Cellular Response to Ionizing Radiation: A MicroRNA Story

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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

Global exponential stability of mixed discrete and distributively delayed cellular neural network

International Nuclear Information System (INIS)

Yao Hong-Xing; Zhou Jia-Yan

2011-01-01

This paper concernes analysis for the global exponential stability of a class of recurrent neural networks with mixed discrete and distributed delays. It first proves the existence and uniqueness of the balance point, then by employing the Lyapunov—Krasovskii functional and Young inequality, it gives the sufficient condition of global exponential stability of cellular neural network with mixed discrete and distributed delays, in addition, the example is provided to illustrate the applicability of the result. (general)

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.

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 ...

Global exponential stability of impulsive fuzzy cellular neural networks with mixed delays and reaction-diffusion terms

International Nuclear Information System (INIS)

Wang Xiaohu; Xu Daoyi

2009-01-01

In this paper, the global exponential stability of impulsive fuzzy cellular neural networks with mixed delays and reaction-diffusion terms is considered. By establishing an integro-differential inequality with impulsive initial condition and using the properties of M-cone and eigenspace of the spectral radius of nonnegative matrices, several new sufficient conditions are obtained to ensure the global exponential stability of the equilibrium point for fuzzy cellular neural networks with delays and reaction-diffusion terms. These results extend and improve the earlier publications. Two examples are given to illustrate the efficiency of the obtained results.

Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation.

Directory of Open Access Journals (Sweden)

Sarah R Smith

2016-12-01

Full Text Available Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved in the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability

Global transcriptomic profiling demonstrates induction of oxidative stress and of compensatory cellular stress responses in brown trout exposed to glyphosate and Roundup.

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Uren Webster, Tamsyn M; Santos, Eduarda M

2015-01-31

Glyphosate, the active ingredient in Roundup formulations, is the most widely used herbicide worldwide, and as a result contaminates surface waters and has been detected in food residues, drinking water and human urine, raising concerns for potential environmental and human health impacts. Research has shown that glyphosate and Roundup can induce a broad range of biological effects in exposed organisms, particularly via generation of oxidative stress. However, there has been no comprehensive investigation of the global molecular mechanisms of toxicity of glyphosate and Roundup for any species. We aimed to characterise and compare the global mechanisms of toxicity of glyphosate and Roundup in the liver of brown trout (Salmo trutta), an ecologically and economically important vertebrate species, using RNA-seq on an Illumina HiSeq 2500 platform. To do this, we exposed juvenile female brown trout to 0, 0.01, 0.5 and 10 mg/L of glyphosate and Roundup (glyphosate acid equivalent) for 14 days, and sequenced 6 replicate liver samples from each treatment. We assembled the brown trout transcriptome using an optimised de novo approach, and subsequent differential expression analysis identified a total of 1020 differentially-regulated transcripts across all treatments. These included transcripts encoding components of the antioxidant system, a number of stress-response proteins and pro-apoptotic signalling molecules. Functional analysis also revealed over-representation of pathways involved in regulating of cell-proliferation and turnover, and up-regulation of energy metabolism and other metabolic processes. These transcriptional changes are consistent with generation of oxidative stress and the widespread induction of compensatory cellular stress response pathways. The mechanisms of toxicity identified were similar across both glyphosate and Roundup treatments, including for environmentally relevant concentrations. The significant alterations in transcript expression observed

Global exponential stability of cellular neural networks with mixed delays and impulses

International Nuclear Information System (INIS)

Xiong Wanmin; Zhou Qiyuan; Xiao Bing; Yu Yuehua

2007-01-01

In this paper cellular neural networks with mixed delays and impulses are considered. Sufficient conditions for the existence and global exponential stability of a unique equilibrium point are established by using the fixed point theorem and differential inequality technique. The results of this paper are new and they complement previously known results

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 ...

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.

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

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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

Title: Freshwater phytoplankton responses to global warming.

Science.gov (United States)

Wagner, Heiko; Fanesi, Andrea; Wilhelm, Christian

2016-09-20

Global warming alters species composition and function of freshwater ecosystems. However, the impact of temperature on primary productivity is not sufficiently understood and water quality models need to be improved in order to assess the quantitative and qualitative changes of aquatic communities. On the basis of experimental data, we demonstrate that the commonly used photosynthetic and water chemistry parameters alone are not sufficient for modeling phytoplankton growth under changing temperature regimes. We present some new aspects of the acclimation process with respect to temperature and how contrasting responses may be explained by a more complete physiological knowledge of the energy flow from photons to new biomass. We further suggest including additional bio-markers/traits for algal growth such as carbon allocation patterns to increase the explanatory power of such models. Although carbon allocation patterns are promising and functional cellular traits for growth prediction under different nutrient and light conditions, their predictive power still waits to be tested with respect to temperature. A great challenge for the near future will be the prediction of primary production efficiencies under the global change scenario using a uniform model for phytoplankton assemblages. Copyright © 2016 Elsevier GmbH. All rights reserved.

A global interaction network maps a wiring diagram of cellular function

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Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

2017-01-01

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

Global exponential stability of cellular neural networks with continuously distributed delays and impulses

International Nuclear Information System (INIS)

Wang Yixuan; Xiong Wanmin; Zhou Qiyuan; Xiao Bing; Yu Yuehua

2006-01-01

In this Letter cellular neural networks with continuously distributed delays and impulses are considered. Sufficient conditions for the existence and global exponential stability of a unique equilibrium point are established by using the fixed point theorem and differential inequality techniques. The results of this Letter are new and they complement previously known results

Coupled pulsating and cellular structure in the propagation of globally planar detonations in free space

International Nuclear Information System (INIS)

Han, Wenhu; Gao, Yang; Wang, Cheng; Law, Chung K.

2015-01-01

The globally planar detonation in free space is numerically simulated, with particular interest to understand and quantify the emergence and evolution of the one-dimensional pulsating instability and the two-dimensional cellular structure which is inherently also affected by pulsating instability. It is found that the pulsation includes three stages: rapid decay of the overdrive, approach to the Chapman-Jouguet state and emergence of weak pulsations, and the formation of strong pulsations; while evolution of the cellular structure also exhibits distinct behavior at these three stages: no cell formation, formation of small-scale, irregular cells, and formation of regular cells of a larger scale. Furthermore, the average shock pressure in the detonation front consists of fine-scale oscillations reflecting the collision dynamics of the triple-shock structure and large-scale oscillations affected by the global pulsation. The common stages of evolution between the cellular structure and the pulsating behavior, as well as the existence of shock-front pressure oscillation, suggest highly correlated mechanisms between them. Detonations with period doubling, period quadrupling, and chaotic amplitudes were also observed and studied for progressively increasing activation energies

From conceptual pluralism to practical agreement on policy: global responsibility for global health.

Science.gov (United States)

Ruger, Jennifer Prah; Hammonds, Rachel; Ooms, Gorik; Barry, Donna; Chapman, Audrey; Van Damme, Wim

2015-10-28

As the human cost of the global economic crisis becomes apparent the ongoing discussions surrounding the post-2015 global development framework continue at a frenzied pace. Given the scale and scope of increased globalization moving forward in a post-Millennium Development Goals era, to protect and realize health equity for all people, has never been more challenging or more important. The unprecedented nature of global interdependence underscores the importance of proposing policy solutions that advance realizing global responsibility for global health. This article argues for advancing global responsibility for global health through the creation of a Global Fund for Health. It suggests harnessing the power of the exceptional response to the combined epidemics of AIDS, TB and Malaria, embodied in the Global Fund to Fight AIDS, Tuberculosis and Malaria, to realize an expanded, reconceptualized Global Fund for Health. However this proposal creates both an analytical quandary embedded in conceptual pluralism and a practical dilemma for the scope and raison d'etre of a new Global Fund for Health. To address these issues we offer a logical framework for moving from conceptual pluralism in the theories supporting global responsibility for health to practical agreement on policy to realize this end. We examine how the innovations flowing from this exceptional response can be coupled with recent ideas and concepts, for example a global social protection floor, a Global Health Constitution or a Framework Convention for Global Health, that share the global responsibility logic that underpins a Global Fund for Health. The 2014 Lancet Commission on Global Governance for Health Report asks whether a single global health protection fund would be better for global health than the current patchwork of global and national social transfers. We concur with this suggestion and argue that there is much room for practical agreement on a Global Fund for Health that moves from the

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 Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations.

Science.gov (United States)

Keenan, Alexandra B; Jenkins, Sherry L; Jagodnik, Kathleen M; Koplev, Simon; He, Edward; Torre, Denis; Wang, Zichen; Dohlman, Anders B; Silverstein, Moshe C; Lachmann, Alexander; Kuleshov, Maxim V; Ma'ayan, Avi; Stathias, Vasileios; Terryn, Raymond; Cooper, Daniel; Forlin, Michele; Koleti, Amar; Vidovic, Dusica; Chung, Caty; Schürer, Stephan C; Vasiliauskas, Jouzas; Pilarczyk, Marcin; Shamsaei, Behrouz; Fazel, Mehdi; Ren, Yan; Niu, Wen; Clark, Nicholas A; White, Shana; Mahi, Naim; Zhang, Lixia; Kouril, Michal; Reichard, John F; Sivaganesan, Siva; Medvedovic, Mario; Meller, Jaroslaw; Koch, Rick J; Birtwistle, Marc R; Iyengar, Ravi; Sobie, Eric A; Azeloglu, Evren U; Kaye, Julia; Osterloh, Jeannette; Haston, Kelly; Kalra, Jaslin; Finkbiener, Steve; Li, Jonathan; Milani, Pamela; Adam, Miriam; Escalante-Chong, Renan; Sachs, Karen; Lenail, Alex; Ramamoorthy, Divya; Fraenkel, Ernest; Daigle, Gavin; Hussain, Uzma; Coye, Alyssa; Rothstein, Jeffrey; Sareen, Dhruv; Ornelas, Loren; Banuelos, Maria; Mandefro, Berhan; Ho, Ritchie; Svendsen, Clive N; Lim, Ryan G; Stocksdale, Jennifer; Casale, Malcolm S; Thompson, Terri G; Wu, Jie; Thompson, Leslie M; Dardov, Victoria; Venkatraman, Vidya; Matlock, Andrea; Van Eyk, Jennifer E; Jaffe, Jacob D; Papanastasiou, Malvina; Subramanian, Aravind; Golub, Todd R; Erickson, Sean D; Fallahi-Sichani, Mohammad; Hafner, Marc; Gray, Nathanael S; Lin, Jia-Ren; Mills, Caitlin E; Muhlich, Jeremy L; Niepel, Mario; Shamu, Caroline E; Williams, Elizabeth H; Wrobel, David; Sorger, Peter K; Heiser, Laura M; Gray, Joe W; Korkola, James E; Mills, Gordon B; LaBarge, Mark; Feiler, Heidi S; Dane, Mark A; Bucher, Elmar; Nederlof, Michel; Sudar, Damir; Gross, Sean; Kilburn, David F; Smith, Rebecca; Devlin, Kaylyn; Margolis, Ron; Derr, Leslie; Lee, Albert; Pillai, Ajay

2018-01-24

The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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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.

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 cellular adaptive response the role in life organisms

International Nuclear Information System (INIS)

Smith, H.

1998-01-01

Exposure of living cells to ionizing radiation may cause DNA damage that are generally harmful to the organism. This paper discuss the cellular adaptive response which may be seen when cells which have already been exposed to low concentration radiation doses are subsequently exposed to high concentration doses. It also discusses evidence of the adaptive response in laboratory animals and from limited epidemiological studies. (Author)

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

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 ...

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.

A global genetic interaction network maps a wiring diagram of cellular function.

Science.gov (United States)

Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D; Pelechano, Vicent; Styles, Erin B; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F; Li, Sheena C; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; San Luis, Bryan-Joseph; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M; Moore, Claire L; Rosebrock, Adam P; Caudy, Amy A; Myers, Chad L; Andrews, Brenda; Boone, Charles

2016-09-23

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. Copyright © 2016, American Association for the Advancement of Science.

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

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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...

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

Responsibility without Guilt: A Youngian Approach to Responsibility for Global Injustice

OpenAIRE

McKeown, M. C.

2015-01-01

What responsibilities do individuals have in relation to global injustice? Iris Young argues that all agents “connected” to global structural injustice bear political responsibility, rather than moral responsibility; the difference being that political responsibility is non-blameworthy, shared and forward-looking, whereas moral responsibility entails blameworthiness, isolates particular agents for censure and is backward-looking. Thus, individuals are not guilty of wrongdoing but they bear re...

The global transcriptional response of fission yeast to hydrogen sulfide.

Directory of Open Access Journals (Sweden)

Xu Jia

Full Text Available BACKGROUND: Hydrogen sulfide (H(2S is a newly identified member of the small family of gasotransmitters that are endogenous gaseous signaling molecules that have a fundamental role in human biology and disease. Although it is a relatively recent discovery and the mechanism of H(2S activity is not completely understood, it is known to be involved in a number of cellular processes; H(2S can affect ion channels, transcription factors and protein kinases in mammals. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we have used fission yeast as a model organism to study the global gene expression profile in response to H(2S by microarray. We initially measured the genome-wide transcriptional response of fission yeast to H(2S. Through the functional classification of genes whose expression profile changed in response to H(2S, we found that H(2S mainly influences genes that encode putative or known stress proteins, membrane transporters, cell cycle/meiotic proteins, transcription factors and respiration protein in the mitochondrion. Our analysis showed that there was a significant overlap between the genes affected by H(2S and the stress response. We identified that the target genes of the MAPK pathway respond to H(2S; we also identified that a number of transporters respond to H(2S, these include sugar/carbohydrate transporters, ion transporters, and amino acid transporters. We found many mitochondrial genes to be down regulated upon H(2S treatment and that H(2S can reduce mitochondrial oxygen consumption. CONCLUSION/SIGNIFICANCE: This study identifies potential molecular targets of the signaling molecule H(2S in fission yeast and provides clues about the identity of homologues human proteins and will further the understanding of the cellular role of H(2S in human diseases.

Global stability of almost periodic solution of shunting inhibitory cellular neural networks with variable coefficients

International Nuclear Information System (INIS)

Chen Ling; Zhao Hongyong

2008-01-01

The paper investigates the almost periodicity of shunting inhibitory cellular neural networks with delays and variable coefficients. Several sufficient conditions are established for the existence and globally exponential stability of almost periodic solutions by employing fixed point theorem and differential inequality technique. The results of this paper are new and they complement previously known results

Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

International Nuclear Information System (INIS)

Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

2002-01-01

Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

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.

Antiviral and Inflammatory Cellular Signaling Associated with Enterovirus 71 Infection

Directory of Open Access Journals (Sweden)

Yuefei Jin

2018-03-01

Full Text Available Enterovirus 71 (EV71 infection has become a major threat to global public health, especially in infants and young children. Epidemiological studies have indicated that EV71 infection is responsible for severe and even fatal cases of hand, foot, and mouth disease (HFMD. Accumulated evidence indicates that EV71 infection triggers a plethora of interactive signaling pathways, resulting in host immune evasion and inflammatory response. This review mainly covers the effects of EV71 infection on major antiviral and inflammatory cellular signal pathways. EV71 can activate cellular signaling networks including multiple cell surface and intracellular receptors, intracellular kinases, calcium flux, and transcription factors that regulate antiviral innate immunity and inflammatory response. Cellular signaling plays a critical role in the regulation of host innate immune and inflammatory pathogenesis. Elucidation of antiviral and inflammatory cellular signaling pathways initiated by EV71 will not only help uncover the potential mechanisms of EV71 infection-induced pathogenesis, but will also provide clues for the design of therapeutic strategies against EV71 infection.

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.

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.

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

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 ...

Study on cellular survival adaptive response induced by low dose irradiation of 153Sm

International Nuclear Information System (INIS)

Zhu Shoupeng; Xiao Dong

1999-01-01

The present study engages in determining whether low dose irradiation of 153 Sm could cut down the responsiveness of cellular survival to subsequent high dose exposure of 153 Sm so as to make an inquiry into approach the protective action of adaptive response by second irradiation of 153 Sm. Experimental results indicate that for inductive low dose of radionuclide 153 Sm 3.7 kBq/ml irradiated beforehand to cells has obvious resistant effect in succession after high dose irradiation of 153 Sm 3.7 x 10 2 kBq/ml was observed. Cells exposed to low dose irradiation of 153 Sm become adapted and therefore the subsequent cellular survival rate induced by high dose of 153 Sm is sufficiently higher than high dose of 153 Sm merely. It is evident that cellular survival adaptive response could be induced by pure low dose irradiation of 153 Sm only

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.

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.

Doing global science a guide to responsible conduct in the global research enterprise

CERN Document Server

InterAcademy Partnership

2016-01-01

This concise introductory guide explains the values that should inform the responsible conduct of scientific research in today's global setting. Featuring accessible discussions and ample real-world scenarios, Doing Global Science covers proper conduct, fraud and bias, the researcher's responsibilities to society, communication with the public, and much more. The book places special emphasis on the international and highly networked environment in which modern research is done, presenting science as an enterprise that is being transformed by globalization, interdisciplinary research projects, team science, and information technologies. Accessibly written by an InterAcademy Partnership committee comprised of leading scientists from around the world, Doing Global Science is required reading for students, practitioners, and anyone concerned about the responsible conduct of science today.

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)

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

Directory of Open Access Journals (Sweden)

Mykyta V Sokolov

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

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.

Is man responsible for global warming?

International Nuclear Information System (INIS)

Legendre, A.

2009-01-01

According to politicians, ecologists and mass media, it is now certain that with our CO 2 emissions, we are all responsible for a major global warming to come with dramatic consequences. But, is this affirmation indisputable? Are we all responsible for the rise of sea level and the summer thawing of the arctic ice shelf? Is this expected global warming without precedent? And is CO 2 , necessary for life, the cause of our misfortune? The answers commonly claimed are maybe more complex in reality and the climate question more subtle than it looks like. This book tries to decode the wheels of the climate machine and the share of human responsibility in climate change. (J.S.)

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.

An analysis of global robust stability of uncertain cellular neural networks with discrete and distributed delays

International Nuclear Information System (INIS)

Park, Ju H.

2007-01-01

This paper considers the robust stability analysis of cellular neural networks with discrete and distributed delays. Based on the Lyapunov stability theory and linear matrix inequality (LMI) technique, a novel stability criterion guaranteeing the global robust convergence of the equilibrium point is derived. The criterion can be solved easily by various convex optimization algorithms. An example is given to illustrate the usefulness of our results

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.

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.

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...

Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika Virus Infection.

Science.gov (United States)

Etebari, Kayvan; Hegde, Shivanand; Saldaña, Miguel A; Widen, Steven G; Wood, Thomas G; Asgari, Sassan; Hughes, Grant L

2017-01-01

Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti , which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including

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.

Global gene expression response to telomerase in bovine adrenocortical cells

International Nuclear Information System (INIS)

Perrault, Steven D.; Hornsby, Peter J.; Betts, Dean H.

2005-01-01

The infinite proliferative capability of most immortalized cells is dependent upon the presence of the enzyme telomerase and its ability to maintain telomere length and structure. However, telomerase may be involved in a greater system than telomere length regulation, as recent evidence has shown it capable of increasing wound healing in vivo, and improving cellular proliferation rate and survival from apoptosis in vitro. Here, we describe the global gene expression response to ectopic telomerase expression in an in vitro bovine adrenocortical cell model. Telomerase-immortalized cells showed an increased ability for proliferation and survival in minimal essential medium above cells transgenic for GFP. cDNA microarray analyses revealed an altered cell state indicative of increased adrenocortical cell proliferation regulated by the IGF2 pathway and alterations in members of the TGF-B family. As well, we identified alterations in genes associated with development and wound healing that support a model that high telomerase expression induces a highly adaptable, progenitor-like state

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).

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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.

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

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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.

Forced Migration and Global Responsibility for Health

Science.gov (United States)

Bozorgmehr, Kayvan; Razum, Oliver

2017-01-01

Forced migration has become a world-wide phenomenon in the past century, affecting increasing numbers of countries and people. It entails important challenges from a global health perspective. Leppold et al have critically discussed the Japanese interpretation of global responsibility for health in the context of forced migration. This commentary complements their analysis by outlining three priority areas of global health responsibility for European Union (EU) countries. We highlight important stages of the migration phases related to forced migration and propose three arguments. First, the chronic neglect of the large number of internally displaced persons (IDPs) in the discourses on the "refugee crisis" needs to be corrected in order to develop sustainable solutions with a framework of the Sustainable Development Goals (SDGs). Second, protection gaps in the global system of protection need to be effectively closed to resolve conflicts with border management and normative global health frameworks. Third, effective policies need to be developed and implemented to meet the health and humanitarian needs of forced migrants; at the same time, the solidarity crisis within the EU needs to be overcome. These stakes are high. EU countries, being committed to global health, should urgently address these areas. PMID:28812838

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.

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

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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

Globalization, financial capitalism, and corporate social responsibility: Structural tensions

OpenAIRE

David Barbosa Ramírez; Christian Medina López; Myriam Vargas López

2014-01-01

Globalization and financial capitalism keep a synergy in a global context whose problems such as environmental degradation, social inequity, economic crises and corruption are intensified. Corporate Social Responsibility emerges as a mechanism that seeks to mitigate some of these problems, although its effectiveness and impact today are challenged. The system which globalization, financial capitalism and social responsibility are a part of, is currently facing a number of structural tensions ...

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...

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

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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.

Culturally Responsive: Art Education in a Global Era

Science.gov (United States)

Lai, Alice

2012-01-01

Facing the era of globalization, culturally responsive art teachers must recognize that students' home culture, including local artistic expression, is inevitably influenced by global forces. They should strive to engage with students systems and issues of globalization and its impact on their community culture and art. In this article, the author…

Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation.

Science.gov (United States)

Benton, Michael G; Somasundaram, Swetha; Glasner, Jeremy D; Palecek, Sean P

2006-12-01

One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation

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Glasner Jeremy D

2006-12-01

Full Text Available Abstract Background One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS and gamma radiation. Results Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1 are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Conclusion Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

Multiscale evaluation of cellular adhesion alteration and cytoskeleton remodeling by magnetic bead twisting.

Science.gov (United States)

Isabey, Daniel; Pelle, Gabriel; André Dias, Sofia; Bottier, Mathieu; Nguyen, Ngoc-Minh; Filoche, Marcel; Louis, Bruno

2016-08-01

Cellular adhesion forces depend on local biological conditions meaning that adhesion characterization must be performed while preserving cellular integrity. We presently postulate that magnetic bead twisting provides an appropriate stress, i.e., basically a clamp, for assessment in living cells of both cellular adhesion and mechanical properties of the cytoskeleton. A global dissociation rate obeying a Bell-type model was used to determine the natural dissociation rate ([Formula: see text]) and a reference stress ([Formula: see text]). These adhesion parameters were determined in parallel to the mechanical properties for a variety of biological conditions in which either adhesion or cytoskeleton was selectively weakened or strengthened by changing successively ligand concentration, actin polymerization level (by treating with cytochalasin D), level of exerted stress (by increasing magnetic torque), and cell environment (by using rigid and soft 3D matrices). On the whole, this multiscale evaluation of the cellular and molecular responses to a controlled stress reveals an evolution which is consistent with stochastic multiple bond theories and with literature results obtained with other molecular techniques. Present results confirm the validity of the proposed bead-twisting approach for its capability to probe cellular and molecular responses in a variety of biological conditions.

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

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

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

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

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 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.

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.

Managing Corporate Responsibility Globally and Locally

DEFF Research Database (Denmark)

Brown, Dana; Knudsen, Jette Steen

2012-01-01

Corporate Responsibility (CR) is today an essential component of corporate global strategy. CR can bolster the institutional context for market expansion fill institutional voids or facilitate market entry as a component of non-market strategy. Yet, in fulfilling these functions, CR may need...... to be highly sensitive to local contexts. How can transnational firms organize CR so as to maximize efficiencies from globalization and to minimize the fragmentation of corporate organizational cultures? provide a framework for analyzing the way that corporations coordinate global and local functions. We build...... on this framework in a case study of Novo Nordisk and its approach to determining global and local CR policies and procedures with regard to its China and US subsidiaries. Our findings suggest that it is important for companies to define a common set of organizational norms. In addition, CR need to be sensitive...

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

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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

Globalization, financial capitalism, and corporate social responsibility: Structural tensions

Directory of Open Access Journals (Sweden)

David Barbosa Ramírez

2014-12-01

Full Text Available Globalization and financial capitalism keep a synergy in a global context whose problems such as environmental degradation, social inequity, economic crises and corruption are intensified. Corporate Social Responsibility emerges as a mechanism that seeks to mitigate some of these problems, although its effectiveness and impact today are challenged. The system which globalization, financial capitalism and social responsibility are a part of, is currently facing a number of structural tensions that contribute to the analysis, understanding and solving of the mentioned problems. This paper identifies and analyzes four of the aforementioned structural tensions.

Conceptualizing psychological processes in response to globalization: Components, antecedents, and consequences of global orientations.

Science.gov (United States)

Chen, Sylvia Xiaohua; Lam, Ben C P; Hui, Bryant P H; Ng, Jacky C K; Mak, Winnie W S; Guan, Yanjun; Buchtel, Emma E; Tang, Willie C S; Lau, Victor C Y

2016-02-01

The influences of globalization have permeated various aspects of life in contemporary society, from technical innovations, economic development, and lifestyles, to communication patterns. The present research proposed a construct termed global orientation to denote individual differences in the psychological processes of acculturating to the globalizing world. It encompasses multicultural acquisition as a proactive response and ethnic protection as a defensive response to globalization. Ten studies examined the applicability of global orientations among majority and minority groups, including immigrants and sojourners, in multicultural and relatively monocultural contexts, and across Eastern and Western cultures. Multicultural acquisition is positively correlated with both independent and interdependent self-construals, bilingual proficiency and usage, and dual cultural identifications. Multicultural acquisition is promotion-focused, while ethnic protection is prevention-focused and related to acculturative stress. Global orientations affect individuating and modest behavior over and above multicultural ideology, predict overlap with outgroups over and above political orientation, and predict psychological adaptation, sociocultural competence, tolerance, and attitudes toward ethnocultural groups over and above acculturation expectations/strategies. Global orientations also predict English and Chinese oral presentation performance in multilevel analyses and the frequency and pleasantness of intercultural contact in cross-lagged panel models. We discuss how the psychological study of global orientations contributes to theory and research on acculturation, cultural identity, and intergroup relations. (c) 2016 APA, all rights reserved).

Biodiversity and global change. Adaptative responses to global change: results and prospective. IFB-GICC restitution colloquium

International Nuclear Information System (INIS)

Despres, L.; Hossaert-Mckey, M.; Martin, J.F.; Pont, D.; Valero, M.; Chave, J.; Benizri, E.; Amiaud, B.; Boury-Esnault, N.; Fritz, H.; Lavelle, P.; Martin, F.; Poulet, S.; Blanchard, F.; Cheddadi, R.; Dupouey, J.L.; Hulle, M.; Michaux, J.; Souissi, S.; Bridault, A.; Dambrine, E.; Gomez, B.; Thevenard, F.; Legendre, S.; Suc, J.P.; Zeitoun, V.; Bezancon, G.; Frascaria-Lacoste, N.; Ponsard, S.; Bourguet, D.; Vigne, J.D.; Doyen, L.; Joly, P.; Gourlet-Fleury, S.; Garnier, E.; Lebaron, Ph.; Boulinier, Th.; Chuine, I.; Jiguet, F.; Couvet, D.; Soussana, J.F.; Weimerskirsch, H.; Grosbois, V.; Bretagnolle, V.

2006-01-01

Global change is the consequence of the worldwide human print on ecology. The uncontrolled use of fossil fuels, the urbanization, the intensifying of agriculture, the homogenization of life styles and cultures, the homogenization of fauna and vegetation, the commercial trades, the bio-invasions, the over-exploitation of resources and the emergence of new economic powers (China, India, Brazil..) represent an adaptative dynamics of interactions which affects the overall biosphere and the adaptative capacities and the future of all species. Biodiversity is an ecological and societal insurance against the risks and uncertainties linked with global change. The French institute of biodiversity (IFB) has created a working group in charge of a study on global change and biodiversity, in particular in terms of: speed and acceleration of processes, interaction between the different organization levels of the world of living, scale changes, and adaptative capacities. 38 projects with an interdisciplinary approach have been retained by the IFB and the Ministry of ecology and sustainable development. The conclusion of these projects were presented at this restitution colloquium and are summarized in this document. The presentations are organized in 7 sessions dealing with: global changes and adaptation mechanisms; functional responses to global changes; spatial responses to global changes; temporal responses to global changes; selective answers to global changes; available tools and ecological services; scenarios and projections. (J.S.)

The Role of Civil Society Organizations in Monitoring the Global AIDS Response.

Science.gov (United States)

Smith, Julia; Mallouris, Christoforos; Lee, Kelley; Alfvén, Tobias

2017-07-01

Civil society organizations (CSOs) are recognized as playing an exceptional role in the global AIDS response. However, there is little detailed research to date on how they contribute to specific governance functions. This article uses Haas' framework on global governance functions to map CSO's participation in the monitoring of global commitments to the AIDS response by institutions and states. Drawing on key informant interviews and primary documents, it focuses specifically on CSO participation in Global AIDS Response Progress Reporting and in Global Fund to Fight AIDS, Tuberculosis and Malaria processes. It argues that the AIDS response is unique within global health governance, in that CSOs fulfill both formal and informal monitoring functions, and considers the strengths and weaknesses of these contributions. It concludes that future global health governance arrangements should include provisions and resources for monitoring by CSOs because their participation creates more inclusive global health governance and contributes to strengthening commitments to human rights.

Phylogenetic responses of forest trees to global change.

Science.gov (United States)

Senior, John K; Schweitzer, Jennifer A; O'Reilly-Wapstra, Julianne; Chapman, Samantha K; Steane, Dorothy; Langley, Adam; Bailey, Joseph K

2013-01-01

In a rapidly changing biosphere, approaches to understanding the ecology and evolution of forest species will be critical to predict and mitigate the effects of anthropogenic global change on forest ecosystems. Utilizing 26 forest species in a factorial experiment with two levels each of atmospheric CO2 and soil nitrogen, we examined the hypothesis that phylogeny would influence plant performance in response to elevated CO2 and nitrogen fertilization. We found highly idiosyncratic responses at the species level. However, significant, among-genetic lineage responses were present across a molecularly determined phylogeny, indicating that past evolutionary history may have an important role in the response of whole genetic lineages to future global change. These data imply that some genetic lineages will perform well and that others will not, depending upon the environmental context.

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....

Matrix metalloproteinase 3 promotes cellular anti-dengue virus response via interaction with transcription factor NFκB in cell nucleus.

Science.gov (United States)

Zuo, Xiangyang; Pan, Wen; Feng, Tingting; Shi, Xiaohong; Dai, Jianfeng

2014-01-01

Dengue virus (DENV), the causative agent of human Dengue hemorrhagic fever, is a mosquito-borne virus of immense global health importance. Characterization of cellular factors promoting or inhibiting DENV infection is important for understanding the mechanism of DENV infection. In this report, MMP3 (stromelysin-1), a secretory endopeptidase that degrades extracellular matrices, has been shown promoting cellular antiviral response against DENV infection. Quantitative RT-PCR and Western Blot showed that the expression of MMP3 was upregulated in DENV-infected RAW264.7 cells. The intracellular viral loads were significantly higher in MMP3 silenced cells compared with controls. The expression level of selective anti-viral cytokines were decreased in MMP3 siRNA treated cells, and the transcription factor activity of NFκB was significantly impaired upon MMP3 silencing during DENV infection. Further, we found that MMP3 moved to cell nucleus upon DENV infection and colocalized with NFκB P65 in nucleus. Co-immunoprecipitation analysis suggested that MMP3 directly interacted with NFκB in nucleus during DENV infection and the C-terminal hemopexin-like domain of MMP3 was required for the interaction. This study suggested a novel role of MMP3 in nucleus during viral infection and provided new evidence for MMPs in immunomodulation.

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....

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

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.

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

Dynamical response of the Arctic winter stratosphere to global warming

Science.gov (United States)

Karpechko, A.; Manzini, E.

2017-12-01

Climate models often simulate dynamical warming of the Arctic stratosphere as a response to global warming in association with a strengthening of the deep branch of the Brewer-Dobson circulation; however until now, no satisfactory mechanism for such a response has been suggested. Here we investigate the role of stationary planetary waves in the dynamical response of the Arctic winter stratosphere circulation to global warming by analysing simulations performed with atmosphere-only Coupled Model Intercomparison Project Phase 5 (CMIP5) models driven by prescribed sea surface temperatures (SSTs). We focus on December-February (DJF) because this is the period when the troposphere and stratosphere are strongly coupled. When forced by increased SSTs, all the models analysed here simulate Arctic stratosphere dynamical warming, mostly due to increased upward propagation of quasi-stationary wave number 1, as diagnosed by the meridional eddy heat flux. By analysing intermodel spread in the response we show that the stratospheric warming and increased wave flux to the stratosphere correlate with the strengthening of the zonal winds in subtropics and mid-latitudes near the tropopause- a robust response to global warming. These results support previous studies of future Arctic stratosphere changes and suggest a dynamical warming of the Arctic wintertime polar vortex as the most likely response to global warming.

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.

Global transcriptional response of Saccharomyces cerevisiae to the deletion of SDH3

DEFF Research Database (Denmark)

Cimini, Donatella; Patil, Kiran Raosaheb; Schiraldi, Chiara

2009-01-01

Background: Mitochondrial respiration is an important and widely conserved cellular function in eukaryotic cells. The succinate dehydrogenase complex (Sdhp) plays an important role in respiration as it connects the mitochondrial respiratory chain to the tricarboxylic acid (TCA) cycle where...... it catalyzes the oxidation of succinate to fumarate. Cellular response to the Sdhp dysfunction (i.e. impaired respiration) thus has important implications not only for biotechnological applications but also for understanding cellular physiology underlying metabolic diseases such as diabetes. We therefore...... conditions is very low, deletion of SDH3 resulted in significant changes in the expression of several genes involved in various cellular processes ranging from metabolism to the cell-cycle. By using various bioinformatics tools we explored the organization of these transcriptional changes in the metabolic...

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)

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

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.

Global Citizenship Incorporated: Competing Responsibilities in the Education of Global Citizens

Science.gov (United States)

Hartung, Catherine

2017-01-01

Interest in the education of young people to be 'responsible global citizens' has grown exponentially since the turn of the century, led by increasingly diverse networks of sectors, including government, community, business and philanthropy. These networks now have a significant influence on education policy and practice, indicative of wider…

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.

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...

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

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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

Impulsive effect on global exponential stability of BAM fuzzy cellular neural networks with time-varying delays

Science.gov (United States)

Li, Kelin

2010-02-01

In this article, a class of impulsive bidirectional associative memory (BAM) fuzzy cellular neural networks (FCNNs) with time-varying delays is formulated and investigated. By employing delay differential inequality and M-matrix theory, some sufficient conditions ensuring the existence, uniqueness and global exponential stability of equilibrium point for impulsive BAM FCNNs with time-varying delays are obtained. In particular, a precise estimate of the exponential convergence rate is also provided, which depends on system parameters and impulsive perturbation intention. It is believed that these results are significant and useful for the design and applications of BAM FCNNs. An example is given to show the effectiveness of the results obtained here.

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

IMPLICATIONS OF SOCIAL RESPONSIBILITY DISCLOSURE ON GLOBAL PRODUCTION NETWORK

OpenAIRE

Le Bo; Dan Shen; Jin Jun Bo

2014-01-01

This paper aims to discuss effectiveness of social responsibility disclosure in promoting global production network. Through a critical review on the theoretical development from supply chain to global production network, the global supply chain management of Apple Inc., as a case, is investigated, with focus on corporate and NGOs’ social disclosure on the environmental and labor rights' issues of its suppliers in China. The paper concludes that effectiveness of corporate social disclosure on...

Global low-carbon transition and China's response strategies

Directory of Open Access Journals (Sweden)

Jian-Kun He

2016-12-01

Full Text Available The Paris Agreement establishes a new mechanism for post-2020 global climate governance, and sets long-term goals for global response to climate change, which will accelerate worldwide low-carbon transformation of economic development pattern, promote the revolutionary reform of energy system, boost a fundamental change in the mode of social production and consumption, and further the civilization of human society from industrial civilization to eco-civilization. The urgency of global low-carbon transition will reshape the competition situation of world's economy, trade and technology. Taking the construction of eco-civilization as a guide, China explores green and low-carbon development paths, establishes ambitious intended nationally determined contribution (INDC targets and action plans, advances energy production and consumption revolution, and speeds up the transformation of economic development pattern. These strategies and actions not only confirm to the trend of the world low-carbon transition, but also meet the intrinsic requirements for easing the domestic resources and environment constraints and realizing sustainable development. They are multi-win-win strategies for promotion of economic development and environmental protection and mitigation of carbon emissions. China should take the global long-term emission reduction targets as a guide, and formulate medium and long-term low-carbon development strategy, build the core competitiveness of low-carbon advanced technology and development pattern, and take an in-depth part in global governance so as to reflect the responsibility of China as a great power in constructing a community of common destiny for all mankind and addressing global ecological crisis.

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

Directory of Open Access Journals (Sweden)

Lingling Zhang

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

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

Social responsibility standards and global environmental accountability : a developing country perspective

OpenAIRE

Bhanu Murthy, K.V.

2007-01-01

This paper argues that accountability, responsibility and governance go hand in hand. Evolving standards is a part of governance. Unless such a global perspective is adopted “Social Responsibility and the implications for Developing Countries”, which is the theme for this workshop, cannot be unraveled. The purpose of this paper is to highlight how Social Responsibility Standards and their relation to environmental sustainability cannot be addressed without relating it to Global Environmental ...

Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise.

Science.gov (United States)

D'Lugos, Andrew C; Patel, Shivam H; Ormsby, Jordan C; Curtis, Donald P; Fry, Christopher S; Carroll, Chad C; Dickinson, Jared M

2018-04-01

Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine whether prior consumption of the COX inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle after RE. In a double-blinded, randomized, crossover design, healthy young men ( n = 8, 25 ± 1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin (mTOR) complex 1 signaling was assessed through immunoblot and immunohistochemistry, and mRNA expression of myogenic genes was examined via RT-qPCR. At 1 h p-rpS6 Ser240/244 was increased in both groups but to a greater extent in PLA. At 3 h p-S6K1 Thr389 was elevated only in PLA. Furthermore, localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to alter the early adaptive cellular response of skeletal muscle to RE. These findings further highlight the mechanisms through which COX-inhibiting drugs impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The extent to which the cellular reaction to acetaminophen impacts the mechanisms regulating the adaptive response of human skeletal muscle to resistance exercise is not well understood. Consumption of acetaminophen before

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.

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.

Corporate social responsibility in the new global economy

OpenAIRE

Lindfelt, Lise-Lotte

2002-01-01

This paper is a discussion of the rights and responsibilities of global corporations. Multinational and transnational corporations of the new economy face a serious difficulty in being ethical today. The environment is subject to the enormous influence of material monism and ethics becomes at times a question of profits. This paper discusses a few aspects on ethical marketing strategies, the use of ethical codes and corporate survival under the pressures of increasing globalization. The purpo...

Model-based synthesis of locally contingent responses to global market signals

Science.gov (United States)

Magliocca, N. R.

2015-12-01

Rural livelihoods and the land systems on which they depend are increasingly influenced by distant markets through economic globalization. Place-based analyses of land and livelihood system sustainability must then consider both proximate and distant influences on local decision-making. Thus, advancing land change theory in the context of economic globalization calls for a systematic understanding of the general processes as well as local contingencies shaping local responses to global signals. Synthesis of insights from place-based case studies of land and livelihood change is a path forward for developing such systematic knowledge. This paper introduces a model-based synthesis approach to investigating the influence of local socio-environmental and agent-level factors in mediating land-use and livelihood responses to changing global market signals. A generalized agent-based modeling framework is applied to six case-study sites that differ in environmental conditions, market access and influence, and livelihood settings. The largest modeled land conversions and livelihood transitions to market-oriented production occurred in sties with relatively productive agricultural land and/or with limited livelihood options. Experimental shifts in the distributions of agents' risk tolerances generally acted to attenuate or amplify responses to changes in global market signals. Importantly, however, responses of agents at different points in the risk tolerance distribution varied widely, with the wealth gap growing wider between agents with higher or lower risk tolerance. These results demonstrate model-based synthesis is a promising approach to overcome many of the challenges of current synthesis methods in land change science, and to identify generalized as well as locally contingent responses to global market signals.

The Idea of a Socially Responsible Global Citizen and its Ethical and Philosophical Basis

OpenAIRE

Isao, Takagi

2012-01-01

An idea of a socially responsible global citizen is required to the emerging global community in order to make it with diversity, sustainability, prosperity, equity and justice. The ethical basis and qualities of a socially responsible global citizen could be provided through introducing some ideas and philosophy consisting of responsible well-being by R. Chambers and philosophy of value creation, global citizenship and creative coexistence by D. Ikeda. Ultimately a comprehensive framework fo...

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...

Comparative Iron Oxide Nanoparticle Cellular Dosimetry and Response in Mice by the Inhalation and Liquid Cell Culture Exposure Routes

Energy Technology Data Exchange (ETDEWEB)

Teeguarden, Justin G.; Mikheev, Vladimir B.; Minard, Kevin R.; Forsythe, William C.; Wang, Wei; Sharma, Gaurav; Karin, Norman J.; Tilton, Susan C.; Waters, Katrina M.; Asgharian, Bahman; Price, Owen; Pounds, Joel G.; Thrall, Brian D.

2014-01-01

testing the rapidly growing number of nanomaterials requires large scale use of in vitro systems under the presumption that these systems are sufficiently predictive or descriptive of responses in in vivo systems for effective use in hazard ranking. We hypothesized that improved relationships between in vitro and in vivo models of experimental toxicology for nanomaterials would result from placing response data in vitro and in vivo on the same dose scale, the amount of material associated with cells (target cell dose). Methods: Balb/c mice were exposed nose-only to an aerosol of 12.8 nm (68.6 nm CMD, 19.9 mg/m3, 4 hours) super paramagnetic iron oxide particles, target cell doses were calculated and biomarkers of response anchored with histological evidence were identified by global transcriptomics. Representative murine epithelial and macrophage cell types were exposed in vitro to the same material in liquid suspension for four hours and levels nanoparticle regulated cytokine transcripts identified in vivo were quantified as a function of measured nanoparticle cellular dose. Results. Target tissue doses of 0.009-0.4 μg SPIO/cm2 lung led to an inflammatory response in the alveolar region characterized by interstitial inflammation and macrophage infiltration. In vitro, higher target tissue doses of ~1.2-4 μg SPIO/ cm2 of cells were required to induce transcriptional regulation of markers of inflammation, CXCL2 CCL3, in C10 lung epithelial cells. Estimated in vivo macrophage SPIO nanoparticle doses ranged from 1-100 pg/cell, and induction of inflammatory markers was observed in vitro in macrophages at doses of 8-35 pg/cell. Conclusions: Application of target tissue dosimetry revealed good correspondence between target cell doses triggering inflammatory processes in vitro and in vivo in the alveolar macrophage population, but not in the epithelial cells of the alveolar region. These findings demonstrate the potential for target tissue dosimetry to enable the more

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.

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

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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

Development of second generation peptides modulating cellular adiponectin receptor responses

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Laszlo eOtvos

2014-10-01

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

Development of second generation peptides modulating cellular adiponectin receptor responses

Science.gov (United States)

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

2014-10-01

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

Is man responsible for global warming?; L'homme est-il responsable du rechauffement climatique?

Energy Technology Data Exchange (ETDEWEB)

Legendre, A

2009-07-01

According to politicians, ecologists and mass media, it is now certain that with our CO{sub 2} emissions, we are all responsible for a major global warming to come with dramatic consequences. But, is this affirmation indisputable? Are we all responsible for the rise of sea level and the summer thawing of the arctic ice shelf? Is this expected global warming without precedent? And is CO{sub 2}, necessary for life, the cause of our misfortune? The answers commonly claimed are maybe more complex in reality and the climate question more subtle than it looks like. This book tries to decode the wheels of the climate machine and the share of human responsibility in climate change. (J.S.)

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.

Inbred Rats as a Model to Study Persistent Renal Leptospirosis and Associated Cellular Immune Responsiveness

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Jarlath E. Nally

2018-03-01

Full Text Available Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Rats are regarded as one of the most significant reservoir hosts of infection for human disease, and in the absence of clinical signs of infection, excrete large numbers of organisms in their urine. A unique biological equilibrium exists between pathogenic leptospires and reservoir hosts of infection, but surprisingly, little is known concerning the host's cellular immune response that facilitates persistent renal colonization. To address this deficiency, we established and applied an immunocompetent inbred rat model of persistent renal colonization; leptospires were detected in urine of experimentally infected rats by 3 weeks post-infection and remained positive until 8 weeks post-infection. However, there was little, if any, evidence of inflammation in colonized renal tubules. At 8 weeks post-infection, a robust antibody response was detected against lipopolysaccharide and protein outer membrane (OM components. Purified B and T cells derived from the spleen of infected and non-infected rats proliferated in response to stimulation with 0.5 μg of OM fractions of Leptospira, including CD4+ T cells, which comprised 40% of proliferating cells, compared to 25% in non-infected controls. However, analysis of gene expression did not determine which immunoregulatory pathways were activated. Lymphocytes purified from the lymph node draining the site of colonization, the renal lymph node, also showed an increase in percentage of proliferating B and T cells. However, in contrast to a phenotype of 40% CD4+ T cells in the spleen, the phenotype of proliferating T cells in the renal lymph node comprised 65% CD4+ T cells. These results confirm that the renal lymph node, the local lymphoid organ, is a dominant site containing Leptospira reactive CD4+ T cells and highlight the need to consider the local, vs

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

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

Terrestrial Feedbacks Incorporated in Global Vegetation Models through Observed Trait-Environment Responses

Science.gov (United States)

Bodegom, P. V.

2015-12-01

Most global vegetation models used to evaluate climate change impacts rely on plant functional types to describe vegetation responses to environmental stresses. In a traditional set-up in which vegetation characteristics are considered constant within a vegetation type, the possibility to implement and infer feedback mechanisms are limited as feedback mechanisms will likely involve a changing expression of community trait values. Based on community assembly concepts, we implemented functional trait-environment relationships into a global dynamic vegetation model to quantitatively assess this feature. For the current climate, a different global vegetation distribution was calculated with and without the inclusion of trait variation, emphasizing the importance of feedbacks -in interaction with competitive processes- for the prevailing global patterns. These trait-environmental responses do, however, not necessarily imply adaptive responses of vegetation to changing conditions and may locally lead to a faster turnover in vegetation upon climate change. Indeed, when running climate projections, simulations with trait variation did not yield a more stable or resilient vegetation than those without. Through the different feedback expressions, global and regional carbon and water fluxes were -however- strongly altered. At a global scale, model projections suggest an increased productivity and hence an increased carbon sink in the next decades to come, when including trait variation. However, by the end of the century, a reduced carbon sink is projected. This effect is due to a downregulation of photosynthesis rates, particularly in the tropical regions, even when accounting for CO2-fertilization effects. Altogether, the various global model simulations suggest the critical importance of including vegetation functional responses to changing environmental conditions to grasp terrestrial feedback mechanisms at global scales in the light of climate change.

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

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

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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.

Global Transcriptomic and Proteomic Responses of Dehalococcoides ethenogenes Strain 195 to Fixed Nitrogen Limitation

Energy Technology Data Exchange (ETDEWEB)

Lee, Patrick K. H. [University of California, Berkeley; Dill, Brian [ORNL; Louie, Tiffany S. [University of California, Berkeley; Shah, Manesh B [ORNL; Verberkmoes, Nathan C [ORNL; Andersen, Gary L. [Lawrence Berkeley National Laboratory (LBNL); Zinder, Stephen H. [Cornell University; Alvarez-Cohen, Lisa [Lawrence Berkeley National Laboratory (LBNL)

2012-01-01

Bacteria of the genus Dehalococcoides play an important role in the reductive dechlorination of chlorinated ethenes. A systems level approach was taken in this study to examine the global transcriptomic and proteomic responses of exponentially growing D. ethenogenes strain 195 to fixed nitrogen limitation (FNL) as dechlorination activity and cell yield both decrease during FNL. As expected, the nitrogen-fixing (nif) genes were differentially up-regulated in the transcriptome and proteome of strain 195 during FNL. Aside from the nif operon, a putative methylglyoxal synthase-encoding gene (DET1576), the product of which is predicted to catalyze the formation of the toxic electrophile methylglyoxal and implicated in the uncoupling of anabolism from catabolism in bacteria, was strongly up-regulated in the transcriptome and could potentially play a role in the observed growth inhibition during FNL. Carbon catabolism genes were generally down regulated in response to FNL and a number of transporters were differentially regulated in response to nitrogen limitation, with some playing apparent roles in nitrogen acquisition while others were associated with general stress responses. A number of genes related to the functions of nucleotide synthesis, replication, transcription, translation, and post-translational modifications were also differentially expressed. One gene coding for a putative reductive dehalogenase (DET1545) and a number coding for oxidoreductases, which have implications in energy generation and redox reactions, were also differentially regulated. Interestingly, most of the genes within the multiple integrated elements were not differentially expressed. Overall, this study elucidates the molecular responses of strain 195 to FNL and identifies differentially expressed genes that are potential biomarkers to evaluate environmental cellular nitrogen status.

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

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.

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.

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.

Liposome-based DNA carriers may induce cellular stress response and change gene expression pattern in transfected cells

Science.gov (United States)

2011-01-01

Background During functional studies on the rat stress-inducible Hspa1b (hsp70.1) gene we noticed that some liposome-based DNA carriers, which are used for transfection, induce its promoter activity. This observation concerned commercial liposome formulations (LA), Lipofectin and Lipofectamine 2000. This work was aimed to understand better the mechanism of this phenomenon and its potential biological and practical consequences. Results We found that a reporter gene driven by Hspa1b promoter is activated both in the case of transient transfections and in the stably transfected cells treated with LA. Using several deletion clones containing different fragments of Hspa1b promoter, we found that the regulatory elements responsible for most efficient LA-driven inducibility were located between nucleotides -269 and +85, relative to the transcription start site. Further studies showed that the induction mechanism was independent of the classical HSE-HSF interaction that is responsible for gene activation during heat stress. Using DNA microarrays we also detected significant activation of the endogenous Hspa1b gene in cells treated with Lipofectamine 2000. Several other stress genes were also induced, along with numerous genes involved in cellular metabolism, cell cycle control and pro-apoptotic pathways. Conclusions Our observations suggest that i) some cationic liposomes may not be suitable for functional studies on hsp promoters, ii) lipofection may cause unintended changes in global gene expression in the transfected cells. PMID:21663599

Liposome-based DNA carriers may induce cellular stress response and change gene expression pattern in transfected cells

Directory of Open Access Journals (Sweden)

Lisowska Katarzyna Marta

2011-06-01

Full Text Available Abstract Background During functional studies on the rat stress-inducible Hspa1b (hsp70.1 gene we noticed that some liposome-based DNA carriers, which are used for transfection, induce its promoter activity. This observation concerned commercial liposome formulations (LA, Lipofectin and Lipofectamine 2000. This work was aimed to understand better the mechanism of this phenomenon and its potential biological and practical consequences. Results We found that a reporter gene driven by Hspa1b promoter is activated both in the case of transient transfections and in the stably transfected cells treated with LA. Using several deletion clones containing different fragments of Hspa1b promoter, we found that the regulatory elements responsible for most efficient LA-driven inducibility were located between nucleotides -269 and +85, relative to the transcription start site. Further studies showed that the induction mechanism was independent of the classical HSE-HSF interaction that is responsible for gene activation during heat stress. Using DNA microarrays we also detected significant activation of the endogenous Hspa1b gene in cells treated with Lipofectamine 2000. Several other stress genes were also induced, along with numerous genes involved in cellular metabolism, cell cycle control and pro-apoptotic pathways. Conclusions Our observations suggest that i some cationic liposomes may not be suitable for functional studies on hsp promoters, ii lipofection may cause unintended changes in global gene expression in the transfected cells.

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

Environmental variation and population responses to global change

NARCIS (Netherlands)

Lawson, Callum R.; Vindenes, Yngvild; Bailey, Liam; van de Pol, Martijn

2015-01-01

Species' responses to environmental changes such as global warming are affected not only by trends in mean conditions, but also by natural and human-induced environmental fluctuations. Methods are needed to predict how such environmental variation affects ecological and evolutionary processes, in

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.

Biodiversity and global change. Adaptative responses to global change: results and prospective. IFB-GICC restitution colloquium; Biodiversite et changement global. Reponses adaptatives au changement global: resultats et prospective. Colloque de restitution IFB-GICC

Energy Technology Data Exchange (ETDEWEB)

Despres, L; Hossaert-Mckey, M; Martin, J F; Pont, D; Valero, M; Chave, J; Benizri, E; Amiaud, B; Boury-Esnault, N; Fritz, H; Lavelle, P; Martin, F; Poulet, S; Blanchard, F; Cheddadi, R; Dupouey, J L; Hulle, M; Michaux, J; Souissi, S; Bridault, A; Dambrine, E; Gomez, B; Thevenard, F; Legendre, S; Suc, J P; Zeitoun, V; Bezancon, G; Frascaria-Lacoste, N; Ponsard, S; Bourguet, D; Vigne, J D; Doyen, L; Joly, P; Gourlet-Fleury, S; Garnier, E; Lebaron, Ph; Boulinier, Th; Chuine, I; Jiguet, F; Couvet, D; Soussana, J F; Weimerskirsch, H; Grosbois, V; Bretagnolle, V

2006-07-01

Global change is the consequence of the worldwide human print on ecology. The uncontrolled use of fossil fuels, the urbanization, the intensifying of agriculture, the homogenization of life styles and cultures, the homogenization of fauna and vegetation, the commercial trades, the bio-invasions, the over-exploitation of resources and the emergence of new economic powers (China, India, Brazil..) represent an adaptative dynamics of interactions which affects the overall biosphere and the adaptative capacities and the future of all species. Biodiversity is an ecological and societal insurance against the risks and uncertainties linked with global change. The French institute of biodiversity (IFB) has created a working group in charge of a study on global change and biodiversity, in particular in terms of: speed and acceleration of processes, interaction between the different organization levels of the world of living, scale changes, and adaptative capacities. 38 projects with an interdisciplinary approach have been retained by the IFB and the Ministry of ecology and sustainable development. The conclusion of these projects were presented at this restitution colloquium and are summarized in this document. The presentations are organized in 7 sessions dealing with: global changes and adaptation mechanisms; functional responses to global changes; spatial responses to global changes; temporal responses to global changes; selective answers to global changes; available tools and ecological services; scenarios and projections. (J.S.)

Ethanol cellular defense induce unfolded protein response in yeast

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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

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...

Literature Review on Dynamic Cellular Manufacturing System

Science.gov (United States)

Nouri Houshyar, A.; Leman, Z.; Pakzad Moghadam, H.; Ariffin, M. K. A. M.; Ismail, N.; Iranmanesh, H.

2014-06-01

In previous decades, manufacturers faced a lot of challenges because of globalization and high competition in markets. These problems arise from shortening product life cycle, rapid variation in demand of products, and also rapid changes in manufcaturing technologies. Nowadays most manufacturing companies expend considerable attention for improving flexibility and responsiveness in order to overcome these kinds of problems and also meet customer's needs. By considering the trend toward the shorter product life cycle, the manufacturing environment is towards manufacturing a wide variety of parts in small batches [1]. One of the major techniques which are applied for improving manufacturing competitiveness is Cellular Manufacturing System (CMS). CMS is type of manufacturing system which tries to combine flexibility of job shop and also productivity of flow shop. In addition, Dynamic cellular manufacturing system which considers different time periods for the manufacturing system becomes an important topic and attracts a lot of attention to itself. Therefore, this paper made attempt to have a brief review on this issue and focused on all published paper on this subject. Although, this topic gains a lot of attention to itself during these years, none of previous researchers focused on reviewing the literature of that which can be helpful and useful for other researchers who intend to do the research on this topic. Therefore, this paper is the first study which has focused and reviewed the literature of dynamic cellular manufacturing system.

Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis

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Boix Loreto

2006-11-01

Full Text Available Abstract Background Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV. Results Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. Conclusion Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.

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].

Circuitry linking the global Csr and σE-dependent cell envelope stress response systems.

Science.gov (United States)

Yakhnin, Helen; Aichele, Robert; Ades, Sarah E; Romeo, Tony; Babitzke, Paul

2017-09-18

CsrA of Escherichia coli is an RNA-binding protein that globally regulates a wide variety of cellular processes and behaviors including carbon metabolism, motility, biofilm formation, and the stringent response. CsrB and CsrC are sRNAs that sequester CsrA, thereby preventing CsrA-mRNA interaction. RpoE (σ E ) is the extracytoplasmic stress response sigma factor of E. coli Previous RNA-seq studies identified rpoE mRNA as a CsrA target. Here we explored the regulation of rpoE by CsrA and found that CsrA represses rpoE translation. Gel mobility shift, footprint and toeprint studies identified three CsrA binding sites in the rpoE leader transcript, one of which overlaps the rpoE Shine-Dalgarno (SD) sequence, while another overlaps the rpoE translation initiation codon. Coupled in vitro transcription-translation experiments showed that CsrA represses rpoE translation by binding to these sites. We further demonstrate that σ E indirectly activates transcription of csrB and csrC , leading to increased sequestration of CsrA such that repression of rpoE by CsrA is reduced. We propose that the Csr system fine-tunes the σ E -dependent cell envelope stress response. We also identified a 51 amino acid coding sequence whose stop codon overlaps the rpoE start codon, and demonstrate that rpoE is translationally coupled with this upstream open reading frame (ORF51). Loss of coupling reduces rpoE translation by more than 50%. Identification of a translationally coupled ORF upstream of rpoE suggests that this previously unannotated protein may participate in the cell envelope stress response. In keeping with existing nomenclature, we name ORF51 as rseD , resulting in an operon arrangement of rseD-rpoE-rseA-rseB-rseC IMPORTANCE CsrA posttranscriptionally represses genes required for bacterial stress responses, including the stringent response, catabolite repression, and the RpoS (σ S )-mediated general stress response. We show that CsrA represses translation of rpoE , encoding the

AIDS: Ushering in a new era of shared responsibility for global health

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Buse Kent

2012-07-01

Full Text Available Abstract For the first time since AIDS erupted as worldwide emergency, global leaders, the scientific community, activists and people living with HIV are venturing to speak about the end to the pandemic. Signs of hope abound: over 8 million people are receiving life-saving treatment, the number of new infections is on significant decline, the remarkable evidence of treatment’s impact on preventing new infections and the aspiration of zero new HIV infections among children is firmly within grasp. This progress, won by people living with HIV and countries with support from partners such as the US programme PEPFAR, the Clinton Health Access Initiative and untold more, embodies global solidarity to bring about an AIDS-free generation. Shared responsibility and global solidarity represents a normative ideal to which both individual stakeholders and the global community must subscribe and embrace if our collective vision of an AIDS-free world is to be realised. The idea of shared responsibility and global solidarity needs to goes further than raising and investing resources and extend to the level of control countries take of their AIDS response. This editorial explores five areas that require further attention.

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.

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.

Global solution for a chemotactic haptotactic model of cancer invasion

Science.gov (United States)

Tao, Youshan; Wang, Mingjun

2008-10-01

This paper deals with a mathematical model of cancer invasion of tissue recently proposed by Chaplain and Lolas. The model consists of a reaction-diffusion-taxis partial differential equation (PDE) describing the evolution of tumour cell density, a reaction-diffusion PDE governing the evolution of the proteolytic enzyme concentration and an ordinary differential equation modelling the proteolysis of the extracellular matrix (ECM). In addition to random motion, the tumour cells are directed not only by haptotaxis (cellular locomotion directed in response to a concentration gradient of adhesive molecules along the ECM) but also by chemotaxis (cellular locomotion directed in response to a concentration gradient of the diffusible proteolytic enzyme). In one space dimension, the global existence and uniqueness of a classical solution to this combined chemotactic-haptotactic model is proved for any chemotactic coefficient χ > 0. In two and three space dimensions, the global existence is proved for small χ/μ (where μ is the logistic growth rate of the tumour cells). The fundamental point of proof is to raise the regularity of a solution from L1 to Lp (p > 1). Furthermore, the existence of blow-up solutions to a sub-model in two space dimensions for large χ shows, to some extent, that the condition that χ/μ is small is necessary for the global existence of a solution to the full model.

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.

Globalisation of tobacco industry influence and new global responses

Science.gov (United States)

Yach, D.; Bettcher, D.

2000-01-01

The globalisation of tobacco marketing, trade, research, and industry influence represents a major threat to public health worldwide. Drawing upon tobacco industry strategy documents prepared over several decades, this paper will demonstrate how the tobacco industry operates as a global force, regarding the world as its operating market by planning, developing, and marketing its products on a global scale. The industry has used a wide range of methods to buy influence and power, and penetrate markets across the world. It has an annual turnover of almost US$400 billion. In contrast, until recently tobacco control lacked global leadership and strategic direction and had been severely underfunded. As part of moving towards a more sustainable form of globalisation, a global enabling environment linked to local actions should focus on the following strategies: global information management; development of nationally and locally grounded action; global regulation, legal instruments, and foreign policy; and establishment of strong partnerships with purpose. As the vector of the tobacco epidemic, the tobacco industry's actions fall far outside of the boundaries of global corporate responsibility. Therefore, global and local actions should not provide the tobacco industry with the two things that it needs to ensure its long term profitability: respectability and predictability.


Keywords: globalisation of tobacco marketing PMID:10841858

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

Directory of Open Access Journals (Sweden)

Gajadhar Bhakta

2014-01-01

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

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)

Combining observations and models to reduce uncertainty in the cloud response to global warming

Science.gov (United States)

Norris, J. R.; Myers, T.; Chellappan, S.

2017-12-01

Currently there is large uncertainty on how subtropical low-level clouds will respond to global warming and whether they will act as a positive feedback or negative feedback. Global climate models substantially agree on what changes in atmospheric structure and circulation will occur with global warming but greatly disagree over how clouds will respond to these changes in structure and circulation. An examination of models with the most realistic simulations of low-level cloudiness indicates that the model cloud response to atmospheric changes associated with global warming is quantitatively similar to the model cloud response to atmospheric changes at interannual time scales. For these models, the cloud response to global warming predicted by multilinear regression using coefficients derived from interannual time scales is quantitatively similar to the cloud response to global warming directly simulated by the model. Since there is a large spread among cloud response coefficients even among models with the most realistic cloud simulations, substitution of coefficients derived from satellite observations reduces the uncertainty range of the low-level cloud feedback. Increased sea surface temperature associated with global warming acts to reduce low-level cloudiness, which is partially offset by increased lower tropospheric stratification that acts to enhance low-level cloudiness. Changes in free-tropospheric relative humidity, subsidence, and horizontal advection have only a small impact on low-level cloud. The net reduction in subtropical low-level cloudiness increases absorption of solar radiation by the climate system, thus resulting in a weak positive feedback.

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

Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

DEFF Research Database (Denmark)

Liu, Y.; Melillo, J.; Niu, S.

2011-01-01

a coordinated approach that combines long-term, large-scale global change experiments with process studies and modeling. Long-term global change manipulative experiments, especially in high-priority ecosystems such as tropical forests and high-latitude regions, are essential to maximize information gain......Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation...... to be the most effective strategy to gain the best information on long-term ecosystem dynamics in response to global change....

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.

Quantifying global soil carbon losses in response to warming.

Science.gov (United States)

Crowther, T W; Todd-Brown, K E O; Rowe, C W; Wieder, W R; Carey, J C; Machmuller, M B; Snoek, B L; Fang, S; Zhou, G; Allison, S D; Blair, J M; Bridgham, S D; Burton, A J; Carrillo, Y; Reich, P B; Clark, J S; Classen, A T; Dijkstra, F A; Elberling, B; Emmett, B A; Estiarte, M; Frey, S D; Guo, J; Harte, J; Jiang, L; Johnson, B R; Kröel-Dulay, G; Larsen, K S; Laudon, H; Lavallee, J M; Luo, Y; Lupascu, M; Ma, L N; Marhan, S; Michelsen, A; Mohan, J; Niu, S; Pendall, E; Peñuelas, J; Pfeifer-Meister, L; Poll, C; Reinsch, S; Reynolds, L L; Schmidt, I K; Sistla, S; Sokol, N W; Templer, P H; Treseder, K K; Welker, J M; Bradford, M A

2016-11-30

The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.

Global Scale Periodic Responses in Saturn’s Magnetosphere

Science.gov (United States)

Jia, Xianzhe; Kivelson, Margaret G.

2017-10-01

Despite having an axisymmetric internal magnetic field, Saturn’s magnetosphere exhibits periodic modulations in a variety of properties at periods close to the planetary rotation period. While the source of the periodicity remains unidentified, it is evident from Cassini observations that much of Saturn’s magnetospheric structure and dynamics is dominated by global-scale responses to the driving source of the periodicity. We have developed a global MHD model in which a rotating field-aligned current system is introduced by imposing vortical flows in the high-latitude ionosphere in order to simulate the magnetospheric periodicities. The model has been utilized to quantitatively characterize various periodic responses in the magnetosphere, such as the displacement of the magnetopause and bow shock and flapping of the tail plasma sheet, all of which show quantitative agreement with Cassini observations. One of our model predictions is periodic release of plasmoids in the tail that occurs preferentially in the midnight-to-dawn local time sector during each rotation cycle. Here we present detailed analysis of the periodic responses seen in our simulations focusing on the properties of plasmoids predicted by the model, including their spatial distribution, occurrence frequency, and mass loss rate. We will compare these modeled parameters with published Cassini observations, and discuss their implications for interpreting in-situ measurements.

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

Directory of Open Access Journals (Sweden)

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

Directory of Open Access Journals (Sweden)

John Wikswo

2009-03-01

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

Soil bacterial community responses to global changes

DEFF Research Database (Denmark)

Bergmark, Lasse

competing and very contrasting plant types (Calluna and Deschampsia) dominated the vegetation. This led to Manuscript 3 where the impact and responses of the climate change manipulations on the microbial community composition was investigated under the contrasting vegetation types. Our results show a high......Soil bacteria and archaea are essential for ecosystem functioning and plant growth through their degradation of organic matter and turnover of nutrients. But since the majority of soil bacteria and archaea are unclassified and “nonculturable” the functionality of the microbial community and its...... overall importance for ecosystem function in soil is poorly understood. Global change factors may affect the diversity and functioning of soil prokaryotes and thereby ecosystem functioning. To gain a better understanding of the effects of global changes it is of fundamental importance to classify...

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.

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

Load and Global Response of Ships

DEFF Research Database (Denmark)

Jensen, Jørgen Juncher

The present monograph covers wave load and global structural response for ships. It is primary written as a textbook for students with an introductionary background in naval architecture and a basic knowledge of statistics and strength of materials. The subjects are treated in details starting from...... first principles. The aim has been to derive and present the necessary theoretical framework for predicting the extreme loads and the corresponding hull girder stresses the ship may be subjected to during its operational lifetime.Although some account is given to reliabiity analysis, the present...

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

Science.gov (United States)

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

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.

Electromagnetic Radiation Exposure from Cellular Base Station: A ...

African Journals Online (AJOL)

Electromagnetic Radiation Exposure from Cellular Base Station: A Concern for Public ... as well as safety guidelines relating to exposure of non-ionizing radiation. Global System for Mobile Communication (GSM) operators claimed that their ...

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.

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.

Generating Global Brand Equity through Corporate Social Responsibility to Key Stakeholders

NARCIS (Netherlands)

Torres Lacomba, Anna; Atribo, Jo; Bijmolt, Tammo H.A.

2010-01-01

In this paper we argue that socially responsible policies have positive short-term and long-term impact on equity of global brands. We find that corporate social responsibility towards all stakeholders, whether primary (customers, shareholders, employees and suppliers) or secondary (community), have

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

Directory of Open Access Journals (Sweden)

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.

Responses of Seasonal Precipitation Intensity to Global Warming

Science.gov (United States)

Lan, Chia-Wei; Lo, Min-Hui; Chou, Chia

2016-04-01

Under global warming, the water vapor increases with rising temperature at the rate of 7%/K. Most previous studies focus on the spatial differences of precipitation and suggest that wet regions become wetter and dry regions become drier. Our recent studies show a temporal disparity of global precipitation, which the wet season becomes wetter and dry season becomes drier; therefore, the annual range increases. However, such changes in the annual range are not homogeneous globally, and in fact, the drier trend over the ocean is much larger than that over the land, where the dry season does not become drier. Such precipitation change over land is likely because of decreased omega at 500hPa (more upward motion) in the reanalysis datasets from 1980 to 2013. The trends of vertical velocity and moist static energy profile over the increased precipitation regions become more unstable. The instability is most likely attributed to the change in specific humility below 400hPa. Further, we will use Coupled Model Intercomparison Project Phase 5 (CMIP5) archives to investigate whether the precipitation responses in dry season are different between the ocean and land under global warming.

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

Science.gov (United States)

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.

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.

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

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...

Local and global responses in complex gene regulation networks

Science.gov (United States)

Tsuchiya, Masa; Selvarajoo, Kumar; Piras, Vincent; Tomita, Masaru; Giuliani, Alessandro

2009-04-01

An exacerbated sensitivity to apparently minor stimuli and a general resilience of the entire system stay together side-by-side in biological systems. This apparent paradox can be explained by the consideration of biological systems as very strongly interconnected network systems. Some nodes of these networks, thanks to their peculiar location in the network architecture, are responsible for the sensitivity aspects, while the large degree of interconnection is at the basis of the resilience properties of the system. One relevant feature of the high degree of connectivity of gene regulation networks is the emergence of collective ordered phenomena influencing the entire genome and not only a specific portion of transcripts. The great majority of existing gene regulation models give the impression of purely local ‘hard-wired’ mechanisms disregarding the emergence of global ordered behavior encompassing thousands of genes while the general, genome wide, aspects are less known. Here we address, on a data analysis perspective, the discrimination between local and global scale regulations, this goal was achieved by means of the examination of two biological systems: innate immune response in macrophages and oscillating growth dynamics in yeast. Our aim was to reconcile the ‘hard-wired’ local view of gene regulation with a global continuous and scalable one borrowed from statistical physics. This reconciliation is based on the network paradigm in which the local ‘hard-wired’ activities correspond to the activation of specific crucial nodes in the regulation network, while the scalable continuous responses can be equated to the collective oscillations of the network after a perturbation.

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

Managing global responsibility

Energy Technology Data Exchange (ETDEWEB)

Saur, K. [Five Winds International, Donzdorf (Germany)

2004-07-01

The electronics industry in particular is a global industry. Local and regional solutions require a globally applicable product design and use global value chains. Operating in increasingly integrated material and product loops offers a unique solution to not only providing markets with compatible solutions, but also offer a chance to significantly reduce the environmental footprint of the industry. Product lifespan extension in emerging economies, utilization of local market needs, utilize available and affordable labour forces and creating wealth and capacity in developing countries may serve as a way to make industry more sustainable and successful. Both the supply side and the product end of life management need to be considered in this global industry. Intelligent solution support the dematerialization and material throughput and help creating markets and build wealth. Critical success factors include knowledge management, capacity building, developing infrastructure. This paper presents a discussion on a solutions oriented approach towards product life cycle management and stewardship combined with sustainable production and consumption considerations, support the industries aspirations and the UNEP Life Cycle Initiative's mission in a perfect manner. The aim of this paper is to offer approaches and develop ideas how economic viable and sustainable solutions can be developed. (orig.)

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.

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.

Corporate Social Responsibility in Supply Chains of Global Brands: A Boundaryless Responsibility? Clarifications, Exceptions and Implications

OpenAIRE

Amaeshi, K.; Nnodim, P.; Osuji, O.

2008-01-01

Corporate social responsibility (CSR) is increasingly becoming a popular business concept in developed economies. As typical of other business concepts, it is on its way to globalization through practices and structures of the globalized capitalist world order, typified in Multinational Corporations (MNCs). However, CSR often sits uncomfortably in this capitalist world order, as MNCs are often challenged by the global reach of their supply chains and the possible irresponsible practices inher...

Global analysis of the yeast osmotic stress response by quantitative proteomics

DEFF Research Database (Denmark)

Soufi, Boumediene; Kelstrup, C.D.; Stoehr, G.

2009-01-01

a comprehensive, quantitative, and time-resolved analysis using high-resolution mass spectrometry of phospho-proteome and proteome changes in response to osmotic stress in yeast. We identified 5534 unique phosphopeptide variants and 3383 yeast proteins. More than 15% of the detected phosphorylation site status...... changed more than two-fold within 5 minutes of treatment. Many of the corresponding phosphoproteins are involved in the early response to environmental stress. Surprisingly, we find that 158 regulated phosphorylation sites are potential substrates of basophilic kinases as opposed to the classical proline......-directed MAP kinase network implicated in stress response mechanisms such as p38 and HOG pathways. Proteome changes reveal an increase in abundance of more than one hundred proteins after 20 min of salt stress. Many of these are involved in the cellular response to increased osmolarity, which include proteins...

Trends and EIE higher education response to the current global technical challenges

DEFF Research Database (Denmark)

Poboroniuc, Marian; Livint, Gheorghe; Friesel, Anna

2014-01-01

Education Institutions (SALEIE), an EU supported project, gathers together a global team aiming to provide higher education models in the EIE disciplines that can respond to the key global technical challenges. This paper deals with findings within the SALEIE project's work package WP3 (Global Challenges......), namely: state-of-the-art in implementation of the Bologna recommendation for Bachelor and Master, technical challenges that the EIE higher education faces nowadays, and existing models in EIE higher education and their degree of response to key global technical challenges....

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.

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)

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-04-04

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

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

Role of cellular adhesions in tissue dynamics spectroscopy

Science.gov (United States)

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.

Cellular reprogramming dynamics follow a simple 1D reaction coordinate

Science.gov (United States)

Teja Pusuluri, Sai; Lang, Alex H.; Mehta, Pankaj; Castillo, Horacio E.

2018-01-01

Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an ongoing problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple 1D reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used. Using Monte-Carlo simulations, we show that such a reaction coordinate emerges from epigenetic landscape models where cellular reprogramming is viewed as a ‘barrier-crossing’ process between cell fates. Overall, our analysis and model suggest that gene expression dynamics during reprogramming follow a canonical trajectory consistent with the idea of an ‘optimal path’ in gene expression space for reprogramming.

A Conceptual Framework for Responsive Global Engagement in Communication Sciences and Disorders

Science.gov (United States)

Hyter, Yvette D.

2014-01-01

The field of speech-language pathology needs a conceptual framework to guide the provision of services in a globalized world. Proposed in this article is a conceptual framework designed to facilitate responsive global engagement for professionals such as speech-language pathologists, who are increasingly serving diverse populations around the…

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

Directory of Open Access Journals (Sweden)

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.

El Nino/Southern Oscillation response to global warming.

Science.gov (United States)

Latif, M; Keenlyside, N S

2009-12-08

The El Niño/Southern Oscillation (ENSO) phenomenon, originating in the Tropical Pacific, is the strongest natural interannual climate signal and has widespread effects on the global climate system and the ecology of the Tropical Pacific. Any strong change in ENSO statistics will therefore have serious climatic and ecological consequences. Most global climate models do simulate ENSO, although large biases exist with respect to its characteristics. The ENSO response to global warming differs strongly from model to model and is thus highly uncertain. Some models simulate an increase in ENSO amplitude, others a decrease, and others virtually no change. Extremely strong changes constituting tipping point behavior are not simulated by any of the models. Nevertheless, some interesting changes in ENSO dynamics can be inferred from observations and model integrations. Although no tipping point behavior is envisaged in the physical climate system, smooth transitions in it may give rise to tipping point behavior in the biological, chemical, and even socioeconomic systems. For example, the simulated weakening of the Pacific zonal sea surface temperature gradient in the Hadley Centre model (with dynamic vegetation included) caused rapid Amazon forest die-back in the mid-twenty-first century, which in turn drove a nonlinear increase in atmospheric CO(2), accelerating global warming.

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

IMPACT OF GLOBAL WARMING ON LIFE: LIFE ON EARTH FROM SINGLE-CELLULAR ORGANISMS TO MULTICELLULAR ORGANISMS

Energy Technology Data Exchange (ETDEWEB)

Kartikey Gupta [Grade X, Mayura School, Jaipur (India)

2008-09-30

Wherever we look, life can be seen...so many different forms of life, that is, uncountable varieties of animals and plants occupy the whole world today! But, where and how did it all start? The story of evolution is one of the most interesting theories ever put forward. It refers to - the way that simple and small living things eventually changed into much more functional and bigger beings, in course of time. Charles Darwin had explored this mystery, and had provided the reason- Evolution. Evolution is changing of life forms into more functional ones with respect to their changing environment. However, as odd as it may sound, evolution and extinction are closely linked. Because, the better evolved species survives, and throughout the timeline of evolution, there have been many extinction waves. They were all occurred naturally thus proving that the very process of extinction is natural. The earth has seen many variations of global temperature; it has suffered various ice ages, which had also many a times threatened to eradicate most life from the planet. But, every time life has found a way to go on. Therefore, whatever life we see today has resulted from the ongoing long process of evolution. After millions of years, finally we humans have come into existence, and today are the leading species of the world. But, we may possibly be very close to another major extinction wave, the root causes of which are both natural and man-made, but the part played by the latter is much more than the former. Global Warming has now started affecting all kinds of life on the planet, and it is our responsibility as the leading and most intellectual species to try to save our earth. A study reveals that 60% Indian people do not actually know about Global Warming, and that the number of youth aware of Global Warming and Its impacts are much more than the number of adults. About 75% Indians believe that it is the sole responsibility of the government to solve the problems related to

A Robust Response of Precipitation to Global Warming from CMIP5 Models

Science.gov (United States)

Lau, K. -M.; Wu, H. -T.; Kim, K. -M.

2012-01-01

How precipitation responds to global warming is a major concern to society and a challenge to climate change research. Based on analyses of rainfall probability distribution functions of 14 state-of-the-art climate models, we find a robust, canonical global rainfall response to a triple CO2 warming scenario, featuring 100 250% more heavy rain, 5-10% less moderate rain, and 10-15% more very light or no-rain events. Regionally, a majority of the models project a consistent response with more heavy rain events over climatologically wet regions of the deep tropics, and more dry events over subtropical and tropical land areas. Results suggest that increased CO2 emissions induce basic structural changes in global rain systems, increasing risks of severe floods and droughts in preferred geographic locations worldwide.

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.

Impact of light on Hypocrea jecorina and the multiple cellular roles of ENVOY in this process

Directory of Open Access Journals (Sweden)

Druzhinina Irina S

2007-12-01

Full Text Available Abstract Background In fungi, light is primarily known to influence general morphogenesis and both sexual and asexual sporulation. In order to expand the knowledge on the effect of light in fungi and to determine the role of the light regulatory protein ENVOY in the implementation of this effect, we performed a global screen for genes, which are specifically effected by light in the fungus Hypocrea jecorina (anamorph Trichoderma reesei using Rapid Subtraction Hybridization (RaSH. Based on these data, we analyzed whether these genes are influenced by ENVOY and if overexpression of ENVOY in darkness would be sufficient to execute its function. Results The cellular functions of the detected light responsive genes comprised a variety of roles in transcription, translation, signal transduction, metabolism, and transport. Their response to light with respect to the involvement of ENVOY could be classified as follows: (i ENVOY-mediated upregulation by light; (ii ENVOY-independent upregulation by light; (iii ENVOY-antagonized upregulation by light; ENVOY-dependent repression by light; (iv ENVOY-independent repression by light; and (v both positive and negative regulation by ENVOY of genes not responsive to light in the wild-type. ENVOY was found to be crucial for normal growth in light on various carbon sources and is not able to execute its regulatory function if overexpressed in the darkness. Conclusion The different responses indicate that light impacts fungi like H. jecorina at several cellular processes, and that it has both positive and negative effects. The data also emphasize that ENVOY has an apparently more widespread cellular role in this process than only in modulating the response to light.

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

DEFF Research Database (Denmark)

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

2015-01-01

This histopathological study was carried out in order to investigate the cellular response in the jejunum to Ascaridia galli during the first 7 weeks of infection. Fourty-two ISA Brown chickens (7 weeks old) were infected orally with 500 embryonated A. galli eggs each while 28 chickens were left.......001), 28 (P layer. No adult worms were seen during the experiment; therefore...

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

DEFF Research Database (Denmark)

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

1992-01-01

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

Global Earth Response to Loading by Ocean Tide Models

Science.gov (United States)

Estes, R. H.; Strayer, J. M.

1979-01-01

Mathematical and programming techniques to numerically calculate Earth response to global semidiurnal and diurnal ocean tide models were developed. Global vertical crustal deformations were evaluated for M sub 2, S sub 2, N sub 2, K sub 2, K sub 1, O sub 1, and P sub 1 ocean tide loading, while horizontal deformations were evaluated for the M sub 2 tidal load. Tidal gravity calculations were performed for M sub 2 tidal loads, and strain tensor elements were evaluated for M sub 2 loads. The M sub 2 solution used for the ocean tide included the effects of self-gravitation and crustal loading.

Political Parties and Social Policy Responses to Global Economic Crises

DEFF Research Database (Denmark)

Starke, Peter; Kaasch, Alexandra; van Hooren, Franca

2014-01-01

Based on empirical findings froma comparative study onwelfare state responses to the four major economic shocks (the 1970s oil shocks, the early 1990s recession, the 2008 financial crisis) in four OECD countries, this article demonstrates that, in contrast to conventional wisdom, policy responses...... to global economic crises vary significantly across countries. What explains the cross-national and within-case variation in responses to crises?We discuss several potential causes of this pattern and argue that political parties and the party composition of governments can play a key role in shaping crisis...

Large-scale integration of small molecule-induced genome-wide transcriptional responses, Kinome-wide binding affinities and cell-growth inhibition profiles reveal global trends characterizing systems-level drug action

Directory of Open Access Journals (Sweden)

Dusica eVidovic

2014-09-01

Full Text Available The Library of Integrated Network-based Cellular Signatures (LINCS project is a large-scale coordinated effort to build a comprehensive systems biology reference resource. The goals of the program include the generation of a very large multidimensional data matrix and informatics and computational tools to integrate, analyze, and make the data readily accessible. LINCS data include genome-wide transcriptional signatures, biochemical protein binding profiles, cellular phenotypic response profiles and various other datasets for a wide range of cell model systems and molecular and genetic perturbations. Here we present a partial survey of this data facilitated by data standards and in particular a robust compound standardization workflow; we integrated several types of LINCS signatures and analyzed the results with a focus on mechanism of action and chemical compounds. We illustrate how kinase targets can be related to disease models and relevant drugs. We identified some fundamental trends that appear to link Kinome binding profiles and transcriptional signatures to chemical information and biochemical binding profiles to transcriptional responses independent of chemical similarity. To fill gaps in the datasets we developed and applied predictive models. The results can be interpreted at the systems level as demonstrated based on a large number of signaling pathways. We can identify clear global relationships, suggesting robustness of cellular responses to chemical perturbation. Overall, the results suggest that chemical similarity is a useful measure at the systems level, which would support phenotypic drug optimization efforts. With this study we demonstrate the potential of such integrated analysis approaches and suggest prioritizing further experiments to fill the gaps in the current data.

Social responsibility and global health: lessons from the Rio Olympics Zika controversy.

Science.gov (United States)

Hellmann, Fernando; Rohde, Luzilena de Souza Prudêncio; Verdi, Marta; Garrafa, Volnei; Manchola-Castillo, Camilo

2018-03-30

The outbreak of Zika virus infection in the Americas and its possible association with microcephaly raised several concerns among global health authorities regarding the organisation of the Olympic and Paralympic Games scheduled for August and September 2016, in the city of Rio de Janeiro, Brazil. It generated an international controversy over the continuation of the Games with debates on the ethical principle of social responsibility. Based on the principles of social responsibility and health in the Universal Declaration of Bioethics and Human Rights, the present comment ponders on the application of such principles in the context of mega-events and global health.

SaeRS Is Responsive to Cellular Respiratory Status and Regulates Fermentative Biofilm Formation in Staphylococcus aureus.

Science.gov (United States)

Mashruwala, Ameya A; Gries, Casey M; Scherr, Tyler D; Kielian, Tammy; Boyd, Jeffrey M

2017-08-01

Biofilms are multicellular communities of microorganisms living as a quorum rather than as individual cells. The bacterial human pathogen Staphylococcus aureus uses oxygen as a terminal electron acceptor during respiration. Infected human tissues are hypoxic or anoxic. We recently reported that impaired respiration elicits a p rogrammed c ell l ysis (PCL) phenomenon in S. aureus leading to the release of cellular polymers that are utilized to form biofilms. PCL is dependent upon the AtlA murein hydrolase and is regulated, in part, by the SrrAB two-component regulatory system (TCRS). In the current study, we report that the SaeRS TCRS also governs fermentative biofilm formation by positively influencing AtlA activity. The SaeRS-modulated factor fibronectin-binding protein A (FnBPA) also contributed to the fermentative biofilm formation phenotype. SaeRS-dependent biofilm formation occurred in response to changes in cellular respiratory status. Genetic evidence presented suggests that a high cellular titer of phosphorylated SaeR is required for biofilm formation. Epistasis analyses found that SaeRS and SrrAB influence biofilm formation independently of one another. Analyses using a mouse model of orthopedic implant-associated biofilm formation found that both SaeRS and SrrAB govern host colonization. Of these two TCRSs, SrrAB was the dominant system driving biofilm formation in vivo We propose a model wherein impaired cellular respiration stimulates SaeRS via an as yet undefined signal molecule(s), resulting in increasing expression of AtlA and FnBPA and biofilm formation. Copyright © 2017 American Society for Microbiology.

