincided with dipyrone plasma levels. In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1. PMID:25789542

  14. Radiation-induced Genomic Instability and Radiation Sensitivity

    SciTech Connect

    Varnum, Susan M.; Sowa, Marianne B.; Kim, Grace J.; Morgan, William F.

    2013-01-19

    The obvious relationships between reactive oxygen and nitrogen species, mitochondrial dysfunction, inflammatory type responses and reactive chemokines and cytokines suggests a general stress response induced by ionizing radiation most likely leads to the non-targeted effects described after radiation exposure. We argue that true bystander effects do not occur in the radiation therapy clinic. But there is no question that effects outside the target volume do occur. These “out of field effects” are considered very low dose effects in the context of therapy. So what are the implications of non-targeted effects on radiation sensitivity? The primary goal of therapy is to eradicate the tumor. Given the genetic diversity of the human population, lifestyle and environment factors it is likely some combination of these will influence patient outcome. Non-targeted effects may contribute to a greater or lesser extent. But consider the potential situation involving a partial body exposure due to a radiation accident or radiological terrorism. Non-targeted effects suggest that the tissue at risk for demonstrating possible detrimental effects of radiation exposure might be greater than the volume actually irradiated.

  15. Spatial confinement effects in laser-induced breakdown spectroscopy

    SciTech Connect

    Shen, X. K.; Sun, J.; Ling, H.; Lu, Y. F.

    2007-08-20

    The spatial confinement effects in laser-induced breakdown of aluminum (Al) targets in air have been investigated both by optical emission spectroscopy and fast photography. A KrF excimer laser was used to produce plasmas from Al targets in air. Al atomic emission lines show an obvious enhancement in the emission intensity when a pair of Al-plate walls were placed to spatially confine the plasma plumes. Images of the Al plasma plumes showed that the plasma plumes evolved into a torus shape and were compressed in the Al walls. The mechanism for the confinement effects was discussed using shock wave theory.

  16. The effect of sodium selenite on lead induced cognitive dysfunction.

    PubMed

    Liu, Ming-Chao; Xu, Yan; Chen, Yao-Ming; Li, Juan; Zhao, Fang; Zheng, Gang; Jing, Jin-Fei; Ke, Tao; Chen, Jing-Yuan; Luo, Wen-Jing

    2013-05-01

    The effect of lead (Pb) on spatial memory and hippocampal long-term potentiation (LTP) as a key risk factor has been widely recognized and the oxidative damage has been proposed as a possible mechanism of lead neurotoxicity. Selenium (Se) is a nutritionally essential trace element with known antioxidant potential. In this study we investigated the effect and the underlying mechanisms of Se supplementary on Pb induced cognition and synaptic plasticity impairment. Lactating Sprague-Dawley rats (SD rats) were randomly divided to four groups: 0ppm lead acetate (Pb); 0ppm Pb and 0.2ppm sodium selenite (Se); 100ppm Pb; 100ppm Pb and 0.2ppm Se. Lactating rats were treated with or without Pb and/or Se throughout lactation until weaning. The levels of hippocampal LTP, the spatial memory, the apoptosis of hippocampal neurons, the levels of lactate dehydrogenase (LDH) release, and the serum level of superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed. It had been observed that in Pb group the spatial memory, the induce level of LTP, the serum SOD level decreased, the LDH release level, the neurons apoptosis level, the serum MDA level increased, while in the Se supplements groups, the spatial memory, the induce level of LTP increased significantly. Compared with the Pb group, Se supplements shown down regulated the level of LDH, the neurons apoptosis and the serum MDA, and up regulated the level of serum SOD. We could draw the conclusion that Se supplements could alleviate toxic effect of lead on hippocampal LTP and spatial memory. The treated with selenium around 0.2ppm may protect against spatial memory dysfunction induced by lead exposure. PMID:23529067

  17. Protective effects of dioscin against alcohol-induced liver injury.

    PubMed

    Xu, Tingting; Zheng, Lingli; Xu, Lina; Yin, Lianhong; Qi, Yan; Xu, Youwei; Han, Xu; Peng, Jinyong

    2014-03-01

    Our previous studies have shown that dioscin has protective effect against liver injury. However, the action of the compound against ethanol-induced liver injury is still unknown. In the present paper, ethanol-induced acute and chronic liver damage rat models were used, and the results showed that dioscin significantly alleviated liver steatosis, reduced the levels of alanine aminotransferase, aspartate aminotransferase, total triglyceride (TG), total cholesterol and malondialdehyde, and increased the levels of high-density lipoprotein, superoxide dismutase, glutathione and glutathione peroxidase. Transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays showed that dioscin prevented mitochondrial ultrastructural alterations and apoptosis caused by ethanol. In addition, dioscin significantly inhibited ethanol-induced cytochrome P450 2E1 activation, down-regulated the levels of mitogen-activated protein kinases phosphorylation, inhibited the expressions of nuclear factor kappa B, glucose regulated protein 78, activating transcription factor 6 and alpha subunit of translation initiation factor 2 to attenuate oxidative damage, decreased the expressions of tumor necrosis factor alpha and interleukin-6, and down-regulated the expressions of apoptosis-related proteins including p53, caspase-3, caspase-9, poly (ADP-ribose)-polymerase and cytokeratin-18. Further investigation indicated that dioscin markedly increased the expressions of peroxisome proliferators-activated receptor α and its target genes including medium-chain acyl-CoA dehydrogenase, carnitine palmitoyl-CoA transferase I and acyl-CoA oxidase to advance fatty acid β-oxidation, up-regulated the expressions of acyl-CoA synthetase long-chain family member 1, acyl-CoA synthetase long-chain family member 5, alpha-aminoadipic semialdehyde dehydrogenase and acyl-CoA dehydrogenase to promote fatty acid metabolism, and down-regulated the expressions of glycerol

