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Sample records for cell responses needed

  1. Biosolar cells: global artificial photosynthesis needs responsive matrices with quantum coherent kinetic control for high yield.

    Science.gov (United States)

    Purchase, R L; de Groot, H J M

    2015-06-01

    This contribution discusses why we should consider developing artificial photosynthesis with the tandem approach followed by the Dutch BioSolar Cells consortium, a current operational paradigm for a global artificial photosynthesis project. We weigh the advantages and disadvantages of a tandem converter against other approaches, including biomass. Owing to the low density of solar energy per unit area, artificial photosynthetic systems must operate at high efficiency to minimize the land (or sea) area required. In particular, tandem converters are a much better option than biomass for densely populated countries and use two photons per electron extracted from water as the raw material into chemical conversion to hydrogen, or carbon-based fuel when CO2 is also used. For the average total light sum of 40 mol m(-2) d(-1) for The Netherlands, the upper limits are many tons of hydrogen or carbon-based fuel per hectare per year. A principal challenge is to forge materials for quantitative conversion of photons to chemical products within the physical limitation of an internal potential of ca 2.9 V. When going from electric charge in the tandem to hydrogen and back to electricity, only the energy equivalent to 1.23 V can be stored in the fuel and regained. A critical step is then to learn from nature how to use the remaining difference of ca 1.7 V effectively by triple use of one overpotential for preventing recombination, kinetic stabilization of catalytic intermediates and finally generating targeted heat for the release of oxygen. Probably the only way to achieve this is by using bioinspired responsive matrices that have quantum-classical pathways for a coherent conversion of photons to fuels, similar to what has been achieved by natural selection in evolution. In appendix A for the expert, we derive a propagator that describes how catalytic reactions can proceed coherently by a convergence of time scales of quantum electron dynamics and classical nuclear dynamics. We

  2. Highlighting a Need to Distinguish Cell Cycle Signatures from Cellular Responses to Chemotherapeutics in SR-FTIR Spectroscopy

    OpenAIRE

    C Hughes, M D Brown, P Dumas, N W Clarke, K R Flower and P Gardner

    2012-01-01

    Previous research has seen difficulties in establishing clear discrimination by principal component analysis (PCA) between drug-treated cells analysed by single point SR-FTIR spectroscopy, relative to multisampling cell monolayers by conventional FTIR. It is suggested that the issue arises due to signal mixing between cellular-response signatures and cell cycle phase contributions in individual cells. Consequently, chemometric distinction of cell spectra treated with multiple drugs is difficu...

  3. Transportation needs assessment: Emergency response section

    International Nuclear Information System (INIS)

    The transportation impacts of moving high level nuclear waste (HLNW) to a repository at Yucca Mountain in Nevada are of concern to the residents of the State as well as to the residents of other states through which the nuclear wastes might be transported. The projected volume of the waste suggests that shipments will occur on a daily basis for some period of time. This will increase the risk of accidents, including a catastrophic incident. Furthermore, as the likelihood of repository construction and operation and waste shipments increase, so will the attention given by the national media. This document is not to be construed as a willingness to accept the HLNW repository on the part of the State. Rather it is an initial step in ensuring that the safety and well-being of Nevada residents and visitors and the State's economy will be adequately addressed in federal decision-making pertaining to the transportation of HLNW into and across Nevada for disposal in the proposed repository. The Preferred Transportation System Needs Assessment identifies critical system design elements and technical and social issues that must be considered in conducting a comprehensive transportation impact analysis. Development of the needs assessment and the impact analysis is especially complex because of the absence of information and experience with shipping HLNW and because of the ''low probability, high consequence'' aspect of the transportation risk

  4. Transportation needs assessment: Emergency response section

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-05-01

    The transportation impacts of moving high level nuclear waste (HLNW) to a repository at Yucca Mountain in Nevada are of concern to the residents of the State as well as to the residents of other states through which the nuclear wastes might be transported. The projected volume of the waste suggests that shipments will occur on a daily basis for some period of time. This will increase the risk of accidents, including a catastrophic incident. Furthermore, as the likelihood of repository construction and operation and waste shipments increase, so will the attention given by the national media. This document is not to be construed as a willingness to accept the HLNW repository on the part of the State. Rather it is an initial step in ensuring that the safety and well-being of Nevada residents and visitors and the State`s economy will be adequately addressed in federal decision-making pertaining to the transportation of HLNW into and across Nevada for disposal in the proposed repository. The Preferred Transportation System Needs Assessment identifies critical system design elements and technical and social issues that must be considered in conducting a comprehensive transportation impact analysis. Development of the needs assessment and the impact analysis is especially complex because of the absence of information and experience with shipping HLNW and because of the ``low probability, high consequence`` aspect of the transportation risk.

  5. Assessment of Research Needs for Advanced Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Penner, S.S.

    1985-11-01

    The DOE Advanced Fuel Cell Working Group (AFCWG) was formed and asked to perform a scientific evaluation of the current status of fuel cells, with emphasis on identification of long-range research that may have a significant impact on the practical utilization of fuel cells in a variety of applications. The AFCWG held six meetings at locations throughout the country where fuel cell research and development are in progress, for presentations by experts on the status of fuel cell research and development efforts, as well as for inputs on research needs. Subsequent discussions by the AFCWG have resulted in the identification of priority research areas that should be explored over the long term in order to advance the design and performance of fuel cells of all types. Surveys describing the salient features of individual fuel cell types are presented in Chapters 2 to 6 and include elaborations of long-term research needs relating to the expeditious introduction of improved fuel cells. The Introduction and the Summary (Chapter 1) were prepared by AFCWG. They were repeatedly revised in response to comments and criticism. The present version represents the closest approach to a consensus that we were able to reach, which should not be interpreted to mean that each member of AFCWG endorses every statement and every unexpressed deletion. The Introduction and Summary always represent a majority view and, occasionally, a unanimous judgment. Chapters 2 to 6 provide background information and carry the names of identified authors. The identified authors of Chapters 2 to 6, rather than AFCWG as a whole, bear full responsibility for the scientific and technical contents of these chapters.

  6. Cell response to surgery.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

    OBJECTIVES: To describe the profound alterations in host immunity that are produced by major surgery as demonstrated by experimental and clinical studies, and to evaluate the benefits of therapeutic strategies aimed at attenuating perioperative immune dysfunction. DATA SOURCES: A review of the English-language literature was conducted, incorporating searches of the MEDLINE, EMBASE, and Cochrane collaboration databases to identify laboratory and clinical studies investigating the cellular response to surgery. STUDY SELECTION: Original articles and case reports describing immune dysfunction secondary to surgical trauma were included. DATA EXTRACTION: The results were compiled to show outcomes of different studies and were compared. DATA SYNTHESIS: Current evidence indicates that the early systemic inflammatory response syndrome observed after major surgery that is characterized by proinflammatory cytokine release, microcirculatory disturbance, and cell-mediated immune dysfunction is followed by a compensatory anti-inflammatory response syndrome, which predisposes the patient to opportunistic infection, multiple organ dysfunction syndrome, and death. Because there are currently no effective treatment options for multiple organ dysfunction syndrome, measures to prevent its onset should be initiated at an early stage. Accumulating experimental evidence suggests that targeted therapeutic strategies involving immunomodulatory agents such as interferon gamma, granulocyte colony-stimulating factor, the prostaglandin E(2) antagonist, indomethacin, and pentoxifylline may be used for the treatment of systemic inflammatory response syndrome to prevent the onset of multiple organ dysfunction syndrome. CONCLUSIONS: Surgical trauma produces profound immunological dysfunction. Therapeutic strategies directed at restoring immune homeostasis should aim to redress the physiological proinflammatory-anti-inflammatory cell imbalance associated with major surgery.

  7. Chronic Disease Management Programmes: an adequate response to patients’ needs?

    OpenAIRE

    Rijken, M; Bekkema, N.; Boeckxstaens, P.; Schellevis, F G; De Maeseneer, J M; Groenewegen, P. P.

    2014-01-01

    Background: Inspired by American examples, several European countries are now developing disease management programmes (DMPs) to improve the quality of care for patients with chronic diseases. Recently, questions have been raised whether the disease management approach is appropriate to respond to patient-defined needs. Objective: In this article we consider the responsiveness of current European DMPs to patients needs defined in terms of multimorbidity, functional and participation problems,...

  8. The need of a nuclear safeguard system under Congress responsibility

    International Nuclear Information System (INIS)

    This work discusses the need of a nuclear safeguard system under the congress responsibility. It is proposed that the National Congress creates a system of safeguards that should control the possible deviations of pacific use of nuclear power to produce nuclear bombs which are forbidden by the Brazilian Constitution. (A.C.A.S.)

  9. An Intersectoral Response to Children with Complex Health Care Needs

    Science.gov (United States)

    Young, Wendy; Earle, Jasmin; Dadebo, Mark

    2004-01-01

    The purpose of this paper is to stimulate debate on how to define and enact public responsibility to children with complex health care needs and their families. We present a program, developed using the Auditor General's framework for accountability that involves Community Care Access Centres, schools and Saint Elizabeth Health Care, a complex…

  10. Hazardous Materials Management and Emergency Response training Center needs assessment

    International Nuclear Information System (INIS)

    For the Hanford Site to provide high-quality training using simulated job-site situations to prepare the 4,000 Site workers and 500 emergency responders for known and unknown hazards a Hazardous Materials Management and Emergency Response Training Center is needed. The center will focus on providing classroom lecture as well as hands-on, realistic training. The establishment of the center will create a partnership among the US Department of Energy; its contractors; labor; local, state, and tribal governments; and Xavier and Tulane Universities of Louisiana. This report presents the background, history, need, benefits, and associated costs of the proposed center

  11. Emergency Response Capability Baseline Needs Assessment Compliance Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, John A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-09-16

    This document is the second of a two-part analysis of Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2013 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2009 BNA, the 2012 BNA document, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, fire department training records, and fire department policies and procedures.

  12. Hydrogen Storage Needs for Early Motive Fuel Cell Markets

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, J.; Ainscough, C.; Simpson, L.; Caton, M.

    2012-11-01

    The National Renewable Energy Laboratory's (NREL) objective for this project is to identify performance needs for onboard energy storage of early motive fuel cell markets by working with end users, manufacturers, and experts. The performance needs analysis is combined with a hydrogen storage technology gap analysis to provide the U.S. Department of Energy (DOE) Fuel Cell Technologies Program with information about the needs and gaps that can be used to focus research and development activities that are capable of supporting market growth.

  13. Hanford Site emergency response needs, Volumes 1 and 2

    Energy Technology Data Exchange (ETDEWEB)

    Good, D.E.

    1996-04-16

    This report presents the results of a comprehensive third party needs assessment of the Hanford Fire Department (HFD), conducted by Hughes Associates Inc. The assessment was commissioned with the intent of obtaining an unbiased report which could be used as a basis for identifying needed changes/modifications to the fire department and its services. This report serves several functions: (1) it documents current and future site operations and associated hazards and risks identified as a result of document review, site and facility surveys, and interviews with knowledgeable personnel; (2) describes the HFD in terms of organization, existing resources and response capabilities; (3) identifies regulatory and other requirements that are applicable to the HFD and includes a discussion of associated legal liabilities; and (4) provides recommendations based on applicable requirements and existing conditions. Each recommendation is followed by a supporting statement to clarify the intent or justification of the recommendation. This report will be followed by a Master Plan document which will present an implementation method for the recommendations (with associated costs) considered to be essential to maintaining adequate, cost effective emergency services at the Hanford site in the next five to seven years.

  14. Hanford Site emergency response needs, Volumes 1 and 2

    International Nuclear Information System (INIS)

    This report presents the results of a comprehensive third party needs assessment of the Hanford Fire Department (HFD), conducted by Hughes Associates Inc. The assessment was commissioned with the intent of obtaining an unbiased report which could be used as a basis for identifying needed changes/modifications to the fire department and its services. This report serves several functions: (1) it documents current and future site operations and associated hazards and risks identified as a result of document review, site and facility surveys, and interviews with knowledgeable personnel; (2) describes the HFD in terms of organization, existing resources and response capabilities; (3) identifies regulatory and other requirements that are applicable to the HFD and includes a discussion of associated legal liabilities; and (4) provides recommendations based on applicable requirements and existing conditions. Each recommendation is followed by a supporting statement to clarify the intent or justification of the recommendation. This report will be followed by a Master Plan document which will present an implementation method for the recommendations (with associated costs) considered to be essential to maintaining adequate, cost effective emergency services at the Hanford site in the next five to seven years

  15. Load Cell Response Correction Using Analog Adaptive Techniques

    OpenAIRE

    Jafaripanah, Mehdi; Al-Hashimi, Bashir; White, Neil M.

    2003-01-01

    Load cell response correction can be used to speed up the process of measurement. This paper investigates the application of analog adaptive techniques in load cell response correction. The load cell is a sensor with an oscillatory output in which the measurand contributes to response parameters. Thus, a compensation filter needs to track variation in measurand whereas a simple, fixed filter is only valid at one load value. To facilitate this investigation, computer models for the load cell a...

  16. Emergency preparedness and response: achievements, future needs and opportunities

    International Nuclear Information System (INIS)

    The Chernobyl accident had a profound effect on emergency preparedness and response world-wide and particularly within Europe. Deficiencies in arrangements for dealing with such a large accident, at both national and international levels (eg, world trade in foodstuffs), led to many problems of both a practical and political nature. Many lessons were learnt and considerable resources have since been committed to improve emergency preparedness and avoid similar problems in future. Improvements have been made at national, regional and international levels and have been diverse in nature. Some of the more notable at an international level are the convention on early notification, limits for the contamination of foodstuffs in international trade and broad agreement on the principles of intervention (albeit less so on their practical interpretation). At a regional level, many bi and multi-lateral agreements have been brought into to force for the timely exchange of information and the efficacy of these arrangements is increasingly being demonstrated by regional exercises. At a national level, the improvements have been diverse, ranging from the installation of extensive networks of gamma monitors to provide early warning of an accident to more robust and effective arrangements between the many organisations with a role or responsibility in an emergency. More than a decade after Chernobyl, it is timely to reflect on what has been achieved in practice and, in particular, whether there is a need for further improvement and, if so, where these aspects will be addressed in the context of the likelihood the decreasing resources will be allocated to this area in future as memories fade post Chernobyl. Particular attention will be given to: the potential for advances in informatics, communications and decision support to provide better emergency preparedness and response at reduced cost; the adequacy of guidance on intervention for the long tern management of containment areas

  17. SUSTAINABILITY AND COMPANY’S CORPORATE SOCIAL RESPONSIBILITY NEED

    Directory of Open Access Journals (Sweden)

    MONICA VIOLETA ACHIM

    2012-05-01

    Full Text Available The company is a living organism, is an entity and its analysis should be made taking into account the whole system. The company is a dynamic environment, which has as a mainly aims to add value for all participants in the economic life. In the organizations, the achievement of the concept of sustainable development is achieved through the concept of societal responsibility of the organizations. For this scope we need to use the term introduced by Elkington namely “The Triple Bottom Line” which involve economic prosperity, environmental compliance and improve social cohesion. [11]. So, “The Triple Bottom Line” can be defined as an approach for measuring the overall performance of an organization according to its triple contribution to the three aspects mentioned above. The new conceptual framework change radically the final aim of a company because it is not anymore maximizing the value of shares held by shareholders, but it is maximizing value for all stakeholders, where shareholders are just another category of stakeholders. Sustainable development and globalization require new performance standards that exceed the economic field, for both national company and international ones. As a consequence, these standards must be integrated into the company's development strategy, to ensure sustainability of activities carried, by the harmonization of economic, social and environmental objectives.

  18. Responsivity to Criminogenic Need in Forensic Intellectual Disability Services

    Science.gov (United States)

    Lindsay, W. R.; Holland, A. J.; Carson, D.; Taylor, J. L.; O'Brien, G.; Steptoe, L.; Wheeler, J.

    2013-01-01

    Background: Research has shown for some time that addressing criminogenic need is one of the crucial aspects of reducing reoffending in all types of offenders. Criminogenic need such as anger or inappropriate sexual interest is considered to be crucial in the commission of the offence. The aim of the present study is to investigate the extent to…

  19. Does decentralization increase responsiveness to local needs?: evidence from Bolivia

    OpenAIRE

    Faguet, Jean-Paul

    2004-01-01

    Significant changes in public investment patterns - in both the sectoral uses of funds, and their geographic distribution - emerged after Bolivia devolved substantial resources from central agencies, to municipalities in 1994. By far the most important determinant of these changes are objective indicators of social need (for example, education investment rises where illiteracy is higher). ...

  20. The critical need for animal disaster response plans.

    Science.gov (United States)

    Rogers, Cheryl

    2016-01-01

    In the tragic aftermath of disasters over the past 30+ years, people have learned that disaster planning for individuals, for communities and for many businesses must include animals. This paper discusses why emergency planning for animals is a necessity for individuals and animal-focused businesses, as well as being a critical element in community disaster response strategies. Communication between affected groups and integration of disaster plans provide for a better response, which allows for a quicker recovery. Ensuring that animals are included in disaster mitigation/preparedness/response/ recovery plans increases resilience. It will provide a framework to manage personal and business preparedness and to launch animal disaster preparedness initiatives in communities. PMID:26897622

  1. Project Responder: technology needs for local emergency response

    Science.gov (United States)

    Beakley, Guy; Garwin, Thomas; Pollard, Neal A.; Singley, George T., III; Tuohy, Robert V.; Lupo, Jasper

    2003-09-01

    Since April 2001, the Oklahoma City National Memorial Institute for the Prevention of Terrorism has funded an effort by Hicks &Associates, Inc. and the Terrorism Research Center, Inc., aimed ultimately at improving local, state, and federal emergency responders" capabilities for mitigating the effects of chemical, biological, radiological, nuclear or explosive/ incendiary (CBRNE) terrorism. This effort, titled "Project Responder," began by developing an understanding of how state and local responders view their current capabilities, shortfalls, and needs. This paper discusses some of the results of this first phase of the effort that has resulted in a comprehensive report titled "Emergency Responders" Needs, Goals, and Priorities." This paper addresses two of the capabilities from that report which we believe are of most interest to this conference. There are ten other capabilities discussed in the report, which may also be of interest.

  2. New Roles, New Responsibilities: Examining Training Needs of Repository Staff

    Directory of Open Access Journals (Sweden)

    Natasha Simons

    2012-05-01

    Full Text Available INTRODUCTION Institutional repositories play a critical role in the research lifecycle. Funding agencies are increasingly seeking an improved return on their investment in research. Repositories facilitate this process by providing storage of, and access to, institutional research outputs and, more recently, research data. While repositories are generally managed within the academic library, repository staff require different skills and knowledge compared with traditional library roles. This study reports on a survey of Australasian institutional repository staff to identify skills and knowledge sets. METHODS Institutional repository staff working at universities in Australia and New Zealand were invited to participate in an online survey which incorporated both open and closed-ended question types. RESULTS The survey found significant gaps in the current provision of formal training and coursework related to institutional repositories, which echoed findings in the United Kingdom, Italy, and the United States. DISCUSSION There is clearly a need for more and varied training opportunities for repository professionals. Repository work requires a specific set of skills that can be difficult to find and institutions will benefit from investing in training and ongoing development opportunities for repository staff. CONCLUSION The data from this study could be used to facilitate staff recruitment, development, training, and retention strategies.

  3. Conspicuous Consumption versus Charitable Behavior in Response to Social Exclusion: A Differential Needs Explanation

    OpenAIRE

    Jaehoon Lee; L. J. SHRUM

    2012-01-01

    Social exclusion has been shown to produce a number of different responses. This research examines the proposition that social exclusion may produce either self-focused or prosocial responses, depending on which needs are threatened. Different types of social exclusion threaten different needs, which in turn produce distinct outcomes (differential needs hypothesis). Social exclusion in the form of being implicitly ignored increased conspicuous consumption, whereas being explicitly rejected in...

  4. The interplay between partners' responsiveness and patients' need for emotional expression in couples coping with cancer

    NARCIS (Netherlands)

    Dagan, Meirav; Sanderman, Robbert; Hoff, Christiaan; Meijerink, W. J. H. Jeroen; Baas, Peter C.; van Haastert, Michiel; Hagedoorn, Mariët

    2014-01-01

    The central aim of this longitudinal observational study was to test whether patients with a high need for emotional expression are especially sensitive to their partners' responsive behavior, and therefore at risk for depressive symptoms when responsiveness is withheld. Patients with colorectal can

  5. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules

    Directory of Open Access Journals (Sweden)

    W.C. Mak

    2015-06-01

    Full Text Available Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line—human umbilical vein endothelial cells (HUVECs. While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation.

  6. Determinants of public T cell responses

    Institute of Scientific and Technical Information of China (English)

    Hanjie Li; Congting Ye; Guoli Ji; Jiahuai Han

    2012-01-01

    Historically,sharing T cell receptors (TCRs) between individuals has been speculated to be impossible,considering the dramatic discrepancy between the potential enormity of the TCR repertoire and the limited number of T cells generated in each individual.However,public T cell response,in which multiple individuals share identical TCRs in responding to a same antigenic epitope,has been extensively observed in a variety of immune responses across many species.Public T cell responses enable individuals within a population to generate similar antigen-specific TCRs against certain ubiquitous pathogens,leading to favorable biological outcomes.However,the relatively concentrated feature of TCR repertoire may limit T cell response in a population to some other pathogens.It could be a great benefit for human health if public T cell responses can be manipulated.Therefore,the mechanistic insight of public TCR generation is important to know.Recently,high-throughput DNA sequencing has revolutionized the study of immune receptor repertoires,which allows a much better understanding of the factors that determine the overlap of TCR repertoire among individuals.Here,we summarize the current knowledge on public T-cell response and discuss future challenges in this field.

  7. Bridging Scientific Model Outputs with Emergency Response Needs in Catastrophic Earthquake Responses

    Science.gov (United States)

    Johannes, Tay W.

    2010-01-01

    In emergency management, scientific models are widely used for running hazard simulations and estimating losses often in support of planning and mitigation efforts. This work expands utility of the scientific model into the response phase of emergency management. The focus is on the common operating picture as it gives context to emergency…

  8. T-cell response in human leishmaniasis

    DEFF Research Database (Denmark)

    Kharazmi, A; Kemp, K; Ismail, A;

    1999-01-01

    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered...... from cutaneous leishmaniasis (CL) responded by IFN-gamma production following stimulation with Leishmania antigens whereas cells from patients recovered from visceral leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The cells producing these cytokines were predominantly CD4......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  9. Cohesin is needed for bipolar mitosis in human cells.

    Science.gov (United States)

    Díaz-Martínez, Laura A; Beauchene, Nicole A; Furniss, Katherine; Esponda, Pedro; Giménez-Abián, Juan F; Clarke, Duncan J

    2010-05-01

    Multi-polar mitosis is strongly linked with aggressive cancers and it is a histological diagnostic of tumor-grade. However, factors that cause chromosomes to segregate to more than two spindle poles are not well understood. Here we show that cohesins Rad21, Smc1 and Smc3 are required for bipolar mitosis in human cells. After Rad21 depletion, chromosomes align at the metaphase plate and bipolar spindles assemble in most cases, but in anaphase the separated chromatids segregate to multiple poles. Time-lapse microscopy revealed that the spindle poles often become split in Rad21-depleted metaphase cells. Interestingly, exogenous expression of non-cleavable Rad21 results in multi-polar anaphase. Since cohesins are present at the spindle poles in mitosis, these data are consistent with a non-chromosomal function of cohesin. PMID:20436271

  10. Corporate philanthropic responses to emergent human needs:the role of organizational attention focus

    OpenAIRE

    Muller, Alan; Whiteman, Gail

    2015-01-01

    Research on corporate philanthropy typically focuses on organization-external pressures and aggregated donation behavior. Hence, our understanding of the organization-internal structures that determine whether a given organization will respond philanthropically to a specific human need remains underdeveloped. We explicate an attention-based framework in which specific dimensions of organization-level attention focus interact to predict philanthropic responses to an emergent human need. Explor...

  11. Projection of responsiveness to needs and the construction of satisfying communal relationships.

    Science.gov (United States)

    Lemay, Edward P; Clark, Margaret S; Feeney, Brooke C

    2007-05-01

    This research tested a social projection model of perceived partner responsiveness to needs. According to this model, people project their own care and supportiveness for a partner onto their perceptions of their partner's caring and supportiveness. In 2 dyadic marriage studies, participants' self-reported responsiveness to the needs of a spouse predicted perceptions of the spouse's responsiveness to the self more strongly than did the spouse's self-reported responsiveness. These projected perceptions of responsiveness, in turn, appeared to promote perceivers' relationship satisfaction. These effects were independent of individual differences in attachment, self-esteem, depression, and communal orientation. A daily-diary component suggested that people projected their own chronic responsiveness as well as their daily enacted support onto perceptions of the specific benefits received from their spouses. A 3rd study found that experimentally manipulated feelings of difficulty in recalling examples of own support provision reduced perceptions of partner responsiveness. Results suggest that projection of own responsiveness is an important determinant of perceived social support and is a means by which caring perceivers maintain satisfying and subjectively communal relationships. PMID:17484608

  12. A NEW VISION IN SALES: SATISFYING CUSTOMER NEEDS AND SOCIAL RESPONSIBILITY

    Directory of Open Access Journals (Sweden)

    Ion Stancu

    2015-09-01

    Full Text Available The new vision in sales requires, among other things, changing the salespeople's position towards the potential client by applying a philosophy that involves taking into consideration the people they come into contact with and providing solutions to address their needs in a disinterested manner, without having to pretend reciprocity. All this must be based on the concept of total sales utility, solutions to solve clients' immediate needs: the urgent ones, those who are directly related to them (financial needs, but also those arising from the use of goods purchased by the seller. The purpose of this article is to analyse how easily we can discover clients' real needs; under what conditions these needs can be satisfied through sales activities, and which the social responsibilities of the salespeople are.

  13. Endothelial Cell Response to Fusobacterium nucleatum.

    Science.gov (United States)

    Mendes, Reila Tainá; Nguyen, Daniel; Stephens, Danielle; Pamuk, Ferda; Fernandes, Daniel; Van Dyke, Thomas E; Kantarci, Alpdogan

    2016-07-01

    Vascular response is an essential aspect of an effective immune response to periodontal disease pathogens, as new blood vessel formation contributes to wound healing and inflammation. Gaining a greater understanding of the factors that affect vascular response may then contribute to future breakthroughs in dental medicine. In this study, we have characterized the endothelial cell response to the common bacterium Fusobacterium nucleatum, an important bridging species that facilitates the activity of late colonizers of the dental biofilm. Endothelial cells were infected with Fusobacterium nucleatum (strain 25586) for periods of 4, 12, 24, or 48 h. Cell proliferation and tube formation were analyzed, and expression of adhesion molecules (CD31 and CD34) and vascular endothelial growth factor (VEGF) receptors 1 and 2 was measured by fluorescence-activated cell sorter (FACS) analysis. Data indicate that F. nucleatum impaired endothelial cell proliferation and tube formation. The findings suggest that the modified endothelial cell response acts as a mechanism promoting the pathogenic progression of periodontal diseases and may potentially suggest the involvement of periodontopathogens in systemic diseases associated with periodontal inflammation. PMID:27185790

  14. T-cell response to allergens.

    Science.gov (United States)

    Ozdemir, Cevdet; Akdis, Mübeccel; Akdis, Cezmi A

    2010-01-01

    Anaphylaxis is a life-threatening IgE-dependent type 1 hypersensitivity reaction in which multiple organ systems are involved. The existence of allergen exposure and specific IgE are the major contributors to this systemic reaction. The decision of the immune system to respond to allergens is highly dependent on factors including the type and load of allergen, behavior and type of antigen-presenting cells, innate immune response stimulating substances in the same micromilieu, the tissue of exposure, interactions between T and B lymphocytes, costimulators, and genetic propensity known as atopy. Antigen-presenting cells introduce processed allergens to T-helper lymphocytes, where a decision of developing different types of T-cell immunity is given under the influence of several cytokines, chemokines, costimulatory signals and regulatory T cells. Among Th2-type cytokines, interleukin (IL)-4 and IL-13 are responsible for class switching in B cells, which results in production of allergen-specific IgE antibodies that bind to specific receptors on mast cells and basophils. After re-exposure to the sensitized allergen, this phase is followed by activation of IgE Fc receptors on mast cells and basophils resulting in biogenic mediator releases responsible for the symptoms and signs of anaphylaxis. Since the discovery of regulatory T cells, the concepts of immune regulation have substantially changed during the last decade. Peripheral T-cell tolerance is a key immunologic mechanism in healthy immune response to self antigens and non-infectious non-self antigens. Both naturally occurring CD4+CD25+ regulatory T (Treg) cells and inducible populations of allergen-specific, IL-10-secreting Treg type 1 cells inhibit allergen-specific effector cells and have been shown to play a central role in the maintenance of peripheral homeostasis and the establishment of controlled immune responses. On the other hand, Th17 cells are characterized by their IL-17 (or IL-17A), IL-17F, IL-6

  15. The need for xenotransplantation as a source of organs and cells for clinical transplantation.

    Science.gov (United States)

    Ekser, Burcin; Cooper, David K C; Tector, A Joseph

    2015-11-01

    The limited availability of deceased human organs and cells for the purposes of clinical transplantation remains critical worldwide. Despite the increasing utilization of 'high-risk', 'marginal', or 'extended criteria' deceased donors, in the U.S. each day 30 patients either die or are removed from the waiting list because they become too sick to undergo organ transplantation. In certain other countries, where there is cultural resistance to deceased donation, e.g., Japan, the increased utilization of living donors, e.g., of a single kidney or partial liver, only very partially addresses the organ shortage. For transplants of tissues and cells, e.g., pancreatic islet transplantation for patients with diabetes, and corneal transplantation for patients with corneal blindness (whose numbers worldwide are potentially in the millions), allotransplantation will never prove a sufficient source. There is an urgent need for an alternative source of organs and cells. The pig could prove to be a satisfactory source, and clinical xenotransplantation using pig organs or cells, particularly with the advantages provided by genetic engineering to provide resistance to the human immune response, may resolve the organ shortage. The physiologic compatibilities and incompatibilities of the pig and the human are briefly reviewed. PMID:26188183

  16. Major U.S. Foundations' and Corporations' Responsiveness to Puerto Rican Needs and Concerns.

    Science.gov (United States)

    National Puerto Rican Coalition, Inc., Alexandria, VA.

    This report assesses the responsiveness of major private foundations, community foundations, and corporate philanthropies in the United States to Puerto Rican needs and concerns. The private sector has increased its financial support of non-profit institutions in both the United States and Puerto Rico in an effort to mitigate the effects of the…

  17. Conducting research that is both ethical and responsive to the health needs of a developing country

    Directory of Open Access Journals (Sweden)

    Joon Wah Mak

    2014-01-01

    Full Text Available There is no substantial difference in conducting research that is both ethical and responsive to the health needs in developing and developed nations. Differences are in financial constraints, technological expertise in identification and addressing needs, and in the perception of equal partnership of all stakeholders. There will be differences in emphasis of research but this is slowly blurred due to globalisation. Public health emergencies in developing countries need timely and effective global collaborative research to implement control strategies. Research needs should be based on predictive models with learning from past emergencies, technological advances, strategic critical appraisal of local and global health information, and dialogue with all stakeholders. Adequate funding will be challenging and resources from national, international and aid foundations will be needed. Issues associated with such funding include deployment of international rapid response teams, collaborating researchers, transfer of technology, and intellectual property ownership. While all types of research ranging from basic, applied, clinical studies, meta-analysis, and translational research are relevant, the relative importance and specific allocation of resources to these may differ. Is the choice related to responsiveness or based on researchers’ perception of their contributions to evidence-based practice and research? Ethical issues relating to vulnerable groups, risk distribution, quality issues, research integrity and oversight are just as important. Internationally funded research including clinical trials must be sensitive to such issues to avoid allegations of exploitation. Thus the potential of utilisation and buy-in of research findings and recommendations must be considered.

  18. Deprivation of human natural killer cells and antitumor immune response

    Directory of Open Access Journals (Sweden)

    Vyacheslav Ogay

    2014-01-01

    Full Text Available Introduction: Cell-based immunotherapy has been given increased attention as a treatment for cancer. Human natural killer (NK cells are resident lymphocyte populations. They exhibit potent antitumor activity without human leukocyte antigen matching and without prior antigen exposure. They also are a promising tool for immunotherapy of solid and hematologic cancers. However, most cancer patients do not have enough NK cells to induce an effective antitumor immune response. This demonstrates a need for a source of NK cells that can supplement the endogenous cell population. Material and methods: In this study, we derived induced pluripotent stem cells (iPSCs from peripheral blood T-lymphocytes using Sendai virus vectors. Results: Generated iPSCs exhibited monoclonal T cell receptors (TCR rearrangement in their genome, a hallmark of mature terminally differentiated T cells. These iPSCs were differentiated into NK cells using a two-stage coculture system: iPSCs into hematopoietic CD34+ cells with feeder cells M210-B4 (ATCC, USA and CD34+ cells into mature NK cells with AFT024 cells (ATCC, USA. Our results showed that iPSC-derived NK cells expressed CD56, CD16, NKp 44 and NKp 46, possessed high cytotoxic activity  and produced high level of interferon-γ. Conclusion: Based on our data, derivation of NK cells from induced pluripotent stem cells should be considered in the treatment of oncologic diseases.This would allow for the development of cell therapy for cancer using immunologically compatible NK cells derived from iPSCs. This may contribute to a more efficient treatment of oncologic diseases in addition to traditional cancer treatment.

  19. A Regional Response to Climate Information Needs during the 1993 Flood.

    Science.gov (United States)

    Kunkel, Kenneth E.; Changnon, Stanley A.; Hollinger, Steven E.; Reinke, Beth C.; Wendland, Wayne M.; Angel, James R.

    1995-12-01

    Effective responses by government agencies, businesses, and private industry to climate disasters such as the disastrous Mississippi River flood of 1993 hinge on the regional availability of diverse up-to-date weather, climate, and water information. In addition to the obvious need for accurate forecasts and warnings of severe weather and floods, other types of meteorologically based information can contribute to effective responses. Some examples of information requested during and after the 1993 flood include 1) hydroclimatic assessments of the magnitude of the event, 2) agricultural assessments of the impacts of heavy rains and flooding on corn and soybean production, and 3) probabilistic outlooks of the recurrence of flooding based on soil moisture conditions. Quick responses to these climate information needs necessitate 1) a real-time climate monitoring system, 2) physical models to assess effects and impacts, and 3) scientific expertise to address complex issues.

  20. Developing responsiveness to the health needs of Hispanic children and families.

    Science.gov (United States)

    Guendelman, S

    1983-01-01

    Admission to a tertiary care pediatric hospital is a stressful experience for the Hispanic child and family. The stress partially stems from the institutional barriers that conflict with the psycho-social needs of Hispanic families. This article identifies six psycho-social needs of Hispanics and examines related risks for coping disturbances encountered during the hospitalization process. These risks can be reduced by increasing health providers' understanding of the psycho-social needs of Hispanics and by specifying culturally appropriate interventions. The development of cross-cultural committees, protocols and hospital based Hispanic self-help networks represent distinct modalities for improving responsiveness to the health needs of Hispanic families in a hospital setting. PMID:6623301

  1. Nonlinear cell response to strong electric fields

    Science.gov (United States)

    Bardos, D. C.; Thompson, C. J.; Yang, Y. S.; Joyner, K. H.

    2000-07-01

    The response of living cells to externally applied electric fields is of widespread interest. In particular, the intensification of electric fields across cell membranes is believed to be responsible, through membrane rupture and reversible membrane breakdown processes, for certain types of tissue damage in electrical trauma cases which cannot be attributed to Joule heating. Large elongated cells such as skeletal muscle fibres are particularly vulnerable to such damage. Previous theoretical studies of field intensification across cell membranes in such cells have assumed the membrane current to be linear in the applied field (Ohmic membrane conductivity) and were limited to sinusoidal applied fields. In this paper, we investigate a simple model of a long cylindrical cell, corresponding to nerve or skeletal muscle cells. