Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation

International Nuclear Information System (INIS)

Ulsh, B.A.; Miller, S.M.; Mallory, F.F.; Mitchel, R.E.J.; Morrison, D.P.; Boreham, D.R.

2004-01-01

In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of 60 Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment

Hanging on for the ride: adhesion to the extracellular matrix mediates cellular responses in skeletal muscle morphogenesis and disease.

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Goody, Michelle F; Sher, Roger B; Henry, Clarissa A

2015-05-01

Skeletal muscle specification and morphogenesis during early development are critical for normal physiology. In addition to mediating locomotion, skeletal muscle is a secretory organ that contributes to metabolic homeostasis. Muscle is a highly adaptable tissue, as evidenced by the ability to increase muscle cell size and/or number in response to weight bearing exercise. Conversely, muscle wasting can occur during aging (sarcopenia), cancer (cancer cachexia), extended hospital stays (disuse atrophy), and in many genetic diseases collectively known as the muscular dystrophies and myopathies. It is therefore of great interest to understand the cellular and molecular mechanisms that mediate skeletal muscle development and adaptation. Muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction. This process requires carefully orchestrated interactions between cells and their extracellular matrix microenvironment. These interactions are dynamic, allowing muscle cells to sense biophysical, structural, organizational, and/or signaling changes within their microenvironment and respond appropriately. In many musculoskeletal diseases, these cell adhesion interactions are disrupted to such a degree that normal cellular adaptive responses are not sufficient to compensate for accumulating damage. Thus, one major focus of current research is to identify the cell adhesion mechanisms that drive muscle morphogenesis, with the hope that understanding how muscle cell adhesion promotes the intrinsic adaptability of muscle tissue during development may provide insight into potential therapeutic approaches for muscle diseases. Our objectives in this review are to highlight recent studies suggesting conserved roles for cell-extracellular matrix adhesion in vertebrate muscle morphogenesis and cellular adaptive responses in animal models of muscle diseases. Copyright © 2015 Elsevier Inc. All rights

Circumvention of camptothecin-induced resistance during the adaptive cellular stress response.

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Tiligada, Ekaterini; Papamichael, Konstantinos; Vovou, Ioanna; Delitheos, Andreas

2006-01-01

Camptothecin-11 (CPT-11) induces the adaptive stress response in yeast, conferring resistance via not fully characterized mechanisms. This study aimed at exploring, pharmacologically, the mechanisms underlying the CPT-11-induced resistance in yeast. Post-logarithmic yeast cultures were submitted to heat shock following preconditioning with suramin and with CPT-11, either alone or in combination with suramin, cycloheximide, sodium molybdate, okadaic acid, or verapamil. The stress response was evaluated by determining cell viability after heat shock. Preconditioning with CPT-11 or suramin conferred thermotolerance to yeast cells. Co-administration of CPT-11 with suramin, cycloheximide or okadaic acid reversed the CPT-11-induced thermotolerant phenotype, while sodium molybdate and verapamil had no effect on CPT-11-induced resistance. The antagonistic effect of the thermotolerance-inducers and the possible contribution of topoisomerase II activity and post-translational modifications mediated by the phosphatases PP1/2A in CPT-11-induced resistance may have important implications on the acquisition of resistance to stress in eukaryotic cells.

Adaptive Response to ionizing Radiation Induced by Low Doses of Gamma Rays in Human Lymphoblastoid Cell Lines

International Nuclear Information System (INIS)

Seong, Jin Sil; Suh, Chang Ok; Kim, Gwi Eon

1994-01-01

When cells are exposed to low doses of a mutagenic or clastogenic agents, they often become less sensitive to the effects of a higher does administered subsequently. Such adaptive responses were first described in Escherichia coli and mammalian cells to low doses of an alkylating agent. Since most of the studies have been carried out with human lymphocytes, it is urgently necessary to study this effect in different cellular systems. Its relation with inherent cellular radiosensitivity and underlying mechanism also remain to be answered. In this study, adaptive response by 1 cGy of gamma rays was investigated in three human lymphoblastoid cell lines which were derived from ataxia telangiectasia homozygote, ataxia telangiectasia heterozygote, and normal individual. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher does (50 cGy). The expression of this adaptive response was similar among three cell lines despite of their different radiosensitivity. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the tested cell lines. Therefore it is suggested that the adaptive response can be observed in human lymphoblastoid cell lines. Which was first documented through this study. The expression of adaptive response was similar among the cell lines regardless of their radiosensitivity. The elimination of the adaptive response by 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanism

Adaptive pressure-controlled cellular structures for shape morphing I: design and analysis

International Nuclear Information System (INIS)

Luo, Quantian; Tong, Liyong

2013-01-01

This work investigates adaptive bio-inspired pressure cellular structures for shape morphing. Optimum designs for cellular structures with void and pressure cells are proposed and then structural analyses are conducted. In the present design, a unit cell is comprised of straight and curved walls. When compressed air is pumped into a pressure cell, the curved walls deform in bending due to the pressure difference in two adjacent cells that leads to overall structural deformation in extension. One-dimensional actuation strain up to 35% can be theoretically achieved. In part I, we present basic design concepts and cellular mechanics. Unlike conventional structural analysis for cellular structures, a statically indeterminate unit cell is considered and novel analytical formulations are derived for the present pressurized cellular structures in linear and nonlinear analyses. In part II, we will present experimental testing and finite element analysis to demonstrate the feasibility of the present pressurized cellular actuators for morphing wings and to validate the present cellular mechanics formulations. (paper)

Modeling adaptive and non-adaptive responses to environmental change

DEFF Research Database (Denmark)

Coulson, Tim; Kendall, Bruce E; Barthold, Julia A.

2017-01-01

, with plastic responses being either adaptive or non-adaptive. We develop an approach that links quantitative genetic theory with data-driven structured models to allow prediction of population responses to environmental change via plasticity and adaptive evolution. After introducing general new theory, we...... construct a number of example models to demonstrate that evolutionary responses to environmental change over the short-term will be considerably slower than plastic responses, and that the rate of adaptive evolution to a new environment depends upon whether plastic responses are adaptive or non-adaptive....... Parameterization of the models we develop requires information on genetic and phenotypic variation and demography that will not always be available, meaning that simpler models will often be required to predict responses to environmental change. We consequently develop a method to examine whether the full...

Dynamic Nature of Noncoding RNA Regulation of Adaptive Immune Response

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Franca Citarella

2013-08-01

Full Text Available Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, and, in particular, adaptive immunity, has improved dramatically. For many years, much of the focus has been on the study of protein regulators; nevertheless, recent evidence points to a fundamental role for specific classes of noncoding RNAs (ncRNAs in regulating development, activation and homeostasis of the immune system. Although microRNAs (miRNAs are the most comprehensive and well-studied, a number of reports suggest the exciting possibility that long ncRNAs (lncRNAs could mediate host response and immune function. Finally, evidence is also accumulating that suggests a role for miRNAs and other small ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting an elaborate network of regulatory interactions mediated by different classes of ncRNAs during immune response. This review will explore the multifaceted roles of ncRNAs in the adaptive immune response. In particular, we will focus on the well-established role of miRNAs and on the emerging role of lncRNAs and circulating ncRNAs, which all make indispensable contributions to the understanding of the multilayered modulation of the adaptive immune response.

Cellular Adaptation: Culture conditions of R. opacus and bioflotation of apatite and quartz

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Antonio Gutiérrez Merma

Full Text Available Abstract It is well known that the culture conditions of microorganisms may affect their surface properties, zeta potential and hydrophobicity via the modification of the cell wall functional groups or metabolic products. The R. opacus bacteria strain was separately adapted to the presence of apatite and quartz, after which a cellular adaptation procedure was developed by repeated sub-culturing with a successive increase in the mineral content. Zeta potential, surface tension, FTIR and microflotation studies were used to evaluate the behavior of the cells that were developed under defined culture conditions. The cellular adaptation induced a modification of the bacterial surface charge. The FTIR results showed a modification of its functional groups. The surface tension results suggested that longer growing time promoted a higher production of metabolites. The use of mineral-adapted cells promoted an improvement in the flotability of both minerals, but it was more significant for apatite flotation. Additionally, the mineral flotability remained unchanged when the cells developed under a longer culture time. Nevertheless, there was a reduction in the surface tension.

Adaptive Response in Animals Exposed to Non-Ionizing Radiofrequency Fields: Some Underlying Mechanisms

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Yi Cao

2014-04-01

Full Text Available During the last few years, our research group has been investigating the phenomenon of adaptive response in animals exposed to non-ionizing radiofrequency fields. The results from several separate studies indicated a significant increase in survival, decreases in genetic damage as well as oxidative damage and, alterations in several cellular processes in mice pre-exposed to radiofrequency fields and subsequently subjected to sub-lethal or lethal doses of γ-radiation or injected with bleomycin, a radiomimetic chemical mutagen. These observations indicated the induction of adaptive response providing the animals the ability to resist subsequent damage. Similar studies conducted by independent researchers in mice and rats have supported our observation on increased survival. In this paper, we have presented a brief review of all of our own and other independent investigations on radiofrequency fields-induced adaptive response and some underlying mechanisms discussed.

Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

OpenAIRE

Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

2012-01-01

Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induce...

Mitochondrial Stress Signaling Promotes Cellular Adaptations

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Jayne Alexandra Barbour

2014-01-01

Full Text Available Mitochondrial dysfunction has been implicated in the aetiology of many complex diseases, as well as the ageing process. Much of the research on mitochondrial dysfunction has focused on how mitochondrial damage may potentiate pathological phenotypes. The purpose of this review is to draw attention to the less well-studied mechanisms by which the cell adapts to mitochondrial perturbations. This involves communication of stress to the cell and successful induction of quality control responses, which include mitophagy, unfolded protein response, upregulation of antioxidant and DNA repair enzymes, morphological changes, and if all else fails apoptosis. The mitochondrion is an inherently stressful environment and we speculate that dysregulation of stress signaling or an inability to switch on these adaptations during times of mitochondrial stress may underpin mitochondrial dysfunction and hence amount to pathological states over time.

Radiation risk of tissue late effects, a net consequence of probabilities of various cellular responses

International Nuclear Information System (INIS)

Feinendegen, L.E.

1991-01-01

Late effects from the exposure to low doses of ionizing radiation are hardly or not at all observed in man mainly due to the low values of risk coefficients that preclude statistical analyses of data from populations that are exposed to doses less than 0.2 Gy. In order to arrive at an assessment of potential risk from radiation exposure in the low dose range, the microdosimetry approach is essential. In the low dose range, ionizing radiation generates particle tracks, mainly electrons, which are distributed rather heterogeneously within the exposed tissue. Taking the individual cell as the elemental unit of life, observations and calculations of cellular responses to being hit by energy depositions events from low LET type are analysed. It emerges that besides the probability of a hit cell to sustain a detrimental effect with the consequense of malignant transformation there are probabilities of various adaptive responses that equipp the hit cell with a benefit. On the one hand, an improvement of cellular radical detoxification was observed in mouse bone marrow cells; another adaptive response pertaining to improved DNA repair, was reported for human lymphocytes. The improved radical detoxification in mouse bone marrow cells lasts for a period of 5-10 hours and improved DNA repair in human lymphocytes was seen for some 60 hours following acute irradiation. It is speculated that improved radical detoxification and improved DNA repair may reduce the probability of spontaneous carcinogenesis. Thus it is proposed to weigh the probability of detriment for a hit cell within a multicellular system against the probability of benefit through adaptive responses in other hit cells in the same system per radiation exposure. In doing this, the net effect of low doses of low LET radiation in tissue with individual cells being hit by energy deposition events could be zero or even beneficial. (orig./MG)

Programmed cellular response to ionizing radiation damage

International Nuclear Information System (INIS)

Crompton, N.E.A.

1998-01-01

Three forms of radiation response were investigated to evaluate the hypothesis that cellular radiation response is the result of active molecular signaling and not simply a passive physicochemical process. The decision whether or not a cell should respond to radiation-induced damage either by induction of rescue systems, e.g. mobilization of repair proteins, or induction of suicide mechanisms, e.g. programmed cell death, appears to be the expression of intricate cellular biochemistry. A cell must recognize damage in its genetic material and then activate the appropriate responses. Cell type is important; the response of a fibroblast to radiation damage is both quantitatively and qualitatively different form that of a lymphocyte. The programmed component of radiation response is significant in radiation oncology and predicted to create unique opportunities for enhanced treatment success. (orig.)

Adaptive response to high LET radiations

International Nuclear Information System (INIS)

Dam, Annamaria; Bogdandi, E. Noemi; Polonyi, Istvan; Sardy, M. Marta; Balashazy, Imre; Palfalvy, Jozsef

2001-01-01

The biological consequences of exposure to ionizing radiation include gene mutation, chromosome aberrations, cellular transformation and cell death. These effects are attributed to the DNA damaging effects of the irradiation resulting in irreversible changes during DNA replication or during the processing of the DNA damage by enzymatic repair processes. These repair processes could initiate some adaptive mechanisms in the cell, which could lead to radioadaptive response (RAR). Adaptive responses have typically been detected by exposing cells to a low radiation dose (1-50 mGy) and then challenging the cells with a higher dose of radiation (2-4 Gy) and comparing the outcome to that seen with the challenge dose only. For adaptive response to be seen the challenge dose must be delivered within 24 hour of the inducing dose. Radio-adaptation is extensively studied for low LET radiation. Nevertheless, few data are available for high LET radiation at very low doses and dose rate. Our study was aimed to investigate the radioadaptive response to low-dose neutron irradiation by detection of the genotoxic damage i.e.: hprt-mutant colonies induced. Altered protein synthesis was also studied to identify stress proteins may responsible for radio-adaptation. New alpha particle irradiator system was also built up to study the biological effects of low dose alpha irradiation. The experiments were carried out on monolayers of human melanoma and CHO (Chines Hamster Ovary) cells irradiated by neutrons produced in the biological irradiation channel of the Research Reactor of Budapest Neutron Center. Cells were exposed to 0.5-50 mGy neutron doses with dose rates of 1.59-10 mGy/min. The challenge doses of 2-4 Gy gamma rays were administrated within 1-48 hours after priming treatment. The induced mutants at hprt locus were selected by adding 6-thioguanine and allow to grow for 10 days for expression of the phenotype. The protein synthesis was studied by PAGE, the molecular mass of specific

Understanding the role of p53 in adaptive response to radiation-induced germline mutations

International Nuclear Information System (INIS)

Langlois, N.L.; Quinn, J.S.; Somers, C.M.; Boreham, D.R.; Mitchel, R.E.J.

2003-01-01

Full text: Radiation-induced adaptive response is now a widely studied area of radiation biology. Studies have demonstrated reduced levels of radiation-induced biological damage when an 'adaptive dose' is given before a higher 'challenge dose' compared to when the challenge dose is given alone. It has been shown in some systems to be a result of inducible cellular repair systems. The adaptive response has been clearly demonstrated in many model systems, however its impact on heritable effects in the mammalian germline has never been studied. Expanded Simple Tandem Repeat (ESTR) loci have been used as markers demonstrating that induced heritable mutations in mice follow a dose-response relationship. Recent data in our laboratory show preliminary evidence of radiation-induced adaptive response suppressing germline mutations at ESTR loci in wild type mice. The frequency of heritable mutations was significantly reduced when a priming dose of 0.1 Gy was given 24 hours prior to a 1 Gy acute challenging dose. We are now conducting a follow-up study to attempt to understand the mechanism of this adaptive response. P53 is known to play a significant role in governing apoptosis, DNA repair and cancer induction. In order to determine what function p53 has in the adaptive response for heritable mutations, we have mated radiation treated Trp53+/- male mice (C57Bl) to untreated, normal females (C57Bl). Using DNA fingerprinting, we are investigating the rate of inherited radiation-induced mutations on pre- and post-meiotic radiation-treated gametocytes by examining mutation frequencies in offspring DNA. If p53 is integral in the mechanism of adaptive response, we should not see an adaptive response in radiation-induced heritable mutations in these mice. This research is significant in that it will provide insight to understanding the mechanism behind radiation-induced adaptive response in the mammalian germline

A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

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Leonard, Bobby E

2008-02-27

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite

The adaptive cruise control vehicles in the cellular automata model

International Nuclear Information System (INIS)

Jiang Rui; Wu Qingsong

2006-01-01

This Letter presented a cellular automata model where the adaptive cruise control vehicles are modelled. In this model, the constant time headway policy is adopted. The fundamental diagram is presented. The simulation results are in good agreement with the analytical ones. The mixture of ACC vehicles with manually driven vehicles is investigated. It is shown that with the introduction of ACC vehicles, the jam can be suppressed

7th International Workshop on Microbeam Probes of Cellular Radiation Response

Energy Technology Data Exchange (ETDEWEB)

Brenner, David J.

2009-07-21

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

The zebrafish miR-125c is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations and embryogenesis.

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He, Yan; Huang, Chun-Xiao; Chen, Nan; Wu, Meng; Huang, Yan; Liu, Hong; Tang, Rong; Wang, Wei-Min; Wang, Huan-Ling

2017-09-26

Hypoxia is a unique environmental stress. Hypoxia inducible factor-lα (HIF-lα) is a major transcriptional regulator of cellular adaptations to hypoxic stress. MicroRNAs (miRNAs) as posttranscriptional gene expression regulators occupy a crucial role in cell survival under low-oxygen environment. Previous evidences suggested that miR-125c is involved in hypoxia adaptation, but its precise biological roles and the regulatory mechanism underlying hypoxic responses remain unknown. The present study showed that zebrafish miR-125c is upregulated by hypoxia in a Hif-lα-mediated manner in vitro and in vivo . Dual-luciferase assay revealed that cdc25a is a novel target of miR-125c. An inverse correlation between miR-125c and cdc25a was further confirmed in vivo , suggesting miR-125c as a crucial physiological inhibitor of cdc25a which responds to cellular hypoxia. Overexpression of miR-125c suppressed cell proliferation, led to cell cycle arrest at the G1 phase in ZF4 cells and induced apoptotic responses during embryo development. More importantly, miR-125c overexpression resulted in severe malformation and reduction of motility during zebrafish embryonic development. Taken together, we conclude that miR-125c plays a pivotal role in cellular adaptations to hypoxic stress at least in part through the Hif-1α/miR-125c/cdc25a signaling and has great impact on zebrafish early embryonic development.

Cellular responses to environmental DNA damage

Energy Technology Data Exchange (ETDEWEB)

1994-08-01

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

Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

Science.gov (United States)

CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

A cascade reaction network mimicking the basic functional steps of adaptive immune response.

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Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

2015-10-01

Biological systems use complex 'information-processing cores' composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

Adaptation in Living Systems

Science.gov (United States)

Tu, Yuhai; Rappel, Wouter-Jan

2018-03-01

Adaptation refers to the biological phenomenon where living systems change their internal states in response to changes in their environments in order to maintain certain key functions critical for their survival and fitness. Adaptation is one of the most ubiquitous and arguably one of the most fundamental properties of living systems. It occurs throughout all biological scales, from adaptation of populations of species over evolutionary time to adaptation of a single cell to different environmental stresses during its life span. In this article, we review some of the recent progress made in understanding molecular mechanisms of cellular-level adaptation. We take the minimalist (or the physicist) approach and study the simplest systems that exhibit generic adaptive behaviors, namely chemotaxis in bacterium cells (Escherichia coli) and eukaryotic cells (Dictyostelium). We focus on understanding the basic biochemical interaction networks that are responsible for adaptation dynamics. By combining theoretical modeling with quantitative experimentation, we demonstrate universal features in adaptation as well as important differences in different cellular systems. Future work in extending the modeling framework to study adaptation in more complex systems such as sensory neurons is also discussed.

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

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Sandra Troschinski

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

The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations.

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Huang, Chun-Xiao; Chen, Nan; Wu, Xin-Jie; Huang, Cui-Hong; He, Yan; Tang, Rong; Wang, Wei-Min; Wang, Huan-Ling

2015-12-01

Hypoxia, a unique and essential environmental stress, evokes highly coordinated cellular responses, and hypoxia-inducible factor (HIF) 1 in the hypoxia signaling pathway, an evolutionarily conserved cellular signaling pathway, acts as a master regulator of the transcriptional response to hypoxic stress. MicroRNAs (miRNAs), a major class of posttranscriptional gene expression regulators, also play pivotal roles in orchestrating hypoxia-mediated cellular adaptations. Here, global miRNA expression profiling and quantitative real-time PCR indicated that the up-regulation of the miR-462/miR-731 cluster in zebrafish larvae is induced by hypoxia. It was further validated that miR-462 and miR-731 are up-regulated in a Hif-1α-mediated manner under hypoxia and specifically target ddx5 and ppm1da, respectively. Overexpression of miR-462 and miR-731 represses cell proliferation through blocking cell cycle progress of DNA replication, and induces apoptosis. In situ detection revealed that the miR-462/miR-731 cluster is highly expressed in a consistent and ubiquitous manner throughout the early developmental stages. Additionally, the transcripts become restricted to the notochord, pharyngeal arch, liver, and gut regions from postfertilization d 3 to 5. These data highlight a previously unidentified role of the miR-462/miR-731 cluster as a crucial signaling mediator for hypoxia-mediated cellular adaptations and provide some insights into the potential function of the cluster during embryonic development. © FASEB.

Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses

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Iwai Ohbayashi

2018-01-01

Full Text Available The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses.

Science.gov (United States)

Ohbayashi, Iwai; Sugiyama, Munetaka

2017-01-01

The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

Cellular Response to Ionizing Radiation: A MicroRNA Story

Science.gov (United States)

Halimi, Mohammad; Asghari, S. Mohsen; Sariri, Reyhaneh; Moslemi, Dariush; Parsian, Hadi

2012-01-01

MicroRNAs (miRNAs) represent a class of small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. They play a crucial role in diverse cellular pathways. Ionizing radiation (IR) is one of the most important treatment protocols for patients that suffer from cancer and affects directly or indirectly cellular integration. Recently it has been discovered that microRNA-mediated gene regulation interferes with radio-related pathways in ionizing radiation. Here, we review the recent discoveries about miRNAs in cellular response to IR. Thoroughly understanding the mechanism of miRNAs in radiation response, it will be possible to design new strategies for improving radiotherapy efficiency and ultimately cancer treatment. PMID:24551775

TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress.

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Raben, Nina; Puertollano, Rosa

2016-10-06

In recent years, our vision of lysosomes has drastically changed. Formerly considered to be mere degradative compartments, they are now recognized as key players in many cellular processes. The ability of lysosomes to respond to different stimuli revealed a complex and coordinated regulation of lysosomal gene expression. This review discusses the participation of the transcription factors TFEB and TFE3 in the regulation of lysosomal function and biogenesis, as well as the role of the lysosomal pathway in cellular adaptation to a variety of stress conditions, including nutrient deprivation, mitochondrial dysfunction, protein misfolding, and pathogen infection. We also describe how cancer cells make use of TFEB and TFE3 to promote their own survival and highlight the potential of these transcription factors as therapeutic targets for the treatment of neurological and lysosomal diseases.

Humoral and cellular immune responses to modified hepatitis B ...

African Journals Online (AJOL)

These findings indicate that the vaccine induced both a humoral and cellular ... Keywords: Hepatitis B virus, Plasmid DNA, Vaccine, Spleen cytokines, Humoral and cellular immune responses ... produced in mice. ... were performed and HBsAg specific IgM and IgG ..... and protection elicited against Plasmodium berghei.

Cellular immune responses to respiratory viruses

NARCIS (Netherlands)

van Helden, M.J.G.

2011-01-01

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

Carica Papaya Seed Extract Enhances Cellular Response to Stress ...

African Journals Online (AJOL)

Therefore, the present study was carried out to investigate the role of Carica papaya seed (CPS) extract that contains, Benzyl Isothiocyanates, one of the inducers of phase II enzymes in the regulation of cellular stress. The cellular responses were observed in U937 cells (human monocyte/macrophage cell line) at the ...

Recombinant proteins of Zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice.

Science.gov (United States)

Lehrer, Axel T; Wong, Teri-Ann S; Lieberman, Michael M; Humphreys, Tom; Clements, David E; Bakken, Russell R; Hart, Mary Kate; Pratt, William D; Dye, John M

2018-05-24

Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death. Questions remain with regard to the few survivors of infection, who manage to mount an effective adaptive immune response. These questions concern the humoral and cellular components of this response, and whether such a response can be elicited by an appropriate prophylactic vaccine. The data reported herein describe the production and evaluation of a recombinant subunit Ebola virus vaccine candidate consisting of insect cell expressed Zaire ebolavirus (EBOV) surface glycoprotein (GP) and the matrix proteins VP24 and VP40. The recombinant subunit proteins are shown to be highly immunogenic in mice, yielding both humoral and cellular responses, as well as highly efficacious, providing up to 100% protection against a lethal challenge with live virus. These results demonstrate proof of concept for such a recombinant non-replicating vaccine candidate in the mouse model of EBOV which helps to elucidate immune correlates of protection and warrants further development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioanalytical evidence that chemicals in tattoo ink can induce adaptive stress responses.

Science.gov (United States)

Neale, Peta A; Stalter, Daniel; Tang, Janet Y M; Escher, Beate I

2015-10-15

Tattooing is becoming increasingly popular, particularly amongst young people. However, tattoo inks contain a complex mixture of chemical impurities that may pose a long-term risk for human health. As a first step towards the risk assessment of these complex mixtures we propose to assess the toxicological hazard potential of tattoo ink chemicals with cell-based bioassays. Targeted modes of toxic action and cellular endpoints included cytotoxicity, genotoxicity and adaptive stress response pathways. The studied tattoo inks, which were extracted with hexane as a proxy for the bioavailable fraction, caused effects in all bioassays, with the red and yellow tattoo inks having the greatest response, particularly inducing genotoxicity and oxidative stress response endpoints. Chemical analysis revealed the presence of polycyclic aromatic hydrocarbons in the tested black tattoo ink at concentrations twice the recommended level. The detected polycyclic aromatic hydrocarbons only explained 0.06% of the oxidative stress response of the black tattoo ink, thus the majority of the effect was caused by unidentified components. The study indicates that currently available tattoo inks contain components that induce adaptive stress response pathways, but to evaluate the risk to human health further work is required to understand the toxicokinetics of tattoo ink chemicals in the body. Copyright © 2015 Elsevier B.V. All rights reserved.

Cellular response of human neuroblastoma cells to α-synuclein fibrils, the main constituent of Lewy bodies.

Science.gov (United States)

Pieri, Laura; Chafey, Philippe; Le Gall, Morgane; Clary, Guilhem; Melki, Ronald; Redeker, Virginie

2016-01-01

α-Synuclein (α-Syn) fibrils are the main constituent of Lewy bodies and a neuropathological hallmark of Parkinson's disease (PD). The propagation of α-Syn assemblies from cell to cell suggests that they are involved in PD progression. We previously showed that α-Syn fibrils are toxic because of their ability to bind and permeabilize cell membranes. Here, we document the cellular response in terms of proteome changes of SH-SY5Y cells exposed to exogenous α-Syn fibrils. We compare the proteomes of cells of neuronal origin exposed or not either to oligomeric or fibrillar α-Syn using two dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry. Only α-Syn fibrils induce significant changes in the proteome of SH-SY5Y cells. In addition to proteins associated to apoptosis and toxicity, or proteins previously linked to neurodegenerative diseases, we report an overexpression of proteins involved in intracellular vesicle trafficking. We also report a remarkable increase in fibrillar α-Syn heterogeneity, mainly due to C-terminal truncations. Our results show that cells of neuronal origin adapt their proteome to exogenous α-Syn fibrils and actively modify those assemblies. Cells of neuronal origin adapt their proteome to exogenous toxic α-Syn fibrils and actively modify those assemblies. Our results bring insights into the cellular response and clearance events the cells implement to face the propagation of α-Syn assemblies associated to pathology.

Impact of Antenna Placement on Frequency Domain Adaptive Antenna Array in Hybrid FRF Cellular System

Directory of Open Access Journals (Sweden)

Sri Maldia Hari Asti

2012-01-01

Full Text Available Frequency domain adaptive antenna array (FDAAA is an effective method to suppress interference caused by frequency selective fading and multiple-access interference (MAI in single-carrier (SC transmission. However, the performance of FDAAA receiver will be affected by the antenna placement parameters such as antenna separation and spread of angle of arrival (AOA. On the other hand, hybrid frequency reuse can be adopted in cellular system to improve the cellular capacity. However, optimal frequency reuse factor (FRF depends on the channel propagation and transceiver scheme as well. In this paper, we analyze the impact of antenna separation and AOA spread on FDAAA receiver and optimize the cellular capacity by using hybrid FRF.

Cellular biomarker responses of bagrid catfish, Chrysichthys ...

African Journals Online (AJOL)

An assessment of the pollution status of Agboyi creek, a water body associated with various anthropogenic activities was carried out in order to determine responses induced in Catfishes, Chrysichthys nigrodigitatus inhabiting it. Cellular biomarkers of stress including the antioxidative stress enzyme, catalase (CAT), lipid ...

Gravity and neuronal adaptation, in vitro and in vivo-from neuronal cells up to neuromuscular responses: a first model.

Science.gov (United States)

Kohn, Florian P M; Ritzmann, Ramona

2018-03-01

For decades it has been shown that acute changes in gravity have an effect on neuronal systems of human and animals on different levels, from the molecular level to the whole nervous system. The functional properties and gravity-dependent adaptations of these system levels have been investigated with no or barely any interconnection. This review summarizes the gravity-dependent adaptation processes in human and animal organisms from the in vitro cellular level with its biophysical properties to the in vivo motor responses and underlying sensorimotor functions of human subjects. Subsequently, a first model for short-term adaptation of neuronal transmission is presented and discussed for the first time, which integrates the responses of the different levels of organization to changes in gravity.

Antioxidant responses and cellular adjustments to oxidative stress.

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

2015-12-01

Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. Copyright © 2015. Published by Elsevier B.V.

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

Science.gov (United States)

Sibonga, J. D.; Iwaniec, U.; Wu, H.

2011-01-01

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal

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

International Nuclear Information System (INIS)

Kitanovic, Ana; Woelfl, Stefan

2006-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2006-02-22

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

Distinctive adaptive response to repeated exposure to hydrogen peroxide associated with upregulation of DNA repair genes and cell cycle arrest

Directory of Open Access Journals (Sweden)

Gloria A. Santa-Gonzalez

2016-10-01

Full Text Available Many environmental and physiological stresses are chronic. Thus, cells are constantly exposed to diverse types of genotoxic insults that challenge genome stability, including those that induce oxidative DNA damage. However, most in vitro studies that model cellular response to oxidative stressors employ short exposures and/or acute stress models. In this study, we tested the hypothesis that chronic and repeated exposure to a micromolar concentration of hydrogen peroxide (H2O2 could activate DNA damage responses, resulting in cellular adaptations. For this purpose, we developed an in vitro model in which we incubated mouse myoblast cells with a steady concentration of ~50 μM H2O2 for one hour daily for seven days, followed by a final challenge of a 10 or 20X higher dose of H2O2 (0.5 or 1 mM. We report that intermittent long-term exposure to this oxidative stimulus nearly eliminated cell toxicity and significantly decreased genotoxicity (in particular, a >5-fold decreased in double-strand breaks resulting from subsequent acute exposure to oxidative stress. This protection was associated with cell cycle arrest in G2/M and induction of expression of nine DNA repair genes. Together, this evidence supports an adaptive response to chronic, low-level oxidative stress that results in genomic protection and up-regulated maintenance of cellular homeostasis.

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

Science.gov (United States)

McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Meyer, Joel N.; Domann, Frederick E.; Van Houten, Bennett; Mostoslavsky, Raul; Bultman, Scott J.; Baccarelli, Andrea A.; Begley, Thomas J.; Sobol, Robert W.; Hirschey, Matthew D.; Ideker, Trey; Santos, Janine H.; Copeland, William C.; Tice, Raymond R.; Balshaw, David M.; Tyson, Frederick L.

2014-01-01

Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to

Phenomenon of adaptive response of cells in radiobiology

International Nuclear Information System (INIS)

Fillipovich, I.V.

1991-01-01

Consideration is given to various adaptive reactions to low-level radiation, their association with an absorbed dose, dose rate, radiation quality and time-interval between exposures, as well as with a cell cycle phase. Possible mechanisms of the adaptive response and the character and role of DNA damages, that can induce gene expression of the adaptive response, are discussed. The data on the influence of a preliminary long-term exposure to low-level radiation on the radiosensitivity of biological objects are analyzed with due regard for the adaptive cell response. It is concluded that the adaptive response of cells to ionizing radiation is a particular case of the phenomenon of cell adaptation of the effect of genotoxic factors of the environment

Adaptation of cell renewal systems under continuous irradiation

International Nuclear Information System (INIS)

Fabrikant, J.I.

1987-01-01

There are adaptive changes in the proliferative characteristics of renewal tissues under the stress of continuous low-dose-rate irradiation which indicate that cell and tissue kinetics will have a considerable effect on the radiation response. Factors that determine the adaptation response involve cellular radiosensitivity, i.e. cell cycle effects, which determine the rate of cell sterilization and death, and compensatory cell proliferation and the capacity for regeneration, i.e. changes in the patterns of cell population kinetics, which determine the rate of cell birth. In rapidly dividing cell renewal systems, there is an effective elimination of damaged cells, with almost complete repair of cellular nonlethal damage. In slowly dividing renewal tissues, there is some repair or elimination of cellular radiation damage and the pattern of cell proliferation during regeneration is relatively little disturbed by prior continuous irradiation. Experimental data on intestinal epithelium, immunohematopoietic tissues, seminiferous epithelium and regenerating liver are presented. Discussion includes differences in adaptation to continuous low-dose-rate irradiation involving intracellular and extracellular control mechanisms which regulate cellular proliferation and differentiation and, thereby, control cell population levels and physiological function. 29 references

Adaptive stress response to menadione-induced oxidative stress in Saccharomyces cerevisiae KNU5377.

Science.gov (United States)

Kim, Il-Sup; Sohn, Ho-Yong; Jin, Ingnyol

2011-10-01

The molecular mechanisms involved in the ability of yeast cells to adapt and respond to oxidative stress are of great interest to the pharmaceutical, medical, food, and fermentation industries. In this study, we investigated the time-dependent, cellular redox homeostasis ability to adapt to menadione-induced oxidative stress, using biochemical and proteomic approaches in Saccharomyces cerevisiae KNU5377. Time-dependent cell viability was inversely proportional to endogenous amounts of ROS measured by a fluorescence assay with 2',7'-dichlorofluorescin diacetate (DCFHDA), and was hypersensitive when cells were exposed to the compound for 60 min. Morphological changes, protein oxidation and lipid peroxidation were also observed. To overcome the unfavorable conditions due to the presence of menadione, yeast cells activated a variety of cell rescue proteins including antioxidant enzymes, molecular chaperones, energy-generating metabolic enzymes, and antioxidant molecules such as trehalose. Thus, these results show that menadione causes ROS generation and high accumulation of cellular ROS levels, which affects cell viability and cell morphology and there is a correlation between resistance to menadione and the high induction of cell rescue proteins after cells enter into this physiological state, which provides a clue about the complex and dynamic stress response in yeast cells.

Temporal partitioning of adaptive responses of the murine heart to fasting.

Science.gov (United States)

Brewer, Rachel A; Collins, Helen E; Berry, Ryan D; Brahma, Manoja K; Tirado, Brian A; Peliciari-Garcia, Rodrigo A; Stanley, Haley L; Wende, Adam R; Taegtmeyer, Heinrich; Rajasekaran, Namakkal Soorappan; Darley-Usmar, Victor; Zhang, Jianhua; Frank, Stuart J; Chatham, John C; Young, Martin E

2018-03-15

Recent studies suggest that the time of day at which food is consumed dramatically influences clinically-relevant cardiometabolic parameters (e.g., adiposity, insulin sensitivity, and cardiac function). Meal feeding benefits may be the result of daily periods of feeding and/or fasting, highlighting the need for improved understanding of the temporal adaptation of cardiometabolic tissues (e.g., heart) to fasting. Such studies may provide mechanistic insight regarding how time-of-day-dependent feeding/fasting cycles influence cardiac function. We hypothesized that fasting during the sleep period elicits beneficial adaptation of the heart at transcriptional, translational, and metabolic levels. To test this hypothesis, temporal adaptation was investigated in wild-type mice fasted for 24-h, or for either the 12-h light/sleep phase or the 12-h dark/awake phase. Fasting maximally induced fatty acid responsive genes (e.g., Pdk4) during the dark/active phase; transcriptional changes were mirrored at translational (e.g., PDK4) and metabolic flux (e.g., glucose/oleate oxidation) levels. Similarly, maximal repression of myocardial p-mTOR and protein synthesis rates occurred during the dark phase; both parameters remained elevated in the heart of fasted mice during the light phase. In contrast, markers of autophagy (e.g., LC3II) exhibited peak responses to fasting during the light phase. Collectively, these data show that responsiveness of the heart to fasting is temporally partitioned. Autophagy peaks during the light/sleep phase, while repression of glucose utilization and protein synthesis is maximized during the dark/active phase. We speculate that sleep phase fasting may benefit cardiac function through augmentation of protein/cellular constituent turnover. Copyright © 2018 Elsevier Inc. All rights reserved.

An Asynchronous Cellular Automata-Based Adaptive Illumination Facility

Science.gov (United States)

Bandini, Stefania; Bonomi, Andrea; Vizzari, Giuseppe; Acconci, Vito

The term Ambient Intelligence refers to electronic environments that are sensitive and responsive to the presence of people; in the described scenario the environment itself is endowed with a set of sensors (to perceive humans or other physical entities such as dogs, bicycles, etc.), interacting with a set of actuators (lights) that choose their actions (i.e. state of illumination) in an attempt improve the overall experience of these users. The model for the interaction and action of sensors and actuators is an asynchronous Cellular Automata (CA) with memory, supporting a self-organization of the system as a response to the presence and movements of people inside it. The paper will introduce the model, as well as an ad hoc user interface for the specification of the relevant parameters of the CA transition rule that determines the overall system behaviour.

Metabolic Adaptation to Muscle Ischemia

Science.gov (United States)

Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

2000-01-01

Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

Repair and mutagenesis in procaryotes as cellular responses to ambiental agents

International Nuclear Information System (INIS)

Gomes, R.A.

1982-01-01

The correct and incorrect mechanisms of DNA repair are discussed, as well as the cellular responses induced by the DNA lesions; the reductone mollecular effects; the cellular interactions among irradiated populations of microorganisms and the utilization of microbial assays for the detection of oncogenic activities of chemicals. (M.A.) [pt

The RBE of tritium-beta exposure for the induction of the adaptive response and apoptosis; cellular defense mechanisms against the biological effects of ionizing radiation

International Nuclear Information System (INIS)

Boreham, D.R.; Bahen, M.E.; Dolling, J-A.

1997-01-01

Adaption to radiation is one of a few biological responses that has been demonstrated to occur in mammalian cells exposed to doses of ionizing radiation in the occupational exposure range. The adaptive response has been well characterized in the yeast Saccharomyces cerevisiae, although the doses required to induce the response are higher than in mammalian cells. When yeast cells are primed with sublethal doses of gamma-radiation, they subsequently undergo an adaptive response and develop resistance to radiation, heat the chemical mutagens in a time and dose dependent manner. We have used this model system to assess the relative ability of tritium-beta radiation to induce the adaptive response the examined tritium-induced radiation resistance, thermal tolerance and suppression of mutation. The results show that sublethal priming doses of tritium caused yeast cells to develop resistance to radiation, heat, and a chemical mutagen MNNG. The magnitude and kinetics of the response, per unit dose, were the same for tritium and gamma-radiation. Therefore, the relative biological effectiveness (RBE) of tritium induction of the adaptive response was about 1.0. Apoptosis is a genetically programmed cell death or cell suicide. Cells damaged by radiation can be selectively removed from the population by apoptosis and therefore eliminated as a potential cancer risk to the organism. Since we have previously shown that apoptosis is a sensitive indicator of radiation damage in human lymphocytes exposed to low doses, we have used this endpoint to investigate the potency of tritium-beta radiation. Initially, tritium was compared to X-rays for relative effectiveness at inducing apoptosis. The results showed the lymphocytes irradiated in vitro with X-rays or tritium had similar levels of apoptosis per unit dose. Therefore the relative biology effectiveness of tritium for induction of apoptosis in human lymphocytes was also about 1. In the work presented here, we have demonstrated that

Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution

DEFF Research Database (Denmark)

Utrilla, José; O'Brien, Edward J.; Chen, Ke

2016-01-01

Pleiotropic regulatory mutations affect diverse cellular processes, posing a challenge to our understanding of genotype-phenotype relationships across multiple biological scales. Adaptive laboratory evolution (ALE) allows for such mutations to be found and characterized in the context of clear se...

Linking physiological and cellular responses to thermal stress: β-adrenergic blockade reduces the heat shock response in fish.

Science.gov (United States)

Templeman, Nicole M; LeBlanc, Sacha; Perry, Steve F; Currie, Suzanne

2014-08-01

When faced with stress, animals use physiological and cellular strategies to preserve homeostasis. We were interested in how these high-level stress responses are integrated at the level of the whole animal. Here, we investigated the capacity of the physiological stress response, and specifically the β-adrenergic response, to affect the induction of the cellular heat shock proteins, HSPs, following a thermal stress in vivo. We predicted that blocking β-adrenergic stimulation during an acute heat stress in the whole animal would result in reduced levels of HSPs in red blood cells (RBCs) of rainbow trout compared to animals where adrenergic signaling remained intact. We first determined that a 1 h heat shock at 25 °C in trout acclimated to 13 °C resulted in RBC adrenergic stimulation as determined by a significant increase in cell swelling, a hallmark of the β-adrenergic response. A whole animal injection with the β2-adrenergic antagonist, ICI-118,551, successfully reduced this heat-induced RBC swelling. The acute heat shock caused a significant induction of HSP70 in RBCs of 13 °C-acclimated trout as well as a significant increase in plasma catecholamines. When heat-shocked fish were treated with ICI-118,551, we observed a significant attenuation of the HSP70 response. We conclude that circulating catecholamines influence the cellular heat shock response in rainbow trout RBCs, demonstrating physiological/hormonal control of the cellular stress response.

Evaluation of the immunological cellular response of Cebus apella exposed to the carcinogen N-methyl-N-nitrosourea and treated with CANOVA®.

Science.gov (United States)

Feio, Danielle Cristinne Azevedo; Muniz, José Augusto Pereira Carneiro; Montenegro, Raquel Carvalho; Burbano, Rommel Rodriguez; De Brito Junior, Lacy Cardoso; De Lima, Patrícia Danielle Lima

2014-01-01

The immune response modifier Canova® is a homeopathic remedy indicated for patients with depressed immune system, since this drug appears to increase adaptive immunity and induce an immune response against multiple and severe pathological conditions, including cancer. We evaluated the pattern of immune cellular response in non-human primates of the species Cebus apella exposed to N-methyl-N-nitrosourea (MNU) with and without Canova®. Twelve animals were divided into four groups, with three animals each: negative control and three experimental groups, MNU-alone (35 days); MNU (35 days)-plus-Canova® (3 days) and Canova®-alone (3 days). The animals received MNU orally and Canova® by three intravenous injections. Evaluation of the cellular immune response was performed by immunophenotyping of T-lymphocytes (CD4(+), CD8(+)), B-lymphocytes and natural killer cells. Analysis was also performed of the cell cycle. Our results suggest an increase of T-lymphocytes (CD4(+)CD3(+)) only in the Canova® group, while in the MNU-plus-Canova® group only B-lymphocytes increased. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Genetic variation in the cellular response of Daphnia magna (Crustacea: Cladocera) to its bacterial parasite.

Science.gov (United States)

Auld, Stuart K J R; Scholefield, Jennifer A; Little, Tom J

2010-11-07

Linking measures of immune function with infection, and ultimately, host and parasite fitness is a major goal in the field of ecological immunology. In this study, we tested for the presence and timing of a cellular immune response in the crustacean Daphnia magna following exposure to its sterilizing endoparasite Pasteuria ramosa. We found that D. magna possesses two cell types circulating in the haemolymph: a spherical one, which we call a granulocyte and an irregular-shaped amoeboid cell first described by Metchnikoff over 125 years ago. Daphnia magna mounts a strong cellular response (of the amoeboid cells) just a few hours after parasite exposure. We further tested for, and found, considerable genetic variation for the magnitude of this cellular response. These data fostered a heuristic model of resistance in this naturally coevolving host-parasite interaction. Specifically, the strongest cellular responses were found in the most susceptible hosts, indicating resistance is not always borne from a response that destroys invading parasites, but rather stems from mechanisms that prevent their initial entry. Thus, D. magna may have a two-stage defence--a genetically determined barrier to parasite establishment and a cellular response once establishment has begun.

The role of thiols in cellular response to radiation and drugs

International Nuclear Information System (INIS)

Biaglow, J.E.; Varnes, M.E.; Clark, E.P.; Epp, E.R.

1983-01-01

Cellular nonprotein thiols (NPSH) consist of glutathione (GSH) and other low molecular weight species such as cysteine, cysteamine, and coenzyme A. GSH is usually less than the total cellular NPSH, and with thiol reactive agents, such as diethyl maleate (DEM), its rate of depletion is in part dependent upon the cellular capacity for its resynthesis. If resynthesis is blocked by buthionine-S,R-sulfoximine(BSO), the NPSH, including GSH, is depleted more rapidly, Cellular thiol depletion by diamide, N-ethylmaleimide, and BSO may render oxygenated cells more sensitive to radiation. These cells may or may not show a reduction in the oxygen enhancement ratio (OER). Human A549 lung carcinoma cells depleted of their NPSH either by prolonged culture or by BSO treatment do not show a reduced OER but do show increased aerobic responses to radiation. Some nitroheterocyclic radiosensitizing drugs also deplete cellular thiols under aerobic conditions. Such reactivity may be the reason that they show anomalous radiation sensitization (i.e., better than predicted on the basis of electron affinity). Other nitrocompounds, such as misonidazole, are activated under hypoxic conditions to radical intermediates. When cellular thiols are depleted peroxide is formed. Under hypoxic conditions thiols are depleted because metabolically reduced intermediates react with GSH instead of oxygen. Thiol depletion, under hypoxic conditions, may be the reason that misonidazole and other nitrocompounds show an extra enhancement ratio with hypoxic cells. Thiol depletion by DEM or BSO alters the radiation response of hypoxic cells to misonidazole

Responsibility for private sector adaptation to climate change

Directory of Open Access Journals (Sweden)

Tina Schneider

2014-06-01

Full Text Available The Intergovernmental Panel on Climate Change (2007 indicates that vulnerable industries should adapt to the increasing likelihood of extreme weather events along with slowly shifting mean annual temperatures and precipitation patterns, to prevent major damages or periods of inoperability in the future. Most articles in the literature on business management frame organizational adaptation to climate change as a private action. This makes adaptation the sole responsibility of a company, for its sole benefit, and overlooks the fact that some companies provide critical goods and services such a food, water, electricity, and medical care, that are so vital to society that even a short-term setback in operations could put public security at risk. This raises the following questions: (1 Who is responsible for climate change adaptation by private-sector suppliers of critical infrastructure? (2 How can those who are identified to be responsible, actually be held to assume their responsibility for adapting to climate change? These questions will be addressed through a comprehensive review of the literature on business management, complemented by a review of specialized literature on public management. This review leads to several conclusions. Even though tasks that formerly belonged to the state have been taken over by private companies, the state still holds ultimate responsibility in the event of failure of private-sector owned utilities, insofar as they are "critical infrastructure." Therefore, it remains the state's responsibility to foster adaptation to climate change with appropriate action. In theory, effective ways of assuming this responsibility, while enabling critical infrastructure providers the flexibility adapt to climate change, would be to delegate adaptation to an agency, or to conduct negotiations with stakeholders. In view of this theory, Germany will be used as a case study to demonstrate how private-sector critical infrastructure

Effect of partially purified fumonisins on cellular immune response in ...

African Journals Online (AJOL)

After 7 days, cellular immune response was evaluated by delayed-type hypersensitivity (DTH) and lymphoproliferative assays (LA) using spleen cells. Nitric oxide (NO) production by spleen cells was also evaluated. The specific LA response to Pb antigen was higher in group PB than in FB and CTR groups (p< 0.05) but not ...

Adaptive response after low level irradiation

Energy Technology Data Exchange (ETDEWEB)

Pelevina, I I; Afanasjev, G G; JaGotlib, V; Tereschenko, D G; Tronov, V A; Serebrjany, A M [Russian Academy of Sciences, Moscow (Russian Federation). Institute of Chemical Physics

1996-02-01

The experiments conducted on cultured HeLa (tissue culture) cells revealed that there is a limit of dose above which adaptive response was not observed and a limit of dose below which this response was not induced. The exposure of cells in the territories with elevated radiation background leads to genome instability which results in enhanced radiosensitivity. Investigations on the blood lymphocytes of people living in contaminated regions revealed that adaptive response was more significant in children whereas in adults there was slight increase. Acute irradiation serves as a tool revealing the changes that took place in DNA during chronic low level irradiations after Chernobyl disaster. (author).

Role of thiols in cellular response to radiation and drugs. Symposium: thiols

International Nuclear Information System (INIS)

Biaglow, J.E.; Varnes, M.E.; Clark, E.P.; Epp, E.R.

1983-01-01

Cellular nonprotein thiols (NPSH) consist of glutathione (GSH) and other low molecular weight species such as cysteine, cysteamine, and coenzyme. A GSH is usually less than the total cellular NPSH, and with thiol reactive agents, such as diethyl maleate (DEM), its rate of depletion is in part dependent upon the cellular capacity for its resynthesis. If resynthesis is blocked by buthionine-S,R-sulfoximine(BSO), the NPSH, including GSH, is depleted more rapidly, Cellular thiol depletion by diamide, N-ethylmaleimide, and BSO may render oxygenated cells more sensitive to radiation. These cells may or may not show a reduction in the oxygen enhancement ratio (OER). Human A549 lung carcinoma cells depleted of their NPSH either by prolonged culture or by BSO treatment do not show a reduced OER but do show increased aerobic responses to radiation. Other nitrocompounds, such as misonidazole, are activated under hypoxic conditions to radical intermediates. When cellular thiols are depleted peroxide is formed. Under hypoxic conditions thiols are depleted because metabolically reduced intermediates react with GSH instead of oxygen. Thiol depletion, under hypoxic conditions, may be the reason that misonidazole and other nitrocompounds show an extra enhancement ratio with hypoxic cells. Thiol depletion by DEM or BSO alters the radiation response of hypoxic cells to misonidazole. In conclusion, we propose an altered thiol model which includes a mechanism for thiol involvement in the aerobic radiation response of cells

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

Directory of Open Access Journals (Sweden)

Chantelle L. Phillips

2015-03-01

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

Studies on adaptive responses in Chinese hamster cells

International Nuclear Information System (INIS)

Michelin, S.C.; Perez, M.R. Del; Dubner, D.; Gisone, P.A.

1997-01-01

For many years the possibility has been considered of low doses of radiation inducing adaptive responses in cells and organisms against the mutagenic effects of radiation. Currently, a number of experimental data appraise the existence of an adaptive response that is characterized by a decrease of radiation induced genetic damages. The understanding of the molecular mechanism involved in this phenomenon permits to estimate the effects and risks of low dose exposure. In this work, preliminary results of studies on the induction of adaptive response in cells subjected to different doses of ionizing radiation are presented

pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity

Directory of Open Access Journals (Sweden)

Eiji Yuba

2017-11-01

Full Text Available (1 Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability. (2 Methods: Interaction of micelles with fluorescence dye-loaded liposomes, intracellular distribution of micelles, and antigenic proteins were observed. Finally, antigen-specific cellular immune response was evaluated in vivo using ELIspot assay. (3 Results: Micelles induced leakage of contents from liposomes via lipid mixing at low pH. Micelles were taken up by dendritic cells mainly via macropinocytosis and delivered ovalbumin (OVA into the cytosol. After intradermal injection of micelles and OVA, OVA-specific cellular immunity was induced in the spleen. (4 Conclusions: pH-responsive micelles composed of DLPC and deoxycholic acid are promising as enhancers of cytosol delivery of antigens and the induction capability of cellular immunity for the treatment of cancer immunotherapy and infectious diseases.

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

OpenAIRE

Clemens Kiecker; Anthony Graham; Malcolm Logan

2016-01-01

A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in compete...

A novel adaptive joint power control algorithm with channel estimation in a CDMA cellular system

Institute of Scientific and Technical Information of China (English)

无

2005-01-01

Joint power control has advantages of multi-user detection and power control; and it can combat the multi-access interference and the near-far problem. A novel adaptive joint power control algorithm with channel estimation in a CDMA cellular system was designed. Simulation results show that the algorithm can control the power not only quickly but also precisely with a time change. The method is useful for increasing system capacity.

Cellular response to DNA damage. Link between p53 and DNA-PK

International Nuclear Information System (INIS)

Salles-Passador, I.; Fotedar, R.; Fotedar, A.

1999-01-01

Cells which lack DNA-activated protein kinase (DNA-PK) are very susceptible to ionizing radiation and display an inability to repair double-strand DNA breaks. DNA-PK is a member of a protein kinase family that includes ATR and ATM which have strong homology in their carboxy-terminal kinase domain with Pl-3 kinase. ATM has been proposed to act upstream of p53 in cellular response to ionizing radiation. DNA-PK may similarly interact with p53 in cellular growth control and in mediation of the response to ionizing radiation. (author)

Characterization of humoral and cellular immune responses in patients with human papilloma virus

International Nuclear Information System (INIS)

Clares Pochet, Maria del Carmen; Ferrer Cosme, Belkis Maria; Dominguez Cardosa, Magda

2012-01-01

A descriptive and cross-sectional study was carried out in 30 females infected with the human papilloma virus, attended in the office of Immunology of the Specialty Polyclinic belonging to 'Saturnino Lora' Provincial Clinical Surgical Teaching Hospital in Santiago de Cuba, from June 2009 to June 2010, in order to characterize them according to immune response. To evaluate the humoral and cellular immune response rosetting assay and quantification of immunoglobulins were used respectively. Women between 25-36 years of age (40 %) infected with this virus, especially those coming from urban areas, prevailed in the series, and a significant decrease of the cellular response as compared to the humoral response was evidenced

The plasma membrane transport systems and adaptation to salinity.

Science.gov (United States)

Mansour, Mohamed Magdy F

2014-11-15

Salt stress represents one of the environmental challenges that drastically affect plant growth and yield. Evidence suggests that glycophytes and halophytes have a salt tolerance mechanisms working at the cellular level, and the plasma membrane (PM) is believed to be one facet of the cellular mechanisms. The responses of the PM transport proteins to salinity in contrasting species/cultivars were discussed. The review provides a comprehensive overview of the recent advances describing the crucial roles that the PM transport systems have in plant adaptation to salt. Several lines of evidence were presented to demonstrate the correlation between the PM transport proteins and adaptation of plants to high salinity. How alterations in these transport systems of the PM allow plants to cope with the salt stress was also addressed. Although inconsistencies exist in some of the information related to the responses of the PM transport proteins to salinity in different species/cultivars, their key roles in adaptation of plants to high salinity is obvious and evident, and cannot be precluded. Despite the promising results, detailed investigations at the cellular/molecular level are needed in some issues of the PM transport systems in response to salinity to further evaluate their implication in salt tolerance. Copyright © 2014 Elsevier GmbH. All rights reserved.

Mechano-adaptation of the stem cell nucleus.

Science.gov (United States)

Heo, Su-Jin; Cosgrove, Brian D; Dai, Eric N; Mauck, Robert L

2018-01-01

Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this "mechano-adaptation" are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation.

Adaptive Queue Management with Restraint on Non-Responsive Flows

Directory of Open Access Journals (Sweden)

Lan Li

2003-12-01

Full Text Available This paper proposes an adaptive queue management scheme (adaptive RED to improve Random Early Detection (RED on restraining non-responsive flows. Due to a lack of flow control mechanism, non-responsive flows can starve responsive flows for buffer and bandwidth at the gateway. In order to solve the disproportionate resource problem, RED framework is modified in this way: on detecting when the non-responsive flows starve the queue, packet-drop intensity (Max_p in RED can be adaptively adjusted to curb non-responsive flows for resource fair-sharing, such as buffer and bandwidth fair-sharing. Based on detection of traffic behaviors, intentionally restraining nonresponsive flows is to increase the throughput and decrease the drop rate of responsive flows. Our experimental results based on adaptive RED shows that the enhancement of responsive traffic and the better sharing of buffer and bandwidth can be achieved under a variety of traffic scenarios.

Adjuvant activity of peanut, cottonseed and rice oils on cellular and humoral response

Directory of Open Access Journals (Sweden)

Erika Freitas

2013-04-01

Full Text Available The potentiality of the usage of vegetable oils such as soybean, corn, olive, sesame, murici seed, rapeseed, linseed, rice and cashew nuts as adjuvant of the humoral and cellular immune response has been recently shown. In the present work, besides of evaluating the adjuvant action of peanut, cottonseed and rice oils on humoral and cellular immune responses against ovalbumin (OVA we also evaluated the protective immune response induced by Leishmania antigens. The peanut oil significantly increased the synthesis of anti-ovalbumin antibodies in the primary response, but it did not favor cellular response. Concerning mice immunized with L. amazonensis antigens emulsified with peanut oil exacerbated skin lesions and lymph node parasite load what suggests stimulation of the Th2 immune response and down regulation of Th1 response. The cottonseed oil was shown to have adjuvant effect to the humoral response, stimulating a secondary response and also favored the delayed-type hypersensitivity (DTH response to OVA. The rice oil stimulated a strong DTH reaction to OVA and enhanced the synthesis of antibodies after the third dose. Mice immunized with L. amazonensis antigens emulsified with rice oil or cotton seed oil were protected from developing skin lesions and lymph node parasite load. These results emphasize the interest and importance of the vegetable oils as tools in different procedures of immunization and their differential role in relation to the other adjuvant under usage.

Relationship between adaptation and cardiovascular response to tonic cold and heat pain Adaptability to tonic pain and cardiovascular responses.

Science.gov (United States)

Devoize, L; Chalaye, P; Lafrenaye, S; Marchand, S; Dallel, R

2016-05-01

The mechanisms of adaptation to tonic pain are not elucidated. We hypothesized that the adaptability to tonic pain is related to the cardiovascular system. Twenty-six subjects received over two sessions in a random order: tonic cold (7 ± 0.2 °C) and heat pain (47.5 ± 0.5 °C) on the hand for 5 min. Pain intensity, blood pressure (BP), and heart rate (HR) were continuously monitored. Pain experience during the heat (HIT) and cold (CIT) immersion tests exhibited different average time courses, being approximated with a linear and cubic function, respectively. In each test, two groups of participants could be identified based on the time course of their tonic thermal pain: one-third of participants were pain adaptive and two-thirds non adaptive. The adaptive group exhibited higher initial pain, lower last pain, and shorter latency to peak pain than the non-adaptive one. Interestingly, some participants were adaptive to both pain stimuli, most were not. HIT as well as CIT produced a stable elevation of BP. However, BP was higher during CIT than HIT (p = 0.034). HR was also increased during CIT and HIT, but the two tests differed with respect to the time course of responses. Finally, the intensity and time course of pain rating to both HIT and CIT correlated with neither BP nor HR responses. These results suggest that individual sensitivity and adaptability to tonic thermal pain is related to the intensity of initial pain rating and the latency to peak pain but not to cardiovascular responses. © 2015 European Pain Federation - EFIC®

From Cellular Attractor Selection to Adaptive Signal Control for Traffic Networks.

Science.gov (United States)

Tian, Daxin; Zhou, Jianshan; Sheng, Zhengguo; Wang, Yunpeng; Ma, Jianming

2016-03-14

The management of varying traffic flows essentially depends on signal controls at intersections. However, design an optimal control that considers the dynamic nature of a traffic network and coordinates all intersections simultaneously in a centralized manner is computationally challenging. Inspired by the stable gene expressions of Escherichia coli in response to environmental changes, we explore the robustness and adaptability performance of signalized intersections by incorporating a biological mechanism in their control policies, specifically, the evolution of each intersection is induced by the dynamics governing an adaptive attractor selection in cells. We employ a mathematical model to capture such biological attractor selection and derive a generic, adaptive and distributed control algorithm which is capable of dynamically adapting signal operations for the entire dynamical traffic network. We show that the proposed scheme based on attractor selection can not only promote the balance of traffic loads on each link of the network but also allows the global network to accommodate dynamical traffic demands. Our work demonstrates the potential of bio-inspired intelligence emerging from cells and provides a deep understanding of adaptive attractor selection-based control formation that is useful to support the designs of adaptive optimization and control in other domains.

Psychosocial adaptation and cellular immunity in breast cancer patients in the weeks after surgery: An exploratory study.

Science.gov (United States)

Blomberg, Bonnie B; Alvarez, Juan P; Diaz, Alain; Romero, Maria G; Lechner, Suzanne C; Carver, Charles S; Holley, Heather; Antoni, Michael H

2009-11-01

The period just after surgery for breast cancer requires psychosocial adaptation and is associated with elevated distress. Distress states have been associated with decreased cellular immune functioning in this population, which could have negative effects on physical recovery. However, little is known about relations between psychological status [negative and positive mood states and overall quality of life (QOL)] and cellular signaling cytokines that could account for these associations in women undergoing treatment for breast cancer. The present study examined associations between psychological adaptation indicators (mood, QOL) and T-helper cell type 1 (Th1) cytokine production from stimulated peripheral mononuclear cells in women who had recently undergone surgery for early-stage breast cancer but had not yet begun adjuvant therapy. These associations were evaluated while controlling for relevant disease/treatment, sociodemographic, and health behavior covariates. Lower anxiety related to greater production of the Th1 cytokine interleukin-2 (IL-2), while greater positive mood (affection) related to greater production of the Th1 cytokines IL-12 and interferon-gamma (IFN-gamma). Better QOL related to greater production of the Th1 cytokine, tumor necrosis factor-alpha (TNF-alpha). Individual differences in psychosocial adaptation in women with breast cancer during the period after surgery relate to biological parameters that may be relevant for health and well-being as they move through treatment.

HSV-I and the cellular DNA damage response.

Science.gov (United States)

Smith, Samantha; Weller, Sandra K

2015-04-01

Peter Wildy first observed genetic recombination between strains of HSV in 1955. At the time, knowledge of DNA repair mechanisms was limited, and it has only been in the last decade that particular DNA damage response (DDR) pathways have been examined in the context of viral infections. One of the first reports addressing the interaction between a cellular DDR protein and HSV-1 was the observation by Lees-Miller et al . that DNA-dependent protein kinase catalytic subunit levels were depleted in an ICP0-dependent manner during Herpes simplex virus 1 infection. Since then, there have been numerous reports describing the interactions between HSV infection and cellular DDR pathways. Due to space limitations, this review will focus predominantly on the most recent observations regarding how HSV navigates a potentially hostile environment to replicate its genome.

Chemotactic response and adaptation dynamics in Escherichia coli.

Directory of Open Access Journals (Sweden)

Diana Clausznitzer

2010-05-01

Full Text Available Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.

Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

Directory of Open Access Journals (Sweden)

Manns Michael P

2007-06-01

Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

Monitoring adaptive genetic responses to environmental change

DEFF Research Database (Denmark)

Hansen, M.M.; Olivieri, I.; Waller, D.M.

2012-01-01

Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how...... for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We...

Human Lung Cancer Risks from Radon – Part II – Influence from Combined Adaptive Response and Bystander Effects – A Microdose Analysis

Science.gov (United States)

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

2010-01-01

In the prior Part I, the potential influence of the low level alpha radiation induced bystander effect (BE) on human lung cancer risks was examined. Recent analysis of adaptive response (AR) research results with a Microdose Model has shown that single low LET radiation induced charged particles traversals through the cell nucleus activates AR. We have here conducted an analysis based on what is presently known about adaptive response and the bystander effect (BE) and what new research is needed that can assist in the further evaluation human cancer risks from radon. We find that, at the UNSCEAR (2000) worldwide average human exposures from natural background and man-made radiations, the human lung receives about a 25% adaptive response protection against the radon alpha bystander damage. At the UNSCEAR (2000) minimum range of background exposure levels, the lung receives minimal AR protection but at higher background levels, in the high UNSCEAR (2000) range, the lung receives essentially 100% protection from both the radon alpha damage and also the endogenic, spontaneously occurring, potentially carcinogenic, lung cellular damage. PMID:22461760

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

Directory of Open Access Journals (Sweden)

Xi-Feng Zhang

2016-09-01

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

The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast

Directory of Open Access Journals (Sweden)

Ana Belén Sanz

2017-12-01

Full Text Available Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies.

Cellular and mucosal immune responses in the respiratory tract of ...

African Journals Online (AJOL)

Summary: This experiment was conducted to evaluate the cellular and mucosal responses in the respiratory tract of Nigerian goats vaccinated intranasally with recombinant Mannheimia hemolytica bacterine. Twenty one goats were divided into five groups, five goats each in three vaccinated groups while three goats each ...

Cellular immune response in prognosis of Bell's palsy and its ...

African Journals Online (AJOL)

Objective: To determine the cellular immune response in Bell's palsy (BP) and its prognostic value in relation to clinical and electrophysiological findings. Methods: Twenty patients with BP were subjected to: Facial nerve paralysis assessment according to House–Brackmann (H&B) grading system, bilateral facial nerve ...

Adaptive downtilt for cellular base stations

NARCIS (Netherlands)

Mestrom, R.M.C.; Coenen, T.J.; Smolders, A.B.

2012-01-01

Efficiency, reconfigurability, and power consumption are paramount for future communication systems in applications such as cellular handsets, base stations and home networking systems. We present our work in the European PANAMA project which addresses the associated challenges. Our work focuses on

Relation between radio-adaptive response and cell to cell communication

International Nuclear Information System (INIS)

Keiichiro Ishii

1996-01-01

Ionizing radiation has been considered to cause severe damages to DNA and do harm to cells in proportion to the dose, however low it might be. In 1984, Wolff et al. showed that human peripheral lymphocytes adapted to the low-dose radiation from 3 H-TdR added in culture medium and became resistant to the subsequent irradiation with high-doses of X-rays. This response, which is called radio-adaptive response, is also induced by X-rays and gamma-rays in human lymphocytes and Chinese hamster V79 cells. However, the mechanisms of and conditions for adaptive responses to radiation have not been clarified. With an objective of clarifying the conditions for adaptive responses of cells to radiation, we examined how the cell to cell communication is involved in the adaptive responses. We irradiated normal human embryo-derived (HE) cells and cancer cells (HeLa) in culture at high density with low-dose X-ray and examined their radio-adaptive responses by measuring the changes in sensitivity to subsequent high-dose X-ray irradiation using the Trypan Blue dye-exclusion test method. We also conducted experiments to examine the effects of Ca 2+ ions and Phorbol 12-Myristate 13-Acetate (TPA) which are supposed to be involved in cell to cell communication. (author)

Studies on adaptive response of lymphocyte transformation induced by low-dose irradiation

International Nuclear Information System (INIS)

Du Zeji; Su Liaoyuan; Tian Hailin; Zou Huawei

1995-10-01

Human peripheral blood lymphocytes stimulated by mitogen in vitro for 24 h were exposed to low-dose γ-ray irradiation (0.5∼4.0 cGy, adaptive dose). They showed an adaptive response to the inhibition of 3 H-TdR incorporation by subsequent higher acute doses of γ-ray (challenge dose). At the interval of 24 h between adaptive dose and challenge dose, the strongest adaptive response induced by low-dose irradiation was found. It is also found that the response induced by 1.0 cGy of adaptive dose was more obvious than that by other doses and that 3.0 Gy of challenge dose produced the strongest adaptive response. As the challenge doses increased, the adaptive response reduced. (2 figs., 2 tabs.)

Incorporating adaptive responses into future projections of coral bleaching.

Science.gov (United States)

Logan, Cheryl A; Dunne, John P; Eakin, C Mark; Donner, Simon D

2014-01-01

Climate warming threatens to increase mass coral bleaching events, and several studies have projected the demise of tropical coral reefs this century. However, recent evidence indicates corals may be able to respond to thermal stress though adaptive processes (e.g., genetic adaptation, acclimatization, and symbiont shuffling). How these mechanisms might influence warming-induced bleaching remains largely unknown. This study compared how different adaptive processes could affect coral bleaching projections. We used the latest bias-corrected global sea surface temperature (SST) output from the NOAA/GFDL Earth System Model 2 (ESM2M) for the preindustrial period through 2100 to project coral bleaching trajectories. Initial results showed that, in the absence of adaptive processes, application of a preindustrial climatology to the NOAA Coral Reef Watch bleaching prediction method overpredicts the present-day bleaching frequency. This suggests that corals may have already responded adaptively to some warming over the industrial period. We then modified the prediction method so that the bleaching threshold either permanently increased in response to thermal history (e.g., simulating directional genetic selection) or temporarily increased for 2-10 years in response to a bleaching event (e.g., simulating symbiont shuffling). A bleaching threshold that changes relative to the preceding 60 years of thermal history reduced the frequency of mass bleaching events by 20-80% compared with the 'no adaptive response' prediction model by 2100, depending on the emissions scenario. When both types of adaptive responses were applied, up to 14% more reef cells avoided high-frequency bleaching by 2100. However, temporary increases in bleaching thresholds alone only delayed the occurrence of high-frequency bleaching by ca. 10 years in all but the lowest emissions scenario. Future research should test the rate and limit of different adaptive responses for coral species across latitudes and

Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

International Nuclear Information System (INIS)

Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E.; Pi, Jingbo

2011-01-01

Highlights: → In 3T3-L1 adipocytes iAs 3+ decreases insulin-stimulated glucose uptake. → iAs 3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs 3+ activates the cellular adaptive oxidative stress response. → iAs 3+ impairs insulin-stimulated ROS signaling. → iAs 3+ decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs 3+ ) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs 3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs 3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in

Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

Energy Technology Data Exchange (ETDEWEB)

Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

2011-04-08

Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

An Immune-inspired Adaptive Automated Intrusion Response System Model

Directory of Open Access Journals (Sweden)

Ling-xi Peng

2012-09-01

Full Text Available An immune-inspired adaptive automated intrusion response system model, named as , is proposed. The descriptions of self, non-self, immunocyte, memory detector, mature detector and immature detector of the network transactions, and the realtime network danger evaluation equations are given. Then, the automated response polices are adaptively performed or adjusted according to the realtime network danger. Thus, not only accurately evaluates the network attacks, but also greatly reduces the response times and response costs.

Frequent cellular phone use modifies hypothalamic-pituitary-adrenal axis response to a cellular phone call after mental stress in healthy children and adolescents: A pilot study.

Science.gov (United States)

Geronikolou, Styliani A; Chamakou, Aikaterini; Mantzou, Aimilia; Chrousos, George; KanakaGantenbein, Christina

2015-12-01

The hypothalamic-pituitary-adrenal (HPA) axis is the main "gate-keeper" of the organism's response to every somatic or mental stress. This prospective study aims to investigate the HPA-axis response to a cellular phone call exposure after mental stress in healthy children and adolescents and to assess the possible predictive role of baseline endocrine markers to this response. Two groups of healthy school-age children aged 11-14 (12.5±1.5) years were included in the study, the one comprising those who are occasional users of a cellular phone (Group A) while the second those who do regularly use one (Group B). Blood samples were obtained from all participants at 8.00 am after a 12-hour overnight fasting for thyroid hormone, glucose, insulin, and cortisol levels determination. The participants performed the Trier Social Stress Test for Children (TSST-C) (5 minoral task followed by 5 min arithmetic task). Salivary cortisol samples were obtained at baseline, 10' and 20' min after the TSST-C and 10' and 20' after a 5 minute cellular phone call. Significant changes in the salivary cortisol levels were noted between 10' and 20' mins after the cellular phone call with different responses between the two groups. Baseline thyroid hormone levels seem to predict the cortisol response to mental stress mainly in group A, while HOMA had no impact on salivary cortisol response at any phase of the test, in either group. HPA axis response to cellular phone after mental stress in children and adolescents follow a different pattern in frequent users than in occasional users that seems to be influenced by the baseline thyroid hormone levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

DEFF Research Database (Denmark)

Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

2011-01-01

The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging......-links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

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

Directory of Open Access Journals (Sweden)

Peng Chen, Koki Kanehira and Akiyoshi Taniguchi

2013-01-01

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

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

International Nuclear Information System (INIS)

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

2016-01-01

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

AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema.

Science.gov (United States)

Cheng, Xiao-Yu; Li, Yang-Yang; Huang, Cheng; Li, Jun; Yao, Hong-Wei

2017-04-04

Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM). Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence. Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells. Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice. This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement. Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs. In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

Adaptation or Resistance: a classification of responses to sea-level rise

Science.gov (United States)

Cooper, J. A.

2016-02-01

Societal responses to sea level rise and associated coastal change are apparently diverse in nature and motivation. Most are commonly referred to as 'adaptation'. Based on a review of current practice, however, it is argued that many of these responses do not involve adaptation, but are rather resisting change. There are several instances where formerly adaptive initiatives involving human adaptability are being replaced by initiatives that resist change. A classification is presented that recognises a continuum of responses ranging from adaptation to resistance, depending upon the willingness to change human activities to accommodate environmental change. In many cases climate change adaptation resources are being used for projects that are purely resistant and which foreclose future adaptation options. It is argued that a more concise definition of adaptation is needed if coastal management is to move beyond the current position of holding the shoreline, other tah n in a few showcase examples.

Optimal time interval for induction of immunologic adaptive response

International Nuclear Information System (INIS)

Ju Guizhi; Song Chunhua; Liu Shuzheng

1994-01-01

The optimal time interval between prior dose (D1) and challenge dose (D2) for the induction of immunologic adaptive response was investigated. Kunming mice were exposed to 75 mGy X-rays at a dose rate of 12.5 mGy/min. 3, 6, 12, 24 or 60 h after the prior irradiation the mice were challenged with a dose of 1.5 Gy at a dose rate of 0.33 Gy/min. 18h after D2, the mice were sacrificed for examination of immunological parameters. The results showed that with an interval of 6 h between D1 and D2, the adaptive response of the reaction of splenocytes to LPS was induced, and with an interval of 12 h the adaptive responses of spontaneous incorporation of 3 H-TdR into thymocytes and the reaction of splenocytes to Con A and LPS were induced with 75 mGy prior irradiation. The data suggested that the optimal time intervals between D1 and D2 for the induction of immunologic adaptive response were 6 h and 12 h with a D1 of 75 mGy and a D2 of 1.5 Gy. The mechanism of immunologic adaptation following low dose radiation is discussed

Linear ubiquitination signals in adaptive immune responses.

Science.gov (United States)

Ikeda, Fumiyo

2015-07-01

Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized tumor necrosis factor (TNF)-induced canonical nuclear factor-κB (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

International Nuclear Information System (INIS)

Takaji Ikushima

1997-01-01

The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

Adaptation and inhibition underlie responses to time-varying interaural phase cues in a model of inferior colliculus neurons.

Science.gov (United States)

Borisyuk, Alla; Semple, Malcolm N; Rinzel, John

2002-10-01

A mathematical model was developed for exploring the sensitivity of low-frequency inferior colliculus (IC) neurons to interaural phase disparity (IPD). The formulation involves a firing-rate-type model that does not include spikes per se. The model IC neuron receives IPD-tuned excitatory and inhibitory inputs (viewed as the output of a collection of cells in the medial superior olive). The model cell possesses cellular properties of firing rate adaptation and postinhibitory rebound (PIR). The descriptions of these mechanisms are biophysically reasonable, but only semi-quantitative. We seek to explain within a minimal model the experimentally observed mismatch between responses to IPD stimuli delivered dynamically and those delivered statically (McAlpine et al. 2000; Spitzer and Semple 1993). The model reproduces many features of the responses to static IPD presentations, binaural beat, and partial range sweep stimuli. These features include differences in responses to a stimulus presented in static or dynamic context: sharper tuning and phase shifts in response to binaural beats, and hysteresis and "rise-from-nowhere" in response to partial range sweeps. Our results suggest that dynamic response features are due to the structure of inputs and the presence of firing rate adaptation and PIR mechanism in IC cells, but do not depend on a specific biophysical mechanism. We demonstrate how the model's various components contribute to shaping the observed phenomena. For example, adaptation, PIR, and transmission delay shape phase advances and delays in responses to binaural beats, adaptation and PIR shape hysteresis in different ranges of IPD, and tuned inhibition underlies asymmetry in dynamic tuning properties. We also suggest experiments to test our modeling predictions: in vitro simulation of the binaural beat (phase advance at low beat frequencies, its dependence on firing rate), in vivo partial range sweep experiments (dependence of the hysteresis curve on

Cellular energy metabolism in T-lymphocytes.

Science.gov (United States)

Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

2015-01-01

Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

Role of X-ray-inducible genes and proteins in adaptive survival responses

International Nuclear Information System (INIS)

Meyers, M.; Schea, R.A.; Petrowski, A.E.; Seabury, H.; McLaughlin, P.W.; Lee, I.; Lee, S.W.; Boothman, D.A.

1992-01-01

Certain X-ray-inducible genes and their corresponding protein products, appearing following low priming doses of ionizing radiation may subsequently give rise to an adaptive survival response, ultimately leading to increased radioresistance. Further, this adaptive radioresistance may be due to increased DNA repair (or misrepair) processes. Ultimately, the function of low-dose-induced cDNA clones within the cell is hoped to elucidate to follow the effects of specific gene turn-off on adaptive responses. Future research must determine the various functions of adaptive response gene products so that the beneficial or deleterious consequences of adaptive responses, which increases resistance to ionizing radiation, can be determined. (author). 19 refs., 1 fig

Evasion of Apoptosis as a Cellular Stress Response in Cancer

Directory of Open Access Journals (Sweden)

Simone Fulda

2010-01-01

Full Text Available One of the hallmarks of human cancers is the intrinsic or acquired resistance to apoptosis. Evasion of apoptosis can be part of a cellular stress response to ensure the cell's survival upon exposure to stressful stimuli. Apoptosis resistance may contribute to carcinogenesis, tumor progression, and also treatment resistance, since most current anticancer therapies including chemotherapy as well as radio- and immunotherapies primarily act by activating cell death pathways including apoptosis in cancer cells. Hence, a better understanding of the molecular mechanisms regarding how cellular stress stimuli trigger antiapoptotic mechanisms and how this contributes to tumor resistance to apoptotic cell death is expected to provide the basis for a rational approach to overcome apoptosis resistance mechanisms in cancers.

The Bioavailability of Soluble Cigarette Smoke Extract Is Reduced through Interactions with Cells and Affects the Cellular Response to CSE Exposure.

Science.gov (United States)

Bourgeois, Jeffrey S; Jacob, Jeeva; Garewal, Aram; Ndahayo, Renata; Paxson, Julia

2016-01-01

Cellular exposure to cigarette smoke leads to an array of complex responses including apoptosis, cellular senescence, telomere dysfunction, cellular aging, and neoplastic transformation. To study the cellular response to cigarette smoke, a common in vitro model exposes cultured cells to a nominal concentration (i.e. initial concentration) of soluble cigarette smoke extract (CSE). However, we report that use of the nominal concentration of CSE as the only measure of cellular exposure is inadequate. Instead, we demonstrate that cellular response to CSE exposure is dependent not only on the nominal concentration of CSE, but also on specific experimental variables, including the total cell number, and the volume of CSE solution used. As found in other similar xenobiotic assays, our work suggests that the effective dose of CSE is more accurately related to the amount of bioavailable chemicals per cell. In particular, interactions of CSE components both with cells and other physical factors limit CSE bioavailability, as demonstrated by a quantifiably reduced cellular response to CSE that is first modified by such interactions. This has broad implications for the nature of cellular response to CSE exposure, and for the design of in vitro assays using CSE.

Target Response Adaptation for Correlation Filter Tracking

KAUST Repository

Bibi, Adel Aamer

2016-09-16

Most correlation filter (CF) based trackers utilize the circulant structure of the training data to learn a linear filter that best regresses this data to a hand-crafted target response. These circularly shifted patches are only approximations to actual translations in the image, which become unreliable in many realistic tracking scenarios including fast motion, occlusion, etc. In these cases, the traditional use of a single centered Gaussian as the target response impedes tracker performance and can lead to unrecoverable drift. To circumvent this major drawback, we propose a generic framework that can adaptively change the target response from frame to frame, so that the tracker is less sensitive to the cases where circular shifts do not reliably approximate translations. To do that, we reformulate the underlying optimization to solve for both the filter and target response jointly, where the latter is regularized by measurements made using actual translations. This joint problem has a closed form solution and thus allows for multiple templates, kernels, and multi-dimensional features. Extensive experiments on the popular OTB100 benchmark show that our target adaptive framework can be combined with many CF trackers to realize significant overall performance improvement (ranging from 3 %-13.5% in precision and 3.2 %-13% in accuracy), especially in categories where this adaptation is necessary (e.g. fast motion, motion blur, etc.). © Springer International Publishing AG 2016.

Proceedings of 6th International Microbeam Workshop/12th L.H. Gray Workshop Microbeam Probes of Cellular Radiation Response

International Nuclear Information System (INIS)

Prise, Kevin M.

2004-01-01

The extended abstracts which are submitted here present a summary of the proceedings of the 6th International Workshop/12th LH Gray Workshop: Microbeam Probes of Cellular Radiation Response, held at St. Catherine's College, University of Oxford, UK on March, 29th-31st, 2003. In 1993 the 4th LH Gray Workshop entitled ''Microbeam Probes of Cellular Radiation Response'' was held at the Gray Cancer Institute in Northwood. This was organized by Prof BD Michael, Dr M. Folkard and Dr KM Prise and brought together 40 participants interested in developing and applying new microbeam technology to problems in radiation biology (1). The workshop was an undoubted success and has spawned a series of subsequent workshops every two years. In the past, these workshops have been highly successful in bringing together groups interested in developing and applying micro-irradiation techniques to the study of cell and tissue damage by ionizing radiations. Following the first microbeam workshop, there has been a rapid growth in the number of centres developing radiobiology microbeams, or planning to do so and there are currently 15-20 worldwide. Much of the recent research using microbeams has used them to study low-dose effects and ''non-targeted'' responses such bystander effects, genomic instability and adaptive responses. The goal of the 6th workshop was to build on our knowledge of the development of microbeam approaches and the application to radiation biology in the future with the meeting stretching over a 3 day period. Over 80 participants reviewed the current state of radiobiology microbeam research worldwide and reported on new technological developments both in the fields of physics and biology

Cellular regulation of the structure and function of aortic valves

Directory of Open Access Journals (Sweden)

Ismail El-Hamamsy

2010-01-01

Full Text Available The aortic valve was long considered a passive structure that opens and closes in response to changes in transvalvular pressure. Recent evidence suggests that the aortic valve performs highly sophisticated functions as a result of its unique microscopic structure. These functions allow it to adapt to its hemodynamic and mechanical environment. Understanding the cellular and molecular mechanisms involved in normal valve physiology is essential to elucidate the mechanisms behind valve disease. We here review the structure and developmental biology of aortic valves; we examine the role of its cellular parts in regulating its function and describe potential pathophysiological and clinical implications.

The possible role of chromatin conformation changes in adaptive responses to ionizing radiation

International Nuclear Information System (INIS)

Ekhtiar, A.; Ammer, A.; Jbawi, A.; Othman, A.

2012-05-01

Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection. The aim of current study was to study the possible role of chromatin conformation changes induced by ionizing radiation on the adaptive responses in human lymphocyte. For this aim the chromatin conformation have been studied in human lymphocytes from three non-smoking and three smoking healthy volunteers prior, and after espouser to gamma radiation (adaptive dose 0.1 Gy, challenge dose 1.5 Gy and adaptive + dose challenge). Chromosomal aberrations and micronucleus have been used as end point to study radio cytotoxicity and adaptive response. Our results indicated individual differences in radio adaptive response and the level of this response was dependent of chromatin de condensation induced by a adaptive small dose.The results showed that different dose of gamma rays induce a chromatin de condensation in human lymphocyte. The maximum chromatin relaxation were record when lymphocyte exposed to adaptive dose (0.1 Gy.). Results also showed that Adaptive dose have affected on the induction of challenge dose (1.5 Gy) of chromosome aberration and micronucleus . The comparison of results of chromatin de condensation induction as measured by flow cytometry and cytogenetic damages measured by chromosomal aberrations or micronucleus, was showed a proportionality of adaptive response with

Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi's anemia

International Nuclear Information System (INIS)

Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F.

1997-01-01

Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to γ-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

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

International Nuclear Information System (INIS)

Ohtsu, Naofumi; Kozuka, Taro; Hirano, Mitsuhiro; Arai, Hirofumi

2015-01-01

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

In vitro studies of cellular response to DNA damage induced by boron neutron capture therapy

International Nuclear Information System (INIS)

Perona, M.; Pontiggia, O.; Carpano, M.; Thomasz, L.; Thorp, S.; Pozzi, E.; Simian, M.; Kahl, S.; Juvenal, G.; Pisarev, M.; Dagrosa, A.

2011-01-01

The aim of these studies was to evaluate the mechanisms of cellular response to DNA damage induced by BNCT. Thyroid carcinoma cells were incubated with 10 BPA or 10 BOPP and irradiated with thermal neutrons. The surviving fraction, the cell cycle distribution and the expression of p53 and Ku70 were analyzed. Different cellular responses were observed for each irradiated group. The decrease of Ku70 in the neutrons +BOPP group could play a role in the increase of sensitization to radiation.

Promoting training adaptations through nutritional interventions.

Science.gov (United States)

Hawley, John A; Tipton, Kevin D; Millard-Stafford, Mindy L

2006-07-01

Training and nutrition are highly interrelated in that optimal adaptation to the demands of repeated training sessions typically requires a diet that can sustain muscle energy reserves. As nutrient stores (i.e. muscle and liver glycogen) play a predominant role in the performance of prolonged, intense, intermittent exercise typical of the patterns of soccer match-play, and in the replenishment of energy reserves for subsequent training sessions, the extent to which acutely altering substrate availability might modify the training impulse has been a key research area among exercise physiologists and sport nutritionists for several decades. Although the major perturbations to cellular homeostasis and muscle substrate stores occur during exercise, the activation of several major signalling pathways important for chronic training adaptations take place during the first few hours of recovery, returning to baseline values within 24 h after exercise. This has led to the paradigm that many chronic training adaptations are generated by the cumulative effects of the transient events that occur during recovery from each (acute) exercise bout. Evidence is accumulating that nutrient supplementation can serve as a potent modulator of many of the acute responses to both endurance and resistance training. In this article, we review the molecular and cellular events that occur in skeletal muscle during exercise and subsequent recovery, and the potential for nutrient supplementation (e.g. carbohydrate, fat, protein) to affect many of the adaptive responses to training.

The Role of Instabilities on the Mechanical Response of Cellular Solids and Structures

National Research Council Canada - National Science Library

Kyriakides, S

1997-01-01

.... The relatively regular and periodic microstructure of these two-dimensional materials makes them excellent models for studying the mechanisms that govern the compressive response of cellular materials...

Relationship between neural response and adaptation selectivity to form and color: an ERP study

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Ilias eRentzeperis

2012-04-01

Full Text Available Adaptation is widely used as a tool for studying selectivity to visual features. In these studies it is usually assumed that the loci of feature selective neural responses and adaptation coincide. We used an adaptation paradigm to investigate the relationship between response and adaptation selectivity in event-related potentials (ERP. ERPs were evoked by the presentation of colored Glass patterns in a form discrimination task. Response selectivities to form and, to some extent, color of the patterns were reflected in the C1 and N1 ERP components. Adaptation selectivity to color was reflected in N1 and was followed by a late (300-500 ms after stimulus onset effect of form adaptation. Thus for form, response and adaptation selectivity were manifested in non-overlapping intervals. These results indicate that adaptation and response selectivity can be associated with different processes. Therefore inferring selectivity from an adaptation paradigm requires analysis of both adaptation and neural response data.

Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome.

Science.gov (United States)

Hanevik, Kurt; Kristoffersen, Einar; Mørch, Kristine; Rye, Kristin Paulsen; Sørnes, Steinar; Svärd, Staffan; Bruserud, Øystein; Langeland, Nina

2017-01-28

The role of pathogen specific cellular immune responses against the eliciting pathogen in development of post-infectious chronic fatigue syndrome (PI-CFS) is not known and such studies are difficult to perform. The aim of this study was to evaluate specific anti-Giardia cellular immunity in cases that developed CFS after Giardia infection compared to cases that recovered well. Patients reporting chronic fatigue in a questionnaire study three years after a Giardia outbreak were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS and idiopathic chronic fatigue. Giardia specific immune responses were evaluated in 39 of these patients by proliferation assay, T cell activation and cytokine release analysis. 20 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Patients were clinically classified into CFS (n = 15), idiopathic chronic fatigue (n = 5), fatigue from other causes (n = 9) and recovered from fatigue (n = 10). There were statistically significant antigen specific differences between these Giardia exposed groups and unexposed controls. However, we did not find differences between the Giardia exposed fatigue classification groups with regard to CD4 T cell activation, proliferation or cytokine levels in 6 days cultured PBMCs. Interestingly, sCD40L was increased in patients with PI-CFS and other persons with fatigue after Giardia infection compared to the non-fatigued group, and correlated well with fatigue levels at the time of sampling. Our data show antigen specific cellular immune responses in the groups previously exposed to Giardia and increased sCD40L in fatigued patients.

Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.

Science.gov (United States)

Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J; Cho, Hearn Jay

2010-01-29

The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.

Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses

OpenAIRE

Iwai Ohbayashi; Munetaka Sugiyama

2018-01-01

The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized p...

Seasonal variations of cellular stress response of the gilthead sea bream (Sparus aurata).

Science.gov (United States)

Feidantsis, Konstantinos; Antonopoulou, Efthimia; Lazou, Antigone; Pörtner, Hans O; Michaelidis, Basile

2013-07-01

The present study aimed to investigate the seasonal cellular stress response in vital organs, like the heart, the liver, the whole blood and the skeletal (red and white) muscles of the Mediterranean fish Sparus aurata during a 1-year acclimatization period in the field, in two examined depths (0-2 m and 10-12 m). Processes studied included heat shock protein expression and protein kinase activation. Molecular responses were addressed through the expression of Hsp70 and Hsp90, the phosphorylation of stress-activated protein kinases and particularly p38 mitogen-activated protein kinase (p38 MAPK), the extracellular signal-regulated kinases (ERK-1/2) and c-Jun N-terminal kinases (JNK1/2/3). The induction of Hsp70 and Hsp90 and the phosphorylation of p38 MAPK, JNKs and ERKs in the examined five tissues of the gilthead sea bream indicated a cellular stress response under the prism of a seasonal pattern which was characterized by distinct tissue specificity. Specifically, Hsp induction and MAPK activation occurred before peak summer water temperatures, with no further increases in their levels despite increases in water temperatures. Moreover, although water temperature did not vary significantly with depth of immersion, significant effects of depth on cellular stress response were observed, probably caused by different light regime. The expression and the activation of these certain proteins can be used as tools to define the extreme thermal limits of the gilthead sea bream.

Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat

International Nuclear Information System (INIS)

Takahashi, Akihisa; Ohnishi, Takeo

2009-01-01

Viable organisms recognize and respond to environmental changes or stresses. When these environmental changes and their responses by organisms are extreme, they can limit viability. However, organisms can adapt to these different stresses by utilizing different possible responses via signal transduction pathways when the stress is not lethal. In particular, prior mild stresses can provide some aid to prepare organisms for subsequent more severe stresses. These adjustments or adaptations for future stresses have been called adaptive responses. These responses are present in bacteria, plants and animals. The following review covers recent research which can help describe or postulate possible mechanisms which may be active in producing adaptive responses to radiation, ultraviolet light, and heat. (author)

Adaptive Responses to Thermal Stress in Mammals

Directory of Open Access Journals (Sweden)

Yasser Lenis Sanin

2015-12-01

Full Text Available The environment animals have to cope with is a combination of natural factors such as temperature. Extreme changes in these factors can alter homeostasis, which can lead to thermal stress. This stress can be due to either high temperatures or low temperatures. Energy transference for thermoregulation in homoeothermic animals occurs through several mechanisms: conduction, convection, radiation and evaporation. When animals are subjected to thermal stress, physiological mechanisms are activated which may include endocrine, neuroendocrine and behavioral responses. Activation of the neuroendocrine system affects the secretion of hormones and neurotransmitters which act collectively as response mechanisms that allow them to adapt to stress. Mechanisms which have developed through evolution to allow animals to adapt to high environmental temperatures and to achieve thermo tolerance include physiological and physical changes in order to reduce food intake and metabolic heat production, to increase surface area of skin to dissipate heat, to increase blood flow to take heat from the body core to the skin and extremities to dissipate the heat, to increase numbers and activity of sweat glands, panting, water intake and color adaptation of integument system to reflect heat. Chronic exposure to thermal stress can cause disease, reduce growth, decrease productive and reproductive performance and, in extreme cases, lead to death. This paper aims to briefly explain the physical and physiological responses of mammals to thermal stress, like a tool for biological environment adaptation, emphasizing knowledge gaps and offering some recommendations to stress control for the animal production system.

Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids.

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Joshua Hakimian

Full Text Available Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA, could offset these adaptations following chronic opioid exposure. We used an 8 week regimen of n-3 PUFA supplementation followed by 8 days of morphine in the presence of this diet. We first assessed the effect of morphine in different behavioral measures and found that morphine increased anxiety and reduced wheel-running behavior. These effects were reduced by dietary n-3 PUFAs without affecting morphine-induced analgesia or hyperlocomotion, known effects of this opiate acting at mu opioid receptors. At the cellular level we found that morphine reduced striatal DHA content and that this was reversed by supplemental n-3 PUFAs. Chronic morphine also increased glutamatergic plasticity and the proportion of Grin2B-NMDARs in striatal projection neurons. This effect was similarly reversed by supplemental n-3 PUFAs. Gene analysis showed that supplemental PUFAs offset the effect of morphine on genes found in neurons of the dopamine receptor 2 (D2-enriched indirect pathway but not of genes found in dopamine receptor 1(D1-enriched direct-pathway neurons. Analysis of the D2 striatal connectome by a retrogradely transported pseudorabies virus showed that n-3 PUFA supplementation reversed the effect of chronic morphine on the innervation of D2 neurons by the dorsomedial prefontal and piriform cortices. Together these changes outline specific behavioral and

High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium.

Science.gov (United States)

Lu, Zhongyan; Shen, Hong; Shen, Zanming

2018-01-01

In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive). In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. These results indicated that the alterations of cellular metabolism promote the alterations in cellular

High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium

Directory of Open Access Journals (Sweden)

Zhongyan Lu

2018-03-01

Full Text Available Background/Aims: In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. Methods: RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive. In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. Results: The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. Conclusions: These results indicated that the

How Language Supports Adaptive Teaching through a Responsive Learning Culture

Science.gov (United States)

Johnston, Peter; Dozier, Cheryl; Smit, Julie

2016-01-01

For students to learn optimally, teachers must design classrooms that are responsive to the full range of student development. The teacher must be adaptive, but so must each student and the learning culture itself. In other words, adaptive teaching means constructing a responsive learning culture that accommodates and even capitalizes on diversity…

Induction of Osmoadaptive Mechanisms and Modulation of Cellular Physiology Help Bacillus licheniformis Strain SSA 61 Adapt to Salt Stress

Energy Technology Data Exchange (ETDEWEB)

Paul, Sangeeta; Aggarwal, Chetana; Thakur, Jyoti Kumar; Bandeppa, G. S.; Khan, Md. Aslam; Pearson, Lauren M.; Babnigg, Gyorgy; Giometti, Carol S.; Joachimiak, Andrzej

2015-01-06

Bacillus licheniformis strain SSA 61, originally isolated from Sambhar salt lake, was observed to grow even in the presence of 25 % salt stress. Osmoadaptive mechanisms of this halotolerant B. licheniformis strain SSA 61, for long-term survival and growth under salt stress, were determined. Proline was the preferentially accumulated compatible osmolyte. There was also increased accumulation of antioxidants ascorbic acid and glutathione. Among the different antioxidative enzymes assayed, superoxide dismutase played the most crucial role in defense against salt-induced stress in the organism. Adaptation to stress by the organism involved modulation of cellular physiology at various levels. There was enhanced expression of known proteins playing essential roles in stress adaptation, such as chaperones DnaK and GroEL, and general stress protein YfkM and polynucleotide phosphorylase/polyadenylase. Proteins involved in amino acid biosynthetic pathway, ribosome structure, and peptide elongation were also overexpressed. Salt stress-induced modulation of expression of enzymes involved in carbon metabolism was observed. There was up-regulation of a number of enzymes involved in generation of NADH and NADPH, indicating increased cellular demand for both energy and reducing power.

Species as Stressors: Heterospecific Interactions and the Cellular Stress Response under Global Change.

Science.gov (United States)

Gunderson, Alex R; King, Emily E; Boyer, Kirsten; Tsukimura, Brian; Stillman, Jonathon H

2017-07-01

Anthropogenic global change is predicted to increase the physiological stress of organisms through changes in abiotic conditions such as temperature, pH, and pollution. However, organisms can also experience physiological stress through interactions with other species, especially parasites, predators, and competitors. The stress of species interactions could be an important driver of species' responses to global change as the composition of biological communities change through factors such as distributional and phenological shifts. Interactions between biotic and abiotic stressors could also induce non-linear physiological stress responses under global change. One of the primary means by which organisms deal with physiological stress is through the cellular stress response (CSR), which is broadly the upregulation of a conserved set of genes that facilitate the removal and repair of damaged macromolecules. Here, we present data on behavioral interactions and CSR gene expression for two competing species of intertidal zone porcelain crab (Petrolisthes cinctipes and Petrolisthes manimaculis). We found that P. cinctipes and P. manimaculis engage in more agonistic behaviors when interacting with heterospecifics than conspecifics; however, we found no evidence that heterospecific interactions induced a CSR in these species. In addition to our new data, we review the literature with respect to CSR induction via species interactions, focusing on predator-prey systems and heterospecific competition. We find extensive evidence for predators to induce cellular stress and aspects of the CSR in prey, even in the absence of direct physical contact between species. Effects of heterospecific competition on the CSR have been studied far less, but we do find evidence that agonistic interactions with heterospecifics can induce components of the CSR. Across all published studies, there is clear evidence that species interactions can lead to cellular stress and induction of the CSR

Radiation-induced adaptive response in fetal mice: a micro-array study

International Nuclear Information System (INIS)

Vares, G.; Bing, Wang; Mitsuru, Nenoi; Tetsuo, Nakajima; Kaoru, Tanaka; Isamu, Hayata

2006-01-01

Exposure of sublethal doses of ionizing radiation can induce protective mechanisms against a subsequent higher dose irradiation. This phenomenon called radio-adaptation (or adaptive response - AR), has been described in a wide range of biological models. In a series of studies, we demonstrated the existence of a radiation-induced AR in mice during late organogenesis. For better understanding of molecular mechanisms underlying AR in our model, we performed a global analysis of transcriptome regulations in cells collected from whole mouse fetuses. Using cDNA micro-arrays, we studied gene expression in these cells after in utero priming exposure to irradiation. Several combinations of radiation dose and dose-rate were applied to induce or not an AR in our system. Gene regulation was observed after exposure to priming radiation in each condition. Student's t-test was performed in order to identify genes whose expression modulation was specifically different in AR-inducing an( non-AR-inducing conditions. Genes were ranked according to their ability in discriminating AR-specific modulations. Since AR genes were implicated in variety of functions and cellular processes, we applied a functional classification algorithm, which clustered genes in a limited number of functionally related group: We established that AR genes are significantly enriched for specific keywords. Our results show a significant modulation of genes implicated in signal transduction pathways. No AR-specific alteration of DNA repair could be observed. Nevertheless, it is likely that modulation of DNA repair activity results, at least partly, from post-transcriptional regulation. One major hypothesis is that de-regulations of signal transduction pathways and apoptosis may be responsible for AR phenotype. In previous work, we demonstrated that radiation-induced AR in mice during organogenesis is related to Trp53 gene status and to the occurrence of radiation-induced apoptosis. Other work proposed that p53

Characterization of the cellular response triggered by gold nanoparticle-mediated laser manipulation.

Science.gov (United States)

Kalies, Stefan; Keil, Sebastian; Sender, Sina; Hammer, Susanne C; Antonopoulos, Georgios C; Schomaker, Markus; Ripken, Tammo; Murua Escobar, Hugo; Meyer, Heiko; Heinemann, Dag

2015-11-01

Laser-based transfection techniques have proven high applicability in several cell biologic applications. The delivery of different molecules using these techniques has been extensively investigated. In particular, new high-throughput approaches such as gold nanoparticle–mediated laser transfection allow efficient delivery of antisense molecules or proteins into cells preserving high cell viabilities. However, the cellular response to the perforation procedure is not well understood. We herein analyzed the perforation kinetics of single cells during resonant gold nanoparticle–mediated laser manipulation with an 850-ps laser system at a wavelength of 532 nm. Inflow velocity of propidium iodide into manipulated cells reached a maximum within a few seconds. Experiments based on the inflow of FM4-64 indicated that the membrane remains permeable for a few minutes for small molecules. To further characterize the cellular response postmanipulation, we analyzed levels of oxidative heat or general stress. Although we observed an increased formation of reactive oxygen species by an increase of dichlorofluorescein fluorescence, heat shock protein 70 was not upregulated in laser-treated cells. Additionally, no evidence of stress granule formation was visible by immunofluorescence staining. The data provided in this study help to identify the cellular reactions to gold nanoparticle–mediated laser manipulation.

DNA damage response pathway in radioadaptive response.

Science.gov (United States)

Sasaki, Masao S; Ejima, Yosuke; Tachibana, Akira; Yamada, Toshiko; Ishizaki, Kanji; Shimizu, Takashi; Nomura, Taisei

2002-07-25

Radioadaptive response is a biological defense mechanism in which low-dose ionizing irradiation elicits cellular resistance to the genotoxic effects of subsequent irradiation. However, its molecular mechanism remains largely unknown. We previously demonstrated that the dose recognition and adaptive response could be mediated by a feedback signaling pathway involving protein kinase C (PKC), p38 mitogen activated protein kinase (p38MAPK) and phospholipase C (PLC). Further, to elucidate the downstream effector pathway, we studied the X-ray-induced adaptive response in cultured mouse and human cells with different genetic background relevant to the DNA damage response pathway, such as deficiencies in TP53, DNA-PKcs, ATM and FANCA genes. The results showed that p53 protein played a key role in the adaptive response while DNA-PKcs, ATM and FANCA were not responsible. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), mimicked the priming irradiation in that the inhibitor alone rendered the cells resistant against the induction of chromosome aberrations and apoptosis by the subsequent X-ray irradiation. The adaptive response, whether it was afforded by low-dose X-rays or wortmannin, occurred in parallel with the reduction of apoptotic cell death by challenging doses. The inhibitor of p38MAPK which blocks the adaptive response did not suppress apoptosis. These observations indicate that the adaptive response and apoptotic cell death constitute a complementary defense system via life-or-death decisions. The p53 has a pivotal role in channeling the radiation-induced DNA double-strand breaks (DSBs) into an adaptive legitimate repair pathway, where the signals are integrated into p53 by a circuitous PKC-p38MAPK-PLC damage sensing pathway, and hence turning off the signals to an alternative pathway to illegitimate repair and apoptosis. A possible molecular mechanism of adaptive response to low-dose ionizing irradiation has been discussed in relation to

Towards Trustworthy Adaptive Case Management with Dynamic Condition Response Graphs

DEFF Research Database (Denmark)

Mukkamala, Raghava Rao; Hildebrandt, Thomas; Slaats, Tijs

2013-01-01

We describe how the declarative Dynamic Condition Response (DCR) Graphs process model can be used for trustworthy adaptive case management by leveraging the flexible execution, dynamic composition and adaptation supported by DCR Graphs. The dynamically composed and adapted graphs are verified for...

The Pupillary Orienting Response Predicts Adaptive Behavioral Adjustment after Errors.

Directory of Open Access Journals (Sweden)

Peter R Murphy

Full Text Available Reaction time (RT is commonly observed to slow down after an error. This post-error slowing (PES has been thought to arise from the strategic adoption of a more cautious response mode following deployment of cognitive control. Recently, an alternative account has suggested that PES results from interference due to an error-evoked orienting response. We investigated whether error-related orienting may in fact be a pre-cursor to adaptive post-error behavioral adjustment when the orienting response resolves before subsequent trial onset. We measured pupil dilation, a prototypical measure of autonomic orienting, during performance of a choice RT task with long inter-stimulus intervals, and found that the trial-by-trial magnitude of the error-evoked pupil response positively predicted both PES magnitude and the likelihood that the following response would be correct. These combined findings suggest that the magnitude of the error-related orienting response predicts an adaptive change of response strategy following errors, and thereby promote a reconciliation of the orienting and adaptive control accounts of PES.

Cellular response of Campylobacter jejuni to trisodium phosphate

DEFF Research Database (Denmark)

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

2012-01-01

The highly alkaline compound trisodium phosphate (TSP) is used as an intervention to reduce the load of Campylobacter on poultry meat in U.S. poultry slaughter plants. The aim of the present study was to investigate the cellular responses of Campylobacter jejuni NCTC11168 when exposed to sublethal...... exposure; however, the response was mainly associated with ion transport processes. C. jejuni NCTC11168 nhaA1 (Cj1655c) and nhaA2 (Cj1654c), which encode orthologues to the Escherichia coli NhaA cation/proton antiporter, were able to partially restore TSP, alkaline, and sodium resistance phenotypes to an E....... coli cation/proton antiporter mutant. In addition, inhibition of resistance-nodulation-cell division (RND) multidrug efflux pumps by the inhibitor PaβN (Phe-Arg β-naphthylamide dihydrochloride) decreased tolerance to sublethal TSP. Therefore, we propose that NhaA1/NhaA2 cation/proton antiporters...

Stability and cellular responses to fluorapatite-collagen composites.

Science.gov (United States)

Yoon, Byung-Ho; Kim, Hae-Won; Lee, Su-Hee; Bae, Chang-Jun; Koh, Young-Hag; Kong, Young-Min; Kim, Hyoun-Ee

2005-06-01

Fluorapatite (FA)-collagen composites were synthesized via a biomimetic coprecipitation method in order to improve the structural stability and cellular responses. Different amounts of ammonium fluoride (NH4F), acting as a fluorine source for FA, were added to the precipitation of the composites. The precipitated composites were freeze-dried and isostatically pressed in a dense body. The added fluorine was incorporated nearly fully into the apatite structure (fluoridation), and a near stoichiometric FA-collagen composite was obtained with complete fluoridation. The freeze-dried composites had a typical biomimetic network, consisting of collagen fibers and precipitates of nano-sized apatite crystals. The human osteoblast-like cells on the FA-collagen composites exhibited significantly higher proliferation and differentiation (according to alkaline phosphatase activity) than those on the hydroxyapatite-collagen composite. These enhanced osteoblastic cell responses were attributed to the fluorine release and the reduced dissolution rate.

PACS—Realization of an adaptive concept using pressure actuated cellular structures

Science.gov (United States)

Gramüller, B.; Boblenz, J.; Hühne, C.

2014-10-01

A biologically inspired concept is investigated which can be utilized to develop energy efficient, lightweight and applicational flexible adaptive structures. Building a real life morphing unit is an ambitious task as the numerous works in the particular field show. Summarizing fundamental demands and barriers regarding shape changing structures, the basic challenges of designing morphing structures are listed. The concept of Pressure Actuated Cellular Structures (PACS) is arranged within the recent morphing activities and it is shown that it complies with the underlying demands. Systematically divided into energy-related and structural subcomponents the working principle is illuminated and relationships between basic design parameters are expressed. The analytical background describing the physical mechanisms of PACS is presented in concentrated manner. This work focuses on the procedure of dimensioning, realizing and experimental testing of a single cell and a single row cantilever made of PACS. The experimental outcomes as well as the results from the FEM computations are used for evaluating the analytical methods. The functionality of the basic principle is thus validated and open issues are determined pointing the way ahead.

PACS—Realization of an adaptive concept using pressure actuated cellular structures

International Nuclear Information System (INIS)

Gramüller, B; Boblenz, J; Hühne, C

2014-01-01

A biologically inspired concept is investigated which can be utilized to develop energy efficient, lightweight and applicational flexible adaptive structures. Building a real life morphing unit is an ambitious task as the numerous works in the particular field show. Summarizing fundamental demands and barriers regarding shape changing structures, the basic challenges of designing morphing structures are listed. The concept of Pressure Actuated Cellular Structures (PACS) is arranged within the recent morphing activities and it is shown that it complies with the underlying demands. Systematically divided into energy-related and structural subcomponents the working principle is illuminated and relationships between basic design parameters are expressed. The analytical background describing the physical mechanisms of PACS is presented in concentrated manner. This work focuses on the procedure of dimensioning, realizing and experimental testing of a single cell and a single row cantilever made of PACS. The experimental outcomes as well as the results from the FEM computations are used for evaluating the analytical methods. The functionality of the basic principle is thus validated and open issues are determined pointing the way ahead. (paper)

Nitric oxide and TNFα are critical regulators of reversible lymph node vascular remodeling and adaptive immune response.

Directory of Open Access Journals (Sweden)

Stephanie L Sellers

Full Text Available Lymph node (LN vascular growth, at the level of the main arteriole, was recently characterized for the first time during infection. Arteriole diameter was shown to increase for at least seven days and to occur via a CD4(+ T cell dependent mechanism, with vascular expansion playing a critical role in regulating induction of adaptive immune response. Here, using intravital microscopy of the inguinal LN during herpes simplex type II (HSV-2 infection, the data provides the first studies that demonstrate arteriole expansion during infection is a reversible vascular event that occurs via eutrophic outward remodeling. Furthermore, using genetic ablation models, and pharmacological blockade, we reveal arteriole remodeling and LN hypertrophy to be dependent upon both endothelial nitric oxide synthase (eNOS and TNFα expression. Additionally, we reveal transient changes in nitric oxide (NO levels to be a notable feature of response to viral infection and LN vascular remodeling and provide evidence that mast cells are the critical source of TNFα required to drive arteriole remodeling. Overall, this study is the first to fully characterize LN arteriole vascular changes throughout the course of infection. It effectively reveals a novel role for NO and TNFα in LN cellularity and changes in LN vascularity, which represent key advances in understanding LN vascular physiology and adaptive immune response.

Health effects of low-dose radiation: Molecular, cellular, and biosystem response

International Nuclear Information System (INIS)

Pollycove, M.; Paperiello, C.J.

1997-01-01

Since the fifties, the prime concern of radiation protection has been protecting DNA from damage. UNSCEAR initiated a focus on biosystem response to damage with its 1994 report, ''Adaptive Responses to Radiation of Cells and Organisms''. The DNA damage-control biosystem is physiologically operative on both metabolic and radiation induced damage, both effected predominantly by free radicals. These adaptive responses are suppressed by high-dose and stimulated by low dose radiation. Increased biosystem efficiently reduces the number of mutations that accumulate during a lifetime and decrease DNA damage-control with resultant aging and malignancy. Several statistically significant epidemiologic studies have shown risk decrements of cancer mortality and mortality from all causes in populations exposed to low-dose radiation. Further biologic and epidemiologic research is needed to establish a valid threshold below which risk decrements occur. (author)

Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi`s anemia

Energy Technology Data Exchange (ETDEWEB)

Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F. [Institut Curie-Recherche, UMR 218, CNRS, 75 - Paris (France)

1997-03-01

Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to {gamma}-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles

Directory of Open Access Journals (Sweden)

Shah Imran

2011-07-01

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

Adaptive response of DNA strand breaks in lymphocytes to low dose and γ-rays

International Nuclear Information System (INIS)

Du Zeji; Su Liaoyuan; Kong Xiangrong; Tian Hailin

1996-01-01

Fluorometric analysis of DNA unwinding was used to study the adaptive response of DNA strand breaks induced by low dose γ-rays and the effect of pADPRT inhibitor-3-AB on the adaptive response. The results indicated that 0.5-4 cGy γ-rays could induce adaptive response of DNA strand breaks in lymphocytes, especially at the doses of 2.0 and 4.0 cGy. This response was not obvious after 8.0 cGy γ-rays irradiation. A challenge dose of 5-20 Gy could make the response expressed, 15 Gy was the best one and 30 Gy was too high to give an adaptive response . 0.5 mM 3-AB could inhibit the response vigorously. As the concentration increased, the adaptive response could be inhibited completely

Possible stimuli for strength and power adaptation : acute metabolic responses.

Science.gov (United States)

Crewther, Blair; Cronin, John; Keogh, Justin

2006-01-01

The metabolic response to resistance exercise, in particular lactic acid or lactate, has a marked influence upon the muscular environment, which may enhance the training stimulus (e.g. motor unit activation, hormones or muscle damage) and thereby contribute to strength and power adaptation. Hypertrophy schemes have resulted in greater lactate responses (%) than neuronal and dynamic power schemes, suggesting possible metabolic-mediated changes in muscle growth. Factors such as age, sex, training experience and nutrition may also influence the lactate responses to resistance exercise and thereafter, muscular adaptation. Although the importance of the mechanical and hormonal stimulus to strength and power adaptation is well recognised, the contribution of the metabolic stimulus is largely unknown. Relatively few studies for example, have examined metabolic change across neuronal and dynamic power schemes, and not withstanding the fact that those mechanisms underpinning muscular adaptation, in relation to the metabolic stimulus, remain highly speculative. Inconsistent findings and methodological limitations within research (e.g. programme design, sampling period, number of samples) make interpretation further difficult. We contend that strength and power research needs to investigate those metabolic mechanisms likely to contribute to weight-training adaptation. Further research is also needed to examine the metabolic responses to different loading schemes, as well as interactions across age, sex and training status, so our understanding of how to optimise strength and power development is improved.

FTIR spectroscopic studies of bacterial cellular responses to environmental factors, plant-bacterial interactions and signalling

OpenAIRE

Kamnev, Alexander A.

2008-01-01

Modern spectroscopic techniques are highly useful in studying diverse processes in microbial cells related to or incited by environmental factors. Spectroscopic data for whole cells, supramolecular structures or isolated cellular constituents can reflect structural and/or compositional changes occurring in the course of cellular metabolic responses to the effects of pollutants, environmental conditions (stress factors); nutrients, signalling molecules (communication factors), etc. This inform...

Adaptation responses to increasing drought frequency

Science.gov (United States)

Loch, A. J.; Adamson, D. C.; Schwabe, K.

2016-12-01

Using state contingent analysis we discuss how and why irrigators adapt to alternative water supply signals. This analysis approach helps to illustrate how and why producers currently use state-general and state-allocable inputs to adapt and respond to known and possible future climatic alternative natures. Focusing on the timing of water allocations, we explore inherent differences in the demand for water by two key irrigation sectors: annual and perennial producers which in Australia have allowed a significant degree of risk-minimisation during droughts. In the absence of land constraints, producers also had a capacity to respond to positive state outcomes and achieve super-normal profits. In the future, however, the probability of positive state outcomes is uncertain; production systems may need to adapt to minimise losses and/or achieve positive returns under altered water supply conditions that may arise as a consequence of more frequent drought states. As such, producers must assess whether altering current input/output choice sets in response to possible future climate states will enhance their long-run competitive advantage for both expected new normal and extreme water supply outcomes. Further, policy supporting agricultural sector climate change resilience must avoid poorly-designed strategies that increase producer vulnerability in the face of drought. Our analysis explores the reliability of alternative water property right bundles and how reduced allocations across time influence alternative responses by producers. We then extend our analysis to explore how management strategies could adapt to two possible future drier state types: i) where an average reduction in water supply is experienced; and ii) where the frequency of droughts increase. The combination of these findings are subsequently used to discuss the role water reform policy has to deal with current and future climate scenarios. We argue current policy strategies could drive producers to

The adaptive response of E. coli to low levels of alkylating agent

International Nuclear Information System (INIS)

Jeggo, P.; Defais, M.; Samson, L.; Schendel, P.

1978-01-01

In an attempt to characterise which gene products may be involved in the repair system induced in E. coli by growth on low levels of alkylating agent (the adaptive response) we have analysed mutants deficient in other known pathways of DNA repair for the ability to adapt to MNNG. Adaptive resistance to the killing effects of MNNG seems to require a functional DNA polymerase I whereas resistance to the mutagenic effects can occur in polymerase I deficient strains; similarly killing adaptation could not be observed in a dam3 mutant, which was nonetheless able to show mutational adaptation. These results suggest that these two parts of the adaptive response must, at least to some extent, be separable. Both adaptive responses can be seen in the absence of uvrD + uvrE + -dependent mismatch repair, DNA polymerase II activity, or recF-mediated recombination and they are not affected by decreased levels of adenyl cyclase. The data presented support our earlier conclusion that adaptive resistance to the killing and mutagenic effect of MNNG is the result of previously uncharacterised repair pathways. (orig.) [de

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

Directory of Open Access Journals (Sweden)

Jorge Muñoz-Sánchez

2014-01-01

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

Cooperative adaptive responses in gene regulatory networks with many degrees of freedom.

Science.gov (United States)

Inoue, Masayo; Kaneko, Kunihiko

2013-04-01

Cells generally adapt to environmental changes by first exhibiting an immediate response and then gradually returning to their original state to achieve homeostasis. Although simple network motifs consisting of a few genes have been shown to exhibit such adaptive dynamics, they do not reflect the complexity of real cells, where the expression of a large number of genes activates or represses other genes, permitting adaptive behaviors. Here, we investigated the responses of gene regulatory networks containing many genes that have undergone numerical evolution to achieve high fitness due to the adaptive response of only a single target gene; this single target gene responds to changes in external inputs and later returns to basal levels. Despite setting a single target, most genes showed adaptive responses after evolution. Such adaptive dynamics were not due to common motifs within a few genes; even without such motifs, almost all genes showed adaptation, albeit sometimes partial adaptation, in the sense that expression levels did not always return to original levels. The genes split into two groups: genes in the first group exhibited an initial increase in expression and then returned to basal levels, while genes in the second group exhibited the opposite changes in expression. From this model, genes in the first group received positive input from other genes within the first group, but negative input from genes in the second group, and vice versa. Thus, the adaptation dynamics of genes from both groups were consolidated. This cooperative adaptive behavior was commonly observed if the number of genes involved was larger than the order of ten. These results have implications in the collective responses of gene expression networks in microarray measurements of yeast Saccharomyces cerevisiae and the significance to the biological homeostasis of systems with many components.

Cellular responses of Saccharomyces cerevisiae to DNA damage

International Nuclear Information System (INIS)

Ciesla, Z.; Sledziewska-Gojska, E.; Nowicka, A.; Mieczkowski, P.; Fikus, M.U.; Koprowski, P.

1998-01-01

Full text. Several experimental strategies have been used to study responses of S. cerevisiae cells to DNA damage. One approach was based on the isolation of novel genes, the expression of which is induced by lesions in DNA. One of these genes, DIN7, was cloned and partially characterized previously. The product of DIN7 belongs to a large family of proteins involved in DNA repair and mutagenesis. This family includes Rad2, Rad27 and ExoI proteins of S. cerevisiae and their respective human homologues, all of which are endowed with DNA nuclease activity. To study cellular function of Din7 we constructed the pPK3 plasmid carrying DIN7 fused to the GAL1 promoter. Effects of DIN7 overproduction on the phenotypes of wild-type cells and of rad27 and exoI mutants were examined. Overproduction of Din7 does not seem to affect the proficiency of wild-type S. cerevisiae cells in recombination and mutagenesis. Also, overexpression of DIN7 does not suppress the deficiency of the EXOI gene product, the closest homologue of Din7, both in recombination and in controlling the fidelity of DNA replication. Unexpectedly, we found that elevated levels of Din7 result in a very high frequency of mitochondrial rho - mutants. A high frequency of production of rho - mutants wa s also observed in strains defective in the functioning of the Dun1 protein kinase involved in signal transmission in cells exposed to DNA damaging agents. Interestingly, deficiency of Dun1 results also in a significant derepression of the DIN7 gene. Experiments are under way to distinguish whether a high cellular level of Din7 specifically decreases stability of mitochondrial DNA or affects stability of chromosomal DNA as well. Analysis of previously constructed S. cerevisiae strains carrying random geno mic fusions with reporter lacZ gene, allowed us to identify the reading frame YBR173c, on chromosome II as a novel damage inducible gene - DIN8. We have shown that DIN8-lacZ fusion is induced in yeast cells treated

Toxicity of cadmium in Japanese quail: Evaluation of body weight, hepatic and renal function, and cellular immune response

International Nuclear Information System (INIS)

Sant'Ana, M.G.; Moraes, R.; Bernardi, M.M.

2005-01-01

Cadmium (Cd) is an environmental pollutant that is able to alter the immune function. Previous studies have shown that, in mammals, chronic exposure to Cd decreases the release of macrophagic cytokines such as IL1 and TNα and decreases phagocytosis activity. On the other hand contradictory results showed an increase in the humoral response. The cellular response could be decreased by exposure to Cd. These alterations were observed in mammals. The present study aimed to investigate some of the toxic effects of Cd exposure in birds. In particular, the main objective of this work was to elucidate the effects of exposure to this pollutant on the cellular immune function of the Japanese quail as a model for the study of toxicity in animals exposed in nature. The animals were exposed to the metal (100 ppm, per os) during development, i.e., from 1 to 28 days old. Body weight, biochemical parameters, and cellular immune response were measured during and at the end of treatment. The results showed that the exposure to Cd for 28 days significantly reduced the body weight and induced hepatic toxicity. The kidney function and cellular immune response were not affected by the Cd exposure

Adaptive response of Peruvian Hake to overfishing

OpenAIRE

Mendo, C.W.; Carrasco, R.G.

2000-01-01

Compensatory mechanisms of the Peruvian hake population (Merluccius gayi peruanus) in response to heavy exploitation and changes in species interaction are discussed. Changes in the rate of cannibalism, diet composition, maximization of fecundity and behavioral adaptation are noted.

Individual differences in response conflict adaptations

Directory of Open Access Journals (Sweden)

Doris eKeye

2013-12-01

Full Text Available Conflict-monitoring theory argues for a general cognitive mechanism that monitors for con-flicts in information-processing. If that mechanism detects conflict, it engages cognitive con-trol to resolve it. A slow-down in response to incongruent trials (conflict effect, and a modu-lation of the conflict effect by the congruence of the preceding trial (Gratton or context effect have been taken as indicators of such a monitoring system. The present study (N = 157 investigated individual differences in the conflict and the context effect in a horizontal and a vertical Simon task, and their correlation with working memory capacity. Strength of conflict was varied by proportion of congruent trials. Coherent factors could be formed representing individual differences in speeded performance, conflict adaptation, and context adaptation. Conflict and context factors were not associated with each other. Contrary to theories assuming a close relation between working memory and cognitive control, working memory capacity showed no relation with any factors representing adaptation to conflict.

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

Science.gov (United States)

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

2017-01-01

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

Extended abstracts: Microbeam Probes of Cellular Radiation Response [final report

International Nuclear Information System (INIS)

Brenner, David J.

2000-01-01

In July 1999, we organized the 4th International Workshop: Microbeam Probes of Cellular Radiation Response, held in Killiney Bay, Dublin, Ireland, on July 17-18. Roughly 75 scientists (about equal numbers of physicists and biologists) attended the workshop, the fourth in a bi-annual series. Extended abstracts from the meeting were published in the Radiation Research journal, vol. 153, iss. 2, pp. 220-238 (February 2000)(attached). All the objectives in the proposal were met

Rapid adaptive responses to climate change in corals

KAUST Repository

Torda, Gergely; Donelson, Jennifer M.; Aranda, Manuel; Barshis, Daniel J.; Bay, Line; Berumen, Michael L.; Bourne, David G.; Cantin, Neal; Foret, Sylvain; Matz, Mikhail; Miller, David J.; Moya, Aurelie; Putnam, Hollie M.; Ravasi, Timothy; van Oppen, Madeleine J. H.; Thurber, Rebecca Vega; Vidal-Dupiol, Jeremie; Voolstra, Christian R.; Watson, Sue-Ann; Whitelaw, Emma; Willis, Bette L.; Munday, Philip L.

2017-01-01

Pivotal to projecting the fate of coral reefs is the capacity of reef-building corals to acclimatize and adapt to climate change. Transgenerational plasticity may enable some marine organisms to acclimatize over several generations and it has been hypothesized that epigenetic processes and microbial associations might facilitate adaptive responses. However, current evidence is equivocal and understanding of the underlying processes is limited. Here, we discuss prospects for observing transgenerational plasticity in corals and the mechanisms that could enable adaptive plasticity in the coral holobiont, including the potential role of epigenetics and coral-associated microbes. Well-designed and strictly controlled experiments are needed to distinguish transgenerational plasticity from other forms of plasticity, and to elucidate the underlying mechanisms and their relative importance compared with genetic adaptation.

Rapid adaptive responses to climate change in corals

KAUST Repository

Torda, Gergely

2017-09-01

Pivotal to projecting the fate of coral reefs is the capacity of reef-building corals to acclimatize and adapt to climate change. Transgenerational plasticity may enable some marine organisms to acclimatize over several generations and it has been hypothesized that epigenetic processes and microbial associations might facilitate adaptive responses. However, current evidence is equivocal and understanding of the underlying processes is limited. Here, we discuss prospects for observing transgenerational plasticity in corals and the mechanisms that could enable adaptive plasticity in the coral holobiont, including the potential role of epigenetics and coral-associated microbes. Well-designed and strictly controlled experiments are needed to distinguish transgenerational plasticity from other forms of plasticity, and to elucidate the underlying mechanisms and their relative importance compared with genetic adaptation.

Cytogenetic adaptive response of cultured fish cells to low doses of X-rays

International Nuclear Information System (INIS)

Kurihara, Yasuyuki; Etoh, Hisami; Rienkjkarn, M.

1992-01-01

The adaptive response was examining chromosomal aberrations and micronucleus in cultured fish cells, ULF-23 (mudminnow) and CAF-31 (gold fish). When cultured fish cells were first irradiated with small doses of X-rays, they became less sensitive to subsequent exposures to high doses. The effective adaptive dose was 4.8 cGy-9.5 cGy. Adaptive doses given cells in the G1 phase were more effective than when given in the S phase. The adaptive response was maximal at 5 hours and disappeared at 10 hours after the adaptive dose. The expression of the response was inhibited by treatment with 3-aminobenzamide, as reported for mammalian cells, and with arabinofuranoside cytosine, an inhibitor of DNA polymerase alpha. Caffeine, an inhibitor of post-replicational repair, had no effect on the response. (author)

Cytogenetic adaptive response of cultured fish cells to low doses of X-rays

Energy Technology Data Exchange (ETDEWEB)

Kurihara, Yasuyuki; Etoh, Hisami (National Inst. of Radiological Sciences, Chiba (Japan)); Rienkjkarn, M.

1992-12-01

The adaptive response was examining chromosomal aberrations and micronucleus in cultured fish cells, ULF-23 (mudminnow) and CAF-31 (gold fish). When cultured fish cells were first irradiated with small doses of X-rays, they became less sensitive to subsequent exposures to high doses. The effective adaptive dose was 4.8 cGy-9.5 cGy. Adaptive doses given cells in the G1 phase were more effective than when given in the S phase. The adaptive response was maximal at 5 hours and disappeared at 10 hours after the adaptive dose. The expression of the response was inhibited by treatment with 3-aminobenzamide, as reported for mammalian cells, and with arabinofuranoside cytosine, an inhibitor of DNA polymerase alpha. Caffeine, an inhibitor of post-replicational repair, had no effect on the response. (author).

The ‘Goldilocks Zone’ from a redox perspective - Adaptive versus deleterious responses to oxidative stress in striated muscle

Directory of Open Access Journals (Sweden)

Rick J Alleman

2014-09-01

Full Text Available Consequences of oxidative stress may be beneficial or detrimental in physiological systems. An organ system’s position on the ‘hormetic curve’ is governed by the source and temporality of reactive oxygen species (ROS production, proximity of ROS to moieties most susceptible to damage, and the capacity of the endogenous cellular ROS scavenging mechanisms. Most importantly, the resilience of the tissue (the capacity to recover from damage is a decisive factor, and this is reflected in the disparate response to ROS in cardiac and skeletal muscle. In myocytes, a high oxidative capacity invariably results in a significant ROS burden which in homeostasis, is rapidly neutralized by the robust antioxidant network. The up-regulation of key pathways in the antioxidant network is a central component of the hormetic response to ROS. Despite such adaptations, persistent oxidative stress over an extended time-frame (e.g. months to years inevitably leads to cumulative damages, maladaptation and ultimately the pathogenesis of chronic diseases. Indeed, persistent oxidative stress in heart and skeletal muscle has been repeatedly demonstrated to have causal roles in the etiology of heart disease and insulin resistance, respectively. Deciphering the mechanisms that underlie the divergence between adaptive and maladaptive responses to oxidative stress remains an active area of research for basic scientists and clinicians alike, as this would undoubtedly lead to novel therapeutic approaches. Here, we provide an overview of major types of ROS in striated muscle and the divergent adaptations that occur in response to them. Emphasis is placed on highlighting newly uncovered areas of research on this topic, with particular focus on the mitochondria, and the diverging roles that ROS play in muscle health (e.g., exercise or preconditioning and disease (e.g., cardiomyopathy, ischemia, metabolic syndrome.

Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: involvement of the adaptive antioxidant response.

Science.gov (United States)

Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E; Pi, Jingbo

2011-04-08

There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs³(+)) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs³(+) exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs³(+) exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes. Taken together our studies suggest that prolonged low-level iAs³(+) exposure activates the cellular adaptive oxidative stress response, which impairs insulin-stimulated ROS signaling that is involved in ISGU, and thus causes insulin resistance in adipocytes. Copyright © 2011 Elsevier Inc. All rights reserved.

Cytogenetic adaptive response of mouse bone marrow cells to low level HTO

International Nuclear Information System (INIS)

Chen Deqing; Zhang Zhaoyang; Zhou Xiangyan

1993-01-01

Mice were abdominally injected with a adaptive dose of 3.7 x 10 2 -3.7 x 10 5 Bq/gbw HTO, and then exposed to a challenge dose of 1.5 Gy of 6 '0Co γ-rays. In bone marrow cells that received both the adaptive and challenge doses, the chromatid breaks are lower than expected on the basis of additivity of the effects of the individual treatment. The adaptive response induced with 3.7 x 10 3 Bq/gbw HTO is the most remarkable, but at 3.7 x 10 5 Bq/gbw the adaptive response seems to disappear. The adaptive response can be observed by exposing to 1.5 Gy γ-rays from 1 to 5 days after injection of 3.7 x 10 3 Bq/gbw HTO, which is the most obvious one to reduce chromatid breaks to 50% of expected at the 5th day, but at the 7th day to equate to expected. The frequency of chromatid breaks is gradually reduced with time after challenge dose, the maximum index number of adaptive response is 0.50 and appears at 24 hr after challenge dose

Adaptive Response Surface Techniques in Reliability Estimation

DEFF Research Database (Denmark)

Enevoldsen, I.; Faber, M. H.; Sørensen, John Dalsgaard

1993-01-01

Problems in connection with estimation of the reliability of a component modelled by a limit state function including noise or first order discontinuitics are considered. A gradient free adaptive response surface algorithm is developed. The algorithm applies second order polynomial surfaces...

The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization.

Science.gov (United States)

Tokusumi, Yumiko; Tokusumi, Tsuyoshi; Schulz, Robert A

2017-05-13

In vertebrates, interaction between the nervous system and immune system is important to protect a challenged host from stress inputs from external sources. In this study, we demonstrate that sensory neurons are involved in the cellular immune response elicited by wasp infestation of Drosophila larvae. Multidendritic class IV neurons sense contacts from external stimuli and induce avoidance behaviors for host defense. Our findings show that inactivation of these sensory neurons impairs the cellular response against wasp parasitization. We also demonstrate that the nociception genes encoding the mechanosensory receptors Painless and Piezo, both expressed in class IV neurons, are essential for the normal cellular immune response to parasite challenge. Copyright © 2017. Published by Elsevier Inc.

Influence of physical and biological factors in cellular radiosensitivity

International Nuclear Information System (INIS)

García Lima, Omar

2016-01-01

The use of therapeutic radiopharmaceuticals is associated with radiation damage, and this at-nuclear physical properties of radionuclides used and the characteristics of the irradiated cells. The work deals with the damage caused by radiation to DNA, factors that condition and tools that can be used to measure it. It presents current concepts of death and cellular radiosensitivity, based on the pioneering work in this field. Enter the neighborhood effect and adaptive response and evaluates the influence of the same in the paradigms of classical radiobiology. (author)

Central adaptation of pain perception in response to rehabilitation of musculoskeletal pain

DEFF Research Database (Denmark)

Andersen, Lars L; Andersen, Christoffer H; Sundstrup, Emil

2012-01-01

Understanding the mechanisms of long-standing musculoskeletal pain and adaptations in response to physical rehabilitation is important for developing optimal treatment strategies. The influence of central adaptations of pain perception in response to rehabilitation of musculoskeletal pain remains...

Adaptive response in human blood lymphocytes exposed to non-ionizing radiofrequency fields: resistance to ionizing radiation-induced damage.

Science.gov (United States)

Sannino, Anna; Zeni, Olga; Romeo, Stefania; Massa, Rita; Gialanella, Giancarlo; Grossi, Gianfranco; Manti, Lorenzo; Vijayalaxmi; Scarfì, Maria Rosaria

2014-03-01

The aim of this preliminary investigation was to assess whether human peripheral blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency fields exhibit an adaptive response (AR) by resisting the induction of genetic damage from subsequent exposure to ionizing radiation. Peripheral blood lymphocytes from four healthy donors were stimulated with phytohemagglutinin for 24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR, challenge dose, CD). After a 72 h total culture period, cells were collected to examine the incidence of micronuclei (MN). There was a significant decrease in the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with those subjected to XR alone (CD). These observations thus suggested a RF-induced AR and induction of resistance to subsequent damage from XR. There was variability between the donors in RF-induced AR. The data reported in our earlier investigations also indicated a similar induction of AR in human blood lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different kinds of lesions in cellular DNA, further studies are required to understand the mechanism(s) involved in the RF-induced adaptive response.

Radioadaptive response. Efficient repair of radiation-induced DNA damage in adapted cells

International Nuclear Information System (INIS)

Ikushima, Takaji; Aritomi, Hisako; Morisita, Jun

1996-01-01

To verify the hypothesis that the induction of a novel, efficient repair mechanism for chromosomal DNA breaks may be involved in the radioadaptive response, the repair kinetics of DNA damage has been studied in cultured Chinese hamster V79 cells with single-cell gel electrophoresis. The cells were adapted by priming exposure with 5 cGy of γ-rays and 4-h incubation at 37C. There were no indication of any difference in the initial yields of DNA double-strand breaks induced by challenging doses from non-adapted cells and from adapted cells. The rejoining of DNA double-strand breaks was monitored over 120 min after the adapted cells were challenged with 5 or 1.5 Gy, doses at the same level to those used in the cytogenetical adaptive response. The rate of DNA damage repair in adapted cells was higher than that in non-adapted cells, and the residual damage was less in adapted cells than in non-adapted cells. These results indicate that the radioadaptive response may result from the induction of a novel, efficient DNA repair mechanism which leads to less residual damage, but not from the induction of protective functions that reduce the initial DNA damage

Rapid feedback responses correlate with reach adaptation and properties of novel upper limb loads.

Science.gov (United States)

Cluff, Tyler; Scott, Stephen H

2013-10-02

A hallmark of voluntary motor control is the ability to adjust motor patterns for novel mechanical or visuomotor contexts. Recent work has also highlighted the importance of feedback for voluntary control, leading to the hypothesis that feedback responses should adapt when we learn new motor skills. We tested this prediction with a novel paradigm requiring that human subjects adapt to a viscous elbow load while reaching to three targets. Target 1 required combined shoulder and elbow motion, target 2 required only elbow motion, and target 3 (probe target) required shoulder but no elbow motion. This simple approach controlled muscle activity at the probe target before, during, and after the application of novel elbow loads. Our paradigm allowed us to perturb the elbow during reaching movements to the probe target and identify several key properties of adapted stretch responses. Adapted long-latency responses expressed (de-) adaptation similar to reaching errors observed when we introduced (removed) the elbow load. Moreover, reaching errors during learning correlated with changes in the long-latency response, showing subjects who adapted more to the elbow load displayed greater modulation of their stretch responses. These adapted responses were sensitive to the size and direction of the viscous training load. Our results highlight an important link between the adaptation of feedforward and feedback control and suggest a key part of motor adaptation is to adjust feedback responses to the requirements of novel motor skills.

Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change

Science.gov (United States)

Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

2014-01-01

Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data. PMID:24454550

Cellular Stress to Low Gamma-ray Dose

International Nuclear Information System (INIS)

Manzanares-Acuna, E.; Vega-Carrillo, H. R.; Letechipia de Leon, C.; Guzman Enriquez, L. J.; Garcia-Talavera, M.

2004-01-01

The purpose of this study was to evaluate the effect of low gamma ray intensity upon Hsp 70 expression in human lymphocytes. the heat shock proteins (Hsp) family, are a group of proteins present in all living organism, therefore there are highly conserved and are related to adaptation and evolution. At cellular level these proteins acts as chaperones correcting denatured proteins. when a stress agent, such heavy metals, UV, heat, etc. is affecting a cell a response to this aggression is triggered through overexpression of Hsp. Several studies has been carried out in which the cellular effect are observed, mostly of these studies uses large doses, but very few studies are related with low doses. Blood of healthy volunteers was obtained and the lymphocytes were isolated by ficoll-histopaque gradient. Experimental lots were irradiated in a ''137Cs gamma-ray. Hsp70 expression was found since 0.5 cGy, indicating a threshold to very low doses of gamma rays. (Author) 27 refs

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy.

Science.gov (United States)

Ren, Jun; Gwin, William R; Zhou, Xinna; Wang, Xiaoli; Huang, Hongyan; Jiang, Ni; Zhou, Lei; Agarwal, Pankaj; Hobeika, Amy; Crosby, Erika; Hartman, Zachary C; Morse, Michael A; H Eng, Kevin; Lyerly, H Kim

2017-01-01

Purpose : Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy. Patients and Methods : We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results : Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR β sequences one month after OVT therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients. Conclusions : Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

Marine Bivalve Cellular Responses to Beta Blocker Exposures ...

Science.gov (United States)

β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated which in turn limits cAMP production and protein kinase A activation, preventing increases in blood pressure and arrhythmias. After being taken therapeutically, commonly prescribed β blockers may make their way to coastal habitats via discharge from waste water treatment plants (WWTP) posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular responses of three commercially important marine bivalves - Eastern oysters, blue mussels and hard clams - upon exposure to two β blocker drugs, propranolol and metoprolol, and to find molecular initiating events (MIEs) indicative of the exposure. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas (HP) tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug. Tissues were bathed in 30 parts per thousand (ppt) filtered seawater, antibiotic mix, Leibovitz nutrient media, and the test drug. Exposures were conducted for 24 hours and samples were saved for cellular biomarker assays. A lysosomal destabilization assay, which is a marker of membrane damage, was also performed at the end of each exposure.

Ready or Not: Microbial Adaptive Responses in Dynamic Symbiosis Environments.

Science.gov (United States)

Cao, Mengyi; Goodrich-Blair, Heidi

2017-08-01

In mutually beneficial and pathogenic symbiotic associations, microbes must adapt to the host environment for optimal fitness. Both within an individual host and during transmission between hosts, microbes are exposed to temporal and spatial variation in environmental conditions. The phenomenon of phenotypic variation, in which different subpopulations of cells express distinctive and potentially adaptive characteristics, can contribute to microbial adaptation to a lifestyle that includes rapidly changing environments. The environments experienced by a symbiotic microbe during its life history can be erratic or predictable, and each can impact the evolution of adaptive responses. In particular, the predictability of a rhythmic or cyclical series of environments may promote the evolution of signal transduction cascades that allow preadaptive responses to environments that are likely to be encountered in the future, a phenomenon known as adaptive prediction. In this review, we summarize environmental variations known to occur in some well-studied models of symbiosis and how these may contribute to the evolution of microbial population heterogeneity and anticipatory behavior. We provide details about the symbiosis between Xenorhabdus bacteria and Steinernema nematodes as a model to investigate the concept of environmental adaptation and adaptive prediction in a microbial symbiosis. Copyright © 2017 American Society for Microbiology.

Cellular responses to modified Plasmodium falciparum MSP119 antigens in individuals previously exposed to natural malaria infection

Directory of Open Access Journals (Sweden)

Awobode Henrietta O

2009-11-01

Full Text Available Abstract Background MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP119, inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP119 had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP119 would affect critical T-cell responses to epitopes in this antigen. Methods The cellular responses to wild-type MSP119 and a panel of modified MSP119 antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. Results Interestingly, stimulation indices (SI for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP119. A protein with four amino acid substitutions (Glu27→Tyr, Leu31→Arg, Tyr34→Ser and Glu43→Leu had the highest stimulation index (SI up to 360 and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. Conclusion This study suggests that specific MSP119 variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.

Pairing of heterochromatin in response to cellular stress

International Nuclear Information System (INIS)

Abdel-Halim, H.I.; Mullenders, L.H.F.; Boei, J.J.W.A.

2006-01-01

We previously reported that exposure of human cells to DNA-damaging agents (X-rays and mitomycin C (MMC)) induces pairing of the homologous paracentromeric heterochromatin of chromosome 9 (9q12-13). Here, we show that UV irradiation and also heat shock treatment of human cells lead to similar effects. Since the various agents induce very different types and frequencies of damage to cellular constituents, the data suggest a general stress response as the underlying mechanism. Moreover, local UV irradiation experiments revealed that pairing of heterochromatin is an event that can be triggered without induction of DNA damage in the heterochromatic sequences. The repair deficient xeroderma pigmentosum cells (group F) previously shown to fail pairing after MMC displayed elevated pairing after heat shock treatment but not after UV exposure. Taken together, the present results indicate that pairing of heterochromatin following exposure to DNA-damaging agents is initiated by a general stress response and that the sensing of stress or the maintenance of the paired status of the heterochromatin might be dependent on DNA repair

FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1.

Directory of Open Access Journals (Sweden)

Carsten C Scholz

2016-01-01

Full Text Available The asparagine hydroxylase, factor inhibiting HIF (FIH, confers oxygen-dependence upon the hypoxia-inducible factor (HIF, a master regulator of the cellular adaptive response to hypoxia. Studies investigating whether asparagine hydroxylation is a general regulatory oxygen-dependent modification have identified multiple non-HIF targets for FIH. However, the functional consequences of this outside of the HIF pathway remain unclear. Here, we demonstrate that the deubiquitinase ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (OTUB1 is a substrate for hydroxylation by FIH on N22. Mutation of N22 leads to a profound change in the interaction of OTUB1 with proteins important in cellular metabolism. Furthermore, in cultured cells, overexpression of N22A mutant OTUB1 impairs cellular metabolic processes when compared to wild type. Based on these data, we hypothesize that OTUB1 is a target for functional hydroxylation by FIH. Additionally, we propose that our results provide new insight into the regulation of cellular energy metabolism during hypoxic stress and the potential for targeting hydroxylases for therapeutic benefit.

Reduced Sleep During Social Isolation Leads to Cellular Stress and Induction of the Unfolded Protein Response.

Science.gov (United States)

Brown, Marishka K; Strus, Ewa; Naidoo, Nirinjini

2017-07-01

Social isolation has a multitude of negative consequences on human health including the ability to endure challenges to the immune system, sleep amount and efficiency, and general morbidity and mortality. These adverse health outcomes are conserved in other social species. In the fruit fly Drosophila melanogaster, social isolation leads to increased aggression, impaired memory, and reduced amounts of daytime sleep. There is a correlation between molecules affected by social isolation and those implicated in sleep in Drosophila. We previously demonstrated that acute sleep loss in flies and mice induced the unfolded protein response (UPR), an adaptive signaling pathway. One mechanism indicating UPR upregulation is elevated levels of the endoplasmic reticular chaperone BiP/GRP78. We previously showed that BiP overexpression in Drosophila led to increased sleep rebound. Increased rebound sleep has also been demonstrated in socially isolated (SI) flies. D. melanogaster were used to study the effect of social isolation on cellular stress. SI flies displayed an increase in UPR markers; there were higher BiP levels, increased phosphorylation of the translation initiation factor eIF2α, and increased splicing of xbp1. These are all indicators of UPR activation. In addition, the effects of isolation on the UPR were reversible; pharmacologically and genetically altering sleep in the flies modulated the UPR. The reduction in sleep observed in SI flies is a cellular stressor that results in UPR induction. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com

Immune and stress responses in oysters with insights on adaptation.

Science.gov (United States)

Guo, Ximing; He, Yan; Zhang, Linlin; Lelong, Christophe; Jouaux, Aude

2015-09-01

Oysters are representative bivalve molluscs that are widely distributed in world oceans. As successful colonizers of estuaries and intertidal zones, oysters are remarkably resilient against harsh environmental conditions including wide fluctuations in temperature and salinity as well as prolonged air exposure. Oysters have no adaptive immunity but can thrive in microbe-rich estuaries as filter-feeders. These unique adaptations make oysters interesting models to study the evolution of host-defense systems. Recent advances in genomic studies including sequencing of the oyster genome have provided insights into oyster's immune and stress responses underlying their amazing resilience. Studies show that the oyster genomes are highly polymorphic and complex, which may be key to their resilience. The oyster genome has a large gene repertoire that is enriched for immune and stress response genes. Thousands of genes are involved in oyster's immune and stress responses, through complex interactions, with many gene families expanded showing high sequence, structural and functional diversity. The high diversity of immune receptors and effectors may provide oysters with enhanced specificity in immune recognition and response to cope with diverse pathogens in the absence of adaptive immunity. Some members of expanded immune gene families have diverged to function at different temperatures and salinities or assumed new roles in abiotic stress response. Most canonical innate immunity pathways are conserved in oysters and supported by a large number of diverse and often novel genes. The great diversity in immune and stress response genes exhibited by expanded gene families as well as high sequence and structural polymorphisms may be central to oyster's adaptation to highly stressful and widely changing environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework

International Nuclear Information System (INIS)

Calabrese, Edward J.; Bachmann, Kenneth A.; Bailer, A. John; Bolger, P. Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M. George; Chiueh, Chuang C.; Clarkson, Thomas W.; Cook, Ralph R.; Diamond, David M.; Doolittle, David J.; Dorato, Michael A.; Duke, Stephen O.; Feinendegen, Ludwig; Gardner, Donald E.; Hart, Ronald W.; Hastings, Kenneth L.; Hayes, A. Wallace; Hoffmann, George R.; Ives, John A.; Jaworowski, Zbigniew; Johnson, Thomas E.; Jonas, Wayne B.; Kaminski, Norbert E.; Keller, John G.; Klaunig, James E.; Knudsen, Thomas B.; Kozumbo, Walter J.; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I.; Masoro, Edward J.; McClellan, Roger O.; Mehendale, Harihara M.; Mothersill, Carmel; Newlin, David B.; Nigg, Herbert N.; Oehme, Frederick W.; Phalen, Robert F.; Philbert, Martin A.; Rattan, Suresh I.S.; Riviere, Jim E.; Rodricks, Joseph; Sapolsky, Robert M.; Scott, Bobby R.; Seymour, Colin; Sinclair, David A.; Smith-Sonneborn, Joan; Snow, Elizabeth T.; Spear, Linda; Stevenson, Donald E.; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M.; Mattson, Mark P.

2007-01-01

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines

The oxygen effect and cellular adaptation

International Nuclear Information System (INIS)

Meshcherikova, V.V.; Vajnson, A.A.; Yarmonenko, S.P.

1979-01-01

The radiomodifying effect of oxygen was shown to depend on the level of cellular oxygenation prior to irradiation. Acute hypoxia created at the time of irradiation protects previously normally oxygenated cells with DMF approximately 1.4 times larger than that of cells cultured for 24 hours under conditions of mild hypoxia. It is suggested that a decrease in the radioprotective effect of acute hypoxia on chronically hypoxic cells is correlated with an appreciable decrease in the rate of oxygen consumption by these cells, due to which the oxygen concentration near the intracellular targets in chronically hypoxic cells may be higher than in normal cells under conditions of poor oxygenation

Identifying a compound modifying a cellular response, comprises attaching cells having a reporter system onto solid supports, releasing a library member, screening and identifying target cells

DEFF Research Database (Denmark)

2011-01-01

The present invention relates to methods for identifying compounds capable of modulating a cellular response. The methods involve attaching living cells to solid supports comprising a library of test compounds. Test compounds modulating a cellular response, for example via a cell surface molecule...... may be identified by selecting solid supports comprising cells, wherein the cellular response of interest has been modulated. The cellular response may for example be changes in signal transduction pathways modulated by a cell surface molecule....

Impact of Heat Stress on Cellular and Transcriptional Adaptation of Mammary Epithelial Cells in Riverine Buffalo (Bubalus Bubalis).

Science.gov (United States)

Kapila, Neha; Sharma, Ankita; Kishore, Amit; Sodhi, Monika; Tripathi, Pawan K; Mohanty, Ashok K; Mukesh, Manishi

2016-01-01

The present study aims to identify the heat responsive genes and biological pathways in heat stressed buffalo mammary epithelial cells (MECs). The primary mammary epithelial cells of riverine buffalo were exposed to thermal stress at 42°C for one hour. The cells were subsequently allowed to recover at 37°C and harvested at different time intervals (30 min to 48 h) along with control samples (un-stressed). In order to assess the impact of heat stress in buffalo MECs, several in-vitro cellular parameters (lactate dehydrogenase activity, cell proliferation assay, cellular viability, cell death and apoptosis) and transcriptional studies were conducted. The heat stress resulted in overall decrease in cell viability and cell proliferation of MECs while induction of cellular apoptosis and necrosis. The transcriptomic profile of heat stressed MECs was generated using Agilent 44 K bovine oligonucleotide array and at cutoff criteria of ≥3-or ≤3 fold change, a total of 153 genes were observed to be upregulated while 8 genes were down regulated across all time points post heat stress. The genes that were specifically up-regulated or down-regulated were identified as heat responsive genes. The upregulated genes in heat stressed MECs belonged to heat shock family viz., HSPA6, HSPB8, DNAJB2, HSPA1A. Along with HSPs, genes like BOLA, MRPL55, PFKFB3, PSMC2, ENDODD1, ARID5A, and SENP3 were also upregulated. Microarray data revealed that the heat responsive genes belonged to different functional classes viz., chaperons; immune responsive; cell proliferation and metabolism related. Gene ontology analysis revealed enrichment of several biological processes like; cellular process, metabolic process, response to stimulus, biological regulation, immune system processes and signaling. The transcriptome analysis data was further validated by RT-qPCR studies. Several HSP (HSP40, HSP60, HSP70, HSP90, and HSPB1), apoptotic (Bax and Bcl2), immune (IL6, TNFα and NF-kβ) and oxidative

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

Directory of Open Access Journals (Sweden)

Fela Mendlovic

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

Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

NARCIS (Netherlands)

Denning, Denise; Roos, Wouter H

2016-01-01

The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

On the synthesis of a bio-inspired dual-cellular fluidic flexible matrix composite adaptive structure based on a non-dimensional dynamics model

International Nuclear Information System (INIS)

Li, Suyi; Wang, K W

2013-01-01

A recent study investigated the dynamic characteristics of an adaptive structure concept featuring dual fluidic flexible matrix composite (F 2 MC) cells inspired by the configuration of plant cells and cell walls. This novel bio-inspired system consists of two F 2 MC cells with different fiber angles connected through internal fluid circuits. It was discovered that the dual F 2 MC cellular structure can be characterized as a two degree of freedom damped mass–spring oscillator, and can be utilized as a vibration absorber or an enhanced actuator under different operation conditions. These results demonstrated that the concept is promising and further investigations are needed to develop methodologies for synthesizing future multi-cellular F 2 MC structural systems. While interesting, the previous study focused on specific case studies and analysis. That is, the outcome did not provide insight that could be generalized, or tools for synthesizing a multiple F 2 MC cellular structure. This paper attempts to address this important issue by developing a non-dimensional dynamic model, which reveals good physical insights as well as identifying crucial constitutive parameters for F 2 MC cellular design. Working with these parameters, rather than physical variables, can greatly simplify the mathematics involved in the study. A synthesis tool is then developed for the dual-cellular structure, and it is found that for each set of achievable target poles and zero, there exist multiple F 2 MC cellular designs, forming a design space. The presented physical insights and synthesis tool for the dual-cellular structure will be the building blocks for future investigation on cellular structures with a larger number of cells. (paper)

An examination of adaptive cellular protective mechanisms using a multi-stage carcinogenesis model

International Nuclear Information System (INIS)

Schollnberger, H.; Stewart, R. D.; Mitchel, R. E. J.; Hofmann, W.

2004-01-01

A multi-stage cancer model that describes the putative rate-limiting steps in carcinogenesis was developed and used to investigate the potential impact on lung cancer incidence of the hormesis mechanisms suggested by Feinendegen and Pollycove. In this deterministic cancer model, radiation and endogenous processes damage the DNA of target cells in the lung. Some fraction of the misrepaired our unrepaired DNA damage induces genomic instability and, ultimately, leads to the accumulation of malignant cells. The model accounts for cell birth and death processes. Ita also includes a rate of malignant transformation and a lag period for tumour formation. Cellular defence mechanisms are incorporated into the model by postulating dose and dose rate dependent radical scavenging. The accuracy of DNA damage repair also depends on dose and dose rate. Sensitivity studies were conducted to identify critical model inputs and to help define the shapes of the cumulative lung cancer incidence curves that may arise when dose and dose rate dependent cellular defence mechanisms are incorporated into a multi-stage cancer model. For lung cancer, both linear no-threshold (LNT) and non-LNT shaped responses can be obtained. The reported studied clearly show that it is critical to know whether or not and to what extent multiply damaged DNA sites are formed by endogenous processes. Model inputs that give rise to U-shaped responses are consistent with an effective cumulative lung cancer incidence threshold that may be as high as 300 mGy (4 mGy per year for 75 years). (Author) 11 refs

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

Science.gov (United States)

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

2017-01-01

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

Kinetics of the early adaptive response and adaptation threshold dose

International Nuclear Information System (INIS)

Mendiola C, M.T.; Morales R, P.

2003-01-01

The expression kinetics of the adaptive response (RA) in mouse leukocytes in vivo and the minimum dose of gamma radiation that induces it was determined. The mice were exposed 0.005 or 0.02 Gy of 137 Cs like adaptation and 1h later to the challenge dose (1.0 Gy), another group was only exposed at 1.0 Gy and the damage is evaluated in the DNA with the rehearsal it makes. The treatment with 0. 005 Gy didn't induce RA and 0. 02 Gy causes a similar effect to the one obtained with 0.01 Gy. The RA was show from an interval of 0.5 h being obtained the maximum expression with 5.0 h. The threshold dose to induce the RA is 0.01 Gy and in 5.0 h the biggest quantity in molecules is presented presumably that are related with the protection of the DNA. (Author)

Involvement of oxygen reactive species in the cellular response of carcinoma cells to irradiation

International Nuclear Information System (INIS)

Tulard, A.

2004-06-01

After a presentation of oxygen reactive species and their sources, the author describes the enzymatic and non-enzymatic anti-oxidative defenses, the physiological roles of oxygen reactive species, the oxidative stress, the water radiolysis, the anti-oxidative enzymes and the effects of ionizing radiations. The author then reports an investigation on the contribution of oxygen reactive species in the cellular response to irradiation, and an investigation on the influence of the breathing chain on the persistence of a radio-induced oxidative stress. He also reports a research on molecular mechanisms involved in the cellular radio-sensitivity

Cellular cytotoxic response induced by highly purified multi-wall carbon nanotube in human lung cells.

Science.gov (United States)

Tsukahara, Tamotsu; Haniu, Hisao

2011-06-01

Carbon nanotubes, a promising nanomaterial with unique characteristics, have applications in a variety of fields. The cytotoxic effects of carbon nanotubes are partially due to the induction of oxidative stress; however, the detailed mechanisms of nanotube cytotoxicity and their interaction with cells remain unclear. In this study, the authors focus on the acute toxicity of vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) by high-temperature thermal treatment. The authors exposed human bronchial epithelial cells (BEAS-2B) to HTT2800 and measured the cellular uptake, mitochondrial function, cellular LDH release, apoptotic signaling, reactive oxygen species (ROS) generation and pro-inflammatory cytokine release. The HTT2800-exposed cells showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. However, the exposed cells showed no obvious intracellular ROS generation. These cellular and molecular findings suggest that HTT2800 could cause a potentially adverse inflammatory response in BEAS-2B cells.

A cellular stress response (CSR) that interacts with NADPH-P450 reductase (NPR) is a new regulator of hypoxic response.

Science.gov (United States)

Oguro, Ami; Koyama, Chika; Xu, Jing; Imaoka, Susumu

2014-02-28

NADPH-P450 reductase (NPR) was previously found to contribute to the hypoxic response of cells, but the mechanism was not clarified. In this study, we identified a cellular stress response (CSR) as a new factor interacting with NPR by a yeast two-hybrid system. Overexpression of CSR enhanced the induction of erythropoietin and hypoxia response element (HRE) activity under hypoxia in human hepatocarcinoma cell lines (Hep3B), while knockdown of CSR suppressed them. This new finding regarding the interaction of NPR with CSR provides insight into the function of NPR in hypoxic response. Copyright © 2014 Elsevier Inc. All rights reserved.

Command Resiliency: An Adaptive Response Strategy for Complex Incidents

National Research Council Canada - National Science Library

Pfeifer, Joseph W

2005-01-01

.... Unless organizations develop a resilient response strategy that can adapt organizational and operational elements to respond to new terrorist incidents, they will find themselves with the same...

Cigarette smoke-exposed saliva suppresses cellular and humoral immune responses in an animal model

International Nuclear Information System (INIS)

Jafarzadeh, A.; Bakhshi, H.; Rezayati, M.T.; Nemati, M.

2009-01-01

To evaluate the effects of cigarette smoke (CS)-exposed saliva on cellular and antibody responses in an animal model. The stimulatory and non-stimulatory saliva samples were collected from 10 healthy subjects and were then exposed to CS for 20 or 80 minutes. The CS-exposed saliva samples were administrated intraperitoneally (i.p) to male Balb/c mice. Then the delayed type hypersensitivity (DTH) and antibody responses to sheep red blood cell (SRBC) was assessed. Moreover, the total white blood cells (WBC) counts and the blood lymphocytes counts were determined. The mean of DTH responses of animal groups received 20 minutes or 80 minutes CS-exposed saliva samples was significantly lower than that observed in control group. Moreover, The mean titer of anti-SRBC antibody was significantly lower in animal groups who received 80 minutes CS-exposed stimulatory or non-stimulatory saliva as compared to control group (P<0.04 and P<0.002, respectively). The mean counts of blood lymphocytes in 80 minutes CS exposed-stimulatory saliva group was also significantly lower as compared to control group (P<0.05). These results show that the CS-exposed saliva samples have profound suppressive effects on both cellular and humoral immune response in a mouse animal model (JPMA 59:760; 2009). (author)

Factors influencing induction of adaptive response

International Nuclear Information System (INIS)

Misonoh, Jun; Ojima, Mitsuaki; Yonezawa, Morio

2000-01-01

Exposure to low doses of X-rays makes ICR mice resistant to subsequent sublethal irradiation and decrease mortality from hematopoietic death. Many factors, however, influence the induction of radioresistance. For instances, in ICR mice, the priming irradiation with 0.50 Gy was effective in the induction of radioresistance, when it is given at 6-week old, 2 weeks prior to subsequent sublethal irradiation. One hundred-fifty kV X-ray filtered off the soft component through 1.0 mm aluminum and 0.2 mm copper induces radioadaptive response as well as the harder radiation such as 260 kV X-ray filtered through 0.5 mm aluminum and 0.3 mm copper. Dose rate of priming irradiation also seemed to influence the induction of radioresistance. Priming irradiation with 0.50 Gy at 0.50 Gy/min and 0.25 Gy/min induced adaptive response, while same 0.50 Gy given at 0.063 Gy/min didn't. To make the matter complicated, when mice were pre-irradiated with 0.50 Gy at 0.013 Gy/min in the irradiation cell which was 1.2 x 1.2 x 1.4 times larger than the usual one, adaptive response was induced again. These results suggested that mice felt more uncomfortable when they were packing in the irradiation cell with little free space even for several minutes than when they were placed in the cell with much free space for about 40 minutes, and such a stress might give the mice some resistance to the subsequent sublethal irradiation. (author)

Guest-responsive structural adaptation of a rationally-designed ...

Indian Academy of Sciences (India)

adaptability of the TB core to undergo subtle structural changes in response to the guest that is included. The structural ... we report the design, synthesis and inclusion behaviour of a novel ..... Based on a rational design, we have shown from ...

Is the bitter rejection response always adaptive?

Science.gov (United States)

Glendinning, J I

1994-12-01

The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially

Ask yeast how to burn your fats: lessons learned from the metabolic adaptation to salt stress.

Science.gov (United States)

Pascual-Ahuir, Amparo; Manzanares-Estreder, Sara; Timón-Gómez, Alba; Proft, Markus

2018-02-01

Here, we review and update the recent advances in the metabolic control during the adaptive response of budding yeast to hyperosmotic and salt stress, which is one of the best understood signaling events at the molecular level. This environmental stress can be easily applied and hence has been exploited in the past to generate an impressively detailed and comprehensive model of cellular adaptation. It is clear now that this stress modulates a great number of different physiological functions of the cell, which altogether contribute to cellular survival and adaptation. Primary defense mechanisms are the massive induction of stress tolerance genes in the nucleus, the activation of cation transport at the plasma membrane, or the production and intracellular accumulation of osmolytes. At the same time and in a coordinated manner, the cell shuts down the expression of housekeeping genes, delays the progression of the cell cycle, inhibits genomic replication, and modulates translation efficiency to optimize the response and to avoid cellular damage. To this fascinating interplay of cellular functions directly regulated by the stress, we have to add yet another layer of control, which is physiologically relevant for stress tolerance. Salt stress induces an immediate metabolic readjustment, which includes the up-regulation of peroxisomal biomass and activity in a coordinated manner with the reinforcement of mitochondrial respiratory metabolism. Our recent findings are consistent with a model, where salt stress triggers a metabolic shift from fermentation to respiration fueled by the enhanced peroxisomal oxidation of fatty acids. We discuss here the regulatory details of this stress-induced metabolic shift and its possible roles in the context of the previously known adaptive functions.

Aberrant cellular immune responses in humans infected persistently with parvovirus B19

DEFF Research Database (Denmark)

Isa, Adiba; Norbeck, Oscar; Hirbod, Taha

2006-01-01

A subset of parvovirus B19 (B19) infected patients retains the infection for years, as defined by detection of B19 DNA in bone marrow. Thus far, analysis of B19-specific humoral immune responses and viral genome variations has not revealed a mechanism for the absent viral clearance. In this study......, ex-vivo cellular immune responses were assessed by enzyme linked immunospot assay mounted against the majority of the translated viral genome. Compared to seropositive healthy individuals, individuals with B19 persistence (2-8 years) showed larger number of responses to the structural proteins (P = 0.......0022), whereas responses to the non-structural protein were of lower magnitude (P = 0.012). These observations provide the first findings of immunological discrepancies between individuals with B19 persistence and healthy individuals, findings that may reflect both failed immunity and antigenic exhaustion....

Comparison of Cellular Uptake and Inflammatory Response via Toll-Like Receptor 4 to Lipopolysaccharide and Titanium Dioxide Nanoparticles

Directory of Open Access Journals (Sweden)

Akiyoshi Taniguchi

2013-06-01

Full Text Available The innate immune response is the earliest cellular response to infectious agents and mediates the interactions between microbes and cells. Toll-like receptors (TLRs play an important role in these interactions. We have already shown that TLRs are involved with the uptake of titanium dioxide nanoparticles (TiO2 NPs and promote inflammatory responses. In this paper, we compared role of cellular uptake and inflammatory response via TLR 4 to lipopolysaccharide (LPS and TiO2 NPs. In the case of LPS, LPS binds to LPS binding protein (LBP and CD 14, and then this complex binds to TLR 4. In the case of TiO2 NPs, the necessity of LBP and CD 14 to induce the inflammatory response and for uptake by cells was investigated using over-expression, antibody blocking, and siRNA knockdown experiments. Our results suggested that for cellular uptake of TiO2 NPs, TLR 4 did not form a complex with LBP and CD 14. In the TiO2 NP-mediated inflammatory response, TLR 4 acted as the signaling receptor without protein complex of LPS, LBP and CD 14. The results suggested that character of TiO2 NPs might be similar to the complex of LPS, LBP and CD 14. These results are important for development of safer nanomaterials.

The role of nuclear factor κB in the cellular response to different radiation qualities

International Nuclear Information System (INIS)

Koch, Kristina

2013-01-01

Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

The role of nuclear factor κB in the cellular response to different radiation qualities

Energy Technology Data Exchange (ETDEWEB)

Koch, Kristina

2013-04-11

Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

Developing a gene biomarker at the tipping point of adaptive and adverse responses in human bronchial epithelial cells

Science.gov (United States)

Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk...

Evolution of plasticity and adaptive responses to climate change along climate gradients.

Science.gov (United States)

Kingsolver, Joel G; Buckley, Lauren B

2017-08-16

The relative contributions of phenotypic plasticity and adaptive evolution to the responses of species to recent and future climate change are poorly understood. We combine recent (1960-2010) climate and phenotypic data with microclimate, heat balance, demographic and evolutionary models to address this issue for a montane butterfly, Colias eriphyle , along an elevational gradient. Our focal phenotype, wing solar absorptivity, responds plastically to developmental (pupal) temperatures and plays a central role in thermoregulatory adaptation in adults. Here, we show that both the phenotypic and adaptive consequences of plasticity vary with elevation. Seasonal changes in weather generate seasonal variation in phenotypic selection on mean and plasticity of absorptivity, especially at lower elevations. In response to climate change in the past 60 years, our models predict evolutionary declines in mean absorptivity (but little change in plasticity) at high elevations, and evolutionary increases in plasticity (but little change in mean) at low elevation. The importance of plasticity depends on the magnitude of seasonal variation in climate relative to interannual variation. Our results suggest that selection and evolution of both trait means and plasticity can contribute to adaptive response to climate change in this system. They also illustrate how plasticity can facilitate rather than retard adaptive evolutionary responses to directional climate change in seasonal environments. © 2017 The Author(s).

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

Science.gov (United States)

Kiecker, Clemens; Graham, Anthony; Logan, Malcolm

2016-01-01

A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in competence for Hedgehog (HH) signalling, a signalling pathway that is reiteratively employed in embryos and adult organisms. We discuss the upstream signals and mechanisms that may establish differential competence for HHs in a range of different tissues. We argue that the changing competence for HH signalling provides a four-dimensional framework for the interpretation of the signal that is essential for the emergence of functional anatomy. A number of diseases—including several types of cancer—are caused by malfunctions of the HH pathway. A better understanding of what provides differential competence for this signal may reveal HH-related disease mechanisms and equip us with more specific tools to manipulate HH signalling in the clinic. PMID:29615599

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

Directory of Open Access Journals (Sweden)

Clemens Kiecker

2016-12-01

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

Adaptive response induced by occupational exposures to ionizing radiation

International Nuclear Information System (INIS)

Barquinero, J.F.; Caballin, M.R.; Barrios, L.; Murtra, P.; Egozcue, J.; Miro, R.; Ribas, M.

1997-01-01

We have found a significant decreased sensitivity to the cytogenetic effects of ionizing radiation (IR) and bleomycin (BLM) in lymphocytes from individuals occupationally exposed to IR when compared with a control population. These results suggest that occupational exposures to IR can induce adaptive response that can be detected by a subsequent treatment by IR or by BLM. However, no correlation between the results obtained with both treatments was observed. A great heterogeneity in the frequencies of chromatid aberrations induced by BLM was observed. The study of the influence of different harvesting times showed that there was no correlation with the frequencies of chromatid breaks. Our results indicate that the use of BLM to detect adaptive response has several difficulties at the individual level. (author)

Adaptive and Pathogenic Responses to Stress by Stem Cells during Development.

Science.gov (United States)

Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

2012-12-10

Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

Directory of Open Access Journals (Sweden)

Daniel A. Rappolee

2012-12-01

Full Text Available Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation.

Science.gov (United States)

Sannino, Anna; Sarti, Maurizio; Reddy, Siddharth B; Prihoda, Thomas J; Vijayalaxmi; Scarfì, Maria Rosaria

2009-06-01

The incidence of micronuclei was evaluated to assess the induction of an adaptive response to non-ionizing radiofrequency (RF) radiation in peripheral blood lymphocytes collected from five different human volunteers. After stimulation with phytohemagglutinin for 24 h, the cells were exposed to an adaptive dose of 900 MHz RF radiation used for mobile communications (at a peak specific absorption rate of 10 W/kg) for 20 h and then challenged with a single genotoxic dose of mitomycin C (100 ng/ml) at 48 h. Lymphocytes were collected at 72 h to examine the frequency of micronuclei in cytokinesis-blocked binucleated cells. Cells collected from four donors exhibited the induction of adaptive response (i.e., responders). Lymphocytes that were pre-exposed to 900 MHz RF radiation had a significantly decreased incidence of micronuclei induced by the challenge dose of mitomycin C compared to those that were not pre-exposed to 900 MHz RF radiation. These preliminary results suggested that the adaptive response can be induced in cells exposed to non-ionizing radiation. A similar phenomenon has been reported in cells as well as in animals exposed to ionizing radiation in several earlier studies. However, induction of adaptive response was not observed in the remaining donor (i.e., non-responder). The incidence of micronuclei induced by the challenge dose of mitomycin C was not significantly different between the cells that were pre-exposed and unexposed to 900 MHz RF radiation. Thus the overall data indicated the existence of heterogeneity in the induction of an adaptive response between individuals exposed to RF radiation and showed that the less time-consuming micronucleus assay can be used to determine whether an individual is a responder or non-responder.

Computerized Adaptive Test (CAT) Applications and Item Response Theory Models for Polytomous Items

Science.gov (United States)

Aybek, Eren Can; Demirtasli, R. Nukhet

2017-01-01

This article aims to provide a theoretical framework for computerized adaptive tests (CAT) and item response theory models for polytomous items. Besides that, it aims to introduce the simulation and live CAT software to the related researchers. Computerized adaptive test algorithm, assumptions of item response theory models, nominal response…

Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?

Science.gov (United States)

Ristow, Michael

2016-01-01

Abstract A popular belief is that reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced during exercise by the mitochondria and other subcellular compartments ubiquitously cause skeletal muscle damage, fatigue and impair recovery. However, the importance of ROS and RNS as signals in the cellular adaptation process to stress is now evident. In an effort to combat the perceived deleterious effects of ROS and RNS it has become common practice for active individuals to ingest supplements with antioxidant properties, but interfering with ROS/RNS signalling in skeletal muscle during acute exercise may blunt favourable adaptation. There is building evidence that antioxidant supplementation can attenuate endurance training‐induced and ROS/RNS‐mediated enhancements in antioxidant capacity, mitochondrial biogenesis, cellular defence mechanisms and insulin sensitivity. However, this is not a universal finding, potentially indicating that there is redundancy in the mechanisms controlling skeletal muscle adaptation to exercise, meaning that in some circumstances the negative impact of antioxidants on acute exercise response can be overcome by training. Antioxidant supplementation has been more consistently reported to have deleterious effects on the response to overload stress and high‐intensity training, suggesting that remodelling of skeletal muscle following resistance and high‐intensity exercise is more dependent on ROS/RNS signalling. Importantly there is no convincing evidence to suggest that antioxidant supplementation enhances exercise‐training adaptions. Overall, ROS/RNS are likely to exhibit a non‐linear (hormetic) pattern on exercise adaptations, where physiological doses are beneficial and high exposure (which would seldom be achieved during normal exercise training) may be detrimental. PMID:26638792

Nuclear and cytoplasmic signalling in the cellular response to ionising radiation

International Nuclear Information System (INIS)

Szumiel, Irena

2001-01-01

DNA is the universal primary target for ionising radiation; however, the cellular response is highly diversified not only by differential DNA repair ability. The monitoring system for the ionising radiation-inflicted DNA damage consists of 3 apparently independently acting enzymes which are activated by DNA breaks: two protein kinases, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase) and a poly(ADP-ribose) polymerase, PARP-1. These 3 enzymes are the source of alarm signals, which affect to various extents DNA repair, progression through the cell cycle and eventually the pathway to cell death. Their functions probably are partly overlapping. On the side of DNA repair their role consists in recruiting and/or activating the repair enzymes, as well as preventing illegitimate recombination of the damaged sites. A large part of the nuclear signalling pathway, including the integrating role of TP53 has been revealed. Two main signalling pathways start at the plasma membrane: the MAPK/ERK (mitogen and extracellular signal regulated protein kinase family) 'survival pathway' and the SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase) 'cell death pathway'. The balance between them is likely to determine the cell's fate. An additional important 'survival pathway' starts at the insulin-like growth factor type I receptor (IGF-IR), involves phosphoinositide- 3 kinase and Akt kinase and is targeted at inactivation of the pro-apoptotic BAD protein. Interestingly, over-expression of IGF-IR almost entirely abrogates the extreme radiation sensitivity of ataxia telangiectasia cells. When DNA break rejoining is impaired, the cell is unconditionally radiation sensitive. The fate of a repair-competent cell is determined by the time factor: the cell cycle arrest should be long enough to ensure the completion of repair. Incomplete repair or misrepair may be tolerated, when generation of the death signal is prevented. So, the character and timing

Robust network topologies for generating switch-like cellular responses.

Directory of Open Access Journals (Sweden)

Najaf A Shah

2011-06-01

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

Adaptive response to ionizing radiation induced by low doses of gamma rays in human cell lines

International Nuclear Information System (INIS)

Seong, Jinsil; Chang, Ok Suh; Gwi, Eon Kim

1995-01-01

Purpose: The aim of this study was to investigate whether the adaptive response could be induced in human lymphoblastoid cell lines and human tumor cell lines. The time necessary for the expression of the adaptive response was also investigated. Materials and Methods: Three lymphoblastoid cell lines from ataxia telangiectasia (AT) homozygote (GM 1526), AT heterozygote (GM 3382), and normal individual (3402p) and two hepatoma cell lines, Hep G2 and Hep 3B, were used in this study. Experiments were carried out by delivering 0.01 Gy followed by 0.5 Gy of gamma radiation to the exponentially growing cells. The time necessary for the expression of the adaptive response was determined by varying the time interval between the two doses from 1 to 72 h. In some experiments, 3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase, was added immediately after the 0.5 Gy exposure. The cultures were fixed 30 min (for the G 2 chromatid) and 6 h (for the S chromatid) after the 0.5 Gy exposure. Metaphase chromosome assay was carried out to score chromatid breaks as an end point. Results: A prior exposure to 0.01 Gy of gamma rays significantly reduced the number of chromatid breaks induced by subsequent higher doses (0.5 Gy) in all the tested cell lines. The magnitude of the adaptive response was similar among the cell lines despite their different radiosensitivities. In the G 2 chromatids, the adaptive response was observed both at short-time intervals, as early as 1 h, and at long-time intervals. In the S chromatids, however, the adaptive response was shown only at long-time intervals. When 3-aminobenzamide was added after the 0.5 Gy, the adaptive responses were abolished in all the experimental groups. Conclusion: The adaptive response was observed in human lymphoblastoid cell lines and hepatoma cell lines. The magnitude of the adaptive response did not seem to be related to the radiosensitivity of the cells. The elimination of the adaptive response with 3

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

DEFF Research Database (Denmark)

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

2013-01-01

uncover a new two-pronged signalling response, which by coupling p38-dependent phosphorylation with MIB1-catalysed ubiquitylation of ciliogenesis-promoting factors plays an important role in controlling centriolar satellite status and key centrosomal functions in a cell stress-regulated manner.......Centriolar satellites are small, granular structures that cluster around centrosomes, but whose biological function and regulation are poorly understood. We show that centriolar satellites undergo striking reorganization in response to cellular stresses such as UV radiation, heat shock......, and transcription blocks, invoking acute and selective displacement of the factors AZI1/CEP131, PCM1, and CEP290 from this compartment triggered by activation of the stress-responsive kinase p38/MAPK14. We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts...

Identification of cellular responses to low-dose radiation by antibody array in human B-lymphoblasts IM-9 cells

Energy Technology Data Exchange (ETDEWEB)

Eom, Hyeon Soo; Kim, Ji Young; Nam, Seon Young [Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro and Nuclear Power Co. LTD., Seoul (Korea, Republic of)

2017-04-15

The low-dose radiation (LDR)-induced various responses can reduce genetic mutation, enhance cell survival, and increase infection resistance (1). The antibody array for global analysis of phosphorylated proteins might be very useful to study signaling networks of LDR-induced cellular responses (2). Therefore, global analysis of phospho- proteins in cells exposed to radiation is important to understand the signaling mechanisms induced by changes of protein phosphorylation which lead to various biological effects by radiation. The aim is to explore the possibility of LDR-specific signaling for various beneficial effects and elucidate the potential signaling pathways representing LDR responses. Our results suggest that LDR did not affect cell death and that the increased proteins phosphorylation by LDR might be involved in various cellular responses for cell homeostasis. These results might be useful to further studies aimed at investigating potential regulatory markers that represent responses to LDR.

Identification of cellular responses to low-dose radiation by antibody array in human B-lymphoblasts IM-9 cells

International Nuclear Information System (INIS)

Eom, Hyeon Soo; Kim, Ji Young; Nam, Seon Young

2017-01-01

The low-dose radiation (LDR)-induced various responses can reduce genetic mutation, enhance cell survival, and increase infection resistance (1). The antibody array for global analysis of phosphorylated proteins might be very useful to study signaling networks of LDR-induced cellular responses (2). Therefore, global analysis of phospho- proteins in cells exposed to radiation is important to understand the signaling mechanisms induced by changes of protein phosphorylation which lead to various biological effects by radiation. The aim is to explore the possibility of LDR-specific signaling for various beneficial effects and elucidate the potential signaling pathways representing LDR responses. Our results suggest that LDR did not affect cell death and that the increased proteins phosphorylation by LDR might be involved in various cellular responses for cell homeostasis. These results might be useful to further studies aimed at investigating potential regulatory markers that represent responses to LDR

Aged blood factors decrease cellular responses associated with delayed gingival wound repair.

Directory of Open Access Journals (Sweden)

María Paz Saldías

Full Text Available Aging is a gradual biological process characterized by a decrease in cell and organism functions. Gingival wound healing is one of the impaired processes found in old rats. Here, we studied the in vivo wound healing process using a gingival repair rat model and an in vitro model using human gingival fibroblast for cellular responses associated to wound healing. To do that, we evaluated cell proliferation of both epithelial and connective tissue cells in gingival wounds and found decreased of Ki67 nuclear staining in old rats when compared to their young counterparts. We next evaluated cellular responses of primary gingival fibroblast obtained from young subjects in the presence human blood serum of individuals of different ages. Eighteen to sixty five years old masculine donors were classified into 3 groups: "young" from 18 to 22 years old, "middle-aged" from 30 to 48 years old and "aged" over 50 years old. Cell proliferation, measured through immunofluorescence for Ki67 and flow cytometry for DNA content, was decreased when middle-aged and aged serum was added to gingival fibroblast compared to young serum. Myofibroblastic differentiation, measured through alpha-smooth muscle actin (α-SMA, was stimulated with young but not middle-aged or aged serum both the protein levels and incorporation of α-SMA into actin stress fibers. High levels of PDGF, VEGF, IL-6R were detected in blood serum from young subjects when compared to middle-aged and aged donors. In addition, the pro-inflammatory cytokines MCP-1 and TNF were increased in the serum of aged donors. In old rat wound there is an increased of staining for TNF compared to young wound. Moreover, healthy gingiva (non injury shows less staining compared to a wound site, suggesting a role in wound healing. Moreover, serum from middle-aged and aged donors was able to stimulate cellular senescence in young cells as determined by the expression of senescence associated beta-galactosidase and histone H2

Submicron and nano formulations of titanium dioxide and zinc oxide stimulate unique cellular toxicological responses in the green microalga Chlamydomonas reinhardtii

Energy Technology Data Exchange (ETDEWEB)

Gunawan, Cindy, E-mail: c.gunawan@unsw.edu.au [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia); Sirimanoonphan, Aunchisa [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia); Teoh, Wey Yang [Clean Energy and Nanotechnology (CLEAN) Laboratory, School of Energy and Environment, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region (Hong Kong); Marquis, Christopher P., E-mail: c.marquis@unsw.edu.au [School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW (Australia); Amal, Rose [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia)

2013-09-15

Highlights: • Uptake of TiO{sub 2} solids by C. reinhardtii generates ROS as an early stress response. • Submicron and nanoTiO{sub 2} exhibit benign effect on cell proliferation. • Uptake of ZnO solids and leached zinc by C. reinhardtii inhibit the alga growth. • No cellular oxidative stress is detected with submicron and nano ZnO exposure. • The toxicity of particles is not necessarily mediated by cellular oxidative stress. -- Abstract: The work investigates the eco-cytoxicity of submicron and nano TiO{sub 2} and ZnO, arising from the unique interactions of freshwater microalga Chlamydomonas reinhardtii to soluble and undissolved components of the metal oxides. In a freshwater medium, submicron and nano TiO{sub 2} exist as suspended aggregates with no-observable leaching. Submicron and nano ZnO undergo comparable concentration-dependent fractional leaching, and exist as dissolved zinc and aggregates of undissolved ZnO. Cellular internalisation of solid TiO{sub 2} stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO{sub 2} exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50 > 100 mg TiO{sub 2}/L). Parallel exposure of C. reinhardtii to submicron and nano ZnO saw cellular uptake of both the leached zinc and solid ZnO and resulting in inhibition of the alga growth (8-day EC50 ≥ 0.01 mg ZnO/L). Despite the sensitivity, no zinc-induced cellular ROS generation was detected, even at 100 mg ZnO/L exposure. Taken together, the observations confront the generally accepted paradigm of cellular oxidative stress-mediated cytotoxicity of particles. The knowledge of speciation of particles and the corresponding stimulation of unique cellular responses and cytotoxicity is vital for assessment of the environmental implications of these materials.

Submicron and nano formulations of titanium dioxide and zinc oxide stimulate unique cellular toxicological responses in the green microalga Chlamydomonas reinhardtii

International Nuclear Information System (INIS)

Gunawan, Cindy; Sirimanoonphan, Aunchisa; Teoh, Wey Yang; Marquis, Christopher P.; Amal, Rose

2013-01-01

Highlights: • Uptake of TiO 2 solids by C. reinhardtii generates ROS as an early stress response. • Submicron and nanoTiO 2 exhibit benign effect on cell proliferation. • Uptake of ZnO solids and leached zinc by C. reinhardtii inhibit the alga growth. • No cellular oxidative stress is detected with submicron and nano ZnO exposure. • The toxicity of particles is not necessarily mediated by cellular oxidative stress. -- Abstract: The work investigates the eco-cytoxicity of submicron and nano TiO 2 and ZnO, arising from the unique interactions of freshwater microalga Chlamydomonas reinhardtii to soluble and undissolved components of the metal oxides. In a freshwater medium, submicron and nano TiO 2 exist as suspended aggregates with no-observable leaching. Submicron and nano ZnO undergo comparable concentration-dependent fractional leaching, and exist as dissolved zinc and aggregates of undissolved ZnO. Cellular internalisation of solid TiO 2 stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO 2 exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50 > 100 mg TiO 2 /L). Parallel exposure of C. reinhardtii to submicron and nano ZnO saw cellular uptake of both the leached zinc and solid ZnO and resulting in inhibition of the alga growth (8-day EC50 ≥ 0.01 mg ZnO/L). Despite the sensitivity, no zinc-induced cellular ROS generation was detected, even at 100 mg ZnO/L exposure. Taken together, the observations confront the generally accepted paradigm of cellular oxidative stress-mediated cytotoxicity of particles. The knowledge of speciation of particles and the corresponding stimulation of unique cellular responses and cytotoxicity is vital for assessment of the environmental implications of these materials

C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4

Science.gov (United States)

Huggins, Christopher J.; Mayekar, Manasi K.; Martin, Nancy; Saylor, Karen L.; Gonit, Mesfin; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C.; Quiñones, Octavio A.

2015-01-01

The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPγ:ATF4 heterodimers, but not C/EBPβ:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPγ and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPβ and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg−/− mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg−/− mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPγ-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg−/− mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPγ as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells. PMID:26667036

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

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Kelly L Robertson

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

Adaptive pressure-controlled cellular structures for shape morphing: II. Numerical and experimental validation

International Nuclear Information System (INIS)

Luo, Quantian; Tong, Liyong

2013-01-01

This part presents finite element analysis to verify the present formulations on mechanics of the pressurized cellular structures derived in Part I and experimental testing for a pressurized cellular actuator to demonstrate feasibility and realization of the proposed pressurized cellular structures. Linear and nonlinear finite element analyses are implemented in a commercial finite element analysis package and the numerical results are compared with those of the novel formulations given in Part I. A pressurized cellular structure specimen with 3 cells is fabricated and tested. The fabricated 3-cell cellular structure is capable of yielding a free actuation strain of around 24%. The measured pressure-induced displacement and blocking force compare favorably with the numerical results predicted by the finite element analysis and analytical formulations. (paper)

Coral bleaching--capacity for acclimatization and adaptation.

Science.gov (United States)

Coles, S L; Brown, Barbara E

2003-01-01

Coral bleaching, i.e., loss of most of the symbiotic zooxanthellae normally found within coral tissue, has occurred with increasing frequency on coral reefs throughout the world in the last 20 years, mostly during periods of El Nino Southern Oscillation (ENSO). Experiments and observations indicate that coral bleaching results primarily from elevated seawater temperatures under high light conditions, which increases rates of biochemical reactions associated with zooxanthellar photosynthesis, producing toxic forms of oxygen that interfere with cellular processes. Published projections of a baseline of increasing ocean temperature resulting from global warming have suggested that annual temperature maxima within 30 years may be at levels that will cause frequent coral bleaching and widespread mortality leading to decline of corals as dominant organisms on reefs. However, these projections have not considered the high variability in bleaching response that occurs among corals both within and among species. There is information that corals and their symbionts may be capable of acclimatization and selective adaptation to elevated temperatures that have already resulted in bleaching resistant coral populations, both locally and regionally, in various areas of the world. There are possible mechanisms that might provide resistance and protection to increased temperature and light. These include inducible heat shock proteins that act in refolding denatured cellular and structural proteins, production of oxidative enzymes that inactivate harmful oxygen radicals, fluorescent coral pigments that both reflect and dissipate light energy, and phenotypic adaptations of zooxanthellae and adaptive shifts in their populations at higher temperatures. Such mechanisms, when considered in conjunction with experimental and observational evidence for coral recovery in areas that have undergone coral bleaching, suggest an as yet undefined capacity in corals and zooxanthellae to adapt to

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus.

Science.gov (United States)

O'Hanlon, Karen A; Margison, Geoffrey P; Hatch, Amy; Fitzpatrick, David A; Owens, Rebecca A; Doyle, Sean; Jones, Gary W

2012-09-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O(6)-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O(6)-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system.

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus

Science.gov (United States)

O’Hanlon, Karen A.; Margison, Geoffrey P.; Hatch, Amy; Fitzpatrick, David A.; Owens, Rebecca A.; Doyle, Sean; Jones, Gary W.

2012-01-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O6-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O6-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID:22669901

Epitope-based vaccines with the Anaplasma marginale MSP1a functional motif induce a balanced humoral and cellular immune response in mice.

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Paula S Santos

Full Text Available Bovine anaplasmosis is a hemoparasitic disease that causes considerable economic loss to the dairy and beef industries. Cattle immunized with the Anaplasma marginale MSP1 outer membrane protein complex presents a protective humoral immune response; however, its efficacy is variable. Immunodominant epitopes seem to be a key-limiting factor for the adaptive immunity. We have successfully demonstrated that critical motifs of the MSP1a functional epitope are essential for antibody recognition of infected animal sera, but its protective immunity is yet to be tested. We have evaluated two synthetic vaccine formulations against A. marginale, using epitope-based approach in mice. Mice infection with bovine anaplasmosis was demonstrated by qPCR analysis of erythrocytes after 15-day exposure. A proof-of-concept was obtained in this murine model, in which peptides conjugated to bovine serum albumin were used for immunization in three 15-day intervals by intraperitoneal injections before challenging with live bacteria. Blood samples were analyzed for the presence of specific IgG2a and IgG1 antibodies, as well as for the rickettsemia analysis. A panel containing the cytokines' transcriptional profile for innate and adaptive immune responses was carried out through qPCR. Immunized BALB/c mice challenged with A. marginale presented stable body weight, reduced number of infected erythrocytes, and no mortality; and among control groups mortality rates ranged from 15% to 29%. Additionally, vaccines have significantly induced higher IgG2a than IgG1 response, followed by increased expression of pro-inflammatory cytokines. This is a successful demonstration of epitope-based vaccines, and protection against anaplasmosis may be associated with elicitation of effector functions of humoral and cellular immune responses in murine model.

On the limitations of fixed-step-size adaptive methods with response confidence.

Science.gov (United States)

Hsu, Yung-Fong; Chin, Ching-Lan

2014-05-01

The family of (non-parametric, fixed-step-size) adaptive methods, also known as 'up-down' or 'staircase' methods, has been used extensively in psychophysical studies for threshold estimation. Extensions of adaptive methods to non-binary responses have also been proposed. An example is the three-category weighted up-down (WUD) method (Kaernbach, 2001) and its four-category extension (Klein, 2001). Such an extension, however, is somewhat restricted, and in this paper we discuss its limitations. To facilitate the discussion, we characterize the extension of WUD by an algorithm that incorporates response confidence into a family of adaptive methods. This algorithm can also be applied to two other adaptive methods, namely Derman's up-down method and the biased-coin design, which are suitable for estimating any threshold quantiles. We then discuss via simulations of the above three methods the limitations of the algorithm. To illustrate, we conduct a small scale of experiment using the extended WUD under different response confidence formats to evaluate the consistency of threshold estimation. © 2013 The British Psychological Society.

Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease

Science.gov (United States)

Anderson, Mark E.; Birren, Susan J.; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B.; Kanazawa, Hideaki; Paterson, David J.; Ripplinger, Crystal M.

2016-01-01

Abstract The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural–cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

Molecular adaptations to phosphorus deprivation and comparison with nitrogen deprivation responses in the diatom Phaeodactylum tricornutum.

Science.gov (United States)

Alipanah, Leila; Winge, Per; Rohloff, Jens; Najafi, Javad; Brembu, Tore; Bones, Atle M

2018-01-01

Phosphorus, an essential element for all living organisms, is a limiting nutrient in many regions of the ocean due to its fast recycling. Changes in phosphate (Pi) availability in aquatic systems affect diatom growth and productivity. We investigated the early adaptive mechanisms in the marine diatom Phaeodactylum tricornutum to P deprivation using a combination of transcriptomics, metabolomics, physiological and biochemical experiments. Our analysis revealed strong induction of gene expression for proteins involved in phosphate acquisition and scavenging, and down-regulation of processes such as photosynthesis, nitrogen assimilation and nucleic acid and ribosome biosynthesis. P deprivation resulted in alterations of carbon allocation through the induction of the pentose phosphate pathway and cytosolic gluconeogenesis, along with repression of the Calvin cycle. Reorganization of cellular lipids was indicated by coordinated induced expression of phospholipases, sulfolipid biosynthesis enzymes and a putative betaine lipid biosynthesis enzyme. A comparative analysis of nitrogen- and phosphorus-deprived P. tricornutum revealed both common and distinct regulation patterns in response to phosphate and nitrate stress. Regulation of central carbon metabolism and amino acid metabolism was similar, whereas unique responses were found in nitrogen assimilation and phosphorus scavenging in nitrogen-deprived and phosphorus-deprived cells, respectively.

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

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Lingling Zhang

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

FORMATION OF INNATE AND ADAPTIVE IMMUNE RESPONSE UNDER THE INFLUENCE OF DIFFERENT FLAVIVIRUS VACCINES

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N. V. Krylova

2015-01-01

Full Text Available The review examines in a comparative perspective the key moments of formation of innate and adaptive immune responses to different types of current flavivirus vaccines: live attenuated against yellow fever virus and inactivated whole virus against tick-borne encephalitis virus. Particular attention is paid to the ability of these different vaccines, containing exogenous pathogen-associated molecular structures, to stimulate innate immunity. Live attenuated vaccine by infecting several subtypes of dendritic cells activates them through various pattern-recognition receptors, such as Tolland RIG-I-like receptors, which leads to significant production of proinflammatory cytokines, including interferon-α primary mediator of innate antiviral immunity. By simulating natural viral infection, this vaccine quickly spreads over the vascular network, and the dendritic cells, activated by it, migrate to the draining lymph nodes and trigger multiple foci of Tand B-cell activation. Inactivated vaccine stimulates the innate immunity predominantly at the injection site, and for the sufficient activation requires the presence in its composition of an adjuvant (aluminum hydroxide, which effects the formation and activation of inflammasomes, ensuring the formation and secretion of IL-1β and IL-18 that, in turn, trigger a cascade of cellular and humoral innate immune responses. We demonstrated the possibility of involvement in the induction of innate immunity, mediated by the inactivated vaccine, endogenous pathogenassociated molecular patterns (uric acid and host cell DNA, forming at the vaccine injection site. We discuss the triggering of Band T-cell responses by flavivirus vaccines that determine various duration of protection against various pathogens. A single injection of the live vaccine against yellow fever virus induces polyvalent adaptive immune response, including the production of cytotoxic T-lymphocytes, Th1and Th2-cells and neutralizing antibodies

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

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Renata eToth

2015-10-01

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

Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees

International Nuclear Information System (INIS)

Shata, Mohamed Tarek; Tricoche, Nancy; Perkus, Marion; Tom, Darley; Brotman, Betsy; McCormack, Patricia; Pfahler, Wolfram; Lee, Dong-Hun; Tobler, Leslie H.; Busch, Michael; Prince, Alfred M.

2003-01-01

In hepatitis C virus (HCV) infection, there is accumulating data suggesting the presence of cellular immune responses to HCV in exposed but seemingly uninfected populations. Some studies have suggested cross-reactive antigens rather than prior HCV exposure as the main reason for the immune responses. In this study we address this question by analyzing the immune response of chimpanzees that have been sequentially exposed to increasing doses of HCV virions. The level of viremia, as well as the immune responses to HCV at different times after virus inoculation, were examined. Our data indicate that HCV infective doses as low as 1-10 RNA (+) virions induce detectable cellular immune responses in chimpanzees without consistently detectable viremia or persistent seroconversion. However, increasing the infective doses of HCV to 100 RNA (+) virions overcame the low-inoculum-induced immune response and produced high-level viremia followed by seroconversion

Adaptive multi-channel downlink assignment for overloaded spectrum-shared multi-antenna overlaid cellular networks

KAUST Repository

Radaydeh, Redha Mahmoud

2012-10-19

Overlaid cellular technology has been considered as a promising candidate to enhance the capacity and extend the coverage of cellular networks, particularly indoors. The deployment of small cells (e.g. femtocells and/or picocells) in an overlaid setup is expected to reduce the operational power and to function satisfactorily with the existing cellular architecture. Among the possible deployments of small-cell access points is to manage many of them to serve specific spatial locations, while reusing the available spectrum universally. This contribution considers the aforementioned scenario with the objective to serve as many active users as possible when the available downlink spectrum is overloaded. The case study is motivated by the importance of realizing universal resource sharing in overlaid networks, while reducing the load of distributing available resources, satisfying downlink multi-channel assignment, controlling the aggregate level of interference, and maintaining desired design/operation requirements. These objectives need to be achieved in distributed manner in each spatial space with as low processing load as possible when the feedback links are capacity-limited, multiple small-cell access points can be shared, and data exchange between access points can not be coordinated. This contribution is summarized as follows. An adaptive downlink multi-channel assignment scheme when multiple co-channel and shared small-cell access points are allocated to serve active users is proposed. It is assumed that the deployed access points employ isotropic antenna arrays of arbitrary sizes, operate using the open-access strategy, and transmit on shared physical channels simultaneously. Moreover, each active user can be served by a single transmit channel per each access point at a time, and can sense the concurrent interference level associated with each transmit antenna channel non-coherently. The proposed scheme aims to identify a suitable subset of transmit channels

New features on the environmental regulation of metabolism revealed by modeling the cellular proteomic adaptations induced by light, carbon and inorganic nitrogen in Chlamydomonas reinhardtii

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Stéphanie Gérin

2016-08-01

Full Text Available Microalgae are currently emerging to be very promising organisms for the production of biofuels and high-added value compounds. Understanding the influence of environmental alterations on their metabolism is a crucial issue. Light, carbon and nitrogen availability have been reported to induce important metabolic adaptations. So far, the influence of these variables has essentially been studied while varying only one or two environmental factors at the same time. The goal of the present work was to model the cellular proteomic adaptations of the green microalga Chlamydomonas reinhardtii upon the simultaneous changes of light intensity, carbon concentrations (CO2 and acetate and inorganic nitrogen concentrations (nitrate and ammonium in the culture medium. Statistical design of experiments (DOE enabled to define 32 culture conditions to be tested experimentally. Relative protein abundance was quantified by two dimensional differential in-gel electrophoresis (2D-DIGE. Additional assays for respiration, photosynthesis, and lipid and pigment concentrations were also carried out. A hierarchical clustering survey enabled to partition biological variables (proteins + assays into eight co-regulated clusters. In most cases, the biological variables partitioned in the same cluster had already been reported to participate to common biological functions (acetate assimilation, bioenergetic processes, light harvesting, Calvin cycle and protein metabolism. The environmental regulation within each cluster was further characterized by a series of multivariate methods including principal component analysis and multiple linear regressions. This metadata analysis enabled to highlight the existence of a clear regulatory pattern for every cluster and to mathematically simulate the effects of light, carbon and nitrogen. The influence of these environmental variables on cellular metabolism is described in details and thoroughly discussed. This work provides an overview

Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system

International Nuclear Information System (INIS)

Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P.

2009-01-01

Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45 high CD11b + ) and CD8 + T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8 + T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-γ) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.

Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model

Science.gov (United States)

Limmer, Stefanie; Haller, Samantha; Drenkard, Eliana; Lee, Janice; Yu, Shen; Kocks, Christine; Ausubel, Frederick M.; Ferrandon, Dominique

2011-01-01

An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host–pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated. PMID:21987808

Meta-Analysis of High-Throughput Datasets Reveals Cellular Responses Following Hemorrhagic Fever Virus Infection

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Gavin C. Bowick

2011-05-01

Full Text Available The continuing use of high-throughput assays to investigate cellular responses to infection is providing a large repository of information. Due to the large number of differentially expressed transcripts, often running into the thousands, the majority of these data have not been thoroughly investigated. Advances in techniques for the downstream analysis of high-throughput datasets are providing additional methods for the generation of additional hypotheses for further investigation. The large number of experimental observations, combined with databases that correlate particular genes and proteins with canonical pathways, functions and diseases, allows for the bioinformatic exploration of functional networks that may be implicated in replication or pathogenesis. Herein, we provide an example of how analysis of published high-throughput datasets of cellular responses to hemorrhagic fever virus infection can generate additional functional data. We describe enrichment of genes involved in metabolism, post-translational modification and cardiac damage; potential roles for specific transcription factors and a conserved involvement of a pathway based around cyclooxygenase-2. We believe that these types of analyses can provide virologists with additional hypotheses for continued investigation.

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.

Science.gov (United States)

Litichevskiy, Lev; Peckner, Ryan; Abelin, Jennifer G; Asiedu, Jacob K; Creech, Amanda L; Davis, John F; Davison, Desiree; Dunning, Caitlin M; Egertson, Jarrett D; Egri, Shawn; Gould, Joshua; Ko, Tak; Johnson, Sarah A; Lahr, David L; Lam, Daniel; Liu, Zihan; Lyons, Nicholas J; Lu, Xiaodong; MacLean, Brendan X; Mungenast, Alison E; Officer, Adam; Natoli, Ted E; Papanastasiou, Malvina; Patel, Jinal; Sharma, Vagisha; Toder, Courtney; Tubelli, Andrew A; Young, Jennie Z; Carr, Steven A; Golub, Todd R; Subramanian, Aravind; MacCoss, Michael J; Tsai, Li-Huei; Jaffe, Jacob D

2018-04-25

Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the "connectivity" framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https://clue.io/proteomics. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Location and cellular stages of NK cell development

Science.gov (United States)

Yu, Jianhua; Freud, Aharon G.; Caligiuri, Michael A

2013-01-01

The identification of distinct tissue-specific natural killer (NK) cell populations that apparently mature from local precursor populations has brought new insight into the diversity and developmental regulation of this important lymphoid subset. NK cells provide a necessary link between the early (innate) and late (adaptive) immune responses to infection. Gaining a better understanding of the processes that govern NK cell development should allow us to better harness NK cell functions in multiple clinical settings as well as to gain further insight into how these cells undergo malignant transformation. In this review, we summarize recent advances in understanding sites and cellular stages of NK cell development in humans and mice. PMID:24055329

Toxicity potentials from waste cellular phones, and a waste management policy integrating consumer, corporate, and government responsibilities

International Nuclear Information System (INIS)

Lim, Seong-Rin; Schoenung, Julie M.

2010-01-01

Cellular phones have high environmental impact potentials because of their heavy metal content and current consumer attitudes toward purchasing new phones with higher functionality and neglecting to return waste phones into proper take-back systems. This study evaluates human health and ecological toxicity potentials from waste cellular phones; highlights consumer, corporate, and government responsibilities for effective waste management; and identifies key elements needed for an effective waste management strategy. The toxicity potentials are evaluated by using heavy metal content, respective characterization factors, and a pathway and impact model for heavy metals that considers end-of-life disposal in landfills or by incineration. Cancer potentials derive primarily from Pb and As; non-cancer potentials primarily from Cu and Pb; and ecotoxicity potentials primarily from Cu and Hg. These results are not completely in agreement with previous work in which leachability thresholds were the metric used to establish priority, thereby indicating the need for multiple or revised metrics. The triple bottom line of consumer, corporate, and government responsibilities is emphasized in terms of consumer attitudes, design for environment (DfE), and establishment and implementation of waste management systems including recycling streams, respectively. The key strategic elements for effective waste management include environmental taxation and a deposit-refund system to motivate consumer responsibility, which is linked and integrated with corporate and government responsibilities. The results of this study can contribute to DfE and waste management policy for cellular phones.

Toxicity potentials from waste cellular phones, and a waste management policy integrating consumer, corporate, and government responsibilities.

Science.gov (United States)

Lim, Seong-Rin; Schoenung, Julie M

2010-01-01

Cellular phones have high environmental impact potentials because of their heavy metal content and current consumer attitudes toward purchasing new phones with higher functionality and neglecting to return waste phones into proper take-back systems. This study evaluates human health and ecological toxicity potentials from waste cellular phones; highlights consumer, corporate, and government responsibilities for effective waste management; and identifies key elements needed for an effective waste management strategy. The toxicity potentials are evaluated by using heavy metal content, respective characterization factors, and a pathway and impact model for heavy metals that considers end-of-life disposal in landfills or by incineration. Cancer potentials derive primarily from Pb and As; non-cancer potentials primarily from Cu and Pb; and ecotoxicity potentials primarily from Cu and Hg. These results are not completely in agreement with previous work in which leachability thresholds were the metric used to establish priority, thereby indicating the need for multiple or revised metrics. The triple bottom line of consumer, corporate, and government responsibilities is emphasized in terms of consumer attitudes, design for environment (DfE), and establishment and implementation of waste management systems including recycling streams, respectively. The key strategic elements for effective waste management include environmental taxation and a deposit-refund system to motivate consumer responsibility, which is linked and integrated with corporate and government responsibilities. The results of this study can contribute to DfE and waste management policy for cellular phones. 2010 Elsevier Ltd. All rights reserved.

Proteomic analysis of cellular response induced by boron neutron capture reaction in human squamous cell carcinoma SAS cells

International Nuclear Information System (INIS)

Sato, Akira; Itoh, Tasuku; Imamichi, Shoji; Kikuhara, Sota; Fujimori, Hiroaki; Hirai, Takahisa; Saito, Soichiro; Sakurai, Yoshinori; Tanaka, Hiroki; Nakamura, Hiroyuki; Suzuki, Minoru

2015-01-01

To understand the mechanism of cell death induced by boron neutron capture reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells after BNCR. Cells were irradiated with thermal neutron beam at KUR after incubation under boronophenylalanine (BPA)(+) and BPA(−) conditions. BNCR mainly induced typical apoptosis in SAS cells 24 h post-irradiation. Proteomic analysis in SAS cells suggested that proteins functioning in endoplasmic reticulum, DNA repair, and RNA processing showed dynamic changes at early phase after BNCR and could be involved in the regulation of cellular response to BNCR. We found that the BNCR induces fragments of endoplasmic reticulum-localized lymphoid-restricted protein (LRMP). The fragmentation of LRMP was also observed in the rat tumor graft model 20 hours after BNCT treatment carried out at the National Nuclear Center of the Republic of Kazakhstan. These data suggest that dynamic changes of LRMP could be involved during cellular response to BNCR. - Highlights: • BNCR in human squamous carcinoma cells caused typical apoptotic features. • BNCR induced fragments of LRMP, in human squamous carcinoma and rat tumor model. • The fragmentation of LRMP could be involved in cellular response to BNCR.

Adaptive response to ionising radiation induced by cadmium in zebrafish embryos

International Nuclear Information System (INIS)

Choi, V W Y; Ng, C Y P; Kong, M K Y; Yu, K N; Cheng, S H

2013-01-01

An adaptive response is a biological response where the exposure of cells or animals to a low priming exposure induces mechanisms that protect the cells or animals against the detrimental effects of a subsequent larger challenging exposure. In realistic environmental situations, living organisms can be exposed to a mixture of stressors, and the resultant effects due to such exposures are referred to as multiple stressor effects. In the present work we demonstrated, via quantification of apoptosis in the embryos, that embryos of the zebrafish (Danio rerio) subjected to a priming exposure provided by one environmental stressor (cadmium in micromolar concentrations) could undergo an adaptive response against a subsequent challenging exposure provided by another environmental stressor (alpha particles). We concluded that zebrafish embryos treated with 1 to 10 μM Cd at 5 h postfertilisation (hpf) for both 1 and 5 h could undergo an adaptive response against subsequent ∼4.4 mGy alpha-particle irradiation at 10 hpf, which could be interpreted as an antagonistic multiple stressor effect between Cd and ionising radiation. The zebrafish has become a popular vertebrate model for studying the in vivo response to ionising radiation. As such, our results suggested that multiple stressor effects should be carefully considered for human radiation risk assessment since the risk may be perturbed by another environmental stressor such as a heavy metal. (paper)

Effect and adaptive response of lymphocytes DNA induced by low dose irradiation

International Nuclear Information System (INIS)

Du Zeji; Su Liaoyuan; Tian Hailin

1994-09-01

Fluorometric analysis of DNA unwinding (FADU) was conducted and was proved to be an optimal method for studying DNA strand breaks induced by low dose irradiation. The linear dose response curve was obtained. The minimum detected dose was 0.3 Gy. There was no effect of low dose γ-rays (0.5∼8.0 cGy) on DNA strand breaks of quiescent and mitogen-induced lymphocytes. The 0.5∼4.0 cGy γ-rats could induce adaptive response of lymphocytes' DNA strand breaks, especially, at the doses of 2.0 and 4.0 cGy. The challenge doses of 5∼20 Gy could make the adaptive response appearance, and the 15 Gy was the best one. The 3-AB could powerfully inhibit the adaptive response. The repair of DNA strand breaks (37 degree C, 15∼60 min) caused by 15 Gy γ-rays could be promoted by the low dose γ-ray irradiation (2.0 cGy), but no difference was found at 37 degree C, 120 min

Comparative transcriptome and gene co-expression network analysis reveal genes and signaling pathways adaptively responsive to varied adverse stresses in the insect fungal pathogen, Beauveria bassiana.

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He, Zhangjiang; Zhao, Xin; Lu, Zhuoyue; Wang, Huifang; Liu, Pengfei; Zeng, Fanqin; Zhang, Yongjun

2018-01-01

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. Beauveria bassiana is an economically important insect-pathogenic fungus which is widely used as a biocontrol agent to control a variety of insect pests. The fungal pathogen unavoidably encounters a variety of adverse environmental stresses and defense response from the host insects during application of the fungal agents. However, few are known about the transcription response of the fungus to respond or adapt varied adverse stresses. Here, we comparatively analyzed the transcriptome of B. bassiana in globe genome under the varied stationary-phase stresses including osmotic agent (0.8 M NaCl), high temperature (32 °C), cell wall-perturbing agent (Congo red), and oxidative agents (H 2 O 2 or menadione). Total of 12,412 reads were obtained, and mapped to the 6767 genes of the B. bassiana. All of these stresses caused transcription responses involved in basal metabolism, cell wall construction, stress response or cell rescue/detoxification, signaling transduction and gene transcription regulation, and likely other cellular processes. An array of genes displayed similar transcription patterns in response to at least two of the five stresses, suggesting a shared transcription response to varied adverse stresses. Gene co-expression network analysis revealed that mTOR signaling pathway, but not HOG1 MAP kinase pathway, played a central role in regulation the varied adverse stress responses, which was verified by RNAi-mediated knockdown of TOR1. Our findings provided an insight of transcription response and gene co-expression network of B. bassiana in adaptation to varied environments. Copyright © 2017 Elsevier Inc. All rights reserved.

Global transcriptional, physiological and metabolite analyses of Desulfovibrio vulgaris Hildenborough responses to salt adaptation

Energy Technology Data Exchange (ETDEWEB)

He, Z.; Zhou, A.; Baidoo, E.; He, Q.; Joachimiak, M. P.; Benke, P.; Phan, R.; Mukhopadhyay, A.; Hemme, C.L.; Huang, K.; Alm, E.J.; Fields, M.W.; Wall, J.; Stahl, D.; Hazen, T.C.; Keasling, J.D.; Arkin, A.P.; Zhou, J.

2009-12-01

The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by physiological, global transcriptional, and metabolite analyses. The growth of D. vulgaris was inhibited by high levels of NaCl, and the growth inhibition could be relieved by the addition of exogenous amino acids (e.g., glutamate, alanine, tryptophan) or yeast extract. Salt adaptation induced the expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). Genes involved in carbon metabolism, cell motility, and phage structures were repressed. Comparison of transcriptomic profiles of D. vulgaris responses to salt adaptation with those of salt shock (short-term NaCl exposure) showed some similarity as well as a significant difference. Metabolite assays showed that glutamate and alanine were accumulated under salt adaptation, suggesting that they may be used as osmoprotectants in D. vulgaris. A conceptual model is proposed to link the observed results to currently available knowledge for further understanding the mechanisms of D. vulgaris adaptation to elevated NaCl.

Complexity and network dynamics in physiological adaptation: an integrated view.

Science.gov (United States)

Baffy, György; Loscalzo, Joseph

2014-05-28

Living organisms constantly interact with their surroundings and sustain internal stability against perturbations. This dynamic process follows three fundamental strategies (restore, explore, and abandon) articulated in historical concepts of physiological adaptation such as homeostasis, allostasis, and the general adaptation syndrome. These strategies correspond to elementary forms of behavior (ordered, chaotic, and static) in complex adaptive systems and invite a network-based analysis of the operational characteristics, allowing us to propose an integrated framework of physiological adaptation from a complex network perspective. Applicability of this concept is illustrated by analyzing molecular and cellular mechanisms of adaptation in response to the pervasive challenge of obesity, a chronic condition resulting from sustained nutrient excess that prompts chaotic exploration for system stability associated with tradeoffs and a risk of adverse outcomes such as diabetes, cardiovascular disease, and cancer. Deconstruction of this complexity holds the promise of gaining novel insights into physiological adaptation in health and disease. Published by Elsevier Inc.

The cellular bases of antibody responses during dengue virus infection

Directory of Open Access Journals (Sweden)

Juan Carlos Yam-Puc

2016-06-01

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

Posintro™-HBsAg, a modified ISCOM including HBsAg, induces strong cellular and humoral responses

DEFF Research Database (Denmark)

Schiött, Asa; Larsson, Kristina; Manniche, Søren

2011-01-01

HBsAg vaccine formulation, Posintro™-HBsAg, was compared to two commercial hepatitis B vaccines including aluminium or monophosphoryl lipid A (MPL) and the two adjuvant systems MF59 and QS21 in their efficiency to prime both cellular and humoral immune responses. The Posintro™-HBsAg induced...

Methodological considerations for global analysis of cellular FLIM/FRET measurements

Science.gov (United States)

Adbul Rahim, Nur Aida; Pelet, Serge; Kamm, Roger D.; So, Peter T. C.

2012-02-01

Global algorithms can improve the analysis of fluorescence energy transfer (FRET) measurement based on fluorescence lifetime microscopy. However, global analysis of FRET data is also susceptible to experimental artifacts. This work examines several common artifacts and suggests remedial experimental protocols. Specifically, we examined the accuracy of different methods for instrument response extraction and propose an adaptive method based on the mean lifetime of fluorescent proteins. We further examined the effects of image segmentation and a priori constraints on the accuracy of lifetime extraction. Methods to test the applicability of global analysis on cellular data are proposed and demonstrated. The accuracy of global fitting degrades with lower photon count. By systematically tracking the effect of the minimum photon count on lifetime and FRET prefactors when carrying out global analysis, we demonstrate a correction procedure to recover the correct FRET parameters, allowing us to obtain protein interaction information even in dim cellular regions with photon counts as low as 100 per decay curve.

Reconstitution of the cellular response to DNA damage in vitro using damage-activated extracts from mammalian cells

International Nuclear Information System (INIS)

Roper, Katherine; Coverley, Dawn

2012-01-01

In proliferating mammalian cells, DNA damage is detected by sensors that elicit a cellular response which arrests the cell cycle and repairs the damage. As part of the DNA damage response, DNA replication is inhibited and, within seconds, histone H2AX is phosphorylated. Here we describe a cell-free system that reconstitutes the cellular response to DNA double strand breaks using damage-activated cell extracts and naïve nuclei. Using this system the effect of damage signalling on nuclei that do not contain DNA lesions can be studied, thereby uncoupling signalling and repair. Soluble extracts from G1/S phase cells that were treated with etoposide before isolation, or pre-incubated with nuclei from etoposide-treated cells during an in vitro activation reaction, restrain both initiation and elongation of DNA replication in naïve nuclei. At the same time, H2AX is phosphorylated in naïve nuclei in a manner that is dependent upon the phosphatidylinositol 3-kinase-like protein kinases. Notably, phosphorylated H2AX is not focal in naïve nuclei, but is evident throughout the nucleus suggesting that in the absence of DNA lesions the signal is not amplified such that discrete foci can be detected. This system offers a novel screening approach for inhibitors of DNA damage response kinases, which we demonstrate using the inhibitors wortmannin and LY294002. -- Highlights: ► A cell free system that reconstitutes the response to DNA damage in the absence of DNA lesions. ► Damage-activated extracts impose the cellular response to DNA damage on naïve nuclei. ► PIKK-dependent response impacts positively and negatively on two separate fluorescent outputs. ► Can be used to screen for inhibitors that impact on the response to damage but not on DNA repair. ► LY294002 and wortmannin demonstrate the system's potential as a pathway focused screening approach.

Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells.

Science.gov (United States)

Wang, Yiping; Cheng, Xiangdong; Samma, Muhammad Kaleem; Kung, Sam K P; Lee, Clement M; Chiu, Sung Kay

2018-06-01

c-Myc is a highly pleiotropic transcription factor known to control cell cycle progression, apoptosis, and cellular transformation. Normally, ectopic expression of c-Myc is associated with promoting cell proliferation or triggering cell death via activating p53. However, it is not clear how the levels of c-Myc lead to different cellular responses. Here, we generated a series of stable RPE cell clones expressing c-Myc at different levels, and found that consistent low level of c-Myc induced cellular senescence by activating AP4 in post-confluent RPE cells, while the cells underwent cell death at high level of c-Myc. In addition, high level of c-Myc could override the effect of AP4 on cellular senescence. Further knockdown of AP4 abrogated senescence-like phenotype in cells expressing low level of c-Myc, and accelerated cell death in cells with medium level of c-Myc, indicating that AP4 was required for cellular senescence induced by low level of c-Myc.

Adaptability: Conceptual and Empirical Perspectives on Responses to Change, Novelty and Uncertainty

Science.gov (United States)

Martin, Andrew J.; Nejad, Harry; Colmar, Susan; Liem, Gregory Arief D.

2012-01-01

Adaptability is proposed as individuals' capacity to constructively regulate psycho-behavioral functions in response to new, changing, and/or uncertain circumstances, conditions and situations. The present investigation explored the internal and external validity of an hypothesised adaptability scale. The sample comprised 2,731 high school…

Topology optimization of adaptive fluid-actuated cellular structures with arbitrary polygonal motor cells

International Nuclear Information System (INIS)

Lv, Jun; Tang, Liang; Li, Wenbo; Liu, Lei; Zhang, Hongwu

2016-01-01

This paper mainly focuses on the fast and efficient design method for plant bioinspired fluidic cellular materials and structures composed of polygonal motor cells. Here we developed a novel structural optimization method with arbitrary polygonal coarse-grid elements based on multiscale finite element frameworks. The fluidic cellular structures are meshed with irregular polygonal coarse-grid elements according to their natural size and the shape of the imbedded motor cells. The multiscale base functions of solid displacement and hydraulic pressure are then constructed to bring the small-scale information of the irregular motor cells to the large-scale simulations on the polygonal coarse-grid elements. On this basis, a new topology optimization method based on the resulting polygonal coarse-grid elements is proposed to determine the optimal distributions or number of motor cells in the smart cellular structures. Three types of optimization problems are solved according to the usages of the fluidic cellular structures. Firstly, the proposed optimization method is utilized to minimize the system compliance of the load-bearing fluidic cellular structures. Second, the method is further extended to design biomimetic compliant actuators of the fluidic cellular materials due to the fact that non-uniform volume expansions of fluid in the cells can induce elastic action. Third, the optimization problem focuses on the weight minimization of the cellular structure under the constraints for the compliance of the whole system. Several representative examples are investigated to validate the effectiveness of the proposed polygon-based topology optimization method of the smart materials. (paper)

Health and Cellular Impacts of Air Pollutants: From Cytoprotection to Cytotoxicity

Directory of Open Access Journals (Sweden)

Karine Andreau

2012-01-01

Full Text Available Air pollution as one of the ravages of our modern societies is primarily linked to urban centers, industrial activities, or road traffic. These atmospheric pollutants have been incriminated in deleterious health effects by numerous epidemiological and in vitro studies. Environmental air pollutants are a heterogeneous mixture of particles suspended into a liquid and gaseous phase which trigger the disruption of redox homeostasis—known under the term of cellular oxidative stress—in relation with the establishment of inflammation and cell death via necrosis, apoptosis, or autophagy. Activation or repression of the apoptotic process as an adaptative response to xenobiotics might lead to either acute or chronic toxicity. The purpose of this paper is to highlight the central role of oxidative stress induced by air pollutants and to focus on the subsequent cellular impacts ranging from cytoprotection to cytotoxicity by decreasing or stimulating apoptosis, respectively.

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure.

Science.gov (United States)

Lacourt, Tamara E; Vichaya, Elisabeth G; Chiu, Gabriel S; Dantzer, Robert; Heijnen, Cobi J

2018-01-01

Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation. In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy. In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure. In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well. There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue.

Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission Rates

Directory of Open Access Journals (Sweden)

María Julia Ruiz

2017-12-01

Full Text Available As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC activity were assessed in nine HIV-exposed seronegative individuals (ESN and their corresponding HIV seropositive partners (HIV+-P, in eighteen chronically infected HIV subjects (C, nine chronically infected subjects known to be HIV transmitters (CT and ten healthy HIV− donors (HD. Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV+-P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4+ T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV+-P. Additionally, evidence of IgA interference with ADCC responses from HIV+-P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection.

Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

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

2015-01-01

Outside the protection of the geomagnetic field, astronauts and other living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, have effects on cellular responses to DNA damage induced by exposure to radiation or cytotoxic chemicals is still unknown, as is their impact on the radiation risks for astronauts and on the mutation rate in microorganisms. Although possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on cellular responses to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB) similar to the ionizing radiation. Damages in the DNA were measured by the phosphorylation of a histone protein H2AX (g-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ki-67 signals. Our results suggested that the difference in g-H2AX focus counts between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect initial transcriptional responses of the DNA damage response genes to

Necroptotic signaling in adaptive and innate immunity.

Science.gov (United States)

Lu, Jennifer V; Chen, Helen C; Walsh, Craig M

2014-11-01

The vertebrate immune system is highly dependent on cell death for efficient responsiveness to microbial pathogens and oncogenically transformed cells. Cell death pathways are vital to the function of many immune cell types during innate, humoral and cellular immune responses. In addition, cell death regulation is imperative for proper adaptive immune self-tolerance and homeostasis. While apoptosis has been found to be involved in several of these roles in immunity, recent data demonstrate that alternative cell death pathways are required. Here, we describe the involvement of a programmed form of cellular necrosis called "necroptosis" in immunity. We consider the signaling pathways that promote necroptosis downstream of death receptors, type I transmembrane proteins of the tumor necrosis factor (TNF) receptor family. The involvement of necroptotic signaling through a "RIPoptosome" assembled in response to innate immune stimuli or genotoxic stress is described. We also characterize the induction of necroptosis following antigenic stimulation in T cells lacking caspase-8 or FADD function. While necroptotic signaling remains poorly understood, it is clear that this pathway is an essential component to effective vertebrate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain-wide neuronal dynamics during motor adaptation in zebrafish.

Science.gov (United States)

Ahrens, Misha B; Li, Jennifer M; Orger, Michael B; Robson, Drew N; Schier, Alexander F; Engert, Florian; Portugues, Ruben

2012-05-09

A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.

Bystander effects, adaptive response and genomic instability induced by prenatal irradiation

Energy Technology Data Exchange (ETDEWEB)

Streffer, Christian [Institute for Science and Ethics, University Duisburg-Essen, Auf dem Sutan 12, D-45239 Essen (Germany)]. E-mail: streffer.essen@t-online.de

2004-12-02

The developing human embryo and fetus undergo very radiosensitive stages during the prenatal development. It is likely that the induction of low dose related effects such as bystander effects, the adaptive response, and genomic instability would have profound effects on embryonic and fetal development. In this paper, I review what has been reported on the induction of these three phenomena in exposed embryos and fetuses. All three phenomena have been shown to occur in murine embryonic or fetal cells and structures, although the induction of an adaptive response (and also likely the induction of bystander effects) are limited in terms of when during development they can be induced and the dose or dose-rate used to treat animals in utero. In contrast, genomic instability can be induced throughout development, and the effects of radiation exposure on genome instability can be observed for long times after irradiation including through pre- and postnatal development and into the next generation of mice. There are clearly strain-specific differences in the induction of these phenomena and all three can lead to long-term detrimental effects. This is true for the adaptive response as well. While induction of an adaptive response can make fetuses more resistant to some gross developmental defects induced by a subsequent high dose challenge with ionizing radiation, the long-term effects of this low dose exposure are detrimental. The negative effects of all three phenomena reflect the complexity of fetal development, a process where even small changes in the timing of gene expression or suppression can have dramatic effects on the pattern of biological events and the subsequent development of the mammalian organism.

Mitochondrial correlates of signaling processes involved with the cellular response to eimeria infection in broiler chickens

Science.gov (United States)

Host cellular responses to coccidiosis infection are consistent with elements of apoptosis, autophagy, and necrosis. These processes are enhanced in the cell through cell-directed signaling or repressed through parasite-derived inhibitors of these processes favoring the survival of the parasite. Acr...

Unraveling the cellular response to oxidative stress in the endoplasmic reticulum

DEFF Research Database (Denmark)

Hansen, Henning Gram

, disulfide bonds are predominantly generated by the two isoforms of the ER oxidoreductin-1 (Ero1) family: Ero1α and Ero1β. Both enzymes oxidize the active-site cysteines in protein disulfide isomerases (PDIs), which in turn introduce disulfide bonds into newly synthesized proteins. Ero1 is re......-oxidized by molecular oxygen and this step generates hydrogen peroxide: a reactive oxygen species. Intramolecular disulfide bonds tightly regulate the oxidase activity of Ero1α. Whereas the regulatory mechanisms that regulate Ero1α activity are well understood, the overall cellular response to oxidative stress....... Interestingly, depletion of GPx8 in cells induced expression of an antioxidant response marker only in the presence of Ero1. These findings imply that GPx8 is an important scavenger of Ero1-generated hydrogen peroxide, and thus provides a critical function in negotiating oxidative stress originating from...

Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae

Science.gov (United States)

López, Javier Hernández; Krainer, Sophie; Engert, Antonia; Schuehly, Wolfgang; Riessberger-Gallé, Ulrike; Crailsheim, Karl

2017-02-01

Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.

Adaptive response of yeast cultures (Saccharomyces Cerevisiae) exposed to low dose of gamma radiation

International Nuclear Information System (INIS)

Kulcsar, Agnes; Savu, D.; Petcu, I.; Gherasim, Raluca

2003-01-01

The present study was planned as follows: (i) setting up of standard experimental conditions for investigation of radio-induced adaptive response in lower Eucaryotes; (ii) developing of procedures for synchronizing Saccharomyces cerevisiae X 310 D cell cultures and cell cycle stages monitoring; (iii) investigation of gamma (Co-60) and UV irradiation effects on the viability of synchronized and non-synchronized cell cultures of Saccharomyces cerevisiae; the effects were correlated with the cell density and cell cycle stage; (iv) study of the adaptive response induced by irradiation and setting up of the experimental conditions for which this response is optimized. The irradiations were performed by using a Co-60 with doses of 10 2 - 10 4 Gy and dose rates ranging from 2.2 x 10 2 Gy/h to 8.7 x 10 3 Gy/h. The study of radioinduced adaptive response was performed by applying a pre-irradiation treatment of 100-500 Gy, followed by challenge doses of 2-4 kGy delivered at different time intervals, ranging from 1 h to 4 h. The survival rate of synchronized and non-synchronized cultures as a function of exposure dose shows an exponential decay shape. No difference in viability of the cells occurred between synchronized and non-synchronized cultures. The pre-irradiation of cells with 100 and 200 Gy were most efficient to induce an adaptive response for the yeast cells. In this stage of work we proved the occurrence of the adaptive response in the case of synchronized yeast cultures exposed to gamma radiation. The results will be used in the future to investigate the dependence of this response on the cell cycle and the possibility to induce such a response by a low level electromagnetic field. (authors)

Adaptive response and split-dose effect of radiation on the survival ...

Indian Academy of Sciences (India)

Unknown

In the present work, we report radioadaptive response in terms of survival of ... Group 4: mice pre-treated with conditioning dose of 0⋅5 Gy ... week in mice exposed to 8 Gy. For mice .... The adaptive response is known to remain for a few hours.

Adaptive responses to salinity stress across multiple life stages in anuran amphibians.

Science.gov (United States)

Albecker, Molly A; McCoy, Michael W

2017-01-01

In many regions, freshwater wetlands are increasing in salinity at rates exceeding historic levels. Some freshwater organisms, like amphibians, may be able to adapt and persist in salt-contaminated wetlands by developing salt tolerance. Yet adaptive responses may be more challenging for organisms with complex life histories, because the same environmental stressor can require responses across different ontogenetic stages. Here we investigated responses to salinity in anuran amphibians: a common, freshwater taxon with a complex life cycle. We conducted a meta-analysis to define how the lethality of saltwater exposure changes across multiple life stages, surveyed wetlands in a coastal region experiencing progressive salinization for the presence of anurans, and used common garden experiments to investigate whether chronic salt exposure alters responses in three sequential life stages (reproductive, egg, and tadpole life stages) in Hyla cinerea , a species repeatedly observed in saline wetlands. Meta-analysis revealed differential vulnerability to salt stress across life stages with the egg stage as the most salt-sensitive. Field surveys revealed that 25% of the species known to occur in the focal region were detected in salt-intruded habitats. Remarkably, Hyla cinerea was found in large abundances in multiple wetlands with salinity concentrations 450% higher than the tadpole-stage LC 50 . Common garden experiments showed that coastal (chronically salt exposed) populations of H. cinerea lay more eggs, have higher hatching success, and greater tadpole survival in higher salinities compared to inland (salt naïve) populations. Collectively, our data suggest that some species of anuran amphibians have divergent and adaptive responses to salt exposure across populations and across different life stages. We propose that anuran amphibians may be a novel and amenable natural model system for empirical explorations of adaptive responses to environmental change.

Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-gamma and IgG3 Responses Compared with Children

DEFF Research Database (Denmark)

Mortensen, Rasmus; Nissen, Thomas Norrelykke; Blauenfeldt, Thomas

2015-01-01

Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first det...... cellular memory response in combination with IgG1/IgG3-dominated humoral immunity that increase with age. The significance of these data regarding both the increased GAS infection rate in children and the development of protective GAS vaccines is discussed.......Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first...... detailed characterization of the human adaptive immune response against S. pyogenes in both children and adults. We report that all adults in our study, as well as most children, showed immunity against the two conserved group A streptococci (GAS) Ags, streptococcal C5a peptidase and immunogenic secreted...

Application of Digital Cellular Radio for Mobile Location Estimation

Directory of Open Access Journals (Sweden)

Farhat Anwar

2012-08-01

Full Text Available The capability to locate the position of mobiles is a prerequisite to implement a wide range of evolving ITS services. Radiolocation has the potential to serve a wide geographical area. This paper reports an investigation regarding the feasibility of utilizing cellular radio for the purpose of mobile location estimation. Basic strategies to be utilized for location estimation are elaborated. Two possible approaches for cellular based location estimation are investigated with the help of computer simulation. Their effectiveness and relative merits and demerits are identified. An algorithm specifically adapted for cellular environment is reported with specific features where mobiles, irrespective of their numbers, can locate their position without adversely loading the cellular system.Key Words: ITS, GSM, Cellular Radio, DRGS, GPS.

Adaptive Subframe Partitioning and Efficient Packet Scheduling in OFDMA Cellular System with Fixed Decode-and-Forward Relays

Science.gov (United States)

Wang, Liping; Ji, Yusheng; Liu, Fuqiang

The integration of multihop relays with orthogonal frequency-division multiple access (OFDMA) cellular infrastructures can meet the growing demands for better coverage and higher throughput. Resource allocation in the OFDMA two-hop relay system is more complex than that in the conventional single-hop OFDMA system. With time division between transmissions from the base station (BS) and those from relay stations (RSs), fixed partitioning of the BS subframe and RS subframes can not adapt to various traffic demands. Moreover, single-hop scheduling algorithms can not be used directly in the two-hop system. Therefore, we propose a semi-distributed algorithm called ASP to adjust the length of every subframe adaptively, and suggest two ways to extend single-hop scheduling algorithms into multihop scenarios: link-based and end-to-end approaches. Simulation results indicate that the ASP algorithm increases system utilization and fairness. The max carrier-to-interference ratio (Max C/I) and proportional fairness (PF) scheduling algorithms extended using the end-to-end approach obtain higher throughput than those using the link-based approach, but at the expense of more overhead for information exchange between the BS and RSs. The resource allocation scheme using ASP and end-to-end PF scheduling achieves a tradeoff between system throughput maximization and fairness.

Transcriptome and Cell Physiological Analyses in Different Rice Cultivars Provide New Insights Into Adaptive and Salinity Stress Responses

Directory of Open Access Journals (Sweden)

Elide Formentin

2018-03-01

Full Text Available Salinity tolerance has been extensively investigated in recent years due to its agricultural importance. Several features, such as the regulation of ionic transporters and metabolic adjustments, have been identified as salt tolerance hallmarks. Nevertheless, due to the complexity of the trait, the results achieved to date have met with limited success in improving the salt tolerance of rice plants when tested in the field, thus suggesting that a better understanding of the tolerance mechanisms is still required. In this work, differences between two varieties of rice with contrasting salt sensitivities were revealed by the imaging of photosynthetic parameters, ion content analysis and a transcriptomic approach. The transcriptomic analysis conducted on tolerant plants supported the setting up of an adaptive program consisting of sodium distribution preferentially limited to the roots and older leaves, and in the activation of regulatory mechanisms of photosynthesis in the new leaves. As a result, plants resumed grow even under prolonged saline stress. In contrast, in the sensitive variety, RNA-seq analysis revealed a misleading response, ending in senescence and cell death. The physiological response at the cellular level was investigated by measuring the intracellular profile of H2O2 in the roots, using a fluorescent probe. In the roots of tolerant plants, a quick response was observed with an increase in H2O2 production within 5 min after salt treatment. The expression analysis of some of the genes involved in perception, signal transduction and salt stress response confirmed their early induction in the roots of tolerant plants compared to sensitive ones. By inhibiting the synthesis of apoplastic H2O2, a reduction in the expression of these genes was detected. Our results indicate that quick H2O2 signaling in the roots is part of a coordinated response that leads to adaptation instead of senescence in salt-treated rice plants.

Training induced adaptation in horse skeletal muscle

NARCIS (Netherlands)

Dam, K.G. van

2006-01-01

It appears that the physiological and biochemical adaptation of skeletal muscle to training in equine species shows a lot of similarities with human and rodent physiological adaptation. On the other hand it is becoming increasingly clear that intra-cellular mechanisms of adaptation (substrate

Humoral and cellular immune responses to synthetic peptides of the Leishmania donovani kinetoplastid membrane protein-11

DEFF Research Database (Denmark)

Jensen, A T; Gasim, S; Ismail, A

1998-01-01

as solid-phase ligands in enzyme-linked immunosorbent assays (ELISAs) and as stimulating antigens in lymphoproliferative assays in order to evaluate humoral and cellular immune responses to well-defined sequences of the protein. Antibody reactivity against the three peptides was measured in plasma from 63...

Data Portal for the Library of Integrated Network-based Cellular Signatures (LINCS) program: integrated access to diverse large-scale cellular perturbation response data

Science.gov (United States)

Koleti, Amar; Terryn, Raymond; Stathias, Vasileios; Chung, Caty; Cooper, Daniel J; Turner, John P; Vidović, Dušica; Forlin, Michele; Kelley, Tanya T; D’Urso, Alessandro; Allen, Bryce K; Torre, Denis; Jagodnik, Kathleen M; Wang, Lily; Jenkins, Sherry L; Mader, Christopher; Niu, Wen; Fazel, Mehdi; Mahi, Naim; Pilarczyk, Marcin; Clark, Nicholas; Shamsaei, Behrouz; Meller, Jarek; Vasiliauskas, Juozas; Reichard, John; Medvedovic, Mario; Ma’ayan, Avi; Pillai, Ajay

2018-01-01

Abstract The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level. In contrast to other large-scale data generation efforts, LINCS Data and Signature Generation Centers (DSGCs) employ a wide range of assay technologies cataloging diverse cellular responses. Integration of, and unified access to LINCS data has therefore been particularly challenging. The Big Data to Knowledge (BD2K) LINCS Data Coordination and Integration Center (DCIC) has developed data standards specifications, data processing pipelines, and a suite of end-user software tools to integrate and annotate LINCS-generated data, to make LINCS signatures searchable and usable for different types of users. Here, we describe the LINCS Data Portal (LDP) (http://lincsportal.ccs.miami.edu/), a unified web interface to access datasets generated by the LINCS DSGCs, and its underlying database, LINCS Data Registry (LDR). LINCS data served on the LDP contains extensive metadata and curated annotations. We highlight the features of the LDP user interface that is designed to enable search, browsing, exploration, download and analysis of LINCS data and related curated content. PMID:29140462

Cellular modeling of fault-tolerant multicomputers

Energy Technology Data Exchange (ETDEWEB)

Morgan, G

1987-01-01

Work described was concerned with a novel method for investigation of fault tolerance in large regular networks of computers. Motivation was to provide a technique useful in rapid evaluation of highly reliable systems that exploit the low cost and ease of volume production of simple microcomputer components. First, a system model and simulator based upon cellular automata are developed. This model is characterized by its simplicity and ease of modification when adapting to new types of network. Second, in order to test and verify the predictive capabilities of the cellular system, a more-detailed simulation is performed based upon an existing computational model, that of the Transputer. An example application is used to exercise various systems designed using the cellular model. Using this simulator, experimental results are obtained both for existing well-understood configurations and for more novel types also developed here. In all cases it was found that the cellular model and simulator successfully predicted the ranking in reliability improvement of the systems studied.

Coupling mechanisms between nucleosome assembly and the cellular response to DNA damage

International Nuclear Information System (INIS)

Lautrette, Aurelie

2006-01-01

Cells are continuously exposed to genotoxic stresses that induce a variety of DNA lesions. To protect their genome, cells have specific pathways that orchestrate the detection, signaling and repair of DNA damages. This work is dedicated to the characterization of such pathways that couple the DNA damage response to the assembly of chromatin, a complex that protects and regulates DNA accessibility. We have focused our study on two multifunctional proteins: Rad53, a central checkpoint kinase in the cellular response to DNA damage and Asf1, a histone chaperone involved in chromatin assembly. We have characterized in vitro the binding mode of Asf1 with Rad53 and Asfl with histones. This study is associated with the functional analysis of the role of these interactions in vivo in yeast cells. (author) [fr

A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

International Nuclear Information System (INIS)

Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude.

Science.gov (United States)

Mariggiò, Maria A; Falone, Stefano; Morabito, Caterina; Guarnieri, Simone; Mirabilio, Alessandro; Pilla, Raffaele; Bucciarelli, Tonino; Verratti, Vittore; Amicarelli, Fernanda

2010-01-01

Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.

A quantitative formulation of the dynamic behaviour of adaptation processes to ionizing radiation

International Nuclear Information System (INIS)

Pfandler, S.

1999-12-01

The discovery of adaptation processes in cells (i.e., increased resistance to effects of a challenge dose administered after a lower adapting dose) has fuelled the debate on possible cellular processes relevant for low dose exposures. However, numerous experiments on radioadaptive response do not provide a clear picture of the nature of adaptive response and the conditions under which it occurs. This work proposes a model that succeeds in modelling data obtained from various experiments on radioadaptation. The model assumes impaired DNA integrity as triggering signal for induction of adaptation. Induction of adaptive response is seen as two-phase process. First, ionizing radiation induces radicals by water radiolysis which give rise to specific DNA lesions. On the other hand, these lesions must be perceived and, in a way, processed by the cell, thereby creating the final signal necessary for the comprehensive adaptive response. This processing occurs through some event in S-phase and can be halted by local conformational changes of chromatin induced by ionizing radiation. Thus, the model assumes two counteracting processes that have to be balanced for the triggering signal of adaptation to occur, each of them related to different target volumes. This work comprises mathematical treatment of radical formation, DNA lesion induction and inhibition of local initiation of replication which finally provides functions that quantify the reduction of double strand breaks introduced by challenge doses in adapted cells as compared to non-adapted cells. Non-linear regression analyses based upon data from experiments on radioadaptation yield regression curves which describe existing data satisfactorily. Thus, it corroborates the existence of adaptive response as, in principle, universal feature of cells and specifies conditions which favor development of radioadaptation. (author)

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

Directory of Open Access Journals (Sweden)

Maryam Yazdanian

2015-01-01

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

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

Science.gov (United States)

Hyldahl, Robert D; Hubal, Monica J

2014-02-01

The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders. Copyright © 2013 Wiley Periodicals, Inc.

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

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Marko eUutela

2014-05-01

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

Development and Standardization of the Diagnostic Adaptive Behavior Scale: Application of Item Response Theory to the Assessment of Adaptive Behavior

Science.gov (United States)

Tassé, Marc J.; Schalock, Robert L.; Thissen, David; Balboni, Giulia; Bersani, Henry, Jr.; Borthwick-Duffy, Sharon A.; Spreat, Scott; Widaman, Keith F.; Zhang, Dalun; Navas, Patricia

2016-01-01

The Diagnostic Adaptive Behavior Scale (DABS) was developed using item response theory (IRT) methods and was constructed to provide the most precise and valid adaptive behavior information at or near the cutoff point of making a decision regarding a diagnosis of intellectual disability. The DABS initial item pool consisted of 260 items. Using IRT…

Cross-adaptation between olfactory responses induced by two subgroups of odorant molecules.

Science.gov (United States)

Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

2003-09-01

It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at -54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 +/- 7 mV (mean +/- SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

Transient expression of protein tyrosine phosphatases encoded in Cotesia plutellae bracovirus inhibits insect cellular immune responses

Science.gov (United States)

Ibrahim, Ahmed M. A.; Kim, Yonggyun

2008-01-01

Several immunosuppressive factors are associated with parasitism of an endoparasitoid wasp, Cotesia plutellae, on the diamondback moth, Plutella xylostella. C. plutellae bracovirus (CpBV) encodes a large number of putative protein tyrosine phosphatases (PTPs), which may play a role in inhibiting host cellular immunity. To address this inhibitory hypothesis of CpBV-PTPs, we performed transient expression of individual CpBV-PTPs in hemocytes of the beet armyworm, Spodoptera exigua, and analyzed their cellular immune responses. Two different forms of CpBV-PTPs were chosen and cloned into a eukaryotic expression vector under the control of the p10 promoter of baculovirus: one with the normal cysteine active site (CpBV-PTP1) and the other with a mutated active site (CpBV-PTP5). The hemocytes transfected with CpBV-PTP1 significantly increased in PTP activity compared to control hemocytes, but those with CpBV-PTP5 exhibited a significant decrease in the PTP activity. All transfected hemocytes exhibited a significant reduction in both cell spreading and encapsulation activities compared to control hemocytes. Co-transfection of CpBV-PTP1 together with its double-stranded RNA reduced the messenger RNA (mRNA) level of CpBV-PTP1 and resulted in recovery of both hemocyte behaviors. This is the first report demonstrating that the polydnaviral PTPs can manipulate PTP activity of the hemocytes to interrupt cellular immune responses.

Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes

Science.gov (United States)

Marchitti, Satori A.; Chen, Ying; Thompson, David C.; Vasiliou, Vasilis

2011-01-01

Solar ultraviolet radiation (UVR) exposes the human eye to near constant oxidative stress. Evidence suggests that UVR is the most important environmental insult leading to the development of a variety of ophthalmoheliosis disorders. UVR-induced reactive oxygen species are highly reactive with DNA, proteins and cellular membranes, resulting in cellular and tissue damage. Antioxidant defense systems present in ocular tissues function to combat reactive oxygen species and protect the eye from oxidative damage. Important enzymatic antioxidants are the superoxide dismutases, catalase, glutathione peroxidases, glutathione reductase and members of the aldehyde dehydrogenase (ALDH) superfamily. Glutathione, ascorbic and uric acids, α-tocopherol, NADPH and ferritin serve as small molecule, nonenzymatic antioxidants. Ocular tissues have high levels of these antioxidants which are essential for the maintenance of redox homeostasis in the eye and protection against oxidative damage. ALDH1A1 and ALDH3A1, present abundantly in the cornea and lens, have been shown to have unique roles in the defense against UVR and the downstream effects of oxidative stress. This review presents the properties and functions of ocular antioxidants that play critical roles in the cellular response to UVR exposure, including a focused discussion of the unique roles that the ALDH1A1 and ALDH3A1 enzymes have as multi-functional ocular antioxidants. PMID:21670692

Stress Responses in Staphylococcus aureus

DEFF Research Database (Denmark)

Frees, Dorte; Ingmer, Hanne

2016-01-01

stress responses allowing it to sense and adapt to its very different niches. The stress responses often involve dramatic cellular reprogramming, and the technological advances provided by the access to whole genome sequences have let to an unprecedented insight into the global reorganization of gene...... and protein expression following stress-exposure. Characterization of global gene responses has been very helpful both in identifying regulators sensing specific environmental stress signals and overlaps between different stress responses. In this chapter we review the recent progress in our understanding...... of the specific and general S. aureusstress responses, with a special emphasis on how stress responses contribute to virulence and antibiotic resistance in this important human pathogen....

47 CFR 22.901 - Cellular service requirements and limitations.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular service requirements and limitations... SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements and limitations. The licensee of each cellular system is responsible for ensuring that its cellular system...

Humoral and Cellular Response of Pheasants Vaccinated against Newcastle Disease and Haemorrhagic Enteritis

Directory of Open Access Journals (Sweden)

S. Graczyk

2006-01-01

Full Text Available The purpose of the experiment was to define whether and to what extent can prophylactic vaccinations against Newcastle disease (ND and haemorrhagic enteritis (HE affect the humoral and cellular response in pheasants. The evaluation of humoral response was performed on a basis of agglutinin titre after administered antigen and the cellular immunity index was the delayed type hypersensitivity (DTH reaction. The pheasants were prophylactically vaccinated against Newcastle Disease (ND on the 1st, 28th and 56th day of life. Moreover, on the 49th day of life, part of the birds was given in the drinking water a vaccine containing the HEV (Haemorrhagic Enteritis Virus. Fourteen days after the HEV vaccination, the birds were intravenously given 0.5 ml of the 10% SRBC (sheep red blood cells suspension. Simultaneously with the SRBC administration the delayed hypersensitivity test was performed by intradermal administration of phytohaemagglutinin (PHA. It was shown that in pheasants vaccinated with NDV and additionally with HEV, the specific agglutinin anti-SRBC titre was significantly (p < 0.05 lower than in birds vaccinated against ND only. It also appeared that, the antibodies resistant to 2-mercaptoethanol were 43% of the total pool of specific anti-SRBC antibodies in the NDV vaccinated birds, whereas in birds vaccinated also with HEV they were 75%. No significant differences were found in the DTH test. Only in the HEV vaccinated pheasants the tendency to increase the wing index value was noted. The results confirm the observations concerning immunosuppressive effects of simultaneous vaccinations. They also indicate that overloading the pheasants with many antigens (ND and HEV vaccination may weaken the humoral response to administered SRBC.

An adaptive two-stage dose-response design method for establishing proof of concept.

Science.gov (United States)

Franchetti, Yoko; Anderson, Stewart J; Sampson, Allan R

2013-01-01

We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish "global" PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.

Innate, adaptive and regulatory responses in schistosomiasis: Relationship to allergy

NARCIS (Netherlands)

Hartgers, F.C.; Smits, H.H.; Kleij, D. van der; Yazdanbakhsh, M.

2006-01-01

Helminth infections have profound effects on the immune system. Here, recent insights in the molecular interactions between schistosomes and the host are described with respect to adaptive but also with respect to innate immune responses. Furthermore, the different mechanisms of immune

Ethanol cellular defense induce unfolded protein response in yeast

Directory of Open Access Journals (Sweden)

Elisabet eNavarro-Tapia

2016-02-01

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

Antioxidant responses of cortex neurons to iron loading

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PABLA AGUIRRE

2006-01-01

Full Text Available Brain cells have a highly active oxidative metabolism, yet they contain only low to moderate superoxide dismutase and catalase activities. Thus, their antioxidant defenses rely mainly on cellular reduced glutathione levels. In this work, in cortical neurons we characterized viability and changes in reduced and oxidized glutathione levels in response to a protocol of iron accumulation. We found that massive death occurred after 2 days in culture with 10 mM Fe. Surviving cells developed an adaptative response that included increased synthesis of GSH and the maintenance of a glutathione-based reduction potential. These results highlight the fundamental role of glutathione homeostasis in the antioxidant response and provide novel insights into the adaptative mechanisms of neurons subjected to progressive iron loads.

Detection of plant adaptation responses to saline environment in rhizosphere using microwave sensing

International Nuclear Information System (INIS)

Shimomachi, T.; Kobashikawa, C.; Tanigawa, H.; Omoda, E.

2008-01-01

The physiological adaptation responses in plants to environmental stress, such as water stress and salt stress induce changes in physicochemical conditions of the plant, since formation of osmotic-regulatory substances can be formed during the environmental adaptation responses. Strong electrolytes, amino acids, proteins and saccharides are well-known as osmoregulatory substances. Since these substances are ionic conductors and their molecules are electrically dipolar, it can be considered that these substances cause changes in the dielectric properties of the plant, which can be detected by microwave sensing. The dielectric properties (0.3 to 3GHz), water content and water potential of plant leaves which reflect the physiological condition of the plant under salt stress were measured and analyzed. Experimental results showed the potential of the microwave sensing as a method for monitoring adaptation responses in plants under saline environment and that suggested the saline environment in rhizosphere can be detected noninvasively and quantitatively by the microwave sensing which detects the changes in complex dielectric properties of the plant

Epigenetics and Cellular Metabolism

OpenAIRE

Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

2016-01-01

Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

Adaptation response surfaces for managing wheat under perturbed climate and CO2 in a Mediterranean environment

DEFF Research Database (Denmark)

Ruiz-Ramos, M.; Ferrise, Roberto; Rodríguez, A

2018-01-01

type were analysed by constructing response surfaces, which we termed, in accordance with their specific purpose, adaptation response surfaces (ARSs). These were created to assess the effect of adaptations through a range of plausible P, T and [CO2] perturbations. The results indicated that impacts....... However, a single sI was sufficient to develop a high adaptation potential, including options mainly based on spring wheat, current cycle duration and early sowing date. Depending on local environment (e.g. soil type), many of these adaptations can maintain current yield levels under moderate changes in T...

Design and conduct of Caudwell Xtreme Everest: an observational cohort study of variation in human adaptation to progressive environmental hypoxia

NARCIS (Netherlands)

Levett, Denny Z. H.; Martin, Daniel S.; Wilson, Mark H.; Mitchell, Kay; Dhillon, Sundeep; Rigat, Fabio; Montgomery, Hugh E.; Mythen, Monty G.; Grocott, Michael P. W.; Ahuja, V.; Aref-Adib, G.; Burnham, R.; Chisholm, A.; Clarke, K.; Coates, D.; Coates, M.; Cook, D.; Cox, M.; Dhillon, S.; Dougall, C.; Doyle, P.; Duncan, P.; Edsell, M.; Edwards, L.; Evans, L.; Gardiner, P.; Grocott, M.; Gunning, P.; Hart, N.; Harrington, J.; Harvey, J.; Holloway, C.; Howard, D.; Hurlbut, D.; Imray, C.; Ince, C.; Jonas, M.; van der Kaaij, J.; Khosravi, M.; Kolfschoten, N.; Levett, D.; Luery, H.; Luks, A.; Martin, D.; McMorrow, R.; Meale, P.; Mitchell, K.; Montgomery, H.; Morgan, G.; Morgan, J.

2010-01-01

The physiological responses to hypoxaemia and cellular hypoxia are poorly understood, and inter-individual differences in performance at altitude and outcome in critical illness remain unexplained. We propose a model for exploring adaptation to hypoxia in the critically ill: the study of healthy

The cellular memory disc of reprogrammed cells.

Science.gov (United States)

Anjamrooz, Seyed Hadi

2013-04-01

The crucial facts underlying the low efficiency of cellular reprogramming are poorly understood. Cellular reprogramming occurs in nuclear transfer, induced pluripotent stem cell (iPSC) formation, cell fusion, and lineage-switching experiments. Despite these advances, there are three fundamental problems to be addressed: (1) the majority of cells cannot be reprogrammed, (2) the efficiency of reprogramming cells is usually low, and (3) the reprogrammed cells developed from a patient's own cells activate immune responses. These shortcomings present major obstacles for using reprogramming approaches in customised cell therapy. In this Perspective, the author synthesises past and present observations in the field of cellular reprogramming to propose a theoretical picture of the cellular memory disc. The current hypothesis is that all cells undergo an endogenous and exogenous holographic memorisation such that parts of the cellular memory dramatically decrease the efficiency of reprogramming cells, act like a barrier against reprogramming in the majority of cells, and activate immune responses. Accordingly, the focus of this review is mainly to describe the cellular memory disc (CMD). Based on the present theory, cellular memory includes three parts: a reprogramming-resistance memory (RRM), a switch-promoting memory (SPM) and a culture-induced memory (CIM). The cellular memory arises genetically, epigenetically and non-genetically and affects cellular behaviours. [corrected].

WOOD CELLULAR DENDROCLIMATOLOGY: TESTING NEW PROXIES IN GREAT BASIN BRISTLECONE PINE

Directory of Open Access Journals (Sweden)

Emanuele Ziaco

2016-10-01

adaptations to external stressors. Integrating xylem cellular features with ring-width chronologies can widen our understanding of past climatic variability (including annual extreme events and improve the evaluation of long-term plant response to drought, especially in connection with future warming scenarios.

Cellular changes in tears associated with keratoconjunctival responses induced by nasal allergy.

Science.gov (United States)

Pelikan, Z

2014-04-01

Allergic keratoconjunctivitis occurs in a primary form, caused by an allergic reaction localized in the conjunctiva, and in a secondary form, induced by an allergic reaction originating in the nasal mucosa. Various hypersensitivity mechanisms involved in the keratoconjunctivitis forms result in different keratoconjunctival response types. To investigate the cytologic changes in tears during the secondary immediate (SIKCR), late (SLKCR), and delayed (SDYKCR) keratoconjunctival responses. In 61 patients, comprising 20 SIKCRs, 23 SLKCRs, and 18 SDYKCRs, nasal provocation tests (NPTs) with allergens and 61 phosphate-buffered control challenges were repeated and supplemented with cell counting in the tears. The SIKCR (Ptears. The SLKCR (Ptears. The cells, except mast, epithelial and goblet cells, displaying no intracellular changes, migrated probably from the conjunctival capillaries, in response to the factors released during the primary allergic reaction in the nasal mucosa and subsequently penetrating into the conjunctiva. These results demonstrate a causal role of nasal allergy and diagnostic value of NPT combined with recording of ocular features and cellular profiles in tears in some keratoconjunctivitis patients.

Altered T-cell responses by the periodontal pathogen Porphyromonas gingivalis.

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Hazem Khalaf

Full Text Available Several studies support an association between the chronic inflammatory diseases periodontitis and atherosclerosis with a crucial role for the periodontal pathogen Porphyromonas gingivalis. However, the interplay between this pathogen and the adaptive immune system, including T-cells, is sparsely investigated. Here we used Jurkat T-cells to determine the effects of P. gingivalis on T-cell-mediated adaptive immune responses. We show that viable P. gingivalis targets IL-2 expression at the protein level. Initial cellular events, including ROS production and [Ca(2+](i, were elevated in response to P. gingivalis, but AP-1 and NF-κB activity dropped below basal levels and T-cells were unable to sustain stable IL-2 accumulation. IL-2 was partially restored by Leupeptin, but not by Cathepsin B Inhibitor, indicating an involvement of Rgp proteinases in the suppression of IL-2 accumulation. This was further confirmed by purified Rgp that caused a dose-dependent decrease in IL-2 levels. These results provide new insights of how this periodontal pathogen evades the host adaptive immune system by inhibiting IL-2 accumulation and thus attenuating T-cell proliferation and cellular communication.

Addition of Alanyl-Glutamine to Dialysis Fluid Restores Peritoneal Cellular Stress Responses - A First-In-Man Trial.

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Klaus Kratochwill

Full Text Available Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysis (PD. Dysfunctional cellular stress responses aggravate peritoneal injury associated with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomized cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamine (AlaGln addition to glucose-based PDF.In a prospective randomized cross-over design, 20 stable PD outpatients underwent paired peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chamber 3.86% glucose PD fluid, with and without 8 mM supplemental AlaGln. Heat-shock protein 72 expression was assessed in peritoneal effluent cells as surrogate parameter of cellular stress responses, complemented by metabolomics and functional immunocompetence assays.AlaGln restored peritoneal glutamine levels and increased the primary outcome heat-shock protein expression (effect 1.51-fold, CI 1.07-2.14; p = 0.022, without changes in peritoneal ultrafiltration, small solute transport, or biomarkers reflecting cell mass and inflammation. Further effects were glutamine-like metabolomic changes and increased ex-vivo LPS-stimulated cytokine release from healthy donor peripheral blood monocytes. In patients with a history of peritonitis (5 of 20, AlaGln supplementation decreased dialysate interleukin-8 levels. Supplemented PD fluid also attenuated inflammation and enhanced stimulated cytokine release in a mouse model of PD-associated peritonitis.We conclude that AlaGln-supplemented, glucose-based PD fluid can restore peritoneal cellular stress responses with attenuation of sterile inflammation, and may improve peritoneal host-defense in the setting of PD.

Genomic adaptations of the halophilic Dead Sea filamentous fungus Eurotium rubrum.

Science.gov (United States)

Kis-Papo, Tamar; Weig, Alfons R; Riley, Robert; Peršoh, Derek; Salamov, Asaf; Sun, Hui; Lipzen, Anna; Wasser, Solomon P; Rambold, Gerhard; Grigoriev, Igor V; Nevo, Eviatar

2014-05-09

The Dead Sea is one of the most hypersaline habitats on Earth. The fungus Eurotium rubrum (Eurotiomycetes) is among the few species able to survive there. Here we highlight its adaptive strategies, based on genome analysis and transcriptome profiling. The 26.2 Mb genome of E. rubrum shows, for example, gains in gene families related to stress response and losses with regard to transport processes. Transcriptome analyses under different salt growth conditions revealed, among other things differentially expressed genes encoding ion and metabolite transporters. Our findings suggest that long-term adaptation to salinity requires cellular and metabolic responses that differ from short-term osmotic stress signalling. The transcriptional response indicates that halophilic E. rubrum actively counteracts the salinity stress. Many of its genes encode for proteins with a significantly higher proportion of acidic amino acid residues. This trait is characteristic of the halophilic prokaryotes as well, supporting the theory of convergent evolution under extreme hypersaline stress.

Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Gustafsson, Åsa, E-mail: asa.gustafsson@foi.se [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Public Health and Clinical Medicine, Umeå University (Sweden); Bergström, Ulrika [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Organismal Biology, Uppsala University, SE-751 Uppsala (Sweden); Ågren, Lina [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Österlund, Lars [Dept of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 Uppsala (Sweden); Sandström, Thomas [Dept of Public Health and Clinical Medicine, Umeå University (Sweden); Bucht, Anders [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Public Health and Clinical Medicine, Umeå University (Sweden)

2015-10-01

The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 and 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials. - Highlights: • Hematite NPs induce differential responses in airways of healthy and allergic mice. • Hematite induced an airway inflammation in healthy mice. • Hematite induced cellular reduction in the alveolus and lymph nodes of allergic mice. • Cell death is possible due to extensive pro-oxidative environment in allergic mice. • It is important to include sensitive individuals when valuing health effects of NPs.

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

Science.gov (United States)

Auld, Stuart K J R; Edel, Kai H; Little, Tom J

2012-10-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

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

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Gajadhar Bhakta

2014-01-01

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

The Effects Radiation on Cellular Components of the Immune

International Nuclear Information System (INIS)

Zubaidah-Alatas

2001-01-01

The immune system describes the body's ability to defend itself against various foreign intruders named as antigens by calling on an immune mechanism. Antigens penetration into body activate the body's immune system that may be humoral response, cellular response, or both. The immune response is primarily mediated by two cell types, lymphocyte and macrophage. This paper will discuss the cellular component of immune system and the radiation effects on various cells involved in system. Moreover, the effects of radiation on humoral and cellular responses and the relation among immunity, cancer and radiotherapy are also described. (author)

Innate scavenger receptor-A regulates adaptive T helper cell responses to pathogen infection

Science.gov (United States)

Xu, Zhipeng; Xu, Lei; Li, Wei; Jin, Xin; Song, Xian; Chen, Xiaojun; Zhu, Jifeng; Zhou, Sha; Li, Yong; Zhang, Weiwei; Dong, Xiaoxiao; Yang, Xiaowei; Liu, Feng; Bai, Hui; Chen, Qi; Su, Chuan

2017-01-01

The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. However, little is known about the role of SR-A in the host adaptive immune responses to pathogen infection. Here we show with mouse models of helminth Schistosoma japonicum infection and heat-inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by pathogens and suppresses IRF5 nuclear translocation by direct interaction. Reduced abundance of nuclear IRF5 shifts macrophage polarization from M1 towards M2, which subsequently switches T-helper responses from type 1 to type 2. Our study identifies a role for SR-A as an innate PRR in regulating adaptive immune responses. PMID:28695899

New insights into microbial adaptation to extreme saline environments

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Vauclare P.

2014-02-01

Full Text Available Extreme halophiles are microorganisms adapted to low water activity living at the upper salt concentration that life can tolerate. We review here recent data that specify the main factors, which determine their peculiar salt-dependent biochemistry. The data suggested that evolution proceeds by stage to modify the molecular dynamics properties of the entire proteome. Extreme halophiles therefore represent tractable models to understand how fast and to what extent microorganisms adapt to environmental changes. Halophiles are also robust organisms, capable to resist multiple stressors. Preliminary studies indicated that they have developed a cellular response specifically aimed to survive when the salt condition fluctuates. Because of these properties halophilic organisms deserve special attention in the search for traces of life on other planets.

Higher Plants in Space: Microgravity Perception, Response, and Adaptation

Science.gov (United States)

Zheng, Hui Qiong; Han, Fei; Le, Jie

2015-11-01

Microgravity is a major abiotic stress in space. Its effects on plants may depend on the duration of exposure. We focused on two different phases of microgravity responses in space. When higher plants are exposed to short-term (seconds to hours) microgravity, such as on board parabolic flights and sounding rockets, their cells usually exhibit abiotic stress responses. For example, Ca 2+-, lipid-, and pH-signaling are rapidly enhanced, then the production of reactive oxygen species and other radicals increase dramatically along with changes in metabolism and auxin signaling. Under long-term (days to months) microgravity exposure, plants acclimatize to the stress by changing their metabolism and oxidative response and by enhancing other tropic responses. We conclude by suggesting that a systematic analysis of regulatory networks at the molecular level of higher plants is needed to understand the molecular signals in the distinct phases of the microgravity response and adaptation.

Genetic dissection of the Arabidopsis spaceflight transcriptome: Are some responses dispensable for the physiological adaptation of plants to spaceflight?

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Anna-Lisa Paul

Full Text Available Experimentation on the International Space Station has reached the stage where repeated and nuanced transcriptome studies are beginning to illuminate the structural and metabolic differences between plants grown in space compared to plants on the Earth. Genes that are important in establishing the spaceflight responses are being identified, their roles in spaceflight physiological adaptation are increasingly understood, and the fact that different genotypes adapt differently is recognized. However, the basic question of whether these spaceflight responses are actually required for survival has yet to be posed, and the fundamental notion that spaceflight responses may be non-adaptive has yet to be explored. Therefore the experiments presented here were designed to ask if portions of the plant spaceflight response can be genetically removed without causing loss of spaceflight survival and without causing increased stress responses. The CARA experiment compared the spaceflight transcriptome responses in the root tips of two Arabidopsis ecotypes, Col-0 and WS, as well as that of a PhyD mutant of Col-0. When grown with the ambient light of the ISS, phyD plants displayed a significantly reduced spaceflight transcriptome response compared to Col-0, suggesting that altering the activity of a single gene can actually improve spaceflight adaptation by reducing the transcriptome cost of physiological adaptation. The WS genotype showed an even simpler spaceflight transcriptome response in the ambient light of the ISS, more broadly indicating that the plant genotype can be manipulated to reduce the cost of spaceflight adaptation, as measured by transcriptional response. These differential genotypic responses suggest that genetic manipulation could further reduce, or perhaps eliminate the metabolic cost of spaceflight adaptation. When plants were germinated and then left in the dark on the ISS, the WS genotype actually mounted a larger transcriptome response

Effects of Mushroom and Herb Polysaccharides on Cellular and Humoral Immune Responses of Eimeria tenella-Infected Chickens

NARCIS (Netherlands)

Guo, F.C.; Kwakkel, R.P.; Williams, B.A.; Parmentier, H.K.; Li, W.K.; Yang, Z.Q.; Verstegen, M.W.A.

2004-01-01

We investigated the effects of polysaccharide extracts from 2 mushrooms, Lentinus edodes (LenE) and Tremella fuciformis (TreE), and an herb, Astragalus membranaceus (AstE), on cellular and humoral immune responses of Eimeria tenella-infected chickens. A total of 150 broiler chicks were assigned to 5

Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei.

Science.gov (United States)

Alam, Shahabuddin; Amemiya, Kei; Bernhards, Robert C; Ulrich, Robert G; Waag, David M; Saikh, Kamal U

2015-01-01

Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans. Our results demonstrated that B. mallei elicited strong primary pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) equivalent to the levels of B. pseudomallei in primary PBMC cultures of NHPs and humans. When we examined IL-1β and other cytokine responses by comparison to Escherichia coli LPS, African Green Monkeys appears to be most responsive to B. mallei than Cynomolgus or Rhesus. Characterization of the immune signaling mechanism for cellular response was conducted by using a ligand induced cell-based reporter assay, and our results demonstrated that MyD88 mediated signaling contributed to the B. mallei and B. pseudomallei induced pro-inflammatory responses. Notably, the induced reporter activity with B. mallei, B. pseudomallei, or purified LPS from these pathogens was inhibited and cytokine production was attenuated by a MyD88 inhibitor. Together, these results show that in the scenario of severe hyper-inflammatory responses to B. mallei infection, MyD88 targeted therapeutic intervention may be a successful strategy for therapy. Published by Elsevier Ltd.

Prediction of adaptive self-regulatory responses to arthritis pain anxiety in exercising adults: does pain acceptance matter?

Science.gov (United States)

Cary, Miranda Ashley; Gyurcsik, Nancy C; Brawley, Lawrence R

2015-01-01

Exercising for ≥ 150 min/week is a recommended strategy for self-managing arthritis. However, exercise nonadherence is a problem. Arthritis pain anxiety may interfere with regular exercise. According to the fear-avoidance model, individuals may confront their pain anxiety by using adaptive self-regulatory responses (eg, changing exercise type or duration). Furthermore, the anxiety-self-regulatory responses relationship may vary as a function of individuals' pain acceptance levels. To investigate pain acceptance as a moderator of the pain anxiety-adaptive self-regulatory responses relationship. The secondary objective was to examine whether groups of patients who differed in meeting exercise recommendations also differed in pain-related and self-regulatory responses. Adults (mean [± SD] age 49.75 ± 13.88 years) with medically diagnosed arthritis completed online measures of arthritis pain-related variables and self-regulatory responses at baseline, and exercise participation two weeks later. Individuals meeting (n=87) and not meeting (n=49) exercise recommendations were identified. Hierarchical multiple regression analysis revealed that pain acceptance moderated the anxiety-adaptive self-regulatory responses relationship. When pain anxiety was lower, greater pain acceptance was associated with less frequent use of adaptive responses. When anxiety was higher, adaptive responses were used regardless of pain acceptance level. MANOVA findings revealed that participants meeting the recommended exercise dose reported significantly lower pain and pain anxiety, and greater pain acceptance (Pself-regulatory capacity to cope with additional challenges to exercise adherence (eg, busy schedule).

Population variability in biological adaptive responses to DNA damage and the shapes of carcinogen dose-response curves

International Nuclear Information System (INIS)

Conolly, Rory B.; Gaylor, David W.; Lutz, Werner K.

2005-01-01

Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health

The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress

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Soriano-Carot María

2012-02-01

Full Text Available Abstract Background The maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. The Saccharomyces cerevisiae SLT2 gene encodes a member of the mitogen-activated protein kinase (MAPK cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest that SLT2 may also have a role related to DNA metabolism. Results This work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses. The slt2 mutant strain was hypersensitive to a variety of genotoxic treatments, including incubation with hydroxyurea (HU, methylmetanosulfonate (MMS, phleomycin or UV irradiation. Furthermore, Slt2 was activated by all these treatments, which suggests that Slt2 plays a central role in the cellular response to genotoxic stresses. Activation of Slt2 was not dependent on the DNA integrity checkpoint. For MMS and UV, Slt2 activation required progression through the cell cycle. In contrast, HU also activated Slt2 in nocodazol-arrested cells, which suggests that Slt2 may respond to dNTP pools alterations. However, neither the protein level of the distinct ribonucleotide reductase subunits nor the dNTP pools were affected in a slt2 mutant strain. An analysis of the checkpoint function revealed that Slt2 was not required for either cell cycle arrest or the activation of the Rad53 checkpoint kinase in response to DNA damage. However, slt2 mutant cells showed an elongated bud and partially impaired Swe1 degradation after replicative stress, indicating that Slt2 could contribute, in parallel with Rad53, to bud morphogenesis control after genotoxic stresses. Conclusions Slt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt

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

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John Wikswo

2009-03-01

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

Micro-evolutionary responses and adaptive costs of Caenorhabditis elegans populations exposed to environmental stress

International Nuclear Information System (INIS)

Dutilleul, M.

2013-01-01

The contemporary evolution of organisms is largely dependent on anthropogenic disturbances. In particular, pollution amplifies the intensity or the quantity of selection pressures on populations. However, these changes may have negative effects on the life, growth and reproduction of individuals, the demographics of the population, and its phenotypic and genetic characteristics over generations. Thus, micro-evolutionary changes are likely to occur in response to selection pressures. These phenomenon lead to collateral damages: adaptive costs. For example, a reduction of genetic diversity in a population entails a decrease in its potential to adapt to other stressors. Populations can be more susceptible to many environmental changes, especially with the increase of human activities. Hence in an ecological risk assessment, studying the mechanisms of action and immediate adverse effects of pollutants on organisms is no longer sufficient. It is also necessary to expand our knowledge on the evolution of populations in polluted environment. In this context, our study aims to determine the micro-evolutionary response of Caenorhabditis elegans populations exposed to environmental stressors, and to measure their costs of adaptation. Populations were experimentally exposed for 22 generations to a high concentration of uranium, sodium chloride or an alternation of both these pollutants. The analysis of phenotypic and genetic changes, observed through measures of life history traits, was accomplished using several quantitative genetics techniques. In particular, we confirmed the genetic differentiation between populations with an increase of resistance in populations exposed to different pollutions. The speed of evolutionary responses depended on the conditions of exposure and their effects on the expression of the genetic structure of traits (e.g. G matrix). Micro-evolutionary changes were linked to costs of adaptation, such as reduced fertility in stressful novel

Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

Directory of Open Access Journals (Sweden)

Geferson Fischer

2010-11-01

Full Text Available Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1. When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05 neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01. Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05. Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.

Time-effect relationship of immunological adaptive response induced by low dose X-irradiation in mice

International Nuclear Information System (INIS)

Zhao Yong; Gong Shouliang; Liu Shuzheng

1995-01-01

Kunming mice irradiated with whole-body X-rays were used to observe time-effect relationship of immunological adaptive response induced by ionizing radiation. The results showed that pre-irradiation dose of 75 mGy X-rays with the intervals of 6-48 h between pre-irradiation and challenge irradiation could induce immunological adaptive response in the spontaneous proliferation of thymocytes and the responses of splenocytes to Con A and LPS in mice at 18-24 h after challenge irradiation with 1.5-2.0 Gy X-rays

Cellular Responses to Beta Blocker Exposures in Marine ...

Science.gov (United States)

β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent activation of adenylate cyclase and increases in blood pressure by limiting cAMP production and protein kinase A activation. After being taken therapeutically, β blockers may make their way to coastal habitats via discharge from waste water treatment plants, posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular biomarkers of β blocker exposure using two drugs, propranolol and metoprolol, in three commercially important marine bivalves -Crassostrea virginica, Mytilus edulis and Mercenaria mercenaria. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug for 24 hours. Samples were preserved for cellular biomarker assays. Elevated cellular damage and changes in enzymatic activities were noted at environmentally relevant concentrations, and M. mercenaria was found to be the most sensitive bivalve out of the three species tested. These studies enhance our understanding of the potential impacts of commonly used prescription medication on organisms in coastal ecosystems, and demonstrate that filter feeders such as marine bivalves may serve as good model organisms to examine the effects of water soluble drugs. Evaluating a suite of biomarkers

A Novel Agonist of the TRIF Pathway Induces a Cellular State Refractory to Replication of Zika, Chikungunya, and Dengue Viruses.

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Pryke, Kara M; Abraham, Jinu; Sali, Tina M; Gall, Bryan J; Archer, Iris; Liu, Andrew; Bambina, Shelly; Baird, Jason; Gough, Michael; Chakhtoura, Marita; Haddad, Elias K; Kirby, Ilsa T; Nilsen, Aaron; Streblow, Daniel N; Hirsch, Alec J; Smith, Jessica L; DeFilippis, Victor R

2017-05-02

The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread. In light of this strategy's potential, we undertook a screen to identify novel interferon-activating small molecules. Here, we describe 1-(2-fluorophenyl)-2-(5-isopropyl-1,3,4-thiadiazol-2-yl)-1,2-dihydrochromeno[2,3- c ]pyrrole-3,9-dione, which we termed AV-C. Treatment of human cells with AV-C activates innate and interferon-associated responses that strongly inhibit replication of Zika, Chikungunya, and dengue viruses. By utilizing genome editing, we investigated the host proteins essential to AV-C-induced cellular states. This showed that the compound requires a TRIF-dependent signaling cascade that culminates in IFN regulatory factor 3 (IRF3)-dependent expression and secretion of type I interferon to elicit antiviral responses. The other canonical IRF3-terminal adaptor proteins STING and IPS-1/MAVS were dispensable for AV-C-induced phenotypes. However, our work revealed an important inhibitory role for IPS-1/MAVS, but not TRIF, in flavivirus replication, implying that TRIF-directed viral evasion may not occur. Additionally, we show that in response to AV-C, primary human peripheral blood mononuclear cells secrete proinflammatory cytokines that are linked with establishment of adaptive immunity to viral pathogens. Ultimately, synthetic innate immune activators such as AV-C may serve multiple therapeutic purposes, including direct antimicrobial responses and facilitation of pathogen

Responses of crayfish photoreceptor cells following intense light adaptation.

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Cummins, D R; Goldsmith, T H

1986-01-01

After intense orange adapting exposures that convert 80% of the rhodopsin in the eye to metarhodopsin, rhabdoms become covered with accessory pigment and appear to lose some microvillar order. Only after a delay of hours or even days is the metarhodopsin replaced by rhodopsin (Cronin and Goldsmith 1984). After 24 h of dark adaptation, when there has been little recovery of visual pigment, the photoreceptor cells have normal resting potentials and input resistances, and the reversal potential of the light response is 10-15 mV (inside positive), unchanged from controls. The log V vs log I curve is shifted about 0.6 log units to the right on the energy axis, quantitatively consistent with the decrease in the probability of quantum catch expected from the lowered concentration of rhodopsin in the rhabdoms. Furthermore, at 24 h the photoreceptors exhibit a broader spectral sensitivity than controls, which is also expected from accumulations of metarhodopsin in the rhabdoms. In three other respects, however, the transduction process appears to be light adapted: The voltage responses are more phasic than those of control photoreceptors. The relatively larger effect (compared to controls) of low extracellular Ca++ (1 mmol/l EGTA) in potentiating the photoresponses suggests that the photoreceptors may have elevated levels of free cytoplasmic Ca++. The saturating depolarization is only about 30% as large as the maximal receptor potentials of contralateral, dark controls, and by that measure the log V-log I curve is shifted downward by 0.54 log units.(ABSTRACT TRUNCATED AT 250 WORDS)

Receptor-mediated endocytosis generates nanomechanical force reflective of ligand identity and cellular property.

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Zhang, Xiao; Ren, Juan; Wang, Jingren; Li, Shixie; Zou, Qingze; Gao, Nan

2018-08-01

Whether environmental (thermal, chemical, and nutrient) signals generate quantifiable, nanoscale, mechanophysical changes in the cellular plasma membrane has not been well elucidated. Assessment of such mechanophysical properties of plasma membrane may shed lights on fundamental cellular process. Atomic force microscopic (AFM) measurement of the mechanical properties of live cells was hampered by the difficulty in accounting for the effects of the cantilever motion and the associated hydrodynamic force on the mechanical measurement. These challenges have been addressed in our recently developed control-based AFM nanomechanical measurement protocol, which enables a fast, noninvasive, broadband measurement of the real-time changes in plasma membrane elasticity in live cells. Here we show using this newly developed AFM platform that the plasma membrane of live mammalian cells exhibits a constant and quantifiable nanomechanical property, the membrane elasticity. This mechanical property sensitively changes in response to environmental factors, such as the thermal, chemical, and growth factor stimuli. We demonstrate that different chemical inhibitors of endocytosis elicit distinct changes in plasma membrane elastic modulus reflecting their specific molecular actions on the lipid configuration or the endocytic machinery. Interestingly, two different growth factors, EGF and Wnt3a, elicited distinct elastic force profiles revealed by AFM at the plasma membrane during receptor-mediated endocytosis. By applying this platform to genetically modified cells, we uncovered a previously unknown contribution of Cdc42, a key component of the cellular trafficking network, to EGF-stimulated endocytosis at plasma membrane. Together, this nanomechanical AFM study establishes an important foundation that is expandable and adaptable for investigation of cellular membrane evolution in response to various key extracellular signals. © 2017 Wiley Periodicals, Inc.

Characteristic of immunological adaptive response induced by low level whole body irradiation with X-rays in mice

International Nuclear Information System (INIS)

Ju Guizhi; Song Chunhua; Qi Jin; Liu Shuzheng

1995-01-01

The range of preirradiated doses (D 1 ) and challenge doses (D 2 ) for the induction of immunological adaptive response and the optimum time intervals between D 1 and D 2 were investigated in Kunming mice. The results were as follows: 1. Single whole body preirradiation by X-rays with D 1 doses of 25∼100 mGy (12.5 mGy/min) could induce adaptive response of spontaneous incorporation of 3 H-TdR into thymocytes and the reaction of splenocytes to LPS. 2. With D 2 doses of 1.0 to 1.5 Gy, the adaptive response of spontaneous incorporation of 3 H-TdR into thymocytes and the reaction of splenocytes to ConA and LPS could be induced. 3. The optimum interval for the induction of immunological adaptive response between D 1 and D 2 could be 6∼12 h

Mixed-valence molecular four-dot unit for quantum cellular automata: Vibronic self-trapping and cell-cell response.

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Tsukerblat, Boris; Palii, Andrew; Clemente-Juan, Juan Modesto; Coronado, Eugenio

2015-10-07

Our interest in this article is prompted by the vibronic problem of charge polarized states in the four-dot molecular quantum cellular automata (mQCA), a paradigm for nanoelectronics, in which binary information is encoded in charge configuration of the mQCA cell. Here, we report the evaluation of the electronic levels and adiabatic potentials of mixed-valence (MV) tetra-ruthenium (2Ru(ii) + 2Ru(iii)) derivatives (assembled as two coupled Creutz-Taube complexes) for which molecular implementations of quantum cellular automata (QCA) was proposed. The cell based on this molecule includes two holes shared among four spinless sites and correspondingly we employ the model which takes into account the two relevant electron transfer processes (through the side and through the diagonal of the square) as well as the difference in Coulomb energies for different instant positions of localization of the hole pair. The combined Jahn-Teller (JT) and pseudo JT vibronic coupling is treated within the conventional Piepho-Krauzs-Schatz model adapted to a bi-electronic MV species with the square-planar topology. The adiabatic potentials are evaluated for the low lying Coulomb levels in which the antipodal sites are occupied, the case just actual for utilization in mQCA. The conditions for the vibronic self-trapping in spin-singlet and spin-triplet states are revealed in terms of the two actual transfer pathways parameters and the strength of the vibronic coupling. Spin related effects in degrees of the localization which are found for spin-singlet and spin-triplet states are discussed. The polarization of the cell is evaluated and we demonstrate how the partial delocalization caused by the joint action of the vibronic coupling and electron transfer processes influences polarization of a four-dot cell. The results obtained within the adiabatic approach are compared with those based on the numerical solution of the dynamic vibronic problem. Finally, the Coulomb interaction between

Participation of intercellular communication and intracellular signal transduction in the radio-adaptive response of human fibroblastic cells

International Nuclear Information System (INIS)

Ishii, Keiichiro; Hoshi, Yuko; Iwasaki, Toshiyasu; Watanabe, Masami

1997-01-01

To investigate the radio-adaptive response of normal cells to low-dose radiation, we irradiated human embryonic cells with low-dose X-rays and examined the changes in sensitivity to subsequent high-dose X-irradiation. When the cells were irradiated by 200 cGy, the growth ratio of the viable cells five days after the irradiation decreased to 37% of that of the cells which received no X-irradiation. When the cells received a conditioning irradiation of 10 to 20 cGy four hours before the irradiation of 200 cGy, the growth ratio increased significantly to 45-53%, and a peak was reached at a conditioning dose of 13 cGy. Cells blocked off intercellular communication either in Ca 2+ ion-free medium or in TPA added medium during the conditioning irradiation of 13 cGy did not show the improvement of growth ratio. Addition of H-7, as an inhibitor of PKC, to the medium during the conditioning irradiation inhibited the induction of the radio-adaptive response. However, addition of either inhibitor of A kinase, H-89, or inhibitor of G kinase, H-8, failed to inhibit the induction of the radio-adaptive response. These results suggest that: (1) normal cells show an adaptive response to low-dose radiation, (2) intercellular communication may play a role in radio-adaptive responses, (3) the transduction of the signal induced in cells by low-dose X-irradiation via protein kinase C was involved in radio-adaptive responses, not via A kinase nor G kinase. (author)

Oral administration of type-II collagen peptide 250-270 suppresses specific cellular and humoral immune response in collagen-induced arthritis.

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Zhu, Ping; Li, Xiao-Yan; Wang, Hong-Kun; Jia, Jun-Feng; Zheng, Zhao-Hui; Ding, Jin; Fan, Chun-Mei

2007-01-01

Oral antigen is an attractive approach for the treatment of autoimmune and inflammatory diseases. Establishment of immune markers and methods in evaluating the effects of antigen-specific cellular and humoral immune responses will help the application of oral tolerance in the treatment of human diseases. The present article observed the effects of chicken collagen II (CII), the recombinant polymerized human collagen II 250-270 (rhCII 250-270) peptide and synthesized human CII 250-270 (syCII 250-270) peptide on the induction of antigen-specific autoimmune response in rheumatoid arthritis (RA) peripheral blood mononuclear cells (PBMC) and on the specific cellular and humoral immune response in collagen-induced arthritis (CIA) and mice fed with CII (250-270) prior to immunization with CII. In the study, proliferation, activation and intracellular cytokine production of antigen-specific T lymphocytes were simultaneously analyzed by bromodeoxyuridine (BrdU) incorporation and flow cytometry at the single-cell level. The antigen-specific antibody and antibody-forming cells were detected by ELISA and ELISPOT, respectively. CII (250-270) was found to have stimulated the response of specific lymphocytes in PBMC from RA patients, including the increase expression of surface activation antigen marker CD69 and CD25, and DNA synthesis. Mice, fed with CII (250-270) before CII immunization, had significantly lower arthritic scores than the mice immunized with CII alone, and the body weight of the former increased during the study period. Furthermore, the specific T cell activity, proliferation and secretion of interferon (IFN)-gamma in spleen cells were actively suppressed in CII (250-270)-fed mice, and the serum anti-CII, anti-CII (250-270) antibody activities and the frequency of specific antibody-forming spleen cells were significantly lower in CII (250-270)-fed mice than in mice immunized with CII alone. These observations suggest that oral administration of CII (250-270) can

Homeostatic responses to amino acid insufficiency

Directory of Open Access Journals (Sweden)

Tracy G. Anthony

2015-09-01

Full Text Available This article provides a brief overview describing how two key signaling pathways, namely the integrated stress response and the mammalian target of rapamycin complex 1, work together to facilitate cellular adaptation to dietary amino acid insufficiency. A deeper understanding of these mechanisms is leading to identification of novel targets which aid in disease treatments, improve stress recovery and increase health span through slowed aging and enhanced metabolic fitness.

Friction transfer of polytetrafluoroethylene (PTFE) to produce nanoscale features and influence cellular response in vitro.

Science.gov (United States)

Kearns, V R; Doherty, P J; Beamson, G; Martin, N; Williams, R L

2010-07-01

A large number of cell types are known to respond to chemical and topographical patterning of substrates. Friction transfer of polytetrafluoroethylene (PTFE) onto substrates has been shown to produce continuous, straight, parallel nanofibres. Ammonia plasma treatment can be used to defluorinate the PTFE, decreasing the dynamic contact angle. Fibroblast and epithelial cells were elongated and oriented with their long axis parallel to the fibres, both individually and in clusters. The fibres restricted cell migration. Cell alignment was slightly reduced on the plasma-treated fibres. These results indicated that although surface topography can affect cellular response, surface chemistry also mediates the extent of this response.

Cellular response to alkylating agent MNNG is impaired in STAT1-deficients cells.

Science.gov (United States)

Ah-Koon, Laurent; Lesage, Denis; Lemadre, Elodie; Souissi, Inès; Fagard, Remi; Varin-Blank, Nadine; Fabre, Emmanuelle E; Schischmanoff, Olivier

2016-10-01

The SN 1 alkylating agents activate the mismatch repair system leading to delayed G2 /M cell cycle arrest and DNA repair with subsequent survival or cell death. STAT1, an anti-proliferative and pro-apoptotic transcription factor is known to potentiate p53 and to affect DNA-damage cellular response. We studied whether STAT1 may modulate cell fate following activation of the mismatch repair system upon exposure to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Using STAT1-proficient or -deficient cell lines, we found that STAT1 is required for: (i) reduction in the extent of DNA lesions, (ii) rapid phosphorylation of T68-CHK2 and of S15-p53, (iii) progression through the G2 /M checkpoint and (iv) long-term survival following treatment with MNNG. Presence of STAT1 is critical for the formation of a p53-DNA complex comprising: STAT1, c-Abl and MLH1 following exposure to MNNG. Importantly, presence of STAT1 allows recruitment of c-Abl to p53-DNA complex and links c-Abl tyrosine kinase activity to MNNG-toxicity. Thus, our data highlight the important modulatory role of STAT1 in the signalling pathway activated by the mismatch repair system. This ability of STAT1 to favour resistance to MNNG indicates the targeting of STAT1 pathway as a therapeutic option for enhancing the efficacy of SN1 alkylating agent-based chemotherapy. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes.

Science.gov (United States)

Ryeznik, Yevgen; Sverdlov, Oleksandr; Wong, Weng Kee

2015-08-01

Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool , a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature.

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

Directory of Open Access Journals (Sweden)

Gillian D McFeat

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

Involvement of p27CIP/KIP in HSP25 or HSP70 Mediated Adaptive Response by Low Dose Radiation

International Nuclear Information System (INIS)

Seo, Hang Rhan; Lee, Yoon Jin; Lee, Su Jae; Bae, Sang woo; Lee, Yun Sil

2005-01-01

Adaptive responses that reduce the harmful effects of subsequent exposure to high-dose radiation have demonstrated in chromosome aberration, cell survival, sister chromatid exchanges, micronucleus induction, mutation and neoplastic transformation. The mechanisms and conditions for the adaptive response to radiation have not been clarified, although the continuous production of free radicals from radiation and other sources has stimulated cells to evolve a repair system for chromosome breaks. An alteration of the DNA molecule triggers the repair system, and frequent activation may increase the general repair capacity, irrespective of the cause of the damage. Besides, cell cycle regulation systems, antioxidant defense systems, molecular chaperone or stress-response systems. Our previous data showed that when cells were preirradiated with 1cGy, they showed the adaptive response. A reduction of apoptosis by low-dose preirradiation is another potential mechanism for this effect. We previously demonstrated that mouse RIF cells, which did not induce HSP25 and HSP70 did not exhibit a adaptive response after 1cGy preirradiation. whereas the thermoresistant TR cells, which expressed inducible HSP25 and HSP70 showed a response. Moreover, when HSP70 and HSP25 were transfected to RIF cells, the cells acquired adaptive response. In this study, to elucidate the mechanisms in induction of adaptiveresponse, we compared cell cycle distribution by low dose radiation after HSP25 or HSP70 transfected cells and p27CIP/KIP is responsible for the different induction of adaptive response

Request for Information Response for the Flight Validation of Adaptive Control to Prevent Loss-of-Control Events. Overview of RFI Responses

Science.gov (United States)

Bosworth, John T.

2009-01-01

Adaptive control should be integrated with a baseline controller and only used when necessary (5 responses). Implementation as an emergency system. Immediately re-stabilize and return to controlled flight. Forced perturbation (excitation) for fine-tuning system a) Check margins; b) Develop requirements for amplitude of excitation. Adaptive system can improve performance by eating into margin constraints imposed on the non-adaptive system. Nonlinear effects due to multi-string voting.

Cellular Response to Doping of High Porosity Foamed Alumina with Ca, P, Mg, and Si

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Edwin Soh

2015-03-01

Full Text Available Foamed alumina was previously synthesised by direct foaming of sulphate salt blends varying ammonium mole fraction (AMF, foaming heating rate and sintering temperature. The optimal product was produced with 0.33AMF, foaming at 100 °C/h and sintering at 1600 °C. This product attained high porosity of 94.39%, large average pore size of 300 µm and the highest compressive strength of 384 kPa. To improve bioactivity, doping of porous alumina by soaking in dilute or saturated solutions of Ca, P, Mg, CaP or CaP + Mg was done. Saturated solutions of Ca, P, Mg, CaP and CaP + Mg were made with excess salt in distilled water and decanted. Dilute solutions were made by diluting the 100% solution to 10% concentration. Doping with Si was done using the sol gel method at 100% concentration only. Cell culture was carried out with MG63 osteosarcoma cells. Cellular response to the Si and P doped samples was positive with high cell populations and cell layer formation. The impact of doping with phosphate produced a result not previously reported. The cellular response showed that both Si and P doping improved the biocompatibility of the foamed alumina.

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes.

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Hooper, Philip L; Balogh, Gabor; Rivas, Eric; Kavanagh, Kylie; Vigh, Laszlo

2014-07-01

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease.

Innovative cellular distance structures from polymeric and metallic threads

Science.gov (United States)

Wieczorek, F.; Trümper, W.; Cherif, C.

2017-10-01

Knitting allows a high individual adaptability of the geometry and properties of flat-knitted spacer fabrics. This offers advantages for the specific adjustment of the mechanical properties of innovative composites based on highly viscous matrix systems such as bone cement, elastomer or foam and cellular reinforcing structures made from e. g. polymeric monofilaments or metallic wires. The prerequisite is the availability of binding solutions for highly productive production of functional, cellular, self-stabilized spacer flat knitted fabrics as supporting and functionalized structures.

Bayesian selective response-adaptive design using the historical control.

Science.gov (United States)

Kim, Mi-Ok; Harun, Nusrat; Liu, Chunyan; Khoury, Jane C; Broderick, Joseph P

2018-06-13

High quality historical control data, if incorporated, may reduce sample size, trial cost, and duration. A too optimistic use of the data, however, may result in bias under prior-data conflict. Motivated by well-publicized two-arm comparative trials in stroke, we propose a Bayesian design that both adaptively incorporates historical control data and selectively adapt the treatment allocation ratios within an ongoing trial responsively to the relative treatment effects. The proposed design differs from existing designs that borrow from historical controls. As opposed to reducing the number of subjects assigned to the control arm blindly, this design does so adaptively to the relative treatment effects only if evaluation of cumulated current trial data combined with the historical control suggests the superiority of the intervention arm. We used the effective historical sample size approach to quantify borrowed information on the control arm and modified the treatment allocation rules of the doubly adaptive biased coin design to incorporate the quantity. The modified allocation rules were then implemented under the Bayesian framework with commensurate priors addressing prior-data conflict. Trials were also more frequently concluded earlier in line with the underlying truth, reducing trial cost, and duration and yielded parameter estimates with smaller standard errors. © 2018 The Authors. Statistics in Medicine Published by John Wiley & Sons, Ltd.

No evidence of local adaptation of immune responses to Gyrodactylus in three-spined stickleback (Gasterosteus aculeatus).

Science.gov (United States)

Robertson, Shaun; Bradley, Janette E; MacColl, Andrew D C

2017-01-01

Parasitism represents one of the most widespread lifestyles in the animal kingdom, with the potential to drive coevolutionary dynamics with their host population. Where hosts and parasites evolve together, we may find local adaptation. As one of the main host defences against infection, there is the potential for the immune response to be adapted to local parasites. In this study, we used the three-spined stickleback and its Gyrodactylus parasites to examine the extent of local adaptation of parasite infection dynamics and the immune response to infection. We took two geographically isolated host populations infected with two distinct Gyrodactylus species and performed a reciprocal cross-infection experiment in controlled laboratory conditions. Parasite burdens were monitored over the course of the infection, and individuals were sampled at multiple time points for immune gene expression analysis. We found large differences in virulence between parasite species, irrespective of host, and maladaptation of parasites to their sympatric host. The immune system responded to infection, with a decrease in expression of innate and Th1-type adaptive response genes in fish infected with the less virulent parasite, representing a marker of a possible resistance mechanism. There was no evidence of local adaptation in immune gene expression levels. Our results add to the growing understanding of the extent of host-parasite local adaptation, and demonstrate a systemic immune response during infection with a common ectoparasite. Further immunological studies using the stickleback-Gyrodactylus system can continue to contribute to our understanding of the function of the immune response in natural populations. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Contextualizing Individual Competencies for Managing the Corporate Social Responsibility Adaptation Process

NARCIS (Netherlands)

Osagie, E.R.; Wesselink, R.; Blok, V.; Mulder, M.

2016-01-01

Companies committed to corporate social responsibility (CSR) should ensure that their managers possess the appropriate competencies to effectively manage the CSR adaptation process. The literature provides insights into the individual competencies these managers need but fails to prioritize them and

Predicting adaptation to parenthood: The role of responsiveness, gratitude, and trust

NARCIS (Netherlands)

Kuile, H. ter; Kluwer, E.S.; Finkenauer, C.; Lippe, A.G. van der

2017-01-01

The influence of positive relationship processes, specifically perceived responsiveness, felt gratitude, and felt trust, on perceived adaptation to parenthood was investigated. It was hypothesized that both higher initial levels prior to pregnancy as well as increases over time in perceived

Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

Science.gov (United States)

Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

2014-01-01

The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

Virtualized cognitive network architecture for 5G cellular networks

KAUST Repository

Elsawy, Hesham

2015-07-17

Cellular networks have preserved an application agnostic and base station (BS) centric architecture1 for decades. Network functionalities (e.g. user association) are decided and performed regardless of the underlying application (e.g. automation, tactile Internet, online gaming, multimedia). Such an ossified architecture imposes several hurdles against achieving the ambitious metrics of next generation cellular systems. This article first highlights the features and drawbacks of such architectural ossification. Then the article proposes a virtualized and cognitive network architecture, wherein network functionalities are implemented via software instances in the cloud, and the underlying architecture can adapt to the application of interest as well as to changes in channels and traffic conditions. The adaptation is done in terms of the network topology by manipulating connectivities and steering traffic via different paths, so as to attain the applications\\' requirements and network design objectives. The article presents cognitive strategies to implement some of the classical network functionalities, along with their related implementation challenges. The article further presents a case study illustrating the performance improvement of the proposed architecture as compared to conventional cellular networks, both in terms of outage probability and handover rate.

Local adaptation in transgenerational responses to predators

Science.gov (United States)

Walsh, Matthew R.; Castoe, Todd; Holmes, Julian; Packer, Michelle; Biles, Kelsey; Walsh, Melissa; Munch, Stephan B.; Post, David M.

2016-01-01

Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. ‘within-generation’ plasticity), such ‘transgenerational plasticity’ (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within-generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations. PMID:26817775

Local adaptation in transgenerational responses to predators.

Science.gov (United States)

Walsh, Matthew R; Castoe, Todd; Holmes, Julian; Packer, Michelle; Biles, Kelsey; Walsh, Melissa; Munch, Stephan B; Post, David M

2016-01-27

Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. 'within-generation' plasticity), such 'transgenerational plasticity' (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within-generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations. © 2016 The Author(s).

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization.

Science.gov (United States)

Smolders, R; Bervoets, L; De Coen, W; Blust, R

2004-05-01

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels.

Nonlinear feedback drives homeostatic plasticity in H2O2 stress response

Science.gov (United States)

Goulev, Youlian; Morlot, Sandrine; Matifas, Audrey; Huang, Bo; Molin, Mikael; Toledano, Michel B; Charvin, Gilles

2017-01-01

Homeostatic systems that rely on genetic regulatory networks are intrinsically limited by the transcriptional response time, which may restrict a cell’s ability to adapt to unanticipated environmental challenges. To bypass this limitation, cells have evolved mechanisms whereby exposure to mild stress increases their resistance to subsequent threats. However, the mechanisms responsible for such adaptive homeostasis remain largely unknown. Here, we used live-cell imaging and microfluidics to investigate the adaptive response of budding yeast to temporally controlled H2O2 stress patterns. We demonstrate that acquisition of tolerance is a systems-level property resulting from nonlinearity of H2O2 scavenging by peroxiredoxins and our study reveals that this regulatory scheme induces a striking hormetic effect of extracellular H2O2 stress on replicative longevity. Our study thus provides a novel quantitative framework bridging the molecular architecture of a cellular homeostatic system to the emergence of nonintuitive adaptive properties. DOI: http://dx.doi.org/10.7554/eLife.23971.001 PMID:28418333

Cellular buckling in long structures

NARCIS (Netherlands)

Hunt, G.W.; Peletier, M.A.; Champneys, A.R.; Woods, P.D.; Wadee, M.A.; Budd, C.J.; Lord, G.J.

2000-01-01

A long structural system with an unstable (subcritical)post-buckling response that subsequently restabilizes typically deformsin a cellular manner, with localized buckles first forming and thenlocking up in sequence. As buckling continues over a growing number ofcells, the response can be described

Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

Science.gov (United States)

Matsumoto, H.; Ohnishi, T.

There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

Lymphatic filariasis-specific immune responses in relation to lymphoedema grade and infection status. I. Cellular responses

DEFF Research Database (Denmark)

Nielsen, N. O.; Bloch, P.; Simonsen, P. E.

2002-01-01

leg lymphoedema of varying severity ranging from early to more advanced grades (pathology groups 1-5). Another group comprised individuals with mixed grades of lymphoedema and positive for mf and/or CFA (mixed pathology group). Three asymptomatic groups consisted of individuals without leg pathology...... in uninfected as compared to infected individuals. High levels of IL-10 were observed in asymptomatic individuals without infection and in asymptomatic CFA-positive but mf-negative individuals. Asymptomatic individuals with mf had relatively low IL-10 levels. Groups presenting with chronic pathology generally......The filariasis-specific cellular responsiveness was assessed in 109 adult individuals from a Wuchereria bancrofti-endemic area in north-east Tanzania. There were 9 study groups. Five groups of individuals were negative for microfilariae (mf) and specific circulating filarial antigen (CFA) and had...

Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance.

Science.gov (United States)

Hammer, V A; Gietzen, D W; Sworts, V D; Beverly, J L; Rogers, Q R

1990-12-01

The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated. In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis. In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy. Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals. In each experiment a 2 X 2 factorial design was used. Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet. The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt. Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model. These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade.

Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak, E-mail: Siamak.haghdoost@su.se

2015-10-15

Highlights: • 50 mGy at 1.4 mGy/h induces adaptive response in MCF-10A at mutation level. • Low dose rate γ-radiation does not induce adaptive response at survival level. • Overall, a dose rate effect is absent at the level of mutation in MCF-10A cells. - Abstract: A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50 mGy adapting dose administered acutely (0.40 Gy/min) or chronically (1.4 mGy/h or 4.1 mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100 mGy and 1 Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50 mGy at 1.4 mGy/h followed by 1 Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100 mGy), no differences at the level of mutation were found comparing different dose rates.

Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles

International Nuclear Information System (INIS)

Pinto, Ligia A.; Viscidi, Raphael; Harro, Clayton D.; Kemp, Troy J.; Garcia-Pineres, Alfonso J.; Trivett, Matthew; Demuth, Franklin; Lowy, Douglas R.; Schiller, John T.; Berzofsky, Jay A.; Hildesheim, Allan

2006-01-01

Human papillomavirus-like particles (HPV VLP) are candidate vaccines that have shown to be efficacious in reducing infection and inducing robust antiviral immunity. Neutralizing antibodies generated by vaccination are largely type-specific, but little is known about the type-specificity of cellular immune responses to VLP vaccination. To determine whether vaccination with HPV-16 L1VLP induces cellular immunity to heterologous HPV types (HPV-18, HPV-31, and HPV-53), we examined proliferative and cytokine responses in vaccine (n = 11) and placebo (n = 5) recipients. Increased proliferative and cytokine responses to heterologous types were observed postvaccination in some individuals. The proportion of women responding to heterologous types postvaccination (36%-55%) was lower than that observed in response to HPV-16 (73%). Response to HPV-16 VLP predicted response to other types. The strongest correlations in response were observed between HPV-16 and HPV-31, consistent with their phylogenetic relatedness. In summary, PBMC from HPV-16 VLP vaccine recipients can respond to L1VLP from heterologous HPV types, suggesting the presence of conserved T cell epitopes

Adaptive Response Against Spontaneous Neoplastic Transformation In Vitro Induced by Ionizing Radiation

International Nuclear Information System (INIS)

Redpath, J. Leslie

2003-01-01

The goal of this project was to establish a dose response curve for radiation-induced neoplastic transformation of HeLa x skin fibroblast human hybrid cells in vitro under experimental conditions were an adaptive response, if it were induced, would have an opportunity to be expressed. During the first two years of the grant an exhaustive series of experiments were performed and the resulting data were reported at the 2000 Annual Meeting of the Radiation Research Society and then Subsequently published. The data showed that an adaptive response against spontaneous neoplastic transformation was seen up to doses of 10cGy of Cs-137 gamma rays. At dose of 30, 50 and 100 cGy the transformation frequencies were above background. This indicated that for this system, under the specific experimental conditions used, there was a threshold of somewhere between 10 and 30 cGy. The results also indicated some unexpected, though very interesting, correlations with relative risk estimates made from human epidemiologic studies

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

Directory of Open Access Journals (Sweden)

Moore Dan

2005-01-01

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

Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

OpenAIRE

Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

2014-01-01

The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initia...

Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

Science.gov (United States)

Kumar, Anoop

2016-01-01

Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

Response of cellular stoichiometry and phosphorus storage of the cyanobacteria Aphanizomenon flos-aquae to small-scale turbulence

Science.gov (United States)

Li, Zhe; Xiao, Yan; Yang, Jixiang; Li, Chao; Gao, Xia; Guo, Jinsong

2017-11-01

Turbulent mixing, in particular on a small scale, affects the growth of microalgae by changing diffusive sublayers and regulating nutrient fluxes of cells. We tested the nutrient flux hypothesis by evaluating the cellular stoichiometry and phosphorus storage of microalgae under different turbulent mixing conditions. Aphanizomenon flos-aquae were cultivated in different stirring batch reactors with turbulent dissipation rates ranging from 0.001 51 m2/s3 to 0.050 58 m2/s3, the latter being the highest range observed in natural aquatic systems. Samples were taken in the exponential growth phase and compared with samples taken when the reactor was completely stagnant. Results indicate that, within a certain range, turbulent mixing stimulates the growth of A. flos-aquae. An inhibitory effect on growth rate was observed at the higher range. Photosynthesis activity, in terms of maximum effective quantum yield of PSII (the ratio of F v/ F m) and cellular chlorophyll a, did not change significantly in response to turbulence. However, Chl a/C mass ratio and C/N molar ratio, showed a unimodal response under a gradient of turbulent mixing, similar to growth rate. Moreover, we found that increases in turbulent mixing might stimulate respiration rates, which might lead to the use of polyphosphate for the synthesis of cellular constituents. More research is required to test and verify the hypothesis that turbulent mixing changes the diffusive sublayer, regulating the nutrient flux of cells.

RNA metabolism in Xylella fastidiosa during cold adaptation and survival responses

Science.gov (United States)

Fastidious plant pathogen Xylella fastidiosa has a reduced ability to adapt to cold temperatures, limiting persistence in perennial hosts, such as grapevine, growing in colder regions. RNA metabolism is an essential part of bacterial response to low temperature, including inducible expression of RNA...

Role of Cellular Immunity in Cow’s Milk Allergy: Pathogenesis, Tolerance Induction, and Beyond

Directory of Open Access Journals (Sweden)

Juandy Jo

2014-01-01

Full Text Available Food allergy is an aberrant immune-mediated reaction against harmless food substances, such as cow’s milk proteins. Due to its very early introduction, cow’s milk allergy is one of the earliest and most common food allergies. For this reason cow’s milk allergy can be recognized as one of the first indications of an aberrant inflammatory response in early life. Classically, cow’s milk allergy, as is true for most other allergies as well, is primarily associated with abnormal humoral immune responses, that is, elevation of specific immunoglobulin E levels. There is growing evidence indicating that cellular components of both innate and adaptive immunity play significant roles during the pathogenesis of cow’s milk allergy. This is true for the initiation of the allergic phenotype (stimulation and skewing towards sensitization, development and outgrowth of the allergic disease. This review discusses findings pertaining to roles of cellular immunity in allergic inflammation, and tolerance induction against cow’s milk proteins. In addition, a possible interaction between immune mechanisms underlying cow’s milk allergy and other types of inflammation (infections and noncommunicable diseases is discussed.

Adaptive responses of cardiac function to fetal postural change as gestational age increases

Science.gov (United States)

Kim, Woo Jin; Choi, Hye Jin; Yang, Sun Young; Koo, Boo Hae; Ahn, Ki Hoon; Hong, Soon Cheol; Oh, Min-Jeong; Kim, Hai-Joong

2016-01-01

Objective The cardiovascular system maintains homeostasis through a series of adaptive responses to physiological requirements. However, little is known about the adaptation of fetal cardiac function to gravity, according to gestational age. In the present study, we aimed to evaluate the adaptive responses of cardiac function to postural changes, using Tei index measurements. Methods Fetal echocardiography and Doppler examination were performed on 114 women with vertex singleton pregnancies at 19 to 40 weeks' gestation. Participants were placed in an upright seated position, and the Tei index for fetal left ventricular cardiac function was measured. The women were then moved into a supine position and the Tei index was re-measured. Results The mean Tei index when measured in an upright seated position was significantly lower than that measured in a supine positioning for all fetuses (0.528±0.103 vs. 0.555±0.106, P=0.014, respectively). This difference was also noted in fetuses with a gestational age of 28–40 weeks (0.539±0.107 vs. 0.574±0.102, P=0.011, respectively). However, there was no difference in the Tei index between an upright seated and a supine position among fetuses with a gestational age of Postural changes from an upright seated to a supine position result in an increased Tei index after a gestational age of 28 weeks. This appears to reflect maturation in the adaptive responses of the fetal cardiovascular system to postural changes. PMID:27896244

A celiac cellular phenotype, with altered LPP sub-cellular distribution, is inducible in controls by the toxic gliadin peptide P31-43.

Directory of Open Access Journals (Sweden)

Merlin Nanayakkara

Full Text Available Celiac disease (CD is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides P31-43 and P57-68 induce innate and adaptive T cell-mediated immune responses, respectively. Alterations in the cell shape and actin cytoskeleton are present in celiac enterocytes, and gliadin peptides induce actin rearrangements in both the CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and focal adhesions, sites of membrane attachment to the extracellular matrix. The locus of the human Lipoma Preferred Partner (LPP gene was identified as strongly associated with CD using genome-wide association studies (GWAS. The LPP protein plays an important role in focal adhesion architecture and acts as a transcription factor in the nucleus. In this study, we examined the hypothesis that a constitutive alteration of the cell shape and the cytoskeleton, involving LPP, occurs in a cell compartment far from the main inflammation site in CD fibroblasts from skin explants. We analyzed the cell shape, actin organization, focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free Diet (GFD and controls, without and with treatment with A-gliadin peptide P31-43. We observed a "CD cellular phenotype" in these fibroblasts, characterized by an altered cell shape and actin organization, increased number of focal adhesions, and altered intracellular LPP protein distribution. The treatment of controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub-cellular distribution, suggesting a close association between these alterations and CD pathogenesis.

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization

International Nuclear Information System (INIS)

Smolders, R.; Bervoets, L.; Coen, W. de; Blust, R.

2004-01-01

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels. - Exposure of zebra mussels along a pollution gradient has adverse effects on the cellular energy allocation, and results can be linked with higher levels of biological organization

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization

Energy Technology Data Exchange (ETDEWEB)

Smolders, R.; Bervoets, L.; Coen, W. de; Blust, R

2004-05-01

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels. - Exposure of zebra mussels along a pollution gradient has adverse effects on the cellular energy allocation, and results can be linked with higher levels of biological organization.

Seasonal variations of cellular stress response in the heart and gastrocnemius muscle of the water frog (Pelophylax ridibundus).

Science.gov (United States)

Feidantsis, Konstantinos; Anestis, Andreas; Vasara, Eleni; Kyriakopoulou-Sklavounou, Pasqualina; Michaelidis, Basile

2012-08-01

The present study aimed to investigate the seasonal cellular stress response in the heart and the gastrocnemius muscle of the amphibian Pelophylax ridibundus (former name Rana ridibunda) during an 8 month acclimatization period in the field. Processes studied included heat shock protein expression and protein kinase activation. The cellular stress response was addressed through the expression of Hsp70 and Hsp90 and the phosphorylation of stress-activated protein kinases and particularly p38 mitogen-activated protein kinase (p38 MAPK), the extracellular signal-regulated kinases (ERK-1/2) and c-Jun N-terminal kinases (JNK1/2/3). Due to a general metabolic depression during winter hibernation, the induction of Hsp70 and Hsp90 and the phosphorylation of p38 MAPK, JNKs and ERKs are retained at low levels of expression in the examined tissues of P. ridibundus. Recovery from hibernation induces increased levels of the specific proteins, probably providing stamina to the animals during their arousal. Copyright © 2012 Elsevier Inc. All rights reserved.

Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

Science.gov (United States)

Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

2017-07-01

Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

Investigating the effects of ABC transporter-based acquired drug resistance mechanisms at the cellular and tissue scale.

Science.gov (United States)

Liu, Cong; Krishnan, J; Xu, Xiao Yun

2013-03-01

In this paper we systematically investigate the effects of acquired drug resistance at the cellular and tissue scale, with a specific focus on ATP-binding cassette (ABC) transporter-based mechanisms and contrast this with other representative intracellular resistance mechanisms. This is done by developing in silico models wherein the drug resistance mechanism is overlaid on a coarse-grained description of apoptosis; these cellular models are coupled with interstitial drug transport, allowing for a transparent examination of the effect of acquired drug resistances at the tissue level. While ABC transporter-mediated resistance mechanisms counteract drug effect at the cellular level, its tissue-level effect is more complicated, revealing unexpected trends in tissue response as drug stimuli are systematically varied. Qualitatively different behaviour is observed in other drug resistance mechanisms. Overall the paper (i) provides insight into the tissue level functioning of a particular resistance mechanism, (ii) shows that this is very different from other resistance mechanisms of an apparently similar type, and (iii) demonstrates a concrete instance of how the functioning of a negative feedback based cellular adaptive mechanism can have unexpected higher scale effects.

Contrast adaptation in the Limulus lateral eye.

Science.gov (United States)

Valtcheva, Tchoudomira M; Passaglia, Christopher L

2015-12-01

Luminance and contrast adaptation are neuronal mechanisms employed by the visual system to adjust our sensitivity to light. They are mediated by an assortment of cellular and network processes distributed across the retina and visual cortex. Both have been demonstrated in the eyes of many vertebrates, but only luminance adaptation has been shown in invertebrate eyes to date. Since the computational benefits of contrast adaptation should apply to all visual systems, we investigated whether this mechanism operates in horseshoe crab eyes, one of the best-understood neural networks in the animal kingdom. The spike trains of optic nerve fibers were recorded in response to light stimuli modulated randomly in time and delivered to single ommatidia or the whole eye. We found that the retina adapts to both the mean luminance and contrast of a white-noise stimulus, that luminance- and contrast-adaptive processes are largely independent, and that they originate within an ommatidium. Network interactions are not involved. A published computer model that simulates existing knowledge of the horseshoe crab eye did not show contrast adaptation, suggesting that a heretofore unknown mechanism may underlie the phenomenon. This mechanism does not appear to reside in photoreceptors because white-noise analysis of electroretinogram recordings did not show contrast adaptation. The likely site of origin is therefore the spike discharge mechanism of optic nerve fibers. The finding of contrast adaption in a retinal network as simple as the horseshoe crab eye underscores the broader importance of this image processing strategy to vision. Copyright © 2015 the American Physiological Society.

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

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

2014-04-04

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

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

International Nuclear Information System (INIS)

Dong, Yan; Hirane, Miku; Araki, Mutsumi; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi

2014-01-01

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

Error Decomposition and Adaptivity for Response Surface Approximations from PDEs with Parametric Uncertainty

KAUST Repository

Bryant, C. M.; Prudhomme, S.; Wildey, T.

2015-01-01

In this work, we investigate adaptive approaches to control errors in response surface approximations computed from numerical approximations of differential equations with uncertain or random data and coefficients. The adaptivity of the response surface approximation is based on a posteriori error estimation, and the approach relies on the ability to decompose the a posteriori error estimate into contributions from the physical discretization and the approximation in parameter space. Errors are evaluated in terms of linear quantities of interest using adjoint-based methodologies. We demonstrate that a significant reduction in the computational cost required to reach a given error tolerance can be achieved by refining the dominant error contributions rather than uniformly refining both the physical and stochastic discretization. Error decomposition is demonstrated for a two-dimensional flow problem, and adaptive procedures are tested on a convection-diffusion problem with discontinuous parameter dependence and a diffusion problem, where the diffusion coefficient is characterized by a 10-dimensional parameter space.

Strains of bacterial species induce a greatly varied acute adaptive immune response: The contribution of the accessory genome.

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Uri Sela

2018-01-01

Full Text Available A fundamental question in human susceptibility to bacterial infections is to what extent variability is a function of differences in the pathogen species or in individual humans. To focus on the pathogen species, we compared in the same individual the human adaptive T and B cell immune response to multiple strains of two major human pathogens, Staphylococcus aureus and Streptococcus pyogenes. We found wide variability in the acute adaptive immune response induced by various strains of a species, with a unique combination of activation within the two arms of the adaptive response. Further, this was also accompanied by a dramatic difference in the intensity of the specific protective T helper (Th response. Importantly, the same immune response differences induced by the individual strains were maintained across multiple healthy human donors. A comparison of isogenic phage KO strains, demonstrated that of the pangenome, prophages were the major contributor to inter-strain immune heterogeneity, as the T cell response to the remaining "core genome" was noticeably blunted. Therefore, these findings extend and modify the notion of an adaptive response to a pathogenic bacterium, by implying that the adaptive immune response signature of a bacterial species should be defined either per strain or alternatively to the species' 'core genome', common to all of its strains. Further, our results demonstrate that the acquired immune response variation is as wide among different strains within a single pathogenic species as it is among different humans, and therefore may explain in part the clinical heterogeneity observed in patients infected with the same species.

Role of cellular adhesions in tissue dynamics spectroscopy

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Merrill, Daniel A.; An, Ran; Turek, John; Nolte, David

2014-02-01

Cellular adhesions play a critical role in cell behavior, and modified expression of cellular adhesion compounds has been linked to various cancers. We tested the role of cellular adhesions in drug response by studying three cellular culture models: three-dimensional tumor spheroids with well-developed cellular adhesions and extracellular matrix (ECM), dense three-dimensional cell pellets with moderate numbers of adhesions, and dilute three-dimensional cell suspensions in agarose having few adhesions. Our technique for measuring the drug response for the spheroids and cell pellets was biodynamic imaging (BDI), and for the suspensions was quasi-elastic light scattering (QELS). We tested several cytoskeletal chemotherapeutic drugs (nocodazole, cytochalasin-D, paclitaxel, and colchicine) on three cancer cell lines chosen from human colorectal adenocarcinoma (HT-29), human pancreatic carcinoma (MIA PaCa-2), and rat osteosarcoma (UMR-106) to exhibit differences in adhesion strength. Comparing tumor spheroid behavior to that of cell suspensions showed shifts in the spectral motion of the cancer tissues that match predictions based on different degrees of cell-cell contacts. The HT-29 cell line, which has the strongest adhesions in the spheroid model, exhibits anomalous behavior in some cases. These results highlight the importance of using three-dimensional tissue models in drug screening with cellular adhesions being a contributory factor in phenotypic differences between the drug responses of tissue and cells.

Toxicity evaluation of e-juice and its soluble aerosols generated by electronic cigarettes using recombinant bioluminescent bacteria responsive to specific cellular damages.

Science.gov (United States)

Bharadwaj, Shiv; Mitchell, Robert J; Qureshi, Anjum; Niazi, Javed H

2017-04-15

Electronic-cigarettes (e-cigarette) are widely used as an alternative to traditional cigarettes but their safety is not well established. Herein, we demonstrate and validate an analytical method to discriminate the deleterious effects of e-cigarette refills (e-juice) and soluble e-juice aerosol (SEA) by employing stress-specific bioluminescent recombinant bacterial cells (RBCs) as whole-cell biosensors. These RBCs carry luxCDABE-operon tightly controlled by promoters that specifically induced to DNA damage (recA), superoxide radicals (sodA), heavy metals (copA) and membrane damage (oprF). The responses of the RBCs following exposure to various concentrations of e-juice/SEA was recorded in real-time that showed dose-dependent stress specific-responses against both the e-juice and vaporized e-juice aerosols produced by the e-cigarette. We also established that high doses of e-juice (4-folds diluted) lead to cell death by repressing the cellular machinery responsible for repairing DNA-damage, superoxide toxicity, ion homeostasis and membrane damage. SEA also caused the cellular damages but the cells showed enhanced bioluminescence expression without significant growth inhibition, indicating that the cells activated their global defense system to repair these damages. DNA fragmentation assay also revealed the disintegration of total cellular DNA at sub-toxic doses of e-juice. Despite their state of matter, the e-juice and its aerosols induce cytotoxicity and alter normal cellular functions, respectively that raises concerns on use of e-cigarettes as alternative to traditional cigarette. The ability of RBCs in detecting both harmful effects and toxicity mechanisms provided a fundamental understanding of biological response to e-juice and aerosols. Copyright © 2016 Elsevier B.V. All rights reserved.

Interval for the expression of the adaptive response induced by gamma radiation in leucocytes of mouse In vivo

International Nuclear Information System (INIS)

Mendiola C, M.T.; Morales R, P.

2002-01-01

The interval between the adaptive gamma radiation dose (0.01 Gy) and challenge (1.0 Gy) capable to induce the maximum expression of the adaptive response in lymphocytes of mouse In vivo. The animals were exposed to the mentioned doses with different intervals among both (1, 1.5, 5 or 18 hr). By means of the unicellular electrophoresis in gel technique, four damage parameters were analysed. The results showed that from the 1 hr interval an adaptive response was produced since in the pretreated organisms with 0.01 Gy the cells present lesser damage than in those not adapted. The maximum response was induced with the intervals between 2.5 and 5 hr and even though it persisted until 18 hr, the effect was reducing. (Author)

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

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Natassya M Noor

Full Text Available Ubiquitin, an 8.5 kDa protein associated with the proteasome degradation pathway has been recently identified as differentially expressed in segment of cord caudal to site of injury in developing spinal cord. Here we describe ubiquitin expression and cellular distribution in spinal cord up to postnatal day P35 in control opossums (Monodelphis domestica and in response to complete spinal transection (T10 at P7, when axonal growth through site of injury occurs, and P28 when this is no longer possible. Cords were collected 1 or 7 days after injury, with age-matched controls and segments rostral to lesion were studied. Following spinal injury ubiquitin levels (western blotting appeared reduced compared to controls especially one day after injury at P28. In contrast, after injury mRNA expression (qRT-PCR was slightly increased at P7 but decreased at P28. Changes in isoelectric point of separated ubiquitin indicated possible post-translational modifications. Cellular distribution demonstrated a developmental shift between earliest (P8 and latest (P35 ages examined, from a predominantly cytoplasmic immunoreactivity to a nuclear expression; staining level and shift to nuclear staining was more pronounced following injury, except 7 days after transection at P28. After injury at P7 immunostaining increased in neurons and additionally in oligodendrocytes at P28. Mass spectrometry showed two ubiquitin bands; the heavier was identified as a fusion product, likely to be an ubiquitin precursor. Apparent changes in ubiquitin expression and cellular distribution in development and response to spinal injury suggest an intricate regulatory system that modulates these responses which, when better understood, may lead to potential therapeutic targets.

Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

Energy Technology Data Exchange (ETDEWEB)

Kiran, Shashi; Oddi, Vineesha [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Laboratory of Cancer Cell Biology, Department of Research, Institute of Liver and Biliary Sciences, Delhi 110070 (India)

2015-02-01

Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

Science.gov (United States)

Wang, Sheng; Zhang, Lei; Dong, Chunhong; Su, Lin; Wang, Hanjie; Chang, Jin

2015-01-01

A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

Abiotic stressors and stress responses: What commonalities appear between species across biological organization levels?

International Nuclear Information System (INIS)

Sulmon, Cécile; Baaren, Joan van; Cabello-Hurtado, Francisco; Gouesbet, Gwenola; Hennion, Françoise; Mony, Cendrine; Renault, David; Bormans, Myriam; El Amrani, Abdelhak; Wiegand, Claudia; Gérard, Claudia

2015-01-01

Organisms are regularly subjected to abiotic stressors related to increasing anthropogenic activities, including chemicals and climatic changes that induce major stresses. Based on various key taxa involved in ecosystem functioning (photosynthetic microorganisms, plants, invertebrates), we review how organisms respond and adapt to chemical- and temperature-induced stresses from molecular to population level. Using field-realistic studies, our integrative analysis aims to compare i) how molecular and physiological mechanisms related to protection, repair and energy allocation can impact life history traits of stressed organisms, and ii) to what extent trait responses influence individual and population responses. Common response mechanisms are evident at molecular and cellular scales but become rather difficult to define at higher levels due to evolutionary distance and environmental complexity. We provide new insights into the understanding of the impact of molecular and cellular responses on individual and population dynamics and assess the potential related effects on communities and ecosystem functioning. - Highlights: • Responses to chemical and thermal stressors are reviewed across organization levels. • Common responses between taxa are evident at the molecular and cellular scales. • At individual level, energy allocation connects species-specific stress responses. • Commonality decreases at higher levels due to increasing environmental complexity. - The commonality of stress responses to chemical and thermal stressors among taxa is evident at the molecular and cellular scales but remains unclear at higher levels of organization

Mechanical Adaptability of the MMP-Responsive Film Improves the Functionality of Endothelial Cell Monolayer.

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Hu, Mi; Chang, Hao; Zhang, He; Wang, Jing; Lei, Wen-Xi; Li, Bo-Chao; Ren, Ke-Feng; Ji, Jian

2017-07-01

Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radio propagation and adaptive antennas for wireless communication networks

CERN Document Server

Blaunstein, Nathan

2014-01-01

Explores novel wireless networks beyond 3G, and advanced 4G technologies, such as MIMO, via propagation phenomena and the fundamentals of adapted antenna usage.Explains how adaptive antennas can improve GoS and QoS for any wireless channel, with specific examples and applications in land, aircraft and satellite communications.Introduces new stochastic approach based on several multi-parametric models describing various terrestrial scenarios, which have been experimentally verified in different environmental conditionsNew chapters on fundamentals of wireless networks, cellular and non-cellular,

Adaptive cellular structures and devices with internal features for enhanced structural performance

Science.gov (United States)

Pontecorvo, Michael Eugene

This dissertation aims to develop a family of cellular and repeatable devices that exhibit a variety of force-displacement behaviors. It is envisioned that these cellular structures might be used either as stand-alone elements, or combined and repeated to create multiple types of structures (i.e. buildings, ship hulls, vehicle subfloors, etc.) with the ability to passively or actively perform multiple functions (harmonic energy dissipation, impact mitigation, modulus change) over a range of loading types, amplitudes, and frequencies. To accomplish this goal, this work combines repeatable structural frameworks, such as that provided by a hexagonal cellular structure, with internal structural elements such as springs, viscous dampers, buckling plates, bi-stable von Mises trusses (VMTs), and pneumatic artificial muscles (PAMs). The repeatable framework serves to position damping and load carrying elements throughout the structure, and the configuration of the internal elements allow each cell to be tuned to exhibit a desired force-displacement response. Therefore, gradient structures or structures with variable load paths can be created for an optimal global response to a range of loads. This dissertation focuses on the development of cellular structures for three functions: combined load-carrying capability with harmonic energy dissipation, impact mitigation, and cell modulus variation. One or more conceptual designs are presented for devices that can perform each of these functions, and both experimental measurements and simulations are used to gain a fundamental understanding of each device. Chapter 2 begins with a presentation of a VMT model that is the basis for many of the elements. The equations of motion for the VMT are derived and the static and dynamic behavior of the VMT are discussed in detail. Next, two metrics for the energy dissipation of the VMT - hysteresis loop area and loss factor - are presented. The responses of the VMT to harmonic displacement

Non-climatic thermal adaptation: implications for species' responses to climate warming.

Science.gov (United States)

Marshall, David J; McQuaid, Christopher D; Williams, Gray A

2010-10-23

There is considerable interest in understanding how ectothermic animals may physiologically and behaviourally buffer the effects of climate warming. Much less consideration is being given to how organisms might adapt to non-climatic heat sources in ways that could confound predictions for responses of species and communities to climate warming. Although adaptation to non-climatic heat sources (solar and geothermal) seems likely in some marine species, climate warming predictions for marine ectotherms are largely based on adaptation to climatically relevant heat sources (air or surface sea water temperature). Here, we show that non-climatic solar heating underlies thermal resistance adaptation in a rocky-eulittoral-fringe snail. Comparisons of the maximum temperatures of the air, the snail's body and the rock substratum with solar irradiance and physiological performance show that the highest body temperature is primarily controlled by solar heating and re-radiation, and that the snail's upper lethal temperature exceeds the highest climatically relevant regional air temperature by approximately 22°C. Non-climatic thermal adaptation probably features widely among marine and terrestrial ectotherms and because it could enable species to tolerate climatic rises in air temperature, it deserves more consideration in general and for inclusion into climate warming models.