  18. Effects of rutin on acrylamide-induced neurotoxicity

    PubMed Central

    2014-01-01

    Background Rutin is an important flavonoid that is consumed in the daily diet. The cytoprotective effects of rutin, including antioxidative, and neuroprotective have been shown in several studies. Neurotoxic effects of acrylamide (ACR) have been established in humans and animals. In this study, the protective effects of rutin in prevention and treatment of neural toxicity of ACR were studied. Results Rutin significantly reduced cell death induced by ACR (5.46 mM) in time- and dose-dependent manners. Rutin treatment decreased the ACR-induced cytotoxicity significantly in comparison to control (P <0.01, P < 0.001). Rutin (100 and 200 mg/kg) could prevent decrease of body weight in rats. In combination treatments with rutin (50, 100 and 200 mg/kg), vitamin E (200 mg/kg) and ACR, gait abnormalities significantly decreased in a dose-dependent manner (P < 0.01 and P < 0.001). The level of malondialdehyde significantly decreased in the brain tissue of rats in both preventive and therapeutic groups that received rutin (100 and 200 mg/kg). Conclusion It seems that rutin could be effective in reducing neurotoxicity and the neuroprotective effect of it might be mediated via antioxidant activity. PMID:24524427

  19. The protective effects of trace elements against side effects induced by ionizing radiation

    PubMed Central

    2015-01-01

    Trace elements play crucial role in the maintenance of genome stability in the cells. Many endogenous defense enzymes are containing trace elements such as superoxide dismutase and metalloproteins. These enzymes are contributing in the detoxification of reactive oxidative species (ROS) induced by ionizing radiation in the cells. Zinc, copper, manganese, and selenium are main trace elements that have protective roles against radiation-induced DNA damages. Trace elements in the free salt forms have protective effect against cell toxicity induced by oxidative stress, metal-complex are more active in the attenuation of ROS particularly through superoxide dismutase mimetic activity. Manganese-complexes in protection of normal cell against radiation without any protective effect on cancer cells are more interesting compounds in this topic. The aim of this paper to review the role of trace elements in protection cells against genotoxicity and side effects induced by ionizing radiation. PMID:26157675

  20. Fundamental edge broadening effects during focused electron beam induced nanosynthesis

    DOE PAGESBeta

    Schmied, Roland; Fowlkes, Jason Davidson; Winkler, Robert; Rack, Phillip D.; Plank, Harald

    2015-02-16

    In this study, we explore lateral broadening effects of 3D structures fabricated through focused electron beam induced deposition using MeCpPt(IV)Me3 precursor. In particular, the scaling behavior of proximity effects as a function of the primary electron energy and the deposit height is investigated through experiments and validated through simulations. Correlated Kelvin force microscopy and conductive atomic force microscopy measurements identified conductive and non-conductive proximity regions. It was determined that the highest primary electron energies enable the highest edge sharpness while lower energies contain a complex convolution of broadening effects. In addition, it is demonstrated that intermediate energies lead to evenmore » more complex proximity effects that significantly reduce lateral edge sharpness and thus should be avoided if desiring high lateral resolution.« less

  1. Fundamental edge broadening effects during focused electron beam induced nanosynthesis

    PubMed Central

    Schmied, Roland; Fowlkes, Jason D; Winkler, Robert; Rack, Phillip D

    2015-01-01

    Summary The present study explores lateral broadening effects of 3D structures fabricated through focused electron beam induced deposition using MeCpPt(IV)Me3 precursor. In particular, the scaling behavior of proximity effects as a function of the primary electron energy and the deposit height is investigated through experiments and validated through simulations. Correlated Kelvin force microscopy and conductive atomic force microscopy measurements identified conductive and non-conductive proximity regions. It was determined that the highest primary electron energies enable the highest edge sharpness while lower energies contain a complex convolution of broadening effects. Moreover, it is demonstrated that intermediate energies lead to even more complex proximity effects that significantly reduce lateral edge sharpness and thus should be avoided if desiring high lateral resolution. PMID:25821687

  2. Fundamental edge broadening effects during focused electron beam induced nanosynthesis

    SciTech Connect

    Schmied, Roland; Fowlkes, Jason Davidson; Winkler, Robert; Rack, Phillip D.; Plank, Harald

    2015-02-16

    In this study, we explore lateral broadening effects of 3D structures fabricated through focused electron beam induced deposition using MeCpPt(IV)Me3 precursor. In particular, the scaling behavior of proximity effects as a function of the primary electron energy and the deposit height is investigated through experiments and validated through simulations. Correlated Kelvin force microscopy and conductive atomic force microscopy measurements identified conductive and non-conductive proximity regions. It was determined that the highest primary electron energies enable the highest edge sharpness while lower energies contain a complex convolution of broadening effects. In addition, it is demonstrated that intermediate energies lead to even more complex proximity effects that significantly reduce lateral edge sharpness and thus should be avoided if desiring high lateral resolution.

  3. New Directions for Gifted Black Males Suffering from Bystander Effects: A Call for Upstanders

    ERIC Educational Resources Information Center

    Grantham, Tarek C.

    2011-01-01

    An educational crisis in Black male representation in gifted programs exists, requiring a new lens through which to view problems and find solutions. Though many people observe that Black males face extraordinary barriers to successful participation in gifted programs, many stand by, watching as they are overlooked for or drop out of gifted…

  4. Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors.

    PubMed

    Leten, Cindy; Trekker, Jesse; Struys, Tom; Roobrouck, Valerie D; Dresselaers, Tom; Vande Velde, Greetje; Lambrichts, Ivo; Verfaillie, Catherine M; Himmelreich, Uwe

    2016-01-01

    Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683) in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI) and magnetic resonance imaging (MRI). Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1) outliers can be detected earlier, (2) GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3) a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents. PMID:26880961

  5. BYSTANDER EFFECTS, GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIATION AND CHEMICAL EXPOSURES

    EPA Science Inventory

    There is an increased interest in utilizing mechanistic data in support of the cancer risk assessment process for ionizing radiation and environmental chemical exposures. In this regard the use of biologically based dose-response models is particularly advocated. The aim is to pr...

  6. Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors

    PubMed Central

    Leten, Cindy; Trekker, Jesse; Struys, Tom; Roobrouck, Valerie D.; Dresselaers, Tom; Vande Velde, Greetje; Lambrichts, Ivo; Verfaillie, Catherine M.; Himmelreich, Uwe

    2016-01-01

    Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683) in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI) and magnetic resonance imaging (MRI). Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1) outliers can be detected earlier, (2) GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3) a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents. PMID:26880961

  7. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    SciTech Connect

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  8. DNA damage induced by the direct effect of radiation

    NASA Astrophysics Data System (ADS)

    Yokoya, A.; Shikazono, N.; Fujii, K.; Urushibara, A.; Akamatsu, K.; Watanabe, R.

    2008-10-01

    We have studied the nature of DNA damage induced by the direct effect of radiation. The yields of single- (SSB) and double-strand breaks (DSB), base lesions and clustered damage were measured using the agarose gel electrophoresis method after exposing to various kinds of radiations to a simple model DNA molecule, fully hydrated closed-circular plasmid DNA (pUC18). The yield of SSB does not show significant dependence on linear energy transfer (LET) values. On the other hand, the yields of base lesions revealed by enzymatic probes, endonuclease III (Nth) and formamidopyrimidine DNA glycosylase (Fpg), which excise base lesions and leave a nick at the damage site, strongly depend on LET values. Soft X-ray photon (150 kVp) irradiation gives a maximum yield of the base lesions detected by the enzymatic probes as SSB and clustered damage, which is composed of one base lesion and proximate other base lesions or SSBs. The clustered damage is visualized as an enzymatically induced DSB. The yields of the enzymatically additional damages strikingly decrease with increasing levels of LET. These results suggest that in higher LET regions, the repair enzymes used as probes are compromised because of the dense damage clustering. The studies using simple plasmid DNA as a irradiation sample, however, have a technical difficulty to detect multiple SSBs in a plasmid DNA. To detect the additional SSBs induced in opposite strand of the first SSB, we have also developed a novel technique of DNA-denaturation assay. This allows us to detect multiply induced SSBs in both strand of DNA, but not induced DSB.

  9. Lightning-induced effects on VLF/LF radio propagation

    NASA Astrophysics Data System (ADS)

    Inan, U. S.; Rodriguez, J. V.

    1993-05-01

    In recent years, at least two different ways in which energy from lightning discharges couples into the lower ionosphere and the radiation belts have come to the fore. In this paper, we briefly review these recent results especially from the point of view of their effects on VLF/LF radio propagation in the earth-ionosphere wave guide. We separately discuss two different mechanisms of coupling, namely lightning-induced electron precipitation, and lightning-induced heating and ionization of the lower ionosphere. We also discuss a planned active VLF wave-injection experiment designed to investigate ionospheric heating by VLF waves under controlled conditions and to generate ELF waves by modulated VLF heating.

  10. Effect of dengue virus-induced cytotoxin on capillary permeability.

    PubMed Central

    Dhawan, R.; Khanna, M.; Chaturvedi, U. C.; Mathur, A.

    1990-01-01

    Capillary permeability is increased in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) but its genesis is not known. Dengue type 2 virus (DV) induces production of a cytokine (CF2) by mouse macrophages. The present study was undertaken to investigate the effect of CF2 on capillary permeability. It was observed that intraperitoneal inoculation of CF2 in mice increased the capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radioactive iodine (125I) or Evan's blue dye in the peritoneal cavity. Peak leakage occurred at 30 min and the vascular integrity was restored by 1-2 h. The increase in capillary permeability was abrogated by pretreatment of mice with avil (H1 receptor blocker) but not by ranitidine (H2 receptor blocker). The findings thus show that DV-induced CF2 increases the capillary permeability via release of histamine. PMID:2310617

  11. Induced gap in topological materials from the superconducting proximity effect

    NASA Astrophysics Data System (ADS)

    Chiu, Ching-Kai; Cole, William

    Topological superconductivity has been of considerable interest lately, with several proposed experimental realizations in solid state systems. A heterostructure of s-wave superconductor and 3D topological insulator is one of the more promising platforms, with topological superconductivity realized on the ''naked'' surface of the topological insulator through the superconducting proximity effect. We theoretically study the induced superconducting gap on the naked surface. Adjusting the Fermi level above the bulk gap (which is the case in experiments), our results for the induced superconducting gap are in agreement with that probed in thin topological insulators (<10nm) in the experiments (Nat. Phys. 10, 943-950 (2014) and Phys. Rev. Lett. 112, 217001 (2014)). We further predict the gap in thick topological insulators (>10nm). This work is supported by LPS-MPO-CMTC, Microsoft Q, and JQI-NSF-PFC.

  12. Ground effects of space weather - geomagnetically induced currents

    NASA Astrophysics Data System (ADS)

    Pirjola, Risto

    2002-03-01

    A space storm creates intense rapidly-varying currents in the ionosphere. The most important are auroral electrojet systems. At the Earth's surface, the currents cause a geomagnetic disturbance and an induced electric field. Besides the primary space currents, the surface fields are also affected by secondary currents flowing in the Earth. The electric field drives harmful "geomagnetically induced currents" (GIC) in technological systems with a possibility of large economic losses. The first observations of space weather effects on technological systems were already made in early telegraph equipment 150 years ago. Theoretical modelling of GIC in a technological system firstly requires a "geophysical" calculation of the electric field at the Earth's surface and secondly an "engineering" computation of GIC in the particular earthed network of conductors. In this paper, we summarize the basic principles associated with GIC and consider the research done on the topic in Finland for almost twenty-five years.

  13. Chiral pumping effect induced by rotating electric fields

    NASA Astrophysics Data System (ADS)

    Ebihara, Shu; Fukushima, Kenji; Oka, Takashi

    2016-04-01

    We propose an experimental setup using 3D Dirac semimetals to access a novel phenomenon induced by the chiral anomaly. We show that the combination of a magnetic field and a circularly polarized laser induces a finite charge density with an accompanying axial current. This is because the circularly polarized laser breaks time-reversal symmetry and the Dirac point splits into two Weyl points, which results in an axial-vector field. We elucidate the appearance of the axial-vector field with the help of the Floquet theory by deriving an effective Hamiltonian for high-frequency electric fields. This anomalous charge density, i.e., the chiral pumping effect, is a phenomenon reminiscent of the chiral magnetic effect with a chiral chemical potential. We explicitly compute the pumped density and the axial-current expectation value. We also take account of coupling to the chiral magnetic effect to calculate a balanced distribution of charge and chirality in a material that behaves as a chiral battery.

  14. Countermeasures for space radiation induced adverse biologic effects

    NASA Astrophysics Data System (ADS)

    Kennedy, A. R.; Wan, X. S.

    2011-11-01

    Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

  15. Effective cosmological equations of induced f(R) gravity

    SciTech Connect

    Apostolopoulos, Pantelis S.; Tetradis, Nikolaos; Brouzakis, Nikolaos E-mail: nbruzak@ifae.es

    2010-08-01

    We expand the study of generalized brane cosmologies by allowing for an f( R-tilde ) gravity term on the brane, with R-tilde the curvature scalar derived from the induced metric. We also include arbitrary matter components on the brane and in the five-dimensional bulk. At low energies, the effect of the bulk on the brane evolution can be described through a mirage component, termed generalized dark radiation, in the effective four-dimensional field equations. Using the covariant formalism, we derive the exact form of these equations. We also derive an effective conservation equation involving the brane matter and the generalized dark radiation. At low energies the coupled brane-bulk system has a purely four-dimensional description. The applications of the formalism include generalizations of the Starobinsky model and the Dvali-Gabadadze-Porrati cosmology.

  16. Collisional effects on Rayleigh-Taylor-induced magnetic fields

    SciTech Connect

    Manuel, M. J.-E.; Flaig, M.; Plewa, T.; Li, C. K.; Séguin, F. H.; Frenje, J. A.; Casey, D. T.; Petrasso, R. D.; Hu, S. X.; Betti, R.; Hager, J.; Meyerhofer, D. D.; Smalyuk, V.

    2015-05-15

    Magnetic-field generation from the Rayleigh-Taylor (RT) instability was predicted more than 30 years ago, though experimental measurements of this phenomenon have only occurred in the past few years. These pioneering observations demonstrated that collisional effects are important to B-field evolution. To produce fields of a measurable strength, high-intensity lasers irradiate solid targets to generate the nonaligned temperature and density gradients required for B-field generation. The ablation process naturally generates an unstable system where RT-induced magnetic fields form. Field strengths inferred from monoenergetic-proton radiographs indicate that in the ablation region diffusive effects caused by finite plasma resistivity are not negligible. Results from the first proof-of-existence experiments are reviewed and the role of collisional effects on B-field evolution is discussed in detail.

  17. Focused Ion Beam Induced Effects on MOS Transistor Parameters

    SciTech Connect

    Abramo, Marsha T.; Antoniou, Nicholas; Campbell, Ann N.; Fleetwood, Daniel M.; Hembree, Charles E.; Jessing, Jeffrey R.; Soden, Jerry M.; Swanson, Scot E.; Tangyunyong, Paiboon; Vanderlinde, William E.

    1999-07-28

    We report on recent studies of the effects of 50 keV focused ion beam (FIB) exposure on MOS transistors. We demonstrate that the changes in value of transistor parameters (such as threshold voltage, V{sub t}) are essentially the same for exposure to a Ga+ ion beam at 30 and 50 keV under the same exposure conditions. We characterize the effects of FIB exposure on test transistors fabricated in both 0.5 {micro}m and 0.225 {micro}m technologies from two different vendors. We report on the effectiveness of overlying metal layers in screening MOS transistors from FIB-induced damage and examine the importance of ion dose rate and the physical dimensions of the exposed area.

  18. Irradiation spectrum and ionization-induced diffusion effects in ceramics

    SciTech Connect

    Zinkle, S.J.

    1997-08-01

    There are two main components to the irradiation spectrum which need to be considered in radiation effects studies on nonmetals, namely the primary knock-on atom energy spectrum and ionizing radiation. The published low-temperature studies on Al{sub 2}O{sub 3} and MgO suggest that the defect production is nearly independent of the average primary knock-on atom energy, in sharp contrast to the situation for metals. On the other hand, ionizing radiation has been shown to exert a pronounced influence on the microstructural evolution of both semiconductors and insulators under certain conditions. Recent work on the microstructure of ion-irradiated ceramics is summarized, which provides evidence for significant ionization-induced diffusion. Polycrystalline samples of MgO, Al{sub 2}O{sub 3}, and MgAl{sub 2}O{sub 4} were irradiated with various ions ranging from 1 MeV H{sup +} to 4 MeV Zr{sup +} ions at temperatures between 25 and 650{degrees}C. Cross-section transmission electron microscopy was used to investigate the depth-dependent microstructural of the irradiated specimens. Dislocation loop nucleation was effectively suppressed in specimens irradiated with light ions, whereas the growth rate of dislocation loops was enhanced. The sensitivity to irradiation spectrum is attributed to ionization-induced diffusion. The interstitial migration energies in MgAl{sub 2}O{sub 4} and Al{sub 2}O{sub 3} are estimated to be {le}0.4 eV and {le}0.8 eV, respectively for irradiation conditions where ionization-induced diffusion effects are expected to be negligible.

  19. The fungicide mancozeb induces toxic effects on mammalian granulosa cells

    SciTech Connect

    Paro, Rita; Tiboni, Gian Mario; Buccione, Roberto; Rossi, Gianna; Cellini, Valerio; Canipari, Rita; Cecconi, Sandra

    2012-04-15

    The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects oocyte meiotic spindle morphology and impairs fertilization rate even when used at very low concentrations. We evaluated the toxic effects of mancozeb on the mouse and human ovarian somatic granulosa cells. We examined parameters such as cell morphology, induction of apoptosis, and p53 expression levels. Mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of their morphology, and acquired the ability to migrate but not to proliferate. The expression level of p53, in terms of mRNA and protein content, decreased significantly in comparison with unexposed cells, but no change in apoptosis was recorded. Toxic effects could be attributed, at least in part, to the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was found in culture medium. Human granulosa cells also showed dose-dependent morphological changes and reduced p53 expression levels after exposure to mancozeb. Altogether, these results indicate that mancozeb affects the somatic cells of the mammalian ovarian follicles by inducing a premalignant-like status, and that such damage occurs to the same extent in both mouse and human GC. These results further substantiate the concept that mancozeb should be regarded as a reproductive toxicant. Highlights: ► The fungicide mancozeb affects oocyte spindle morphology and fertilization rate. ► We investigated the toxic effects of mancozeb on mouse and human granulosa cells. ► Granulosa cells modify their morphology and expression level of p53. ► Mancozeb induces a premalignant-like status in exposed cells.

  20. Induced magnetic-field effects in inductively coupled plasmas

    SciTech Connect

    Cohen, R.H.; Rognlien, T.D.

    1995-11-04

    In inductive plasma sources, the rapid spatial decay of the electric field arising from the skin effect produces a large radio frequency (RF) magnetic field via Faraday`s law. We previously determined that this magnetic field leads to a reduction of the electron density in the skin region, as well as a reduction in the collisionless heating rate. The electron deficit leads to the formation of an electrostatic potential which pulls electrons in to restore quasineutrality. Here we calculate the electron density including both the induced and electrostatic fields. If the wave frequency is not too low, the ions respond only to the averaged fields, and hence the electrostatic field is oscillatory, predominantly at the second harmonic of the applied field. We calculate the potential required to establish a constant electron density, and compare with numerical orbit-code calculations. For times short compared to ion transit times, the quasineutral density is just the initial ion density. For timescales long enough that the ions can relax, the density profile can be found from the solution of fluid equations with an effective (ponderomotive-like) potential added. Although the time-varying electrostatic potential is an extra source of heating, the net effect of the induced magnetic and electrostatic fields through trapping, early turning, and direct heating is a significant reduction in collisionless heating for parameters of interest.

  1. Protective effect of crocin on liver toxicity induced by morphine

    PubMed Central

    Salahshoor, Mohammad Reza; khashiadeh, Mojtaba; Roshankhah, Shiva; Kakabaraei, Seyran; Jalili, Cyrus

    2016-01-01

    Crocin, a bioactive molecule of saffron can be purely isolated from the saffron extract. It has different pharmacological effects such as antioxidant and anticancer activities. Morphine is an opioid analgesic drug. It is mainly metabolized in liver and causes devastating effects. It can increase the generation of free radicals. This study was designed to evaluate the protective role of crocin against morphine-induced toxicity in the mouse liver. In this study, various doses of crocin (12.5, 25 and 50 mg/kg) and crocin plus morphine were administered interaperitoneally once daily to 48 male mice for 20 consecutive days. These mice were randomly assigned to 8 groups of 6 each. The liver weight and histology, aspartate amino transferase, alanine aminotransferase, alkaline phosphatase (ALP) and serum nitric oxide levels were studied. The results indicated that morphine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein diameters, liver enzyme levels, and blood serum nitric oxide level compared to saline group (P<0.05). However, crocin administration significantly boosted liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes and nitric oxide levels in all groups compared to the group received morphine alone (P<0.05). It seems that crocin administration could protect the liver damage induced by morphine. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters. PMID:27168751

  2. Effect of induced transverse chromatic aberration on peripheral vision.

    PubMed

    Winter, Simon; Fathi, Mohammad Taghi; Venkataraman, Abinaya Priya; Rosén, Robert; Seidemann, Anne; Esser, Gregor; Lundström, Linda; Unsbo, Peter

    2015-10-01

    Transverse chromatic aberration (TCA) is one of the largest optical errors affecting the peripheral image quality in the human eye. However, the effect of chromatic aberrations on our peripheral vision is largely unknown. This study investigates the effect of prism-induced horizontal TCA on vision, in the central as well as in the 20° nasal visual field, for four subjects. Additionally, the magnitude of induced TCA (in minutes of arc) was measured subjectively in the fovea with a Vernier alignment method. During all measurements, the monochromatic optical errors of the eye were compensated for by adaptive optics. The average reduction in foveal grating resolution was about 0.032 ± 0.005  logMAR/arcmin of TCA (mean ± std). For peripheral grating detection, the reduction was 0.057 ± 0.012  logMAR/arcmin. This means that the prismatic effect of highly dispersive spectacles may reduce the ability to detect objects in the peripheral visual field. PMID:26479929

  3. Protective effect of crocin on liver toxicity induced by morphine.

    PubMed

    Salahshoor, Mohammad Reza; Khashiadeh, Mojtaba; Roshankhah, Shiva; Kakabaraei, Seyran; Jalili, Cyrus

    2016-01-01

    Crocin, a bioactive molecule of saffron can be purely isolated from the saffron extract. It has different pharmacological effects such as antioxidant and anticancer activities. Morphine is an opioid analgesic drug. It is mainly metabolized in liver and causes devastating effects. It can increase the generation of free radicals. This study was designed to evaluate the protective role of crocin against morphine-induced toxicity in the mouse liver. In this study, various doses of crocin (12.5, 25 and 50 mg/kg) and crocin plus morphine were administered interaperitoneally once daily to 48 male mice for 20 consecutive days. These mice were randomly assigned to 8 groups of 6 each. The liver weight and histology, aspartate amino transferase, alanine aminotransferase, alkaline phosphatase (ALP) and serum nitric oxide levels were studied. The results indicated that morphine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein diameters, liver enzyme levels, and blood serum nitric oxide level compared to saline group (P<0.05). However, crocin administration significantly boosted liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes and nitric oxide levels in all groups compared to the group received morphine alone (P<0.05). It seems that crocin administration could protect the liver damage induced by morphine. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters. PMID:27168751

  4. Effect of surrounding gases and water vapor on the induced electric current associated with a laser-induced plasma

    NASA Astrophysics Data System (ADS)

    Matsuta, Hideyuki

    2016-04-01

    The effect of surrounding gases and water vapor on the laser-induced electric current was investigated. Laser-induced plasma was generated on an aluminum alloy target. The laser-induced plasma was optically examined to estimate the excitation temperature and electron density in room air. There was a linear relationship between the maximum amplitude of the laser-induced current and the electron density. As the electron mean free path of the surrounding gas increased, the observed amplitude of the current increased. The amplitude of the induced current signal in dry air became maximum upon mixing with the optimum amount of water vapor. This enhancement of the induced current signal might be due to the large relative permittivity of water vapor. The laser-induced plasma as a whole seems to be a low-temperature plasma consisting of electrons, a large amount of cold surrounding gas, injected hot atoms, hot ions, and hot particles.

  5. Effects of Lipoic Acid on Acrylamide Induced Testicular Damage

    PubMed Central

    Lebda, Mohamed; Gad, Shereen; Gaafar, Hossam

    2014-01-01

    Introduction: Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. Aim of the study: This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. Material and methods: Forty adult male rats were divided into four groups (10 rats each). Control group; acrylamide treated group administered acrylamide 0.05% (w/v) in drinking water for 21 days; alpha-lipoic acid group received basal diet supplemented with 1% alpha-lipoic acid and forth group was exposed to acrylamide and treated with alpha-lipoic acid at the same doses and treatment regimen mentioned before. Results: The administration of acrylamide resulted in significant elevation in testicular and epididymal malondialdehyde level (MDA) and significant reduction in the level of reduced glutathione (GSH) and the activities of glutathione-S-transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GR). Also, acrylamide significantly reduced serum total testosterone and progesterone but increased estradiol (E2) levels. Treatment with alpha-lipoic acid prior to acrylamide induced protective effects and attenuated these biochemical changes. Conclusion: Alpha-lipoic acid has been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by acrylamide administration. PMID:25126019

  6. Effect of simulated weightlessness on exercise-induced anaerobic threshold

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Karst, G. M.; Kirby, C. R.; Goldwater, D. J.

    1986-01-01

    The effect of simulated weightlessness, induced by ten days of continuous bedrest (BR) in the -6 deg head-down position, on the exercise-induced anaerobic threshold (AT) was determined by comparing specific ventilatory and gas-exchange measurements during an incremental ergometer test performed before and after BR. The primary index for determining the exercise-induced AT values of each subject was visual identification of the workrate or oxygen uptake (VO2) at which the ratio of the expired minute ventilation volume (VE) to VO2 exhibited a systematic increase without a concomitant increase in the VE/VCO2 value. Following BR, the mean VO2max of the subjects decreased by 7.0 percent, and the AT decreased from a mean of 1.26 L/min VO2 before BR to 0.95 L/min VO2 after BR. The decrease in AT was manifested by a decrease in both absolute and relative workrates. The change in AT correlated significantly with the change in plasma volume but not with the change in VO2max. The results suggest that the reduction in AT cannot be completely explained by the reduction in VO2, and that the AT decrease is associated with the reduction in intravascular fluid volume.

  7. Corneal toxicity induced by vesicating agents and effective treatment options.

    PubMed

    Goswami, Dinesh G; Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

    The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial cells and rabbit corneal organ culture models with the SM analog nitrogen mustard, which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries. PMID:27327041

  8. Attenuating homologous recombination stimulates an AID-induced antileukemic effect

    PubMed Central

    Lamont, Kristin R.; Hasham, Muneer G.; Donghia, Nina M.; Branca, Jane; Chavaree, Margaret; Chase, Betsy; Breggia, Anne; Hedlund, Jacquelyn; Emery, Ivette; Cavallo, Francesca; Jasin, Maria; Rüter, Jens

    2013-01-01

    Activation-induced cytidine deaminase (AID) is critical in normal B cells to initiate somatic hypermutation and immunoglobulin class switch recombination. Accumulating evidence suggests that AID is also prooncogenic, inducing cancer-promoting mutations or chromosome rearrangements. In this context, we find that AID is expressed in >40% of primary human chronic lymphocytic leukemia (CLL) cases, consistent with other reports. Using a combination of human B lymphoid leukemia cells and mouse models, we now show that AID expression can be harnessed for antileukemic effect, after inhibition of the RAD51 homologous recombination (HR) factor with 4,4′-diisothiocyanatostilbene-2-2′-disulfonic acid (DIDS). As a proof of principle, we show that DIDS treatment inhibits repair of AID-initiated DNA breaks, induces apoptosis, and promotes cytotoxicity preferentially in AID-expressing human CLL. This reveals a novel antineoplastic role of AID that can be triggered by inhibition of HR, suggesting a potential new paradigm to treat AID-expressing tumors. Given the growing list of tumor types with aberrant AID expression, this novel therapeutic approach has potential to impact a significant patient population. PMID:23589568

  9. Oncogene Induced Cellular Senescence Elicits an Anti-Warburg Effect

    PubMed Central

    Li, Mingxi; Durbin, Kenneth R.; Sweet, Steve M. M.; Tipton, Jeremiah D.; Zheng, Yupeng; Kelleher, Neil L.

    2013-01-01

    Cellular senescence, an irreversible cell cycle arrest induced by a diversity of stimuli, has been considered as an innate tumor suppressing mechanism with implications and applications in cancer therapy. Using a targeted proteomics approach we show that fibroblasts induced into senescence by expression of oncogenic Ras exhibit a decrease of global acetylation on all core histones, consistent with formation of senescence-associated heterochromatic foci. We also detected clear increases in repressive markers (e.g., >50% elevation of H3K27me2/3) along with decreases in histone marks associated with increased transcriptional expression/elongation (e.g., H3K36me2/3). Despite the increases in repressive marks of chromatin, 179 loci (of 2206 total) were found to be upregulated by global quantitative proteomics. The changes in the cytosolic proteome indicated an upregulation of mitochondrial proteins and downregulation of proteins involved in glycolysis. These alterations in primary metabolism are opposite of the well-known Warburg effect observed in cancer cells. This study significantly improves our understanding of stress-induced senescence and provides a potential application for triggering it in anti-proliferative strategies that target the primary metabolism in cancer cells. PMID:23798001

  10. Barocaloric effect and the pressure induced solid state refrigerator

    SciTech Connect

    Oliveira, N. A. de

    2011-03-01

    The current refrigerators are based on the heating and cooling of fluids under external pressure variation. The great inconvenience of this refrigeration technology is the damage caused to the environment by the refrigerant fluids. In this paper, we discuss the magnetic barocaloric effect, i.e., the heating or cooling of magnetic materials under pressure variation and its application in the construction of refrigerators using solid magnetic compounds as refrigerant materials and pressure as the external agent. The discussion presented in this paper points out that such a pressure induced solid state refrigerator can be very interesting because it is not harmful to the environment and can exhibit a good performance.

  11. Diffraction Interference Induced Superfocusing in Nonlinear Talbot Effect

    PubMed Central

    Liu, Dongmei; Zhang, Yong; Wen, Jianming; Chen, Zhenhua; Wei, Dunzhao; Hu, Xiaopeng; Zhao, Gang; Zhu, S. N.; Xiao, Min

    2014-01-01

    We report a simple, novel subdiffraction method, i.e. diffraction interference induced superfocusing in second-harmonic (SH) Talbot effect, to achieve focusing size of less than λSH/4 (or λpump/8) without involving evanescent waves or subwavelength apertures. By tailoring point spread functions with Fresnel diffraction interference, we observe periodic SH subdiffracted spots over a hundred of micrometers away from the sample. Our demonstration is the first experimental realization of the Toraldo di Francia's proposal pioneered 62 years ago for superresolution imaging. PMID:25138077

  12. Glycopyrrolate-induced respiratory arrest: an unusual side effect.

    PubMed

    D'souza, S; Gowler, V

    2015-03-01

    A descriptive case report of a 22-year-old woman, scheduled for elective laparotomy who had a respiratory arrest after premedication with inj glycopyrrolate and ondansetron. Respiratory arrest is an uncommon side effect of glycopyrrolate with very few published reports. Ondansteron can also cause respiratory arrest, however is most often associated with bradycardia. This patient had tachycardia and respiratory arrest and is suggestive of glycopyrrolate-induced respiratory arrest. This case report highlights the importance of strict vigilance by the anaesthesiologist even during premedication. PMID:25557856

  13. Linezolid induced black hairy tongue: a rare side effect.

    PubMed

    Aijazi, Ishma; Abdulla, Fadhil M

    2014-01-01

    Linezolid induced black hairy tongue is a rare benign reversible side effect of linezolid therapy. We report a case of a 61 year old diabetic lady who developed thrombocytopenia and black hairy discoloration of the tongue after being prescribed linezolid for foot osteomyelitis by the orthopaedic surgeon. Patient was encouraged to practice good oral dental hygiene, advised to use a soft tooth brush, regular mouth wash and baking soda containing tooth paste. The condition resolved four weeks after cessation of the antibiotic therapy. PMID:25671958

  14. Force-induced stretched state: effects of temperature.

    PubMed

    Kumar, Sanjay; Mishra, Garima

    2008-07-01

    A model of self-avoiding walks with suitable constraint has been developed to study the effect of temperature on a single-stranded DNA (ssDNA) in the constant force ensemble. Our exact calculations for small chains show that the extension (reaction coordinate) may increase or decrease with the temperature depending on the applied force. The simple model developed here, which incorporates semimicroscopic details of base direction, provides an explanation of the force-induced transitions in ssDNA as observed in experiments. PMID:18763982

  15. Preventive Effects of Multi-Lamellar Emulsion on Low Potency Topical Steroid Induced Local Adverse Effect

    PubMed Central

    Sul, Geun Dong; Park, Hyun Jung; Bae, Jong Hwan; Hong, Keum Duck; Park, Byeong Deog; Chun, Jaesun; Jeong, Se Kyoo; Lee, Seung Hun; Ahn, Sung Ku

    2013-01-01

    Background Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. Objective Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. Methods Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. Results Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. Conclusion Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment. PMID:23467730

  16. Effect of coriander on thioacetamide-induced hepatotoxicity in rats.

    PubMed

    Moustafa, Abdel Halim A; Ali, Ehab Mostafa M; Moselhey, Said S; Tousson, Ehab; El-Said, Karim S

    2014-08-01

    the adverse effect of TAA-induced hepatotoxicity; also the histological study confirms this finding. PMID:23042592