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

Directory of Open Access Journals (Sweden)

Zhang Quanfu

2011-06-01

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

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

Directory of Open Access Journals (Sweden)

Wagner Santos Coelho

2016-11-01

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

Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection.

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Wafa Kammoun-Rebai

2017-10-01

Full Text Available Sand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome. Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding their effect on parasite transmission and establishment in humans.We explored the cellular and humoral immune responses to Phlebotomus (P. papatasi salivary gland extracts (SGE in individuals living in cutaneous leishmaniasis (CL old or emerging foci (OF, EF. OF was characterized by a higher infection prevalence as assessed by higher proportions of leishmanin skin test (LST positive individuals compared to EF. Subjects were further subdivided into healed, asymptomatic or naïve groups. We showed anti-SGE proliferation in less than 30% of the individuals, regardless of the immune status, in both foci. IFN-γ production was higher in OF and only observed in immune individuals from OF and naïve subjects from EF. Although IL-10 was not detected, addition of anti-human IL-10 antibodies revealed an increase in proliferation and IFN-γ production only in individuals from OF. The percentage of seropositive individuals was similar in immune and naïves groups but was significantly higher in OF. No correlation was observed between anti-saliva immune responses and LST response. High anti-SGE-IgG responses were associated with an increased risk of developing ZCL. No differences were observed for anti-SGE humoral or cellular responses among naïve individuals who converted or not their LST response or developed or not ZCL after the transmission season.These data suggest that individuals living in an old focus characterized by a frequent exposure to sand fly bites and a high prevalence of infection, develop higher anti-saliva IgG responses and IFN-γ levels and a skew towards a Th2-type cellular response, probably in favor of parasite establishment

Mechanisms and circumvention of cellular resistance to cisplatin.

NARCIS (Netherlands)

Hospers, Geesiena Alberdina Petronella

1989-01-01

Cisplatin (CDDP) is an active cytostatic agent. A limitation to its effectiveness initially or appearing during cystatic treatment is the occurrence of resistance. This thesis describes mechanisms wich are responsible for acquired cellular CDDP resistance. To investigate cellular CDDP resistance, a

A Computational Model of Cellular Response to Modulated Radiation Fields

Energy Technology Data Exchange (ETDEWEB)

McMahon, Stephen J., E-mail: stephen.mcmahon@qub.ac.uk [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); Butterworth, Karl T. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); McGarry, Conor K. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); Radiotherapy Physics, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Northern Ireland (United Kingdom); Trainor, Colman [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); O' Sullivan, Joe M. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); Clinical Oncology, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, Northern Ireland (United Kingdom); Hounsell, Alan R. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); Radiotherapy Physics, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Northern Ireland (United Kingdom); Prise, Kevin M. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom)

2012-09-01

Purpose: To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies. Materials and Methods: A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields. Results: The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses. Conclusions: The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.

A Computational Model of Cellular Response to Modulated Radiation Fields

International Nuclear Information System (INIS)

McMahon, Stephen J.; Butterworth, Karl T.; McGarry, Conor K.; Trainor, Colman; O’Sullivan, Joe M.; Hounsell, Alan R.; Prise, Kevin M.

2012-01-01

Purpose: To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies. Materials and Methods: A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields. Results: The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses. Conclusions: The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.

Epigenetics and Cellular Metabolism

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Wenyi Xu

2016-01-01

Full Text Available 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 processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

Cellular-based preemption system

Science.gov (United States)

Bachelder, Aaron D. (Inventor)

2011-01-01

A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

Cosmopolitan Species As Models for Ecophysiological Responses to Global Change: The Common Reed Phragmites australis

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Franziska Eller

2017-11-01

Full Text Available Phragmites australis is a cosmopolitan grass and often the dominant species in the ecosystems it inhabits. Due to high intraspecific diversity and phenotypic plasticity, P. australis has an extensive ecological amplitude and a great capacity to acclimate to adverse environmental conditions; it can therefore offer valuable insights into plant responses to global change. Here we review the ecology and ecophysiology of prominent P. australis lineages and their responses to multiple forms of global change. Key findings of our review are that: (1 P. australis lineages are well-adapted to regions of their phylogeographic origin and therefore respond differently to changes in climatic conditions such as temperature or atmospheric CO2; (2 each lineage consists of populations that may occur in geographically different habitats and contain multiple genotypes; (3 the phenotypic plasticity of functional and fitness-related traits of a genotype determine the responses to global change factors; (4 genotypes with high plasticity to environmental drivers may acclimate or even vastly expand their ranges, genotypes of medium plasticity must acclimate or experience range-shifts, and those with low plasticity may face local extinction; (5 responses to ancillary types of global change, like shifting levels of soil salinity, flooding, and drought, are not consistent within lineages and depend on adaptation of individual genotypes. These patterns suggest that the diverse lineages of P. australis will undergo intense selective pressure in the face of global change such that the distributions and interactions of co-occurring lineages, as well as those of genotypes within-lineages, are very likely to be altered. We propose that the strong latitudinal clines within and between P. australis lineages can be a useful tool for predicting plant responses to climate change in general and present a conceptual framework for using P. australis lineages to predict plant responses

 Evaluation of the humoral and cellular immune responses after implantation of a PTFE vascular prosthesis.

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Skóra, Jan; Pupka, Artur; Dorobisz, Andrzej; Barć, Piotr; Korta, Krzysztof; Dawiskiba, Tomasz

2012-07-02

The experiment was designed in order to determine the immunological processes that occur during the healing in synthetic vascular grafts, especially to establish the differences in the location of the complement system proteins between the proximal and distal anastomosis and the differences in the arrangement of inflammatory cells in those anastomoses. The understanding of those processes will provide a true basis for determining risk factors for complications after arterial repair procedures. The experiment was carried out on 16 dogs that underwent implantation of unilateral aorto-femoral bypass with expanded polytetrafluoroethylene (ePTFE). After 6 months all animals were euthanized to dissect the vascular grafts. Immunohistochemical assays and electron microscopic examinations were performed. Immunohistochemical findings in the structure of neointima between anastomoses of vascular prostheses demonstrated significant differences between humoral and cellular responses. The area of proximal anastomosis revealed the presence of fibroblasts, but no macrophages were detected. The histological structure of the proximal anastomosis indicates that inflammatory processes were ended during the prosthesis healing. The immunological response obtained in the distal anastomosis corresponded to the chronic inflammatory reaction with the presence of macrophages, myofibroblasts and deposits of complement C3. The identification of differences in the presence of macrophages and myofibroblasts and the presence of the C3 component between the anastomoses is the original achievement of the present study. In the available literature, no such significant differences have been shown so far in the humoral and cellular immune response caused by the presence of an artificial vessel in the arterial system.

Participation of ATM in cellular response to DNA damage induced by ionizing radiation

International Nuclear Information System (INIS)

Meng Xiangbing; Song Yi; Mao Jianping; Gong Bo; Dong Yan; Liu Bin; Sun Zhixian

2000-01-01

Objective: To clone ATM full length cDNA and cDNA fragments containing some functional domains and to identify proteins that interact with ATM and mediate DNA damage signal transduction in cellular response to DNA damage. Methods: ATM cDNA was amplified from MarthomTM-Ready cDNA kit of human leukocytes by LD-PCR. ATM-interacting proteins were screened by yeast two hybrid system. Results: ATM full-length cDNA and cDNA fragments containing PI3K kinase domain, leucine zipper and proline rich region were amplified from human cDNAs. Several candidate clones that interacted with ATM PI3K domain were identified. Conclusion: ATM mediates DNA damage signal transduction by interacting with many proteins

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

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Patrick Maier

2016-01-01

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

Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

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Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R

2016-08-01

Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

HTLV-1 Tax Oncoprotein Subverts the Cellular DNA Damage Response via Binding to DNA-dependent Protein Kinase*S⃞

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Durkin, Sarah S.; Guo, Xin; Fryrear, Kimberly A.; Mihaylova, Valia T.; Gupta, Saurabh K.; Belgnaoui, S. Mehdi; Haoudi, Abdelali; Kupfer, Gary M.; Semmes, O. John

2008-01-01

Human T-cell leukemia virus type-1 is the causative agent for adult T-cell leukemia. Previous research has established that the viral oncoprotein Tax mediates the transformation process by impairing cell cycle control and cellular response to DNA damage. We showed previously that Tax sequesters huChk2 within chromatin and impairs the response to ionizing radiation. Here we demonstrate that DNA-dependent protein kinase (DNA-PK) is a member of the Tax·Chk2 nuclear complex. The catalytic subunit, DNA-PKcs, and the regulatory subunit, Ku70, were present. Tax-containing nuclear extracts showed increased DNA-PK activity, and specific inhibition of DNA-PK prevented Tax-induced activation of Chk2 kinase activity. Expression of Tax induced foci formation and phosphorylation of H2AX. However, Tax-induced constitutive signaling of the DNA-PK pathway impaired cellular response to new damage, as reflected in suppression of ionizing radiation-induced DNA-PK phosphorylation and γH2AX stabilization. Tax co-localized with phospho-DNA-PK into nuclear speckles and a nuclear excluded Tax mutant sequestered endogenous phospho-DNA-PK into the cytoplasm, suggesting that Tax interaction with DNA-PK is an initiating event. We also describe a novel interaction between DNA-PK and Chk2 that requires Tax. We propose that Tax binds to and stabilizes a protein complex with DNA-PK and Chk2, resulting in a saturation of DNA-PK-mediated damage repair response. PMID:18957425

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

Science.gov (United States)

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

Will surface winds weaken in response to global warming?

Science.gov (United States)

Ma, Jian; Foltz, Gregory R.; Soden, Brian J.; Huang, Gang; He, Jie; Dong, Changming

2016-12-01

The surface Walker and tropical tropospheric circulations have been inferred to slow down from historical observations and model projections, yet analysis of large-scale surface wind predictions is lacking. Satellite measurements of surface wind speed indicate strengthening trends averaged over the global and tropical oceans that are supported by precipitation and evaporation changes. Here we use corrected anemometer-based observations to show that the surface wind speed has not decreased in the averaged tropical oceans, despite its reduction in the region of the Walker circulation. Historical simulations and future projections for climate change also suggest a near-zero wind speed trend averaged in space, regardless of the Walker cell change. In the tropics, the sea surface temperature pattern effect acts against the large-scale circulation slow-down. For higher latitudes, the surface winds shift poleward along with the eddy-driven mid-latitude westerlies, resulting in a very small contribution to the global change in surface wind speed. Despite its importance for surface wind speed change, the influence of the SST pattern change on global-mean rainfall is insignificant since it cannot substantially alter the global energy balance. As a result, the precipitation response to global warming remains ‘muted’ relative to atmospheric moisture increase. Our results therefore show consistency between projections and observations of surface winds and precipitation.

Canada's international response to HIV during times of global transition: a qualitative inquiry.

Science.gov (United States)

Nixon, Stephanie

2011-04-01

Canada's international response to HIV may be under threat given CIDA's new aid priorities that appear to exclude health. Drivers of this recent priority shift have been the influence of global aid trends among public sector donors and changes within the global HIV milieu itself. However, this is not the first time Canada has shifted in response to these two global trends. The era from 2000-2004 also witnessed dramatic changes in both the HIV field and in global thinking around international aid. As such, this article presents an evaluation of the Government of Canada's international response to HIV during the first era of transition (2000-2004) in order to derive lessons for decision-making around HIV in the current climate of change. In-depth, semi-structured interviews were conducted with 23 key informants with expertise regarding Canada's international response to HIV over time. Analysis involved multiple readings of transcripts to identify descriptive codes and establish intimacy with the data. Descriptive codes were then collapsed into thematic categories using a process of inductive reasoning. Canada's international response to HIV was perceived to be exemplary at times (e.g. seminal funding to WHO's "3-by-5" strategy), but also inconsistent (e.g., underutilized technical assistance capacity) and non-strategic (e.g., contradiction between investing in training health providers while poaching professionals to bolster Canada's workforce). Lessons from the 2000-2004 era of transition focus on strategic investments, the inextricable connection between HIV and development and strategy coherence. These results highlight that it is more constructive to ensure that Canadian development responses in all areas engage with both the upstream drivers of HIV as well as the impacts of the epidemic itself in order to achieve the greatest results from international investment and the most effective contributions to the lives of the people that these endeavours seek to

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

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Balaji Balakrishnan

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

Enhanced Medial Collateral Ligament Healing using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

Science.gov (United States)

Saether, Erin E.; Chamberlain, Connie S.; Leiferman, Ellen M.; Kondratko-Mittnacht, Jaclyn R.; Li, Wan Ju; Brickson, Stacey L.; Vanderby, Ray

2013-01-01

Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1×106 or high dose 4×106 MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties. PMID:24174129

UV laser-ablated surface textures as potential regulator of cellular response.

Science.gov (United States)

Chandra, Prafulla; Lai, Karen; Sung, Hak-Joon; Murthy, N Sanjeeva; Kohn, Joachim

2010-06-01

Textured surfaces obtained by UV laser ablation of poly(ethylene terephthalate) films were used to study the effect of shape and spacing of surface features on cellular response. Two distinct patterns, cones and ripples with spacing from 2 to 25 μm, were produced. Surface features with different shapes and spacings were produced by varying pulse repetition rate, laser fluence, and exposure time. The effects of the surface texture parameters, i.e., shape and spacing, on cell attachment, proliferation, and morphology of neonatal human dermal fibroblasts and mouse fibroblasts were studied. Cell attachment was the highest in the regions with cones at ∼4 μm spacing. As feature spacing increased, cell spreading decreased, and the fibroblasts became more circular, indicating a stress-mediated cell shrinkage. This study shows that UV laser ablation is a useful alternative to lithographic techniques to produce surface patterns for controlling cell attachment and growth on biomaterial surfaces.

JC virus induces altered patterns of cellular gene expression: Interferon-inducible genes as major transcriptional targets

International Nuclear Information System (INIS)

Verma, Saguna; Ziegler, Katja; Ananthula, Praveen; Co, Juliene K.G.; Frisque, Richard J.; Yanagihara, Richard; Nerurkar, Vivek R.

2006-01-01

Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary infection, typically occurring during childhood, is asymptomatic in immunocompetent individuals and results in lifelong latency and persistent infection. However, among the severely immunocompromised, JCV may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Virus-host interactions influencing persistence and pathogenicity are not well understood, although significant regulation of JCV activity is thought to occur at the level of transcription. Regulation of the JCV early and late promoters during the lytic cycle is a complex event that requires participation of both viral and cellular factors. We have used cDNA microarray technology to analyze global alterations in gene expression in JCV-permissive primary human fetal glial cells (PHFG). Expression of more than 400 cellular genes was altered, including many that influence cell proliferation, cell communication and interferon (IFN)-mediated host defense responses. Genes in the latter category included signal transducer and activator of transcription 1 (STAT1), interferon stimulating gene 56 (ISG56), myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS), and cig5. The expression of these genes was further confirmed in JCV-infected PHFG cells and the human glioblastoma cell line U87MG to ensure the specificity of JCV in inducing this strong antiviral response. Results obtained by real-time RT-PCR and Western blot analyses supported the microarray data and provide temporal information related to virus-induced changes in the IFN response pathway. Our data indicate that the induction of an antiviral response may be one of the cellular factors regulating/controlling JCV replication in immunocompetent hosts and therefore constraining the development of PML

Symposium cellular response to DNA damage the role of poly(ADP-ribose) poly(ADP-ribose) in the cellular response to DNA damage

International Nuclear Information System (INIS)

Berger, N.A.

1985-01-01

Poly(ADP-ribose) polymerase is a chromatin-bound enzyme which, on activation by DNA strand breaks, catalyzes the successive transfer of ADP-ribose units from NAD to nuclear proteins. Poly(ADP-ribose) synthesis is stimulated by DNA strand breaks, and the polymer may alter the structure and/or function of chromosomal proteins to facilitate the DNA repair process. Inhibitors of Poly(ADP-ribose) polymerase or deficiencies of the substrate, NAD, lead to retardation of the DNA repair process. When DNA strand breaks are extensive or when breaks fail to be repaired, the stimulus for activation of Poly(ADP-ribose) persists and the activated enzyme is capable of totaly consuming cellular pools of NAD. Depletion of NAD and consequent lowering of cellular ATP pools, due to activation of Poly(ADP-ribose) polymerase, may account for rapid cell death before DNA repair takes place and before the genetic effects of DNA damage become manifest

Educating for Responsible Global Citizenship.

Science.gov (United States)

Drake, Christine

1987-01-01

Discusses geographical illiteracy in the United States and the problems of inadequate international awareness and poor understanding of major global issues. Examines what citizens should know, why they should care, and what people should do about the lack of global knowledge. Presents a list of 57 references dealing with global issues. (GEA)

Mean-state SST Response to global warming caused by the ENSO Nonlinearity

Science.gov (United States)

Kohyama, T.; Hartmann, D. L.

2017-12-01

The majority of the models that participated in the Coupled Model Intercomparison Project phase 5 (CMIP5) exhibit El Niño-like trends under global warming. GFDL-ESM2M, however, is an exception that exhibits a La Niña-like response with strengthened trade winds. Our previous studies have shown that this La Niña-like trend could be a physically consistent warming response, and we proposed the Nonlinear ENSO Warming Suppression (NEWS) mechanism to explain this La Niña-like response to global warming. The most important necessary condition of NEWS is the ENSO skewness (El Niños are stronger than La Niñas). Most CMIP5 models do not reproduce the observed ENSO skewness, while GFDL-ESM2M exhibits the realistic ENSO skewness, which suggests that, despite being in the minority, the La Niña-like trend of GFDL-ESM2M could be a plausible equatorial Pacific response to warming. In this study, we introduce another interesting outlier, MIROC5, which reproduces the observed skewness, yet exhibits an El Niño-like response. By decomposing the source of the ENSO nonlinearity into the following three components: "SST anomalies modulate winds", "winds excite oceanic waves", and "oceanic waves modulate the subsurface temperature", we show that the large inter-model spread of the third component appears to explain the most important cause of the poor reproducibility of the ENSO nonlinearity in CMIP5 models. It is concluded that the change in the response of subsurface temperature to oceanic waves is the primary explanation for the different warming response of GFDL-ESM2M and MIROC5. Our analyses suggest that the difference of the warming response are caused by difference in the climatological thermal stratification. This study may shed new light on the fundamental question of why observed ENSO has a strong skewness and on the implications of this skewed ENSO for the mean-state sea surface temperature response to global warming.

The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally.

Directory of Open Access Journals (Sweden)

Dan M Park

Full Text Available Despite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by mapping the regulon of the response regulator ArcA from Escherichia coli, which responds to the quinone/quinol redox couple via its membrane-bound sensor kinase, ArcB. Our genome-wide analysis reveals that ArcA reprograms metabolism under anaerobic conditions such that carbon oxidation pathways that recycle redox carriers via respiration are transcriptionally repressed by ArcA. We propose that this strategy favors use of catabolic pathways that recycle redox carriers via fermentation akin to lactate production in mammalian cells. Unexpectedly, bioinformatic analysis of the sequences bound by ArcA in ChIP-seq revealed that most ArcA binding sites contain additional direct repeat elements beyond the two required for binding an ArcA dimer. DNase I footprinting assays suggest that non-canonical arrangements of cis-regulatory modules dictate both the length and concentration-sensitive occupancy of DNA sites. We propose that this plasticity in ArcA binding site architecture provides both an efficient means of encoding binding sites for ArcA, σ(70-RNAP and perhaps other transcription factors within the same narrow sequence space and an effective mechanism for global control of carbon metabolism to maintain redox homeostasis.

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.

Three-dimensional microscopic deformation measurements on cellular solids.

Science.gov (United States)

Genovese, K

2016-07-01

The increasing interest in small-scale problems demands novel experimental protocols providing dense sets of 3D deformation data of complex shaped microstructures. Obtaining such information is particularly significant for the study of natural and engineered cellular solids for which experimental data collected at macro scale and describing the global mechanical response provide only limited information on their function/structure relationship. Cellular solids, in fact, due their superior mechanical performances to a unique arrangement of the bulk material properties (i.e. anisotropy and heterogeneity) and cell structural features (i.e. pores shape, size and distribution) at the micro- and nano-scales. To address the need for full-field experimental data down to the cell level, this paper proposes a single-camera stereo-Digital Image Correlation (DIC) system that makes use of a wedge prism in series to a telecentric lens for performing surface shape and deformation measurements on microstructures in three dimensions. Although the system possesses a limited measurement volume (FOV~2.8×4.3mm(2), error-free DOF ~1mm), large surface areas of cellular samples can be accurately covered by employing a sequential image capturing scheme followed by an optimization-based mosaicing procedure. The basic principles of the proposed method together with the results of the benchmarking of its metrological performances and error analysis are here reported and discussed in detail. Finally, the potential utility of this method is illustrated with micro-resolution three-dimensional measurements on a 3D printed honeycomb and on a block sample of a Luffa sponge under compression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

Science.gov (United States)

Gao, Ziyang

Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of

The New Cellular Immunology

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Claman, Henry N.

1973-01-01

Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

Molecular and Cellular Signaling

CERN Document Server

Beckerman, Martin

2005-01-01

A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

Global biodiversity, stoichiometry and ecosystem function responses to human-induced C-N-P imbalances

NARCIS (Netherlands)

Carnicer, Jofre; Sardans, Jordi; Stefanescu, Constanti; Ubach, Andreu; Bartrons, Mireia; Asensio, Dolores; Penuelas, Josep

2015-01-01

Global change analyses usually consider biodiversity as a global asset that needs to be preserved. Biodiversity is frequently analysed mainly as a response variable affected by diverse environmental drivers. However, recent studies highlight that gradients of biodiversity are associated with gradual

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.

Science.gov (United States)

Francis, J P; Richmond, P C; Strickland, D; Prescott, S L; Pomat, W S; Michael, A; Nadal-Sims, M A; Edwards-Devitt, C J; Holt, P G; Lehmann, D; van den Biggelaar, A H J

2017-03-01

In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease. © 2016 British Society for Immunology.

A Conceptual Model for Projecting Coccolithophorid Growth, Calcification and Photosynthetic Carbon Fixation Rates in Response to Global Ocean Change

Directory of Open Access Journals (Sweden)

Natasha A. Gafar

2018-01-01

Full Text Available Temperature, light and carbonate chemistry all influence the growth, calcification and photosynthetic rates of coccolithophores to a similar degree. There have been multiple attempts to project the responses of coccolithophores to changes in carbonate chemistry, but the interaction with light and temperature remains elusive. Here we devise a simple conceptual model to derive a fit equation for coccolithophorid growth, photosynthetic and calcification rates in response to simultaneous changes in carbonate chemistry, temperature and light conditions. The fit equation is able to account for up to 88% of the variability in measured metabolic rates. Equation projections indicate that temperature, light and carbonate chemistry all have different modulating effects on both optimal growth conditions and the sensitivity of responses to extreme environmental conditions. Calculations suggest that a single extreme environmental condition (CO2, temperature, light will reduce maximum rates regardless of how optimal the other environmental conditions may be. Thus, while the response of coccolithophores to ocean change depends on multiple variables, the one which is least optimal will have the most impact on overall rates. Finally, responses to ocean change are usually reported in terms of cellular rates. However, changes in cellular rates can be a poor predictor for assessing changes in production at the community level. We therefore introduce a new metric, the calcium carbonate production potential (CCPP, which combines the independent effects of changes in growth rate and cellular calcium carbonate content to assess how environmental changes will impact coccolith production. Direct comparison of CO2 impacts on cellular CaCO3 production rates and CCPP shows that while the former is still at 45% of its pre-industrial capacity at 1,000 μatm, the latter is reduced to 10%.

Effect of fibronectin adsorption on osteoblastic cellular responses to hydroxyapatite and alumina

International Nuclear Information System (INIS)

Kawashita, Masakazu; Hasegawa, Maki; Kudo, Tada-aki; Kanetaka, Hiroyasu; Miyazaki, Toshiki; Hashimoto, Masami

2016-01-01

Initial cellular responses following implantation are important for inducing osteoconduction. We investigated cell adhesion, spreading, proliferation and differentiation of mouse MC3T3-E1 osteoblastic cells on untreated or fibronectin (Fn)-coated discs of hydroxyapatite (HAp) or alpha-type alumina (α-Al 2 O 3 ). Fn coating significantly enhanced adhesion and spreading of MC3T3-E1 cells on HAp, but did not affect MC3T3-E1 cell proliferation and differentiation on HAp or α-Al 2 O 3 . Fn-coated HAp likely does not stimulate pre-osteoblast cells to initiate the process of osteoconduction; however, Fn adsorption might affect the response of inflammatory cells to the implanted material or, in conjunction with other serum proteins, stimulate pre-osteoblast cell proliferation and differentiation. Further studies on the effect of serum proteins in cell culture and the efficacy of Fn-coated HAp and α-Al 2 O 3 in vivo are warranted. - Highlights: • We studied osteoblast-like MC3T3-E1 cell responses on fibronectin (Fn)-coated discs (HAp/α-Al 2 O 3 ). • Fn adsorption enhanced adhesion and spreading of MC3T3-E1 cells on HAp but not on α-Al 2 O 3 . • Fn adsorption hardly affected proliferation and differentiation of MC3T3-E1 cells on HAp and α-Al 2 O 3 . • Fn adsorption might stimulate osteoconduction on HAp along with other serum proteins.

Cellular metabolism

International Nuclear Information System (INIS)

Hildebrand, C.E.; Walters, R.A.

1977-01-01

Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

Energy Technology Data Exchange (ETDEWEB)

Pan, Xiao [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Whitten, Douglas A. [Research Technology Support Facility, Proteomics Core, Michigan State University, East Lansing, MI 48824 (United States); Wu, Ming [Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824 (United States); Chan, Christina [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824 (United States); Wilkerson, Curtis G. [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Research Technology Support Facility, Proteomics Core, Michigan State University, East Lansing, MI 48824 (United States); Pestka, James J., E-mail: pestka@msu.edu [Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States); Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States)

2013-04-15

Deoxynivalenol (DON), a trichothecene mycotoxin produced by Fusarium that commonly contaminates food, is capable of activating mononuclear phagocytes of the innate immune system via a process termed the ribotoxic stress response (RSR). To encapture global signaling events mediating RSR, we quantified the early temporal (≤ 30 min) phosphoproteome changes that occurred in RAW 264.7 murine macrophage during exposure to a toxicologically relevant concentration of DON (250 ng/mL). Large-scale phosphoproteomic analysis employing stable isotope labeling of amino acids in cell culture (SILAC) in conjunction with titanium dioxide chromatography revealed that DON significantly upregulated or downregulated phosphorylation of 188 proteins at both known and yet-to-be functionally characterized phosphosites. DON-induced RSR is extremely complex and goes far beyond its prior known capacity to inhibit translation and activate MAPKs. Transcriptional regulation was the main target during early DON-induced RSR, covering over 20% of the altered phosphoproteins as indicated by Gene Ontology annotation and including transcription factors/cofactors and epigenetic modulators. Other biological processes impacted included cell cycle, RNA processing, translation, ribosome biogenesis, monocyte differentiation and cytoskeleton organization. Some of these processes could be mediated by signaling networks involving MAPK-, NFκB-, AKT- and AMPK-linked pathways. Fuzzy c-means clustering revealed that DON-regulated phosphosites could be discretely classified with regard to the kinetics of phosphorylation/dephosphorylation. The cellular response networks identified provide a template for further exploration of the mechanisms of trichothecenemycotoxins and other ribotoxins, and ultimately, could contribute to improved mechanism-based human health risk assessment. - Highlights: ► Mycotoxin deoxynivalenol (DON) induces immunotoxicity via ribotoxic stress response. ► SILAC phosphoproteomics using

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

International Nuclear Information System (INIS)

Pan, Xiao; Whitten, Douglas A.; Wu, Ming; Chan, Christina; Wilkerson, Curtis G.; Pestka, James J.

2013-01-01

Deoxynivalenol (DON), a trichothecene mycotoxin produced by Fusarium that commonly contaminates food, is capable of activating mononuclear phagocytes of the innate immune system via a process termed the ribotoxic stress response (RSR). To encapture global signaling events mediating RSR, we quantified the early temporal (≤ 30 min) phosphoproteome changes that occurred in RAW 264.7 murine macrophage during exposure to a toxicologically relevant concentration of DON (250 ng/mL). Large-scale phosphoproteomic analysis employing stable isotope labeling of amino acids in cell culture (SILAC) in conjunction with titanium dioxide chromatography revealed that DON significantly upregulated or downregulated phosphorylation of 188 proteins at both known and yet-to-be functionally characterized phosphosites. DON-induced RSR is extremely complex and goes far beyond its prior known capacity to inhibit translation and activate MAPKs. Transcriptional regulation was the main target during early DON-induced RSR, covering over 20% of the altered phosphoproteins as indicated by Gene Ontology annotation and including transcription factors/cofactors and epigenetic modulators. Other biological processes impacted included cell cycle, RNA processing, translation, ribosome biogenesis, monocyte differentiation and cytoskeleton organization. Some of these processes could be mediated by signaling networks involving MAPK-, NFκB-, AKT- and AMPK-linked pathways. Fuzzy c-means clustering revealed that DON-regulated phosphosites could be discretely classified with regard to the kinetics of phosphorylation/dephosphorylation. The cellular response networks identified provide a template for further exploration of the mechanisms of trichothecenemycotoxins and other ribotoxins, and ultimately, could contribute to improved mechanism-based human health risk assessment. - Highlights: ► Mycotoxin deoxynivalenol (DON) induces immunotoxicity via ribotoxic stress response. ► SILAC phosphoproteomics using

Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide

Science.gov (United States)

Fomenko, Dmitri E.; Koc, Ahmet; Agisheva, Natalia; Jacobsen, Michael; Kaya, Alaattin; Malinouski, Mikalai; Rutherford, Julian C.; Siu, Kam-Leung; Jin, Dong-Yan; Winge, Dennis R.; Gladyshev, Vadim N.

2011-01-01

Hydrogen peroxide is thought to regulate cellular processes by direct oxidation of numerous cellular proteins, whereas antioxidants, most notably thiol peroxidases, are thought to reduce peroxides and inhibit H2O2 response. However, thiol peroxidases have also been implicated in activation of transcription factors and signaling. It remains unclear if these enzymes stimulate or inhibit redox regulation and whether this regulation is widespread or limited to a few cellular components. Herein, we found that Saccharomyces cerevisiae cells lacking all eight thiol peroxidases were viable and withstood redox stresses. They transcriptionally responded to various redox treatments, but were unable to activate and repress gene expression in response to H2O2. Further studies involving redox transcription factors suggested that thiol peroxidases are major regulators of global gene expression in response to H2O2. The data suggest that thiol peroxidases sense and transfer oxidative signals to the signaling proteins and regulate transcription, whereas a direct interaction between H2O2 and other cellular proteins plays a secondary role. PMID:21282621

Heterogeneous global crop yield response to biochar: a meta-regression analysis

International Nuclear Information System (INIS)

Crane-Droesch, Andrew; Torn, Margaret S; Abiven, Samuel; Jeffery, Simon

2013-01-01

Biochar may contribute to climate change mitigation at negative cost by sequestering photosynthetically fixed carbon in soil while increasing crop yields. The magnitude of biochar’s potential in this regard will depend on crop yield benefits, which have not been well-characterized across different soils and biochars. Using data from 84 studies, we employ meta-analytical, missing data, and semiparametric statistical methods to explain heterogeneity in crop yield responses across different soils, biochars, and agricultural management factors, and then estimate potential changes in yield across different soil environments globally. We find that soil cation exchange capacity and organic carbon were strong predictors of yield response, with low cation exchange and low carbon associated with positive response. We also find that yield response increases over time since initial application, compared to non-biochar controls. High reported soil clay content and low soil pH were weaker predictors of higher yield response. No biochar parameters in our dataset—biochar pH, percentage carbon content, or temperature of pyrolysis—were significant predictors of yield impacts. Projecting our fitted model onto a global soil database, we find the largest potential increases in areas with highly weathered soils, such as those characterizing much of the humid tropics. Richer soils characterizing much of the world’s important agricultural areas appear to be less likely to benefit from biochar. (letter)

Do Surface Porosity and Pore Size Influence Mechanical Properties and Cellular Response to PEEK?

Science.gov (United States)

Torstrick, F Brennan; Evans, Nathan T; Stevens, Hazel Y; Gall, Ken; Guldberg, Robert E

2016-11-01

Despite its widespread use in orthopaedic implants such as soft tissue fasteners and spinal intervertebral implants, polyetheretherketone (PEEK) often suffers from poor osseointegration. Introducing porosity can overcome this limitation by encouraging bone ingrowth; however, the corresponding decrease in implant strength can potentially reduce the implant's ability to bear physiologic loads. We have previously shown, using a single pore size, that limiting porosity to the surface of PEEK implants preserves strength while supporting in vivo osseointegration. However, additional work is needed to investigate the effect of pore size on both the mechanical properties and cellular response to PEEK. (1) Can surface porous PEEK (PEEK-SP) microstructure be reliably controlled? (2) What is the effect of pore size on the mechanical properties of PEEK-SP? (3) Do surface porosity and pore size influence the cellular response to PEEK? PEEK-SP was created by extruding PEEK through NaCl crystals of three controlled ranges: 200 to 312, 312 to 425, and 425 to 508 µm. Micro-CT was used to characterize the microstructure of PEEK-SP. Tensile, fatigue, and interfacial shear tests were performed to compare the mechanical properties of PEEK-SP with injection-molded PEEK (PEEK-IM). The cellular response to PEEK-SP, assessed by proliferation, alkaline phosphatase activity, vascular endothelial growth factor production, and calcium content of osteoblast, mesenchymal stem cell, and preosteoblast (MC3T3-E1) cultures, was compared with that of machined smooth PEEK and Ti6Al4V. Micro-CT analysis showed that PEEK-SP layers possessed pores that were 284 ± 35 µm, 341 ± 49 µm, and 416 ± 54 µm for each pore size group. Porosity and pore layer depth ranged from 61% to 69% and 303 to 391 µm, respectively. Mechanical testing revealed tensile strengths > 67 MPa and interfacial shear strengths > 20 MPa for all three pore size groups. All PEEK-SP groups exhibited > 50% decrease

Global transcriptional responses of Bacillus subtilis to xenocoumacin 1.

Science.gov (United States)

Zhou, T; Zeng, H; Qiu, D; Yang, X; Wang, B; Chen, M; Guo, L; Wang, S

2011-09-01

To determine the global transcriptional response of Bacillus subtilis to an antimicrobial agent, xenocoumacin 1 (Xcn1). Subinhibitory concentration of Xcn1 applied to B. subtilis was measured according to Hutter's method for determining optimal concentrations. cDNA microarray technology was used to study the global transcriptional response of B. subtilis to Xcn1. Real-time RT-PCR was employed to verify alterations in the transcript levels of six genes. The subinhibitory concentration was determined to be 1 μg ml(-1). The microarray data demonstrated that Xcn1 treatment of B. subtilis led to more than a 2.0-fold up-regulation of 480 genes and more than a 2.0-fold down-regulation of 479 genes (q ≤ 0.05). The transcriptional responses of B. subtilis to Xcn1 were determined, and several processes were affected by Xcn1. Additionally, cluster analysis of gene expression profiles after treatment with Xcn1 or 37 previously studied antibiotics indicated that Xcn1 has similar mechanisms of action to protein synthesis inhibitors. These microarray data showed alterations of gene expression in B. subtilis after exposure to Xcn1. From the results, we identified various processes affected by Xcn1. This study provides a whole-genome perspective to elucidate the action of Xcn1 as a potential antimicrobial agent. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

Trichothiodystrophy, a human DNA repair disorder with heterogeneity in the cellular response to ultraviolet light

International Nuclear Information System (INIS)

Lehmann, A.R.; Arlett, C.F.; Broughton, B.C.

1988-01-01

Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and physical retardation. Some patients are photosensitive. A previous study by Stefanini et al. showed that cells from four photosensitive patients with TTD had a molecular defect in DNA repair, which was not complemented by cells from xeroderma pigmentosum, complementation group D. In a detailed molecular and cellular study of the effects of UV light on cells cultured from three further TTD patients who did not exhibit photosensitivity we have found an array of different responses. In cells from the first patient, survival, excision repair, and DNA and RNA synthesis following UV irradiation were all normal, whereas in cells from the second patient all these responses were similar to those of excision-defective xeroderma pigmentosum (group D) cells. With the third patient, cell survival measured by colony-forming ability was normal following UV irradiation, even though repair synthesis was only 50% of normal and RNA synthesis was severely reduced. The excision-repair defect in these cells was not complemented by other TTD cell strains. These cellular characteristics of patient 3 have not been described previously for any other cell line. The normal survival may be attributed to the finding that the deficiency in excision-repair is confined to early times after irradiation. Our results pose a number of questions about the relationship between the molecular defect in DNA repair and the clinical symptoms of xeroderma pigmentosum and TTD

Humoral and cellular CMV responses in healthy donors; identification of a frequent population of CMV-specific, CD4+ T cells in seronegative donors

DEFF Research Database (Denmark)

Loeth, Nina; Assing, Kristian; Madsen, Hans O

2012-01-01

.e., T lymphocyte) assays. Here, we have analyzed the CMV status of 100 healthy blood bank donors using both serology and cellular assays. About half (56%) were found to be CMV seropositive, and they all mounted strong CD8+ and/or moderate CD4+ T cell responses ex vivo against the immunodominant CMV...... protein, pp65. Of the 44 seronegative donors, only five (11%) mounted ex vivo T cell responses; surprisingly, 33 (75%) mounted strong CD4+ T cell responses after a brief in vitro peptide stimulation culture. This may have significant implications for the analysis and selection of HCT donors.......CMV status is an important risk factor in immune compromised patients. In hematopoeitic cell transplantations (HCT), both donor and recipient are tested routinely for CMV status by serological assays; however, one might argue that it might also be of relevance to examine CMV status by cellular (i...

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

Science.gov (United States)

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

2013-01-01

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

Global transcriptional analysis of short-term hepatic stress responses in Atlantic salmon (Salmo salar) exposed to depleted uranium

Science.gov (United States)

Song, You; Salbu, Brit; Teien, Hans-Christian; Heier, Lene Sørlie; Rosseland, Bjørn Olav; Høgåsen, Tore; Tollefsen, Knut Erik

2014-01-01

Potential environmental hazards of radionuclides are often studied at the individual level. Sufficient toxicogenomics data at the molecular/cellular level for understanding the effects and modes of toxic action (MoAs) of radionuclide is still lacking. The current article introduces transcriptomic data generated from a recent ecotoxicological study, with the aims to characterize the MoAs of a metallic radionuclide, deplete uranium (DU) in an ecologically and commercially important fish species, Atlantic salmon (Salmo salar). Salmon were exposed to three concentrations (0.25, 0.5 and 1.0 mg/L) of DU for 48 h. Short-term global transcriptional responses were studied using Agilent custom-designed high density 60,000-feature (60 k) salmonid oligonucleotide microarrays (oligoarray). The microarray datasets deposited at Gene Expression Omnibus (GEO ID: GSE58824) were associated with a recently published study by Song et al. (2014) in BMC Genomics. The authors describe the experimental data herein to build a platform for better understanding the toxic mechanisms and ecological hazard of radionuclides such as DU in fish. PMID:26484125

Global transcriptional analysis of short-term hepatic stress responses in Atlantic salmon (Salmo salar exposed to depleted uranium

Directory of Open Access Journals (Sweden)

You Song

2014-12-01

Full Text Available Potential environmental hazards of radionuclides are often studied at the individual level. Sufficient toxicogenomics data at the molecular/cellular level for understanding the effects and modes of toxic action (MoAs of radionuclide is still lacking. The current article introduces transcriptomic data generated from a recent ecotoxicological study, with the aims to characterize the MoAs of a metallic radionuclide, deplete uranium (DU in an ecologically and commercially important fish species, Atlantic salmon (Salmo salar. Salmon were exposed to three concentrations (0.25, 0.5 and 1.0 mg/L of DU for 48 h. Short-term global transcriptional responses were studied using Agilent custom-designed high density 60,000-feature (60 k salmonid oligonucleotide microarrays (oligoarray. The microarray datasets deposited at Gene Expression Omnibus (GEO ID: GSE58824 were associated with a recently published study by Song et al. (2014 in BMC Genomics. The authors describe the experimental data herein to build a platform for better understanding the toxic mechanisms and ecological hazard of radionuclides such as DU in fish.

Linking above and belowground responses to global change at community and ecosystem scales.

Energy Technology Data Exchange (ETDEWEB)

Antoninka, Anita [Northern Arizona University; Wolf, Julie [Northern Arizona University; Bowker, Matt [Northern Arizona University; Classen, Aimee T [ORNL; JohnsonPhD, Dr Nancy C [Northern Arizona University

2009-01-01

Cryptic belowground organisms are difficult to observe and their responses to global changes are not well understood. Nevertheless, there is reason to believe that interactions among above- and belowground communities may mediate ecosystem responses to global change. We used grassland mesocosms to manipulate the abundance of one important group of soil organisms, arbuscular mycorrhizal (AM) fungi, and to study community and ecosystem responses to CO2 and N enrichment. After two growing seasons, biomass responses of plant communities were recorded, and soil community responses were measured using microscopy, phospholipid fatty acids (PLFA) and community-level physiological profiles (CLPP). Ecosystem responses were examined by measuring net primary production (NPP), evapotranspiration, total soil organic matter (SOM), and extractable mineral N. Structural equation modeling was used to examine the causal relationships among treatments and response variables. We found that while CO2 and N tended to directly impact ecosystem functions (evapotranspiration and NPP, respectively), AM fungi indirectly impacted ecosystem functions by strongly influencing the composition of plant and soil communities. For example, the presence of AM fungi had a strong influence on other root and soil fungi and soil bacteria. We found that the mycotrophic status of the dominant plant species in the mesocosms determined whether the presence of AM fungi increased or decreased NPP. Mycotrophic grasses dominated the mesocosm communities during the first growing season, and thus, the mycorrhizal treatments had the highest NPP. In contrast, non-mycotrophic forbs were dominant during the second growing season and thus, the mycorrhizal treatments had the lowest NPP. The composition of the plant community strongly influenced soil N; and the composition of the soil organisms strongly influenced SOM accumulation in the mesocosms. These results show how linkages between above- and belowground communities

Cellular and molecular immune responses of the sea bass (Dicentrarchus labrax) experimentally infected with betanodavirus

DEFF Research Database (Denmark)

Scapigliati, G.; Buonocore, F.; Randelli, E.

2010-01-01

and acquired responses: type I IFN, Mx, IL-1, Cox-2; IL-10, TGF-β, TCRβ, CD4, CD8α, IgM, by using a quantitative PCR array system developed for sea bass. The obtained results showed a detectable increase of T cells and B cells in PBL during betanodavirus infection. Furthermore, leucocytes obtained from blood...... was also observed, while the other tested genes did not show any significant variations with respect to mock-treated fish. Overall, our work represents a first comprehensive analysis of cellular and molecular immune parameters in a fish species exposed to a pathogenic virus....

Generating global brand equity through corporate social responsibility to key stakeholders

NARCIS (Netherlands)

Torres, Anna; Bijmolt, Tammo H. A.; Tribo, Josep A.; Verhoef, Peter

In this paper, we argue that corporate social responsibility (CSR) to various stakeholders (customers, shareholders, employees, suppliers, and community) has a positive effect on global brand equity (BE). In addition, policies aimed at satisfying community interests help reinforce the credibility of

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.

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

Science.gov (United States)

Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

2011-02-01

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Barkha Khilwani

2015-08-01

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

The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection.

Directory of Open Access Journals (Sweden)

Ana Filipovic

Full Text Available Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviae-containing eye solution in the conjunctival sac in three different doses: 1×102, 1×104, and 1×106 inclusion forming units (IFUs. Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only guinea pigs infected with the higher doses showed significant changes in C. caviae-specific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4+ and CD8+ cells within guinea pigs' submandibular lymph node (SMLN lymphocytes while the higher doses increased the percentages of CD4+ and CD8+ cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4+ and CD8+ cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1×104, and 1×106 IFU infected guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections.

BRIC-21: Global Transcriptome Profiling to Identify Cellular Stress Mechanisms Responsible for Spaceflight-Induced Antibiotic Resistance

Science.gov (United States)

Nicholson, Wayne L.; Fajardo-Cavazos, Patricia

2015-01-01

Comparisons of spaceflight stress responses in Bacillus subtilis spores and Staphylococcus epidermidis cells to ground-based controls will be conducted to uncover alterations in their antibiotic susceptibility.

Parallel Implementation of Triangular Cellular Automata for Computing Two-Dimensional Elastodynamic Response on Arbitrary Domains

Science.gov (United States)

Leamy, Michael J.; Springer, Adam C.

In this research we report parallel implementation of a Cellular Automata-based simulation tool for computing elastodynamic response on complex, two-dimensional domains. Elastodynamic simulation using Cellular Automata (CA) has recently been presented as an alternative, inherently object-oriented technique for accurately and efficiently computing linear and nonlinear wave propagation in arbitrarily-shaped geometries. The local, autonomous nature of the method should lead to straight-forward and efficient parallelization. We address this notion on symmetric multiprocessor (SMP) hardware using a Java-based object-oriented CA code implementing triangular state machines (i.e., automata) and the MPI bindings written in Java (MPJ Express). We use MPJ Express to reconfigure our existing CA code to distribute a domain's automata to cores present on a dual quad-core shared-memory system (eight total processors). We note that this message passing parallelization strategy is directly applicable to computer clustered computing, which will be the focus of follow-on research. Results on the shared memory platform indicate nearly-ideal, linear speed-up. We conclude that the CA-based elastodynamic simulator is easily configured to run in parallel, and yields excellent speed-up on SMP hardware.

The grand illusion? corporate social responsibility in global garment production networks

OpenAIRE

Starmanns, M

2010-01-01

This PhD aims to generate a better understanding of corporate social responsibility (CSR) in global production networks. CSR is an umbrella term that deals with voluntary activities undertaken by companies and that indicate an ethos to act responsibly in society. This research focuses on CSR practices that aim towards improving working conditions in outsourced production factories by implementing so-called social standards, which often derive from core norms of the International Labour Organi...

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-07-15

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

Interplay between Ubiquitin, SUMO, and Poly(ADP-Ribose) in the Cellular Response to Genotoxic Stress

Science.gov (United States)

Pellegrino, Stefania; Altmeyer, Matthias

2016-01-01

Cells employ a complex network of molecular pathways to cope with endogenous and exogenous genotoxic stress. This multilayered response ensures that genomic lesions are efficiently detected and faithfully repaired in order to safeguard genome integrity. The molecular choreography at sites of DNA damage relies heavily on post-translational modifications (PTMs). Protein modifications with ubiquitin and the small ubiquitin-like modifier SUMO have recently emerged as important regulatory means to coordinate DNA damage signaling and repair. Both ubiquitylation and SUMOylation can lead to extensive chain-like protein modifications, a feature that is shared with yet another DNA damage-induced PTM, the modification of proteins with poly(ADP-ribose) (PAR). Chains of ubiquitin, SUMO, and PAR all contribute to the multi-protein assemblies found at sites of DNA damage and regulate their spatio-temporal dynamics. Here, we review recent advancements in our understanding of how ubiquitin, SUMO, and PAR coordinate the DNA damage response and highlight emerging examples of an intricate interplay between these chain-like modifications during the cellular response to genotoxic stress. PMID:27148359

Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida

DEFF Research Database (Denmark)

Bojanovic, Klara; D'Arrigo, Isotta; Long, Katherine

2017-01-01

functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through which P. putida responds to different stress conditions...... intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous......Bacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response of Pseudomonas putida KT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification...

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.

Delay-dependent exponential stability of cellular neural networks with time-varying delays

International Nuclear Information System (INIS)

Zhang Qiang; Wei Xiaopeng; Xu Jin

2005-01-01

The global exponential stability of cellular neural networks (CNNs) with time-varying delays is analyzed. Two new sufficient conditions ensuring global exponential stability for delayed CNNs are obtained. The conditions presented here are related to the size of delay. The stability results improve the earlier publications. Two examples are given to demonstrate the effectiveness of the obtained results

Toxicology and cellular effect of manufactured nanomaterials

Science.gov (United States)

Chen, Fanqing

2014-07-22

The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

Predicting the Responses of Soil Nitrite-Oxidizers to Multi-Factorial Global Change: A Trait-Based Approach

DEFF Research Database (Denmark)

Le Roux, Xavier; Bouskill, Nicholas J.; Niboyet, Audrey

2016-01-01

Soil microbial diversity is huge and a few grams of soil contain more bacterial taxa than there are bird species on Earth. This high diversity often makes predicting the responses of soil bacteria to environmental change intractable and restricts our capacity to predict the responses of soil...... functions to global change. Here, using a long-term field experiment in a California grassland, we studied the main and interactive effects of three global change factors (increased atmospheric CO2 concentration, precipitation and nitrogen addition, and all their factorial combinations, based on global...

Mentoring health researchers globally: Diverse experiences, programmes, challenges and responses.

Science.gov (United States)

Cole, Donald C; Johnson, Nancy; Mejia, Raul; McCullough, Hazel; Turcotte-Tremblay, Anne-Marie; Barnoya, Joaquin; Falabella Luco, María Soledad

2016-10-01

Mentoring experiences and programmes are becoming increasingly recognised as important by those engaged in capacity strengthening in global health research. Using a primarily qualitative study design, we studied three experiences of mentorship and eight mentorship programmes for early career global health researchers based in high-income and low- and middle-income countries. For the latter, we drew upon programme materials, existing unpublished data and more formal mixed-method evaluations, supplemented by individual email questionnaire responses. Research team members wrote stories, and the team assembled and analysed them for key themes. Across the diverse experiences and programmes, key emergent themes included: great mentors inspire others in an inter-generational cascade, mentorship is transformative in personal and professional development and involves reciprocity, and finding the right balance in mentoring relationships and programmes includes responding creatively to failure. Among the challenges encountered were: struggling for more level playing fields for new health researchers globally, changing mindsets in institutions that do not have a culture of mentorship and building collaboration not competition. Mentoring networks spanning institutions and countries using multiple virtual and face-to-face methods are a potential avenue for fostering organisational cultures supporting quality mentorship in global health research.

Forest responses to tropospheric ozone and global climate change: an analysis.

Science.gov (United States)

Kickert, R N; Krupa, S V

1990-01-01

In this paper an analysis is provided on: what we know, what we need to know, and what we need to do, to further our understanding of the relationships between tropospheric ozone (O(3)), global climate change and forest responses. The relationships between global geographic distributions of forest ecosystems and potential geographic regions of high photochemical smog by the year 2025 AD are described. While the emphasis is on the effects of tropospheric O(3) on forest ecosystems, discussion is presented to understand such effects in the context of global climate change. One particular strong point of this paper is the audit of published surface O(3) data by photochemical smog region that reveals important forest/woodland geographic regions where little or no O(3) data exist even though the potential threat to forests in those regions appears to be large. The concepts and considerations relevant to the examination of ecosystem responses as a whole, rather than simply tree stands alone are reviewed. A brief argument is provided to stimulate the modification of the concept of simple cause and effect relationships in viewing total ecosystems. Our knowledge of O(3) exposure and its effects on the energy, nutrient and hydrological flow within the ecosystem are described. Modeling strategies for such systems are reviewed. A discussion of responses of forests to potential multiple climatic changes is provided. An important concept in this paper is that changes in water exchange processes throughout the hydrological cycle can be used as early warning indicators of forest responses to O(3). Another strength of this paper is the integration of information on structural and functional processes of ecosystems and their responses to O(3). An admitted weakness of this analysis is that the information on integrated ecosystem responses is based overwhelmingly on the San Bernardino Forest ecosystem research program of the 1970s because of a lack of similar studies. In the final

Public Policy Responses to the Global Financial and Economic Crisis

African Journals Online (AJOL)

This article aims to assess the impact of the global fi nancial and economic crisis on two sectors in South Africa, namely, the automobile sector and the textile and clothing sector. It also examines the role of public policy in responding to that crisis. Its main objective is to determine whether or not those responses were ...

A change in inflammatory footprint precedes plaque instability: a systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis

NARCIS (Netherlands)

van Dijk, R. A.; Duinisveld, A. J. F.; Schaapherder, A. F.; Mulder-Stapel, A.; Hamming, J. F.; Kuiper, J.; de Boer, O. J.; van der Wal, A. C.; Kolodgie, F. D.; Virmani, R.; Lindeman, J. H. N.

2015-01-01

Experimental studies characterize adaptive immune response as a critical factor in the progression and complications of atherosclerosis. Yet, it is unclear whether these observations translate to the human situation. This study systematically evaluates cellular components of the adaptive immune

Activity against Mycobacterium tuberculosis with concomitant induction of cellular immune responses by a tetraaza-macrocycle with acetate pendant arms.

Science.gov (United States)

David, S; Ordway, D; Arroz, M J; Costa, J; Delgado, R

2001-01-01

The novel tetraaza-macrocyclic compound 3,7,11-tris(carboxymethyl)-3,7,11,17-tetraaza-bicyclo[11.3.1]heptadeca-1(17),13,15-triene, abbreviated as ac3py14, was investigated for its activity against Mycobacterium tuberculosis and for induction of protective cellular immune responses. Perspective results show that ac3py14 and its Fe3+ 1:1 complex, [Fe(ac3py14)], inhibited radiometric growth of several strains of M. tuberculosis. Inhibition with 25 microg/mL varied from 99% for H37Rv to 80% and above for multiple drug-resistant clinical isolates. The capacity of ac3py14 to elicit a beneficial immune response without cellular apoptosis was assessed and compared to the effects of virulent M. tuberculosis. The present study produces evidence that after stimulation with ac3py14 there was significant production of interferon gamma (IFN-gamma), whereas the production of interleukin-5 (IL-5) remained low, and there was development of a memory population (CD45RO). The level of binding of Annexin V, a marker of apoptosis, was not sufficient to result in toxic effects toward alphabeta and gammadelta T cells and CD14+ macrophages. This preliminary study is the first report of a compound that simultaneously exerts an inhibitory effect against M. tuberculosis and induces factors associated with protective immune responses.

Effect of fibronectin adsorption on osteoblastic cellular responses to hydroxyapatite and alumina

Energy Technology Data Exchange (ETDEWEB)

Kawashita, Masakazu, E-mail: m-kawa@ecei.tohoku.ac.jp [Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8579 (Japan); Hasegawa, Maki [Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8579 (Japan); Kudo, Tada-aki; Kanetaka, Hiroyasu [Graduate School of Dentistry, Tohoku University, Sendai 980-8575 (Japan); Miyazaki, Toshiki [Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196 (Japan); Hashimoto, Masami [Japan Fine Ceramics Center, Nagoya 456-8587 (Japan)

2016-12-01

Initial cellular responses following implantation are important for inducing osteoconduction. We investigated cell adhesion, spreading, proliferation and differentiation of mouse MC3T3-E1 osteoblastic cells on untreated or fibronectin (Fn)-coated discs of hydroxyapatite (HAp) or alpha-type alumina (α-Al{sub 2}O{sub 3}). Fn coating significantly enhanced adhesion and spreading of MC3T3-E1 cells on HAp, but did not affect MC3T3-E1 cell proliferation and differentiation on HAp or α-Al{sub 2}O{sub 3}. Fn-coated HAp likely does not stimulate pre-osteoblast cells to initiate the process of osteoconduction; however, Fn adsorption might affect the response of inflammatory cells to the implanted material or, in conjunction with other serum proteins, stimulate pre-osteoblast cell proliferation and differentiation. Further studies on the effect of serum proteins in cell culture and the efficacy of Fn-coated HAp and α-Al{sub 2}O{sub 3}in vivo are warranted. - Highlights: • We studied osteoblast-like MC3T3-E1 cell responses on fibronectin (Fn)-coated discs (HAp/α-Al{sub 2}O{sub 3}). • Fn adsorption enhanced adhesion and spreading of MC3T3-E1 cells on HAp but not on α-Al{sub 2}O{sub 3}. • Fn adsorption hardly affected proliferation and differentiation of MC3T3-E1 cells on HAp and α-Al{sub 2}O{sub 3}. • Fn adsorption might stimulate osteoconduction on HAp along with other serum proteins.

Giardiasis in mice: analysis of humoral and cellular immune responses to Giardia muris.

Science.gov (United States)

Anders, R F; Roberts-Thomson, I C; Mitchell, G F

1982-01-01

Humoral and cellular immune responses have been evaluated in two inbred strains of mice which differ markedly in their susceptibility to infection with Giardia muris. Serum IgG and IgA antibody levels and IgA levels in intestinal washes were determined by a solid-phase radioimmunoassay using G. muris antigen prepared by sonication of trophozoites, while cell-mediated immunity was assessed by a radiometric ear-assay for delayed-type hypersensitivity. Following infection of BALB/c mice (resistant) and C3H/He mice (susceptible), the IgG and IgA antibody levels in serum progressively increased over the period of study with C3H/He mice having significantly higher titres of IgA antibodies than BALB/c late in the infection. Systemic immunization with G. muris trophozoites resulted in high titres of IgG antibodies in the serum. IgA antibodies were detected in intestinal washes 2 weeks after infection with a subsequent fall in levels in BALB/c mice but a progressive increase levels in C3H/He mice. Prior immunization resulted in IgA antibodies being detected earlier in the intestinal washings after a challenge infection. Delayed-type hypersensitivity to G. muris antigens could not be detected during an infection but a positive response was elicited following antigen priming in mice pretreated with cyclophosphamide. The immune responses evaluated in this study were assessed using a whole G. muris trophozoite sonicate and variations in the quantitative aspects of the responses did not account for observed differences in the course of infection in the two strains of mice.

Terminal addition in a cellular world.

Science.gov (United States)

Torday, J S; Miller, William B

2018-07-01

Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of 'reverse evolution' of the self-same processes. Copyright © 2017. Published by Elsevier Ltd.

Synchronization, TIGoRS, and Information Flow in Complex Systems: Dispositional Cellular Automata.

Science.gov (United States)

Sulis, William H

2016-04-01

Synchronization has a long history in physics where it refers to the phase matching of two identical oscillators. This notion has been extensively studied in physics as well as in biology, where it has been applied to such widely varying phenomena as the flashing of fireflies and firing of neurons in the brain. Human behavior, however, may be recurrent but it is not oscillatory even though many physiological systems do exhibit oscillatory tendencies. Moreover, much of human behaviour is collaborative and cooperative, where the individual behaviours may be distinct yet contemporaneous (if not simultaneous) and taken collectively express some functionality. In the context of behaviour, the important aspect is the repeated co-occurrence in time of behaviours that facilitate the propagation of information or of functionality, regardless of whether or not these behaviours are similar or identical. An example of this weaker notion of synchronization is transient induced global response synchronization (TIGoRS). Previous work has shown that TIGoRS is a ubiquitous phenomenon among complex systems, enabling them to stably parse environmental transients into salient units to which they stably respond. This leads to the notion of Sulis machines, which emergently generate a primitive linguistic structure through their dynamics. This article reviews the notion of TIGoRS and its expression in several complex systems models including tempered neural networks, driven cellular automata and cocktail party automata. The emergent linguistics of Sulis machines are discussed. A new class of complex systems model, the dispositional cellular automaton is introduced. A new metric for TIGoRS, the excess synchronization, is introduced and applied to the study of TIGoRS in dispositional cellular automata. It is shown that these automata exhibit a nonlinear synchronization response to certain perturbing transients.

Maturity Assessment of Knowledge Management at PT. Cellular Tbk.: A Case Study at A Telecommunication Operator in Indonesia

Science.gov (United States)

Ghazali, Achmad; Vivaldi, Harly; Putranto, Nur Arief Rahmatsyah

2017-01-01

Managing knowledge integrally as one of the company's asset is now a necessity to be part of the knowledge-based economy in the global industry. PT Cellular Tbk. (Cellular) has been a player of mobile communication service for more than 20 years. Cellular shows business transformation through increased gross revenue from Data services while…

Training practices of cell processing laboratory staff: analysis of a survey by the Alliance for Harmonization of Cellular Therapy Accreditation.

Science.gov (United States)

Keever-Taylor, Carolyn A; Slaper-Cortenbach, Ineke; Celluzzi, Christina; Loper, Kathy; Aljurf, Mahmoud; Schwartz, Joseph; Mcgrath, Eoin; Eldridge, Paul

2015-12-01

Methods for processing products used for hematopoietic progenitor cell (HPC) transplantation must ensure their safety and efficacy. Personnel training and ongoing competency assessment is critical to this goal. Here we present results from a global survey of methods used by a diverse array of cell processing facilities for the initial training and ongoing competency assessment of key personnel. The Alliance for Harmonisation of Cellular Therapy Accreditation (AHCTA) created a survey to identify facility type, location, activity, personnel, and methods used for training and competency. A survey link was disseminated through organizations represented in AHCTA to processing facilities worldwide. Responses were tabulated and analyzed as a percentage of total responses and as a percentage of response by region group. Most facilities were based at academic medical centers or hospitals. Facilities with a broad range of activity, product sources and processing procedures were represented. Facilities reported using a combination of training and competency methods. However, some methods predominated. Cellular sources for training differed for training versus competency and also differed based on frequency of procedures performed. Most facilities had responsibilities for procedures in addition to processing for which training and competency methods differed. Although regional variation was observed, training and competency requirements were generally consistent. Survey data showed the use of a variety of training and competency methods but some methods predominated, suggesting their utility. These results could help new and established facilities in making decisions for their own training and competency programs. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Biochemical Factors Modulating Cellular Neurotoxicity of Methylmercury

Directory of Open Access Journals (Sweden)

Parvinder Kaur

2011-01-01

Full Text Available Methylmercury (MeHg, an environmental toxicant primarily found in fish and seafood, poses a dilemma to both consumers and regulatory authorities, given the nutritional benefits of fish consumption versus the possible adverse neurological damage. Several studies have shown that MeHg toxicity is influenced by a number of biochemical factors, such as glutathione (GSH, fatty acids, vitamins, and essential elements, but the cellular mechanisms underlying these complex interactions have not yet been fully elucidated. The objective of this paper is to outline the cellular response to dietary nutrients, as well as to describe the neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s of toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl cysteine, (NAC; diethyl maleate, (DEM; docosahexaenoic acid, (DHA; selenomethionine, SeM; Trolox and MeHg treatment on intercellular antioxidant status, MeHg content, and other endpoints was evaluated. This paper emphasizes that the protection against oxidative stress offered by these biochemical factors is among one of the major mechanisms responsible for conferring neuroprotection. It is therefore critical to ascertain the cellular mechanisms associated with various dietary nutrients as well as to determine the potential effects of neurotoxic exposures for accurately assessing the risks and benefits associated with fish consumption.

Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans.

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Sonia Gullón

Full Text Available Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase and a Tat-dependent model protein (agarase in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients' depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host.

Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

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Tetu Bernard

2008-02-01

Full Text Available Abstract Background Chemotherapy (CT resistance in ovarian cancer (OC is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155, following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism, signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes, cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular

Ocean cleaning stations under a changing climate: biological responses of tropical and temperate fish-cleaner shrimp to global warming.

Science.gov (United States)

Rosa, Rui; Lopes, Ana Rita; Pimentel, Marta; Faleiro, Filipa; Baptista, Miguel; Trübenbach, Katja; Narciso, Luis; Dionísio, Gisela; Pegado, Maria Rita; Repolho, Tiago; Calado, Ricardo; Diniz, Mário

2014-10-01

Cleaning symbioses play an important role in the health of certain coastal marine communities. These interspecific associations often occur at specific sites (cleaning stations) where a cleaner organism (commonly a fish or shrimp) removes ectoparasites/damaged tissue from a 'client' (a larger cooperating fish). At present, the potential impact of climate change on the fitness of cleaner organisms remains unknown. This study investigated the physiological and biochemical responses of tropical (Lysmata amboinensis) and temperate (L. seticaudata) cleaner shrimp to global warming. Specifically, thermal limits (CTMax), metabolic rates, thermal sensitivity, heat shock response (HSR), lipid peroxidation [malondialdehyde (MDA) concentration], lactate levels, antioxidant (GST, SOD and catalase) and digestive enzyme activities (trypsin and alkaline phosphatase) at current and warming (+3 °C) temperature conditions. In contrast to the temperate species, CTMax values decreased significantly from current (24-27 °C) to warming temperature conditions (30 °C) for the tropical shrimp, where metabolic thermal sensitivity was affected and the HSR was significantly reduced. MDA levels in tropical shrimp increased dramatically, indicating extreme cellular lipid peroxidation, which was not observed in the temperate shrimp. Lactate levels, GST and SOD activities were significantly enhanced within the muscle tissue of the tropical species. Digestive enzyme activities in the hepatopancreas of both species were significantly decreased by warmer temperatures. Our data suggest that the tropical cleaner shrimp will be more vulnerable to global warming than the temperate Lysmata seticaudata; the latter evolved in a relatively unstable environment with seasonal thermal variations that may have conferred greater adaptive plasticity. Thus, tropical cleaning symbioses may be challenged at a greater degree by warming-related anthropogenic forcing, with potential cascading effects on the health

Evolutionary History Underlies Plant Physiological Responses to Global Change Since the Last Glacial Maximum

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Becklin, K. M.; Medeiros, J. S.; Sale, K. R.; Ward, J. K.

2014-12-01

Assessing family and species-level variation in physiological responses to global change across geologic time is critical for understanding factors that underlie changes in species distributions and community composition. Ancient plant specimens preserved within packrat middens are invaluable in this context since they allow for comparisons between co-occurring plant lineages. Here we used modern and ancient plant specimens preserved within packrat middens from the Snake Range, NV to investigate the physiological responses of a mixed montane conifer community to global change since the last glacial maximum. We used a conceptual model to infer relative changes in stomatal conductance and maximum photosynthetic capacity from measures of leaf carbon isotopes, stomatal characteristics, and leaf nitrogen content. Our results indicate that most of the sampled taxa decreased stomatal conductance and/or photosynthetic capacity from glacial to modern times. However, plant families differed in the timing and magnitude of these physiological responses. Additionally, leaf-level responses were more similar within plant families than within co-occurring species assemblages. This suggests that adaptation at the level of leaf physiology may not be the main determinant of shifts in community composition, and that plant evolutionary history may drive physiological adaptation to global change over recent geologic time.

Global Analysis of Ecosystem Evapotranspiration Response to Precipitation Deficits

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He, Bin; Wang, Haiyan; Guo, Lanlan; Liu, Junjie

2017-12-01

Changes in ecosystem evapotranspiration (ET) due to precipitation deficits (PD) can relieve or aggravate soil moisture shortages, thus impacting drought severity. Previous findings have conflicted with regard to response of ET to PD. The present study relies on a global land ET synthesis data set (ETsyn) and observations from eddy-covariance towers (ETobs) to thoroughly examine the sensitivity of ET to PD, which is represented by the standardized precipitation index. There was a contrast in the response to PD between arid and humid ecosystems. ETsyn of arid ecosystems was typically reduced promptly in response to a reduction of precipitation, while ETsyn in humid ecosystems experienced a two-staged change: First, there was an enhancement, and then a reduction associated with persisting PD. Compared with ETsyn, ETobs suggests the occurrence of a more significant ET transition in response to PD. In arid ecosystems, ET typically negatively correlated with low PD, but this was limited by a large PD. Findings from this study are crucial for understanding the role of ET in drought evolution.

Symmetry analysis of cellular automata

International Nuclear Information System (INIS)

García-Morales, V.

2013-01-01

By means of B-calculus [V. García-Morales, Phys. Lett. A 376 (2012) 2645] a universal map for deterministic cellular automata (CAs) has been derived. The latter is shown here to be invariant upon certain transformations (global complementation, reflection and shift). When constructing CA rules in terms of rules of lower range a new symmetry, “invariance under construction” is uncovered. Modular arithmetic is also reformulated within B-calculus and a new symmetry of certain totalistic CA rules, which calculate the Pascal simplices modulo an integer number p, is then also uncovered.

Clouds and the extratropical circulation response to global warming in a hierarchy of global atmosphere models

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Voigt, A.

2017-12-01

Climate models project that global warming will lead to substantial changes in extratropical jet streams. Yet, many quantitative aspects of warming-induced jet stream changes remain uncertain, and recent work has indicated an important role of clouds and their radiative interactions. Here, I will investigate how cloud-radiative changes impact the zonal-mean extratropical circulation response under global warming using a hierarchy of global atmosphere models. I will first focus on aquaplanet setups with prescribed sea-surface temperatures (SSTs), which reproduce the model spread found in realistic simulations with interactive SSTs. Simulations with two CMIP5 models MPI-ESM and IPSL-CM5A and prescribed clouds show that half of the circulation response can be attributed to cloud changes. The rise of tropical high-level clouds and the upward and poleward movement of midlatitude high-level clouds lead to poleward jet shifts. High-latitude low-level cloud changes shift the jet poleward in one model but not in the other. The impact of clouds on the jet operates via the atmospheric radiative forcing that is created by the cloud changes and is qualitatively reproduced in a dry Held-Suarez model, although the latter is too sensitive because of its simplified treatment of diabatic processes. I will then show that the aquaplanet results also hold when the models are used in a realistic setup that includes continents and seasonality. I will further juxtapose these prescribed-SST simulations with interactive-SST simulations and show that atmospheric and surface cloud-radiative interactions impact the jet poleward jet shifts in about equal measure. Finally, I will discuss the cloud impact on regional and seasonal circulation changes.

El Niño/Southern Oscillation response to global warming

Science.gov (United States)

Latif, M.; Keenlyside, N. S.

2009-01-01

The El Niño/Southern Oscillation (ENSO) phenomenon, originating in the Tropical Pacific, is the strongest natural interannual climate signal and has widespread effects on the global climate system and the ecology of the Tropical Pacific. Any strong change in ENSO statistics will therefore have serious climatic and ecological consequences. Most global climate models do simulate ENSO, although large biases exist with respect to its characteristics. The ENSO response to global warming differs strongly from model to model and is thus highly uncertain. Some models simulate an increase in ENSO amplitude, others a decrease, and others virtually no change. Extremely strong changes constituting tipping point behavior are not simulated by any of the models. Nevertheless, some interesting changes in ENSO dynamics can be inferred from observations and model integrations. Although no tipping point behavior is envisaged in the physical climate system, smooth transitions in it may give rise to tipping point behavior in the biological, chemical, and even socioeconomic systems. For example, the simulated weakening of the Pacific zonal sea surface temperature gradient in the Hadley Centre model (with dynamic vegetation included) caused rapid Amazon forest die-back in the mid-twenty-first century, which in turn drove a nonlinear increase in atmospheric CO2, accelerating global warming. PMID:19060210

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

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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

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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

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

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Wilson Gómez Manrique

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

Forced Migration and Global Responsibility for Health; Comment on “Defining and Acting on Global Health: The Case of Japan and the Refugee Crisis”

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Kayvan Bozorgmehr

2017-07-01

Full Text Available Forced migration has become a world-wide phenomenon in the past century, affecting increasing numbers of countries and people. It entails important challenges from a global health perspective. Leppold et al have critically discussed the Japanese interpretation of global responsibility for health in the context of forced migration. This commentary complements their analysis by outlining three priority areas of global health responsibility for European Union (EU countries. We highlight important stages of the migration phases related to forced migration and propose three arguments. First, the chronic neglect of the large number of internally displaced persons (IDPs in the discourses on the “refugee crisis” needs to be corrected in order to develop sustainable solutions with a framework of the Sustainable Development Goals (SDGs. Second, protection gaps in the global system of protection need to be effectively closed to resolve conflicts with border management and normative global health frameworks. Third, effective policies need to be developed and implemented to meet the health and humanitarian needs of forced migrants; at the same time, the solidarity crisis within the EU needs to be overcome. These stakes are high. EU countries, being committed to global health, should urgently address these areas.

Global Ecosystem Response Types Derived from the Standardized Precipitation Evapotranspiration Index and FPAR3g Series

DEFF Research Database (Denmark)

Ivits, Eva; Horion, Stéphanie Marie Anne F; Fensholt, Rasmus

2014-01-01

Observing trends in global ecosystem dynamics is an important first step, but attributing these trends to climate variability represents a further step in understanding Earth system changes. In the present study, we classified global Ecosystem Response Types (ERTs) based on common spatio-temporal......Observing trends in global ecosystem dynamics is an important first step, but attributing these trends to climate variability represents a further step in understanding Earth system changes. In the present study, we classified global Ecosystem Response Types (ERTs) based on common spatio...... were observed in Asia and North America. These ERTs complement traditional pixel based methods by enabling the combined assessment of the location, timing, duration, frequency and severity of climatic and vegetation anomalies with the joint assessment of wetting and drying climatic conditions. The ERTs...

Cellular immune responses in the lungs of pigs infected in utero with PRRSV: An immunohistochemical study

DEFF Research Database (Denmark)

Tingstedt, Jens Erik; Nielsen, Jens

2004-01-01

The cellular response in the lungs of pigs transplacentally infected with porcine reproductive and respiratory syndrome virus (PRRSV) was examined by immunohistochemistry. Double staining for the T-cell marker antigen CD3 and PRRSV demonstrated that the appearance and distribution of T-cells homing...... to the lungs of infected pigs correlated well with the presence and location of virus-infected cells. Single stainings showed that cells positive for the CD2 and CD8 antigen were almost as numerous in pneumonic lesions as CD3 positive cells whereas cells expressing the CD4 antigen were rare. The morphology...

Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks

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White, Forest M.; Wolf-Yadlin, Alejandro

2016-06-01

Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.

Influence of corona charging in cellular polyethylene film

International Nuclear Information System (INIS)

Ortega Brana, Gustavo; Magraner, Francisco; Quijano, Alfredo; Llovera Segovia, Pedro

2011-01-01

Cellular polymers have recently attracted attention for their property of exhibiting a piezoelectric constant when they are electrically charged. The electrostatic charge generated in the voids by the internal discharges creates and internal macrodipole which is responsible for the piezoelectric effect. Charging by corona discharge is the most used method for cellular polymers. Many works has been published on polypropylene and polyethylene films mainly focused on the required expansion process or on the results obtained for raw cellular materials electrically activated. Our work is based on commercial polyethylene cellular films which have been physically characterized and electrically activated. The effect of thermal treatment, physical uniaxial or biaxial stretching and corona charging was investigated. The new method of corona charging improved the piezoelectric constant under other activation conditions.

Influence of corona charging in cellular polyethylene film

Energy Technology Data Exchange (ETDEWEB)

Ortega Brana, Gustavo; Magraner, Francisco; Quijano, Alfredo [Instituto Tecnologico de la Energia (ITE), Av. Juan de la Cierva 24, Parque Tecnologico de Valencia, 46980 Paterna-Valencia (Spain); Llovera Segovia, Pedro, E-mail: gustavo.ortega@ite.es [Instituto de TecnologIa Electrica - Universitat Politecnica de Valencia, Camino de Vera s/n 46022-Valencia (Spain)

2011-06-23

Cellular polymers have recently attracted attention for their property of exhibiting a piezoelectric constant when they are electrically charged. The electrostatic charge generated in the voids by the internal discharges creates and internal macrodipole which is responsible for the piezoelectric effect. Charging by corona discharge is the most used method for cellular polymers. Many works has been published on polypropylene and polyethylene films mainly focused on the required expansion process or on the results obtained for raw cellular materials electrically activated. Our work is based on commercial polyethylene cellular films which have been physically characterized and electrically activated. The effect of thermal treatment, physical uniaxial or biaxial stretching and corona charging was investigated. The new method of corona charging improved the piezoelectric constant under other activation conditions.

Significance of novel bioinorganic anodic aluminum oxide nanoscaffolds for promoting cellular response

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Gérrard Eddy Jai Poinern

2011-01-01

Full Text Available Gérrard Eddy Jai Poinern, Robert Shackleton, Shariful Islam Mamun, Derek FawcettMurdoch Applied Nanotechnology Research Group, Department of Physics, Energy Studies and Nanotechnology, School of Engineering and Energy, Murdoch University, Murdoch, Western Australia, AustraliaAbstract: Tissue engineering is a multidisciplinary field that can directly benefit from the many advancements in nanotechnology and nanoscience. This article reviews a novel biocompatible anodic aluminum oxide (AAO, alumina membrane in terms of tissue engineering. Cells respond and interact with their natural environment, the extracellular matrix, and the landscape of the substrate. The interaction with the topographical features of the landscape occurs both in the micrometer and nanoscales. If all these parameters are favorable to the cell, the cell will respond in terms of adhesion, proliferation, and migration. The role of the substrate/scaffold is crucial in soliciting a favorable response from the cell. The size and type of surface feature can directly influence the response and behavior of the cell. In the case of using an AAO membrane, the surface features and porosity of the membrane can be dictated at the nanoscale during the manufacturing stage. This is achieved by using general laboratory equipment to perform a relatively straightforward electrochemical process. During this technique, changing the operational parameters of the process directly controls the nanoscale features produced. For example, the pore size, pore density, and, hence, density can be effectively controlled during the synthesis of the AAO membrane. In addition, being able to control the pore size and porosity of a biomaterial such as AAO significantly broadens its application in tissue engineering.Keywords: anodic aluminum oxide, nanoscaffolds, cellular response, tissue engineering

The regions and global warming: Impacts and response strategies

International Nuclear Information System (INIS)

1991-01-01

To date, much of the attention given to global warming in scientific research as well as in policy development has focused on the global picture. International negotiations and agreements to stabilize, and eventually reduce, greenhouse gas emissions are very important. By themselves, however, they are not sufficient to address global warming. Regional strategies are also needed. They can help reduce greenhouse gas emissions, and they will be the most effective way to mitigate the consequences of global warming. Adaptive strategies must respond to local and regional conditions. In many countries, subnational jurisdictions such as states and provinces or community organizations can already take effective actions without direction from their national government or waiting for international agreements. An important factor in defining regional approaches is the disparate consequences of climate change for developed and developing areas. Different strategies will also be needed for industrial and agricultural regions. Wealthy industrial regions may be better able to develop capital-intensive, adaptive infrastructure than regions with fewer discretionary resources where people are more vulnerable to the vagaries of weather patterns. On the other hand, regions that rely on indigenous knowledge and local resources may be better equipped to make incremental adaptations and more willing to modify life-styles. Ultimately, all climate change effects are experienced in specific places and effective response depends upon local action. We recognize that individual localities cannot solve a problem of global proportions by acting alone. However, a regional strategy can supplement international and national action and be the focal point for addressing risks in the unique social and economic context of a particular area. These meetings discussions dealt with the impacts and implications of climate change on such things as agriculture, forestry, and policy

Pathogen-mimicking vaccine delivery system designed with a bioactive polymer (inulin acetate) for robust humoral and cellular immune responses.

Science.gov (United States)

Kumar, Sunny; Kesharwani, Siddharth S; Kuppast, Bhimanna; Bakkari, Mohammed Ali; Tummala, Hemachand

2017-09-10

New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired. Copyright © 2017 Elsevier B.V. All rights reserved.

Emery-Dreifuss Muscular Dystrophy-Associated Mutant Forms of Lamin A Recruit the Stress Responsive Protein Ankrd2 into the Nucleus, Affecting the Cellular Response to Oxidative Stress

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Silvia Angori

2017-05-01

Full Text Available Background: Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2 is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear. Methods: Experiments were performed in EDMD2-lamin A overexpressing cell lines and EDMD2-affected human myotubes. Oxidative stress was produced by H2O2 treatment. Co-immunoprecipitation, cellular subfractionation and immunofluorescence analysis were used to validate the relation between Ankrd2 and forms of lamin A; cellular sensibility to stress was monitored by the analysis of Reactive Oxygen Species (ROS release and cell viability. Results: Our data demonstrate that oxidative stress induces the formation of a complex between Ankrd2 and lamin A. However, EDMD2-lamin A mutants were able to bind and mislocalize Ankrd2 in the nucleus even under basal conditions. Nonetheless, cells co-expressing Ankrd2 and EDMD2-lamin A mutants were more sensitive to oxidative stress than the Ankrd2-wild type lamin A counterpart. Conclusions: For the first time, we present evidence that in muscle fibers from patients affected by EDMD2, Ankrd2 has an unusual nuclear localization. By introducing a plausible mechanism ruling this accumulation, our data hint at a novel function of Ankrd2 in the pathogenesis of EDMD2-affected cells.

Cellular and molecular responses of E. fetida cœlomocytes exposed to TiO2 nanoparticles

Science.gov (United States)

Bigorgne, Emilie; Foucaud, Laurent; Caillet, Céline; Giambérini, Laure; Nahmani, Johanne; Thomas, Fabien; Rodius, François

2012-07-01

An in vitro approach using cœlomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO2 nanoparticles. Cœlomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO2 nanoparticles (1-25 μg/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO2 nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 μg/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO2 in our experimental conditions. This in vitro approach showed that TiO2 nanoparticles were taken up by cœlomocytes and they could modify the molecular response of immune and detoxification system.

The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.

Science.gov (United States)

Smith, Gina A; Fearnley, Gareth W; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

2015-08-18

VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. © 2015 Authors.

Terrestrial ecosystem responses to global change: A research strategy

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-09-01

Uncertainty about the magnitude of global change effects on terrestrial ecosystems and consequent feedbacks to the atmosphere impedes sound policy planning at regional, national, and global scales. A strategy to reduce these uncertainties must include a substantial increase in funding for large-scale ecosystem experiments and a careful prioritization of research efforts. Prioritization criteria should be based on the magnitude of potential changes in environmental properties of concern to society, including productivity; biodiversity; the storage and cycling of carbon, water, and nutrients; and sensitivity of specific ecosystems to environmental change. A research strategy is proposed that builds on existing knowledge of ecosystem responses to global change by (1) expanding the spatial and temporal scale of experimental ecosystem manipulations to include processes known to occur at large scales and over long time periods; (2) quantifying poorly understood linkages among processes through the use of experiments that manipulate multiple interacting environmental factors over a broader range of relevant conditions than did past experiments; and (3) prioritizing ecosystems for major experimental manipulations on the basis of potential positive and negative impacts on ecosystem properties and processes of intrinsic and/or utilitarian value to humans and on feedbacks of terrestrial ecosystems to the atmosphere.

Global health and global health ethics

National Research Council Canada - National Science Library

Benatar, S. R; Brock, Gillian

2011-01-01

...? What are our responsibilities and how can we improve global health? Global Health and Global Health Ethics addresses these questions from the perspective of a range of disciplines, including medicine, philosophy and the social sciences...

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

A learning algorithm for oscillatory cellular neural networks.

Science.gov (United States)

Ho, C Y.; Kurokawa, H

1999-07-01

We present a cellular type oscillatory neural network for temporal segregation of stationary input patterns. The model comprises an array of locally connected neural oscillators with connections limited to a 4-connected neighborhood. The architecture is reminiscent of the well-known cellular neural network that consists of local connection for feature extraction. By means of a novel learning rule and an initialization scheme, global synchronization can be accomplished without incurring any erroneous synchrony among uncorrelated objects. Each oscillator comprises two mutually coupled neurons, and neurons share a piecewise-linear activation function characteristic. The dynamics of traditional oscillatory models is simplified by using only one plastic synapse, and the overall complexity for hardware implementation is reduced. Based on the connectedness of image segments, it is shown that global synchronization and desynchronization can be achieved by means of locally connected synapses, and this opens up a tremendous application potential for the proposed architecture. Furthermore, by using special grouping synapses it is demonstrated that temporal segregation of overlapping gray-level and color segments can also be achieved. Finally, simulation results show that the learning rule proposed circumvents the problem of component mismatches, and hence facilitates a large-scale integration.

Salmonella adhesion, invasion and cellular immune responses are differentially affected by iron concentrations in a combined in vitro gut fermentation-cell model.

Science.gov (United States)

Dostal, Alexandra; Gagnon, Mélanie; Chassard, Christophe; Zimmermann, Michael Bruce; O'Mahony, Liam; Lacroix, Christophe

2014-01-01

In regions with a high infectious disease burden, concerns have been raised about the safety of iron supplementation because higher iron concentrations in the gut lumen may increase risk of enteropathogen infection. The aim of this study was to investigate interactions of the enteropathogen Salmonella enterica ssp. enterica Typhimurium with intestinal cells under different iron concentrations encountered in the gut lumen during iron deficiency and supplementation using an in vitro colonic fermentation system inoculated with immobilized child gut microbiota combined with Caco-2/HT29-MTX co-culture monolayers. Colonic fermentation effluents obtained during normal, low (chelation by 2,2'-dipyridyl) and high iron (26.5 mg iron/L) fermentation conditions containing Salmonella or pure Salmonella cultures with similar iron conditions were applied to cellular monolayers. Salmonella adhesion and invasion capacity, cellular integrity and immune response were assessed. Under high iron conditions in pure culture, Salmonella adhesion was 8-fold increased compared to normal iron conditions while invasion was not affected leading to decreased invasion efficiency (-86%). Moreover, cellular cytokines IL-1β, IL-6, IL-8 and TNF-α secretion as well as NF-κB activation in THP-1 cells were attenuated under high iron conditions. Low iron conditions in pure culture increased Salmonella invasion correlating with an increase in IL-8 release. In fermentation effluents, Salmonella adhesion was 12-fold and invasion was 428-fold reduced compared to pure culture. Salmonella in high iron fermentation effluents had decreased invasion efficiency (-77.1%) and cellular TNF-α release compared to normal iron effluent. The presence of commensal microbiota and bacterial metabolites in fermentation effluents reduced adhesion and invasion of Salmonella compared to pure culture highlighting the importance of the gut microbiota as a barrier during pathogen invasion. High iron concentrations as

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

Science.gov (United States)

Haase, A.; Tentschert, J.; Jungnickel, H.; Graf, P.; Mantion, A.; Draude, F.; Plendl, J.; Goetz, M. E.; Galla, S.; Mašić, A.; Thuenemann, A. F.; Taubert, A.; Arlinghaus, H. F.; Luch, A.

2011-07-01

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

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

International Nuclear Information System (INIS)

Haase, A; Tentschert, J; Jungnickel, H; Goetz, M E; Luch, A; Graf, P; Mantion, A; Thuenemann, A F; Draude, F; Galla, S; Arlinghaus, H F; Plendl, J; Masic, A; Taubert, A

2011-01-01

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

Circuitry linking the Csr and stringent response global regulatory systems.

Science.gov (United States)

Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

2011-06-01

CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

Directory of Open Access Journals (Sweden)

Stephanie Munk

2017-10-01

Full Text Available The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essential role for SUMOs (small ubiquitin-like modifiers has also been established. Here, we investigate the global interplay between phosphorylation and SUMOylation in response to replication stress. Using SUMO and phosphoproteomic technologies, we identify thousands of regulated modification sites. We find co-regulation of central DNA damage and replication stress responders, of which the ATR-activating factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of the DNA damage response kinases ATR and ATM, we find that these factors regulate global protein SUMOylation in the protein networks that protect DNA upon replication stress and fork breakage, pointing to integration between phosphorylation and SUMOylation in the cellular systems that protect DNA integrity.

The induced expression of heat shock proteins as a part of the early cellular response to gamma radiation

International Nuclear Information System (INIS)

Stankova, K.; Ivanova, K.; Georgieva, R.; Rupova, I.; Boteva, R.

2008-01-01

A variety of stressful stimuli including gamma radiation can induce increase in the synthesis of heat shock proteins (Hsp). This family of molecular chaperones includes members with molecular masses ranging from 10 to 150 kDa and has been identified in all organisms from bacteria to humans. Hsp70 chaperones are very important. The present study aimed to characterize the radiation-induced changes in Hsp70 synthesis in human lymphocytes as a part of the early cellular response to gamma irradiation. The expression of Hsp70 was determined with Western blot and the radiation-induced apoptotic changes were registered by staining with fluorescent dyes. Part of the experiments were performed in the presence of the organic solvent DMSO. At low concentrations this reagent shows antioxidant activity and can reduce the level of the radiation-induced oxidant stress which determines the predominant biological effects of the ionizing radiation. Irradiation with 0.5 to 8 Gy caused statistically significant increase in the synthesis of Hsp70 which was strongest after irradiation with 4 Gy. In the range 0.5-2 Gy the enhancement of the radiation-induced synthesis of Hsp70 reached 60%. Our experimental results characterize changes in the Hsp70 synthesis after gamma irradiation as a part of the early cellular stress response in lymphocytes. (authors)

Fly-By medical care: Conceptualizing the global and local social responsibilities of medical tourists and physician voluntourists

Science.gov (United States)

2011-01-01

Background Medical tourism is a global health practice where patients travel abroad to receive health care. Voluntourism is a practice where physicians travel abroad to deliver health care. Both of these practices often entail travel from high income to low and middle income countries and both have been associated with possible negative impacts. In this paper, we explore the social responsibilities of medical tourists and voluntourists to identify commonalities and distinctions that can be used to develop a wider understanding of social responsibility in global health care practices. Discussion Social responsibility is a responsibility to promote the welfare of the communities to which one belongs or with which one interacts. Physicians stress their social responsibility to care for the welfare of their patients and their domestic communities. When physicians choose to travel to another county to provide medical care, this social responsibility is expanded to this new community. Patients too have a social responsibility to use their community's health resources efficiently and to promote the health of their community. When these patients choose to go abroad to receive medical care, this social responsibility applies to the new community as well. While voluntourists and medical tourists both see the scope of their social responsibilities expand by engaging in these global practices, the social responsibilities of physician voluntourists are much better defined than those of medical tourists. Guidelines for engaging in ethical voluntourism and training for voluntourists still need better development, but medical tourism as a practice should follow the lead of voluntourism by developing clearer norms for ethical medical tourism. Summary Much can be learned by examining the social responsibilities of medical tourists and voluntourists when they engage in global health practices. While each group needs better guidance for engaging in responsible forms of these practices

Fly-By medical care: Conceptualizing the global and local social responsibilities of medical tourists and physician voluntourists

Directory of Open Access Journals (Sweden)

Crooks Valorie A

2011-04-01

Full Text Available Abstract Background Medical tourism is a global health practice where patients travel abroad to receive health care. Voluntourism is a practice where physicians travel abroad to deliver health care. Both of these practices often entail travel from high income to low and middle income countries and both have been associated with possible negative impacts. In this paper, we explore the social responsibilities of medical tourists and voluntourists to identify commonalities and distinctions that can be used to develop a wider understanding of social responsibility in global health care practices. Discussion Social responsibility is a responsibility to promote the welfare of the communities to which one belongs or with which one interacts. Physicians stress their social responsibility to care for the welfare of their patients and their domestic communities. When physicians choose to travel to another county to provide medical care, this social responsibility is expanded to this new community. Patients too have a social responsibility to use their community's health resources efficiently and to promote the health of their community. When these patients choose to go abroad to receive medical care, this social responsibility applies to the new community as well. While voluntourists and medical tourists both see the scope of their social responsibilities expand by engaging in these global practices, the social responsibilities of physician voluntourists are much better defined than those of medical tourists. Guidelines for engaging in ethical voluntourism and training for voluntourists still need better development, but medical tourism as a practice should follow the lead of voluntourism by developing clearer norms for ethical medical tourism. Summary Much can be learned by examining the social responsibilities of medical tourists and voluntourists when they engage in global health practices. While each group needs better guidance for engaging in

Fly-By medical care: Conceptualizing the global and local social responsibilities of medical tourists and physician voluntourists.

Science.gov (United States)

Snyder, Jeremy; Dharamsi, Shafik; Crooks, Valorie A

2011-04-06

Medical tourism is a global health practice where patients travel abroad to receive health care. Voluntourism is a practice where physicians travel abroad to deliver health care. Both of these practices often entail travel from high income to low and middle income countries and both have been associated with possible negative impacts. In this paper, we explore the social responsibilities of medical tourists and voluntourists to identify commonalities and distinctions that can be used to develop a wider understanding of social responsibility in global health care practices. Social responsibility is a responsibility to promote the welfare of the communities to which one belongs or with which one interacts. Physicians stress their social responsibility to care for the welfare of their patients and their domestic communities. When physicians choose to travel to another county to provide medical care, this social responsibility is expanded to this new community. Patients too have a social responsibility to use their community's health resources efficiently and to promote the health of their community. When these patients choose to go abroad to receive medical care, this social responsibility applies to the new community as well. While voluntourists and medical tourists both see the scope of their social responsibilities expand by engaging in these global practices, the social responsibilities of physician voluntourists are much better defined than those of medical tourists. Guidelines for engaging in ethical voluntourism and training for voluntourists still need better development, but medical tourism as a practice should follow the lead of voluntourism by developing clearer norms for ethical medical tourism. Much can be learned by examining the social responsibilities of medical tourists and voluntourists when they engage in global health practices. While each group needs better guidance for engaging in responsible forms of these practices, patients are at a

Molecular events basic to cellular radiation response. Progress report

International Nuclear Information System (INIS)

Kolodny, G.M.

1974-01-01

Work during the past year has been focused on three areas related to the cellular effects of radiation. Radiation effects on RNA and the regulation of gene expression and amino acid-nucleic acid interactions were studied. Studies on the radiation response of RNA in growing and confluent cells were continued. We have derived radiation survival curves and demonstrated repair of potentially lethal damage in 3T3 cells. Studies of giant cell formation and turnover of ribosomal RNA in irradiated cells has demonstrated differences in growing and confluent cells. We have sought evidence consistent with our hypothesis for regulation of eukaryotic gene expression with segments of RNA reutilized to prime new RNA synthesis. Data derived from the turnover of ribosomal RNA and the methylation pattern of ribosomal RNA during turnover are consistent with the possibility that a segment of 18s ribosomal RNA is being conserved during new RNA synthesis. We were unable to show reutilization of the 5' trinucleotide of 18s and 28s ribosomal RNA but did find a ribonuclease resistant oligonucleotide in 18s RNA which appeared to be reutilized. In studies of amino acid nucleic-acid interactions using nuclear magnetic resonance spectroscopy we have been able to successfully synthesize an amidate and begin an examination of the intramolecular interactions. We have also studied intermolecular interactions betweentryptophan and nucleoside monophosphates and found upfield shifts which provide evidence for preferential stacking of the 6-membered ring of tryptophan with adenine and evidence for specific geometry of interactions of tryptophan with cytosine. (U.S.)

Adoption of Technology as a Response Strategy to Globalization: A Study of Manufacturing Firms in Kenya

OpenAIRE

Solomon Kinyanjui; Margaret A. Oloko; Hazel G. Gachunga; Beatrice G. Gathondu

2014-01-01

Globalization affects local and international firms in many ways. Studies have shown that factors in the internal as well as external environments of firms influence the rate to which globalization will affect them. On the local scene however, no known studies have been done on the response of manufacturing firms to counter globalization. In addition, since the concept of globalization is multidimensional and its influence is varied in nature, this study aimed at investigating how manufacturi...

Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia.

Science.gov (United States)

Lerman, Oren Z; Galiano, Robert D; Armour, Mary; Levine, Jamie P; Gurtner, Geoffrey C

2003-01-01

Although it is known that systemic diseases such as diabetes result in impaired wound healing, the mechanism for this impairment is not understood. Because fibroblasts are essential for wound repair, we compared the in vitro behavior of fibroblasts cultured from diabetic, leptin receptor-deficient (db/db) mice with wild-type fibroblasts from mice of the same genetic background in processes important during tissue repair. Adult diabetic mouse fibroblast migration exhibited a 75% reduction in migration compared to normal fibroblasts (P under basal or hypoxic conditions, confirming that the results from db/db fibroblasts in mature mice resulted from the diabetic state and were not because of alterations in the leptin-leptin receptor axis. Markers of cellular viability including proliferation and senescence were not significantly different between diabetic and wild-type fibroblasts. We conclude that, in vitro, diabetic fibroblasts show selective impairments in discrete cellular processes critical for tissue repair including cellular migration, VEGF production, and the response to hypoxia. The VEGF abnormalities developed concurrently with the onset of hyperglycemia and were not seen in normoglycemic, leptin receptor-deficient db/db mice. These observations support a role for fibroblast dysfunction in the impaired wound healing observed in human diabetics, and also suggest a mechanism for the poor clinical outcomes that occur after ischemic injury in diabetic patients.

The financial crisis and global health: the International Monetary Fund's (IMF) policy response.

Science.gov (United States)

Ruckert, Arne; Labonté, Ronald

2013-09-01

In this article, we interrogate the policy response of the International Monetary Fund (IMF) to the global financial crisis, and discuss the likely global health implications, especially in low-income countries. In doing so, we ask if the IMF has meaningfully loosened its fiscal deficit targets in light of the economic challenges posed by the financial crisis and adjusted its macro-economic policy advice to this new reality; or has the rhetoric of counter-cyclical spending failed to translate into additional fiscal space for IMF loan-recipient countries, with negative health consequences? To answer these questions, we assess several post-crisis IMF lending agreements with countries requiring financial assistance, and draw upon recent academic studies and civil society reports examining policy conditionalities still being prescribed by the IMF. We also reference recent studies examining the health impacts of these conditionalities. We demonstrate that while the IMF has been somewhat more flexible in its crisis response than in previous episodes of financial upheaval, there has been no meaningful rethinking in the application of dominant neoliberal macro-economic policies. After showing some flexibility in the initial crisis response, the IMF is pushing for excessive contraction in most low and middle-income countries. We conclude that there remains a wide gap between the rhetoric and the reality of the IMF's policy and programming advice, with negative implications for global health.

Hydrogen peroxide probes directed to different cellular compartments.

OpenAIRE

Mikalai Malinouski; You Zhou; Vsevolod V Belousov; Dolph L Hatfield; Vadim N Gladyshev

2011-01-01

Background Controlled generation and removal of hydrogen peroxide play important roles in cellular redox homeostasis and signaling. We used a hydrogen peroxide biosensor HyPer, targeted to different compartments, to examine these processes in mammalian cells. Principal Findings Reversible responses were observed to various redox perturbations and signaling events. HyPer expressed in HEK 293 cells was found to sense low micromolar levels of hydrogen peroxide. When targeted to various cellular ...

Global robust stability for shunting inhibitory CNNs with delays.

Science.gov (United States)

Wang, Lingna; Lin, Yiping

2004-08-01

In this paper, the problem of global robust stability for shunting inhibitory cellular neural networks (SICNNs) is studied. A sufficient condition guaranteeing the network's global robust stability is established. The result can easily be used to verify globally robust stable networks. An example is given to illustrate that the conditions of our results are feasible.

Mechanisms of motor recovery after subtotal spinal cord injury: insights from the study of mice carrying a mutation (WldS) that delays cellular responses to injury.

Science.gov (United States)

Zhang, Z; Guth, L; Steward, O

1998-01-01

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.

Effects of Initial Symmetry on the Global Symmetry of One-Dimensional Legal Cellular Automata

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Ikuko Tanaka

2015-09-01

Full Text Available To examine the development of pattern formation from the viewpoint of symmetry, we applied a two-dimensional discrete Walsh analysis to a one-dimensional cellular automata model under two types of regular initial conditions. The amount of symmetropy of cellular automata (CA models under regular and random initial conditions corresponds to three Wolfram’s classes of CAs, identified as Classes II, III, and IV. Regular initial conditions occur in two groups. One group that makes a broken, regular pattern formation has four types of symmetry, whereas the other group that makes a higher hierarchy pattern formation has only two types. Additionally, both final pattern formations show an increased amount of symmetropy as time passes. Moreover, the final pattern formations are affected by iterations of base rules of CA models of chaos dynamical systems. The growth design formations limit possibilities: the ratio of developing final pattern formations under a regular initial condition decreases in the order of Classes III, II, and IV. This might be related to the difference in degree in reference to surrounding conditions. These findings suggest that calculations of symmetries of the structures of one-dimensional cellular automata models are useful for revealing rules of pattern generation for animal bodies.

The Green Function cellular method and its relation to multiple scattering theory

International Nuclear Information System (INIS)

Butler, W.H.; Zhang, X.G.; Gonis, A.

1992-01-01

This paper investigates techniques for solving the wave equation which are based on the idea of obtaining exact local solutions within each potential cell, which are then joined to form a global solution. The authors derive full potential multiple scattering theory (MST) from the Lippmann-Schwinger equation and show that it as well as a closely related cellular method are techniques of this type. This cellular method appears to have all of the advantages of MST and the added advantage of having a secular matrix with only nearest neighbor interactions. Since this cellular method is easily linearized one can rigorously reduce electronic structure calculation to the problem of solving a nearest neighbor tight-binding problem

Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100

Directory of Open Access Journals (Sweden)

Matthew P Morrow

2016-01-01

Full Text Available We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFNγ production, tumor necrosis factor (TNFα production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth “booster” dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100.

A Canonical Response in Rainfall Characteristics to Global Warming: Projections by IPCC CMIP5 Models

Science.gov (United States)

Lau, William K. M.; Wu, H. T.; Kim, K. M.

2012-01-01

Changes in rainfall characteristics induced by global warming are examined based on probability distribution function (PDF) analysis, from outputs of 14 IPCC (Intergovernmental Panel on Climate Change), CMIP (5th Coupled Model Intercomparison Project) models under various scenarios of increased CO2 emissions. Results show that collectively CMIP5 models project a robust and consistent global and regional rainfall response to CO2 warming. Globally, the models show a 1-3% increase in rainfall per degree rise in temperature, with a canonical response featuring large increase (100-250 %) in frequency of occurrence of very heavy rain, a reduction (5-10%) of moderate rain, and an increase (10-15%) of light rain events. Regionally, even though details vary among models, a majority of the models (>10 out of 14) project a consistent large scale response with more heavy rain events in climatologically wet regions, most pronounced in the Pacific ITCZ and the Asian monsoon. Moderate rain events are found to decrease over extensive regions of the subtropical and extratropical oceans, but increases over the extratropical land regions, and the Southern Oceans. The spatial distribution of light rain resembles that of moderate rain, but mostly with opposite polarity. The majority of the models also show increase in the number of dry events (absence or only trace amount of rain) over subtropical and tropical land regions in both hemispheres. These results suggest that rainfall characteristics are changing and that increased extreme rainfall events and droughts occurrences are connected, as a consequent of a global adjustment of the large scale circulation to global warming.

Cellular Interactions and Biological Responses to Titanium Dioxide Nanoparticles in HepG2 and BEAS-2B Cells: Role of Cell Culture Media

Science.gov (United States)

ABSTRACT We have shown previously that the composition of the biological medium used in vitro can affect the cellular interaction and biological response of titanium dioxide nanoparticles (nano-TiO2) in human lung epithelial cells. However, it is unclear if these effects are co...

A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

Science.gov (United States)

Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

2006-01-01

The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377

Asymmetric responses to simulated global warming by populations of Colobanthus quitensis along a latitudinal gradient

Directory of Open Access Journals (Sweden)

Ian S. Acuña-Rodríguez

2017-09-01

Full Text Available The increase in temperature as consequence of the recent global warming has been reported to generate new ice-free areas in the Antarctic continent, facilitating the colonization and spread of plant populations. Consequently, Antarctic vascular plants have been observed extending their southern distribution. But as the environmental conditions toward southern localities become progressively more departed from the species’ physiological optimum, the ecophysiological responses and survival to the expected global warming could be reduced. However, if processes of local adaptation are the main cause of the observed southern expansion, those populations could appear constrained to respond positively to the expected global warming. Using individuals from the southern tip of South America, the South Shetland Islands and the Antarctic Peninsula, we assess with a long term experiment (three years under controlled conditions if the responsiveness of Colobanthus quitensis populations to the expected global warming, is related with their different foliar traits and photoprotective mechanisms along the latitudinal gradient. In addition, we tested if the release of the stress condition by the global warming in these cold environments increases the ecophysiological performance. For this, we describe the latitudinal pattern of net photosynthetic capacity, biomass accumulation, and number of flowers under current and future temperatures respective to each site of origin after three growing seasons. Overall, was found a clinal trend was found in the foliar traits and photoprotective mechanisms in the evaluated C. quitensis populations. On the other hand, an asymmetric response to warming was observed for southern populations in all ecophysiological traits evaluated, suggesting that low temperature is limiting the performance of C. quitensis populations. Our results suggest that under a global warming scenario, plant populations that inhabiting cold zones at

Asymmetric responses to simulated global warming by populations of Colobanthus quitensis along a latitudinal gradient.

Science.gov (United States)

Acuña-Rodríguez, Ian S; Torres-Díaz, Cristian; Hereme, Rasme; Molina-Montenegro, Marco A

2017-01-01

The increase in temperature as consequence of the recent global warming has been reported to generate new ice-free areas in the Antarctic continent, facilitating the colonization and spread of plant populations. Consequently, Antarctic vascular plants have been observed extending their southern distribution. But as the environmental conditions toward southern localities become progressively more departed from the species' physiological optimum, the ecophysiological responses and survival to the expected global warming could be reduced. However, if processes of local adaptation are the main cause of the observed southern expansion, those populations could appear constrained to respond positively to the expected global warming. Using individuals from the southern tip of South America, the South Shetland Islands and the Antarctic Peninsula, we assess with a long term experiment (three years) under controlled conditions if the responsiveness of Colobanthus quitensis populations to the expected global warming, is related with their different foliar traits and photoprotective mechanisms along the latitudinal gradient. In addition, we tested if the release of the stress condition by the global warming in these cold environments increases the ecophysiological performance. For this, we describe the latitudinal pattern of net photosynthetic capacity, biomass accumulation, and number of flowers under current and future temperatures respective to each site of origin after three growing seasons. Overall, was found a clinal trend was found in the foliar traits and photoprotective mechanisms in the evaluated C. quitensis populations. On the other hand, an asymmetric response to warming was observed for southern populations in all ecophysiological traits evaluated, suggesting that low temperature is limiting the performance of C. quitensis populations. Our results suggest that under a global warming scenario, plant populations that inhabiting cold zones at high latitudes could

Modeling evolution and immune system by cellular automata

International Nuclear Information System (INIS)

Bezzi, M.

2001-01-01

In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section

Public Health Control Measures in Response to Global Pandemics and Drug Resistance.

Science.gov (United States)

Price, Polly J

2015-01-01

These teaching materials provide problem-based exercises exploring the specific powers of governments to implement control measures in response to communicable disease. Topics include global pandemic disease and, in the United States, legal issues in tuberculosis control. © 2015 American Society of Law, Medicine & Ethics, Inc.

Theoretical aspects of cellular decision-making and information-processing.

Science.gov (United States)

Kobayashi, Tetsuya J; Kamimura, Atsushi

2012-01-01

Microscopic biological processes have extraordinary complexity and variety at the sub-cellular, intra-cellular, and multi-cellular levels. In dealing with such complex phenomena, conceptual and theoretical frameworks are crucial, which enable us to understand seemingly different intra- and inter-cellular phenomena from unified viewpoints. Decision-making is one such concept that has attracted much attention recently. Since a number of cellular behavior can be regarded as processes to make specific actions in response to external stimuli, decision-making can cover and has been used to explain a broad range of different cellular phenomena [Balázsi et al. (Cell 144(6):910, 2011), Zeng et al. (Cell 141(4):682, 2010)]. Decision-making is also closely related to cellular information-processing because appropriate decisions cannot be made without exploiting the information that the external stimuli contain. Efficiency of information transduction and processing by intra-cellular networks determines the amount of information obtained, which in turn limits the efficiency of subsequent decision-making. Furthermore, information-processing itself can serve as another concept that is crucial for understanding of other biological processes than decision-making. In this work, we review recent theoretical developments on cellular decision-making and information-processing by focusing on the relation between these two concepts.

Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.

Directory of Open Access Journals (Sweden)

Nadine T Nehme

2011-03-01

Full Text Available Two NF-kappaB signaling pathways, Toll and immune deficiency (imd, are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense.In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus, we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response.Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.

Forced Migration and Global Responsibility for Health Comment on "Defining and Acting on Global Health: The Case of Japan and the Refugee Crisis".

Science.gov (United States)

Bozorgmehr, Kayvan; Razum, Oliver

2016-11-05

Forced migration has become a world-wide phenomenon in the past century, affecting increasing numbers of countries and people. It entails important challenges from a global health perspective. Leppold et al have critically discussed the Japanese interpretation of global responsibility for health in the context of forced migration. This commentary complements their analysis by outlining three priority areas of global health responsibility for European Union (EU) countries. We highlight important stages of the migration phases related to forced migration and propose three arguments. First, the chronic neglect of the large number of internally displaced persons (IDPs) in the discourses on the "refugee crisis" needs to be corrected in order to develop sustainable solutions with a framework of the Sustainable Development Goals (SDGs). Second, protection gaps in the global system of protection need to be effectively closed to resolve conflicts with border management and normative global health frameworks. Third, effective policies need to be developed and implemented to meet the health and humanitarian needs of forced migrants; at the same time, the solidarity crisis within the EU needs to be overcome. These stakes are high. EU countries, being committed to global health, should urgently address these areas. © 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Increased cellular proliferation in rat skeletal muscle and tendon in response to exercise

DEFF Research Database (Denmark)

Skovgaard, Dorthe; Bayer, Monika L; Mackey, Abigail

2010-01-01

PURPOSE: The purpose of this study is to investigate exercise-induced cellular proliferation in rat skeletal muscle/tendon with the use of 3'-[F-18]fluoro-3'deoxythymidine (FLT) and to quantitatively study concomitant changes in the proliferation-associated factor, Ki67. PROCEDURES: Wistar rats (...... = 13) performed 3 days of treadmill running. Cellular proliferation was investigated 3 days before and 48 h after the running exercise with the use of FLT and positron emission tomography/computed tomography (PET/CT). Results were compared to a sedentary control group (n = 10). Image......-derived results were supported by a correlation in calf muscle to Ki67 (protein and mRNA level), while this coherence was not found in tendon. CONCLUSION: FLT-PET seems to be a promising tool for imaging of exercise-induced cellular proliferation in musculo-tendinous tissue....

Biosynthetic hydrogels--studies on chemical and physical characteristics on long-term cellular response for tissue engineering.

Science.gov (United States)

Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2014-07-01

Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate-poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering. © 2013 Wiley Periodicals, Inc.

Effect of drought and rewatering on the cellular status and antioxidant response of Medicago truncatula plants.

Science.gov (United States)

Filippou, Panagiota; Antoniou, Chrystalla; Fotopoulos, Vasileios

2011-02-01

Effects of water stress on plants have been well-documented. However, the combined responses to drought and rewatering and their underlying mechanisms are relatively unknown. The present study attempts to describe spatiotemporal alterations in the physiology and cellular status of Medicago truncatula tissues that result from and subsequently follow a period of moderate water deficit. Physiological processes and cellular damage levels were monitored in roots and leaves by determining lipid peroxidation levels, as well as nitric oxide and hydrogen peroxide content, further supported by stomatal conductance and chlorophyll fluorescence measurements in leaves. During water stress, cells in both organs displayed increased damage levels and reactive oxygen and nitrogen species content, while leaves showed reduced stomatal conductance. Furthermore, both tissues demonstrated increased proline content. Upon rewatering, plants recovered displaying readings similar to pre-stress control conditions. Furthermore, molecular analysis of antioxidant gene expression by quantitative real-time RT-PCR revealed differential spatiotemporal regulation in a number of genes examined (including catalase, cytosolic ascorbate peroxidase, copper/zinc and iron superoxide dismutase and alternative oxidase). Overall, M. truncatula plants demonstrated increased sensitivity to drought-induced oxidative damage; however, this was reversed following rewatering indicating a great elasticity in the plant's capacity to cope with free oxygen radicals. 

IN VITRO CELLULAR RESPONSE TO INTERFERON-α2 IN CHILDREN WITH INFECTIOUS MONONUCLEOSIS CAUSED BY EPSTEIN-BARR VIRUS

Directory of Open Access Journals (Sweden)

L. M. Kurtasova

2016-01-01

Full Text Available Our objective was to study in vitro response of blood leukocytes to IFNα2 in children with infectious mononucleosis, caused by the Epstein-Barr virus, during the acute phase of disease. Patients and methods. Sixty-five children at the age of 4 to 6 years, being in acute phase of infectious mononucleosis caused by the Epstein-Barr virus (EBV were under study. The control group consisted of 36 healthy children. In vitro response of blood leukocytes to IFNα2 was determined by the original technique (L.M. Kurtasova et al., 2007. Chemiluminescence of the blood leukocytes was studied according to De Sole et al. (1989. Results. We observed that clinical condition of the children with EBV infection in acute phase of the disease was characterized by decreased ranges of blood leukocyte response to IFNα2, and dependence of the cellular response on the dose, as well as severity of the disease. In conclusion, these data suggest a need for individual strategy of interferon therapy for the children with infectious mononucleosis caused by the Epstein-Barr virus.

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

An Analysis of the Global Code of Ethics for Tourism in the Context of Corporate Social Responsibility

Directory of Open Access Journals (Sweden)

Buzar Stipe

2015-12-01

Full Text Available The author analyzes the Global Code of Ethics for Tourism in the context of corporate social responsibility and the need for discussing this topic in ethical codes within the business and tourism sector. The text first offers an overview of the fundamental ethical concepts in business ethics and corporate social responsibility and briefly conceptualizes the relationship between these two fields. At the end, the author analyzes the content of the Global Code of Ethics for Tourism with emphasis on the elements pertaining to corporate social responsibility, after which he offers a critical opinion about the contribution of the aforemntioned code.

Sub-cellular distribution and translocation of TRP channels.

Science.gov (United States)

Toro, Carlos A; Arias, Luis A; Brauchi, Sebastian

2011-01-01

Cellular electrical activity is the result of a highly complex processes that involve the activation of ion channel proteins. Ion channels make pores on cell membranes that rapidly transit between conductive and non-conductive states, allowing different ions to flow down their electrochemical gradients across cell membranes. In the case of neuronal cells, ion channel activity orchestrates action potentials traveling through axons, enabling electrical communication between cells in distant parts of the body. Somatic sensation -our ability to feel touch, temperature and noxious stimuli- require ion channels able to sense and respond to our peripheral environment. Sensory integration involves the summing of various environmental cues and their conversion into electrical signals. Members of the Transient Receptor Potential (TRP) family of ion channels have emerged as important mediators of both cellular sensing and sensory integration. The regulation of the spatial and temporal distribution of membrane receptors is recognized as an important mechanism for controlling the magnitude of the cellular response and the time scale on which cellular signaling occurs. Several studies have shown that this mechanism is also used by TRP channels to modulate cellular response and ultimately fulfill their physiological function as sensors. However, the inner-working of this mode of control for TRP channels remains poorly understood. The question of whether TRPs intrinsically regulate their own vesicular trafficking or weather the dynamic regulation of TRP channel residence on the cell surface is caused by extrinsic changes in the rates of vesicle insertion or retrieval remain open. This review will examine the evidence that sub-cellular redistribution of TRP channels plays an important role in regulating their activity and explore the mechanisms that control the trafficking of vesicles containing TRP channels.

DEVELOPMENT OF CORPORATE SOCIAL RESPONSIBILITY UNDER AGGRAVATION OF THE CONTEMPORARY GLOBAL ISSUES

Directory of Open Access Journals (Sweden)

N. Grazhevska

2015-10-01

Full Text Available The article deals with the role and importance of corporate social responsibility as an important mechanism for overcoming the crisis of the welfare state and to mitigate the social problems caused by the world globalization processes. The experience of post-socialist countries, the Baltic States and Ukraine in this field is analyzed and barriers to effective implementation of CSR in the national economy are identified. The priority of the state policy to promote socially responsible business behavior in Ukraine is proved.

The degree of microbiome complexity influences the epithelial response to infection

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Baker Henry V

2009-08-01

Full Text Available Abstract Background The human microflora is known to be extremely complex, yet most pathogenesis research is conducted in mono-species models of infection. Consequently, it remains unclear whether the level of complexity of a host's indigenous flora can affect the virulence potential of pathogenic species. Furthermore, it remains unclear whether the colonization by commensal species affects a host cell's response to pathogenic species beyond the direct physical saturation of surface receptors, the sequestration of nutrients, the modulation of the physico-chemical environment in the oral cavity, or the production of bacteriocins. Using oral epithelial cells as a model, we hypothesized that the virulence of pathogenic species may vary depending on the complexity of the flora that interacts with host cells. Results This is the first report that determines the global epithelial transcriptional response to co-culture with defined complex microbiota. In our model, human immortalized gingival keratinocytes (HIGK were infected with mono- and mixed cultures of commensal and pathogenic species. The global transcriptional response of infected cells was validated and confirmed phenotypically. In our model, commensal species were able to modulate the expression of host genes with a broad diversity of physiological functions and antagonize the effect of pathogenic species at the cellular level. Unexpectedly, the inhibitory effect of commensal species was not correlated with its ability to inhibit adhesion or invasion by pathogenic species. Conclusion Studying the global transcriptome of epithelial cells to single and complex microbial challenges offers clues towards a better understanding of how bacteria-bacteria interactions and bacteria-host interactions impact the overall host response. This work provides evidence that the degree of complexity of a mixed microbiota does influence the transcriptional response to infection of host epithelial cells, and

Cellular response after irradiation: Cell cycle control and apoptosis

International Nuclear Information System (INIS)

Siles, E.; Valenzuela, M.T.; Nunez, M.I.; Guerrero, R.; Villalobos, M.; Ruiz de Almodovar, J.M.

1997-01-01

The importance of apoptotic death was assessed in a set of experiments, involving eight human tumour cell lines (breast cancer, bladder carcinoma, medulloblastoma). Various aspects of the quantitative study of apoptosis and methods based on the detection of DNA fragmentation (in situ tailing and comet assay) are described and discussed. Data obtained support the hypothesis that apoptosis is not crucial for cellular radiosensitivity and that the relationship between p53 functionality or clonogenic survival and apoptosis may bee cell type specific. (author)

The influence of cellular phone "speak" on isiXhosa rules of ...

African Journals Online (AJOL)

Cellular telephones have revolutionised the art of communication across all societies, and. South Africa is no exception. Access to this form of communication has made personal contact easier, in both rural and urban contexts. Globally this form of communication has been readily embraced. However, cultural rules that ...

Symposium on molecular and cellular mechanisms of mutagenesis

International Nuclear Information System (INIS)

1981-01-01

These proceedings contain abstracts only of the 21 papers presented at the Sympsoium. The papers dealt with molecular mechanisms of mutagenesis and cellular responses to chemical and physical mutagenic agents

Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females Contribute to Sex-Related Differences in the Innate Immune Response

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Zoltan Spolarics

2017-11-01

Full Text Available Females have a longer lifespan and better general health than males. Considerable number of studies also demonstrated that, after trauma and sepsis, females present better outcomes as compared to males indicating sex-related differences in the innate immune response. The current notion is that differences in the immuno-modulatory effects of sex hormones are the underlying causative mechanism. However, the field remains controversial and the exclusive role of sex hormones has been challenged. Here, we propose that polymorphic X-linked immune competent genes, which are abundant in the population are important players in sex-based immuno-modulation and play a key role in causing sex-related outcome differences following trauma or sepsis. We describe the differences in X chromosome (ChrX regulation between males and females and its consequences in the context of common X-linked polymorphisms at the individual as well as population level. We also discuss the potential pathophysiological and immune-modulatory aspects of ChrX cellular mosaicism, which is unique to females and how this may contribute to sex-biased immune-modulation. The potential confounding effects of ChrX skewing of cell progenitors at the bone marrow is also presented together with aspects of acute trauma-induced de novo ChrX skewing at the periphery. In support of the hypothesis, novel observations indicating ChrX skewing in a female trauma cohort as well as case studies depicting the temporal relationship between trauma-induced cellular skewing and the clinical course are also described. Finally, we list and discuss a selected set of polymorphic X-linked genes, which are frequent in the population and have key regulatory or metabolic functions in the innate immune response and, therefore, are primary candidates for mediating sex-biased immune responses. We conclude that sex-related differences in a variety of disease processes including the innate inflammatory response to injury

An Analysis of the Global Code of Ethics for Tourism in the Context of Corporate Social Responsibility

OpenAIRE

Buzar Stipe

2015-01-01

The author analyzes the Global Code of Ethics for Tourism in the context of corporate social responsibility and the need for discussing this topic in ethical codes within the business and tourism sector. The text first offers an overview of the fundamental ethical concepts in business ethics and corporate social responsibility and briefly conceptualizes the relationship between these two fields. At the end, the author analyzes the content of the Global Code of Ethics for Tourism with emphasis...

United Nations Global Compact as a Corporate Social Responsibility Mechanism: A Case Study of Krüger A/S

OpenAIRE

Bereng, Reitumetse Esther

2017-01-01

Abstract: Over the years, copious research has been done on variety of voluntary sustainable development initiatives including Corporate Social Responsibility. This research takes a different route to Corporate Social Responsibility, by looking into this voluntary initiative through the spectrum of the United Nations Global Compact. It looks into the United Nations Global Compact as a mechanism for Corporate Social Responsibility in order to find out the true motives behind Krüger A/S engagin...

Global Transcriptomic Analysis of the Response of Corynebacterium glutamicum to Vanillin.

Science.gov (United States)

Chen, Can; Pan, Junfeng; Yang, Xiaobing; Guo, Chenghao; Ding, Wei; Si, Meiru; Zhang, Yi; Shen, Xihui; Wang, Yao

2016-01-01

Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

Ethical Challenges Facing Greenland in the Present Era of Globalization: Towards Global Responsibility

Directory of Open Access Journals (Sweden)

Jacob Dahl Rendtorff

2013-06-01

Full Text Available Recently, the developments of ethics and politics in the Arctic region have again become an issue for international discussion. One main issue is the problem of climate change and sustainability of the Arctic region. This problem is linked to the issue of exploitation of natural resources in the Arctic region, not at least in Greenland. Indeed, the general issue is how we should define ethics of the environment and sustainability as a general principle for the Arctic region. It is important to discuss what is at stake and how we define the problem in relation to the different participating stakeholders. This paper deals with these problems as a case for global ethics and it proposes a vision of ethical and political responsibility for sustainable development in order to deal with such problems.

Symposium on molecular and cellular mechanisms of mutagenesis

Energy Technology Data Exchange (ETDEWEB)

1981-01-01

These proceedings contain abstracts only of the 21 papers presented at the Sympsoium. The papers dealt with molecular mechanisms of mutagenesis and cellular responses to chemical and physical mutagenic agents. (ERB)

Cellular Signaling in Health and Disease

CERN Document Server

Beckerman, Martin

2009-01-01

In today’s world, three great classes of non-infectious diseases – the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders – have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular sign...

Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth

Directory of Open Access Journals (Sweden)

Charalampos Rallis

2014-01-01

Target of rapamycin complex 1 (TORC1, which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We screened a deletion library, comprising ∼84% of all non-essential fission yeast genes, for drug-resistant mutants. This screen identified 33 genes encoding functions such as transcription, kinases, mitochondrial respiration, biosynthesis, intra-cellular trafficking, and stress response. Among the corresponding mutants, 5 showed shortened and 21 showed increased maximal chronological lifespans; 15 of the latter mutants showed no further lifespan increase with rapamycin and might thus represent key targets downstream of TORC1. We pursued the long-lived sck2 mutant with additional functional analyses, revealing that the Sck2p kinase functions within the TORC1 network and is required for normal cell growth, global protein translation, and ribosomal S6 protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth was associated with all long-lived mutants while oxidative-stress resistance was not.

Stability analysis for cellular neural networks with variable delays

International Nuclear Information System (INIS)

Zhang Qiang; Wei Xiaopeng; Xu Jin

2006-01-01

Some sufficient conditions for the global exponential stability of cellular neural networks with variable delay are obtained by means of a method based on delay differential inequality. The method, which does not make use of Lyapunov functionals, is simple and effective for the stability analysis of neural networks with delay. Some previously established results in the literature are shown to be special cases of the presented result

SILICOMB PEEK Kirigami cellular structures: mechanical response and energy dissipation through zero and negative stiffness

International Nuclear Information System (INIS)

Virk, K; Marsh, M; Monti, A; Trehard, T; Hazra, K; Boba, K; Remillat, C D L; Scarpa, F; Farrow, I R

2013-01-01

The work describes the manufacturing, testing and parametric analysis of cellular structures exhibiting zero Poisson’s ratio-type behaviour, together with zero and negative stiffness effects. The cellular structures are produced in flat panels and curved configurations, using a combination of rapid prototyping techniques and Kirigami (Origami and cutting) procedures for PEEK (Polyether Ether Ketone) thermoplastic composites. The curved cellular configurations show remarkable large deformation behaviours, with zero and negative stiffness regimes depending also on the strain rate applied. These unusual stiffness characteristics lead to a large increase of energy absorption during cyclic tests. (paper)

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

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Xingsheng Hou

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

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

Science.gov (United States)

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

2014-01-01

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

Cellular immobilization within microfluidic microenvironments: dielectrophoresis with polyelectrolyte multilayers.

Science.gov (United States)

Forry, Samuel P; Reyes, Darwin R; Gaitan, Michael; Locascio, Laurie E

2006-10-25

The development of biomimetic microenvironments will improve cell culture techniques by enabling in vitro cell cultures that mimic in vivo behavior; however, experimental control over attachment, cellular position, or intercellular distances within such microenvironments remains challenging. We report here the rapid and controllable immobilization of suspended mammalian cells within microfabricated environments using a combination of electronic (dielectrophoresis, DEP) and chemical (polyelectrolyte multilayers, PEMS) forces. While cellular position within the microsystem is rapidly patterned via intermittent DEP trapping, persistent adhesion after removal of electronic forces is enabled by surface treatment with PEMS that are amenable to cellular attachment. In contrast to DEP trapping alone, persistent adhesion enables the soluble microenvironment to be systematically varied, facilitating the use of soluble probes of cell state and enabling cellular characterization in response to various soluble stimuli.

Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce Humoral and Cellular Immune Responses in Mice

Directory of Open Access Journals (Sweden)

Shoufeng Ren

2018-01-01

Full Text Available Ebola virus (EBOV causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP is the major protective antigen of EBOV, and can generate virus-like particles (VLPs by co-expression with matrix protein (VP40. In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV replicon vector DREP to express EBOV GP and matrix viral protein (VP40. EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40. Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention.

Cellular injury evidenced by impedance technology and infrared microspectroscopy

Science.gov (United States)

le Roux, K.; Prinsloo, L. C.; Meyer, D.

2015-03-01

Fourier Transform Infrared (FTIR) spectroscopy is finding increasing biological application, for example in the analysis of diseased tissues and cells, cell cycle studies and investigating the mechanisms of action of anticancer drugs. Cancer treatment studies routinely define the types of cell-drug responses as either total cell destruction by the drug (all cells die), moderate damage (cell deterioration where some cells survive) or reversible cell cycle arrest (cytostasis). In this study the loss of viability and related chemical stress experienced by cells treated with the medicinal plant, Plectranthus ciliatus, was investigated using real time cell electronic sensing (RT-CES) technology and FTIR microspectroscopy. The use of plants as medicines is well established and ethnobotany has proven that crude extracts can serve as treatments against various ailments. The aim of this study was to determine whether FTIR microspectroscopy would successfully distinguish between different types of cellular injury induced by a potentially anticancerous plant extract. Cervical adenocarcinoma (HeLa) cells were treated with a crude extract of Pciliatus and cells monitored using RT-CES to characterize the type of cellular responses induced. Cell populations were then investigated using FTIR microspectroscopy and statistically analysed using One-way Analysis of Variance (ANOVA) and Principal Component Analysis (PCA). The plant extract and a cancer drug control (actinomycin D) induced concentration dependent cellular responses ranging from nontoxic, cytostatic or cytotoxic. Thirteen spectral peaks (915 cm-1, 933 cm-1, 989 cm-1, 1192 cm-1, 1369 cm-1, 1437 cm-1, 1450 cm-1, 1546 cm-1, 1634 cm-1, 1679 cm-1 1772 cm-1, 2874 cm-1 and 2962 cm-1) associated with cytotoxicity were significantly (p value < 0.05, one way ANOVA, Tukey test, Bonferroni) altered, while two of the bands were also indicative of early stress related responses. In PCA, poor separation between nontoxic and cytostatic

Dual-Level Game-Based Energy Efficiency and Fairness for Green Cellular Networks

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Sungwook Kim

2016-01-01

Full Text Available In the recent decades, cellular networks have revolutionized the way of next generation communication networks. However, due to the global climate change, reducing the energy consumption of cellular infrastructures is an important and urgent problem. In this study, we propose a novel two-level cooperative game framework for improving the energy efficiency and fairness in cellular networks. For the energy efficiency, base stations (BSs constantly monitor the current traffic load and cooperate with each other to maximize the energy saving. For the energy fairness, renewable energy can be shared dynamically while ensuring the fairness among BSs. To achieve an excellent cellular network performance, the concepts of the Raiffa Bargaining Solution and Jain’s fairness are extended and practically applied to our dual-level cooperative game model. Through system level simulations, the proposed scheme is evaluated and compared with other existing schemes. The simulation results show that our two-level game approach outperforms the existing schemes in providing a better fair-efficient system performance.

Global warming: Economic policy responses

International Nuclear Information System (INIS)

Dornbusch, R.; Poterba, J.M.

1991-01-01

This volume contains the proceedings of a conference that brought together economic experts from Europe, the US, Latin America, and Japan to evaluate key issues in the policy debate in global warming. The following issues are at the center of debates on alternative policies to address global warming: scientific evidence on the magnitude of global warming and the extent to which it is due to human activities; availability of economic tools to control the anthropogenic emissions of greenhouse gases, and how vigorously should they be applied; and political economy considerations which influence the design of an international program for controlling greenhouse gases. Many perspectives are offered on the approaches to remedying environmental problems that are currently being pursued in Europe and the Pacific Rim. Deforestation in the Amazon is discussed, as well as ways to slow it. Public finance assessments are presented of both the domestic and international policy issues raised by plans to levy a tax on the carbon emissions from various fossil fuels. Nine chapters have been processed separately for inclusion in the appropriate data bases

Numerical simulations of cellular detonation diffraction in a stable gaseous mixture

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Jian Li

2016-09-01

Full Text Available In this paper, the diffraction phenomenon of gaseous cellular detonations emerging from a confined tube into a sudden open space is simulated using the reactive Euler equations with a two-step Arrhenius chemistry model. Both two-dimensional and axisymmetric configurations are used for modeling cylindrical and spherical expansions, respectively. The chemical parameters are chosen for a stable gaseous explosive mixture in which the cellular detonation structure is highly regular. Adaptive mesh refinement (AMR is used to resolve the detonation wave structure and its evolution during the transmission. The numerical results show that the critical channel width and critical diameter over the detonation cell size are about 13±1 and 25±1, respectively. These numerical findings are comparable with the experimental observation and confirm again that the critical channel width and critical diameter differ essentially by a factor close to 2, equal to the geometrical scaling based on front curvature theory. Unlike unstable mixtures where instabilities manifested in the detonation front structure play a significant role during the transmission, the present numerical results and the observed geometrical scaling provide again evidence that the failure of detonation diffraction in stable mixtures with a regular detonation cellular pattern is dominantly caused by the global curvature due to the wave divergence resulting in the global decoupling of the reaction zone with the expanding shock front.

Cellular automaton-based position sensitive detector equalization

Energy Technology Data Exchange (ETDEWEB)

Ferrando, Nestor [Grupo de Diseno de Sistemas Digitales, Instituto de Aplicaciones de las Tecnologias de la Informacion y de las Comunicaciones Avanzadas, Universidad Politecnica de Valencia, Camino de Vera s/n, 46022 Valencia (Spain)], E-mail: nesferjo@upvnet.upv.es; Herrero, V.; Cerda, J.; Lerche, C.W.; Colom, R.J.; Gadea, R.; Martinez, J.D.; Monzo, J.M.; Mateo, F.; Sebastia, A.; Benlloch, J.M. [Grupo de Diseno de Sistemas Digitales, Instituto de Aplicaciones de las Tecnologias de la Informacion y de las Comunicaciones Avanzadas, Universidad Politecnica de Valencia, Camino de Vera s/n, 46022 Valencia (Spain)

2009-06-01

Indirect position detectors based on scintillator crystals lack of spacial uniformity in their response. This happens due to crystal inhomogeneities and gain differences among the photomultiplier anodes. In order to solve this, PESIC, an integrated front-end for multianode photomultiplier based nuclear imaging devices was created. One of its main features is the digitally programmable gain adjustment for every photomultiplier output. On another front, cellular automata have been proved to be a useful method for dynamic system modeling. In this paper, a cellular automaton which emulates the behavior of the scintillator crystal, the photomultiplier and the front-end is introduced. Thanks to this model, an automatic energy-based calibration of the detector can be done by configuring the cellular automaton with experimental data and making it evolve up to an stable state. This can be useful as a precalibration method of the detector.

Cellular automaton-based position sensitive detector equalization

International Nuclear Information System (INIS)

Ferrando, Nestor; Herrero, V.; Cerda, J.; Lerche, C.W.; Colom, R.J.; Gadea, R.; Martinez, J.D.; Monzo, J.M.; Mateo, F.; Sebastia, A.; Benlloch, J.M.

2009-01-01

Indirect position detectors based on scintillator crystals lack of spacial uniformity in their response. This happens due to crystal inhomogeneities and gain differences among the photomultiplier anodes. In order to solve this, PESIC, an integrated front-end for multianode photomultiplier based nuclear imaging devices was created. One of its main features is the digitally programmable gain adjustment for every photomultiplier output. On another front, cellular automata have been proved to be a useful method for dynamic system modeling. In this paper, a cellular automaton which emulates the behavior of the scintillator crystal, the photomultiplier and the front-end is introduced. Thanks to this model, an automatic energy-based calibration of the detector can be done by configuring the cellular automaton with experimental data and making it evolve up to an stable state. This can be useful as a precalibration method of the detector.

Global dissipativity of continuous-time recurrent neural networks with time delay

International Nuclear Information System (INIS)

Liao Xiaoxin; Wang Jun

2003-01-01

This paper addresses the global dissipativity of a general class of continuous-time recurrent neural networks. First, the concepts of global dissipation and global exponential dissipation are defined and elaborated. Next, the sets of global dissipativity and global exponentially dissipativity are characterized using the parameters of recurrent neural network models. In particular, it is shown that the Hopfield network and cellular neural networks with or without time delays are dissipative systems

HDACi: cellular effects, opportunities for restorative dentistry.

LENUS (Irish Health Repository)

Duncan, H F

2011-12-01

Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

Compression behavior of cellular metals with inhomogeneous mass distribution

International Nuclear Information System (INIS)

Foroughi, B.

2001-05-01

Mechanical behavior of two types of closed cell metals (ALULIGHT and ALPORAS) is investigated experimentally and numerically. Compressive tests performed on prismatic specimens indicate that inhomogeneities in the mass density distribution are a key factor in the deformation behavior of cellular metals. The three dimensional cellular structure of the investigated specimens is recorded using x-ray medical computed tomography (CT). A special procedure called density mapping method has been used to transfer the recorded CT data into a continuum by averaging over a certain domain (averaging domain). This continuum model is implemented using finite elements to study the effect of variations in local mass densities. The finite element model is performed by a simple regular discretization of a specimen's volume with elements which have constant edge length. Mechanical properties derived from compression tests of ALPORAS samples are assigned to the corresponding mesoscopic density value of each element. The effect of averaging domain size is studied to obtain a suitable dimension which fulfils the homogenization requirements and allows the evaluation of inhomogenities in the specimens. The formation and propagation of deformation band(s) and stress-strain responses of tested cellular metals are modeled with respect to their mass distribution. It is shown that the inhomogeneous density distribution leads to plastic strain localization and causes a monotonically increase of the stress in the plateau regime although no hardening response was considered for homogeneous material in this regime. The simulated plastic strain localization and the calculated stress-strain responses are compared with the experimental results. The stiffness values of experiment and simulation agree very well for both cellular materials. The values of plateau strength as well, but it differs in some cases of ALULIGHT samples, where the hardening response can be predicted at least qualitatively

A study on the cellular stromal reaction and immunologic response of regional lymph nodes in gastric cancer

International Nuclear Information System (INIS)

Jyokoh, Hiroshi

1986-01-01

In an attempt to find a correlation between background factors and prognosis, cellular stromal reaction and PHA blastformation in the regional lymph nodes in gastric cancer were investigated in a total of 234 cases with advanced gastric cancer consisting of 104 patients who had undergone preoperative radiaiton therapy and 130 non-irradiated patients. The following results were obtained: 1) Interstitial matrix and fibrotic components around the gastric cancer cells proliferate. In addition, cellular components consisting mainly of lymphocytes appear in varied degrees. 2) In both non-irradiated and irradiated groups, there was no remarkable difference in the cellular stromal reaction among any major cancer sites. 3) In non-irradiated patients, no correlation existed between tumor diameters and cellular stromal reaction, while, in the irradiated cases, there were increases in the cellular stromal reaction where the tumor size is 5 cm or less. 4) In both non-irradiated and irradiated groups, cellular stromal reaction was more remarkable in highly differentiated carcinoma. 5) There were decreases in the cellular stromal reaction in ps(+) cases, of both non-irradiated and irradiated groups. 6) The cellular stromal reaction was remarkable in non-irradiated and irradiated patients who were found to be histologically negative in lymph node metastasis. 7) With the advance in staging, the cellular stromal reaction decreased in both irradiated and non-irradiated patients. 8) In both non-irradiated and irradiated groups, the cellular stromal reaction decreased in the patients who had shown vascular invasion. 9) PHA blastformation of the lymphocytes in lymph nodes of non-metastatic cases was more remarkable than that of metastatic cases, retaining high degrees of immunity. 10) In the non-metastatic patients in the lymph nodes outside the irradiated area, the lymphocytes in the lymph nodes demonstrated high degrees of PHA blastformation. (J.P.N.)

Dynamics of a class of cellular neural networks with time-varying delays

International Nuclear Information System (INIS)

Huang Lihong; Huang Chuangxia; Liu Bingwen

2005-01-01

Employing Brouwer's fixed point theorem, matrix theory, a continuation theorem of the coincidence degree and inequality analysis, the authors make a further investigation of a class of cellular neural networks with delays (DCNNs) in this Letter. A family of sufficient conditions are given for checking global exponential stability and the existence of periodic solutions of DCNNs. These results have important leading significance in the design and applications of globally stable DCNNs and periodic oscillatory DCNNs. Our results extend and improve some earlier publications

Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

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Giovanni Dalmasso

Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

Pathway towards Programmable Wave Anisotropy in Cellular Metamaterials

Science.gov (United States)

Celli, Paolo; Zhang, Weiting; Gonella, Stefano

2018-01-01

In this work, we provide a proof-of-concept experimental demonstration of the wave-control capabilities of cellular metamaterials endowed with populations of tunable electromechanical resonators. Each independently tunable resonator comprises a piezoelectric patch and a resistor-inductor shunt, and its resonant frequency can be seamlessly reprogrammed without interfering with the cellular structure's default properties. We show that, by strategically placing the resonators in the lattice domain and by deliberately activating only selected subsets of them, chosen to conform to the directional features of the beamed wave response, it is possible to override the inherent wave anisotropy of the cellular medium. The outcome is the establishment of tunable spatial patterns of energy distillation resulting in a nonsymmetric correction of the wave fields.

Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

Science.gov (United States)

Stephens, T. C.; Peacock, J. H.

1977-01-01

The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY. PMID:921888

Global Transcriptomic Analysis of the Response of Corynebacterium glutamicum to Vanillin.

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Can Chen

Full Text Available Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

Poly-ADP-ribosylation of proteins responds to cellular perturbations

International Nuclear Information System (INIS)

Schneeweiss, F.H.A.; Sharan, R.N.

1999-01-01

From the results presented above it is quite obvious that poly-ADP-ribosylation reaction is a sensitive parameter to monitor cellular responses to a wide variety of perturbations. Having developed a monolayer assay system using 32 P-NAD + as a marker, it has become possible to measure levels of cellular ADP-ribosylation more precisely. It has been demonstrated that the trigger of poly-ADP-ribosylation reaction may involve different cellular components for different perturbations. In this, membrane has been found to be important. The study has been particularly informative in the realm of DNA damage and repair following qualitatively different radiation assaults. As poly-ADP-ribosylation in eukaryotic cells primarily affects chromosomal proteins, notably histones, the reaction is strongly triggered in response to single and double strand breaks in DNA. Therefore, level of cellular poly-ADP-ribosylation can potentially be used as a biosensor of radiation induced strand breaks and can be specially useful in clinical monitoring of progress of radiotherapy. The assay of poly-ADP-ribosylation, however, requires use of radiolabelled tracer, e.g. 32 P-NAD + . Due to this, study of poly-ADP-ribosylation can not be extended to monitor effects of incorporated radionuclides. In order to overcome this shortcoming and to make the assay more sensitive and quick, a Western blot immunoassay has been developed. The preliminary indications are that the immunoassay of poly-ADP-ribosylation will fulfil the requirements to use poly-ADP-ribosylation as a sensitive, convenient and clinically applicable biosensor of cell response not only to radiations but also to different perturbations. (orig.)

A global synthesis of animal phenological responses to climate change

Science.gov (United States)

Cohen, Jeremy M.; Lajeunesse, Marc J.; Rohr, Jason R.

2018-03-01

Shifts in phenology are already resulting in disruptions to the timing of migration and breeding, and asynchronies between interacting species1-5. Recent syntheses have concluded that trophic level1, latitude6 and how phenological responses are measured7 are key to determining the strength of phenological responses to climate change. However, researchers still lack a comprehensive framework that can predict responses to climate change globally and across diverse taxa. Here, we synthesize hundreds of published time series of animal phenology from across the planet to show that temperature primarily drives phenological responses at mid-latitudes, with precipitation becoming important at lower latitudes, probably reflecting factors that drive seasonality in each region. Phylogeny and body size are associated with the strength of phenological shifts, suggesting emerging asynchronies between interacting species that differ in body size, such as hosts and parasites and predators and prey. Finally, although there are many compelling biological explanations for spring phenological delays, some examples of delays are associated with short annual records that are prone to sampling error. Our findings arm biologists with predictions concerning which climatic variables and organismal traits drive phenological shifts.

Global Awareness in the Classroom: Global Classroom Initiative

Science.gov (United States)

Education Canada, 2004

2004-01-01

As countries around the world move toward global integration, knowledge of how Canada interrelates globally is becoming an increasingly useful asset. It is important that young Canadians learn what it means to become responsible global citizens. Awareness about global issues and appreciation of Canada's efforts in international development offer a…

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

Science.gov (United States)

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.

Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis.

Science.gov (United States)

Topf, Ulrike; Wrobel, Lidia; Chacinska, Agnieszka

2016-08-01

Mitochondria are multifunctional cellular organelles that host many biochemical pathways including oxidative phosphorylation (OXPHOS). Defective mitochondria pose a threat to cellular homeostasis and compensatory responses exist to curtail the source of stress and/or its consequences. The mitochondrial proteome comprises proteins encoded by the nuclear and mitochondrial genomes. Disturbances in protein homeostasis may originate from mistargeting of nuclear encoded mitochondrial proteins. Defective protein import and accumulation of mistargeted proteins leads to stress that triggers translation alterations and proteasomal activation. These cytosolic pathways are complementary to the mitochondrial unfolded protein response (UPRmt) that aims to increase the capacity of protein quality control mechanisms inside mitochondria. They constitute putative targets for interventions aimed at increasing the fitness, stress resistance, and longevity of cells and organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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Laura D Mydlarz

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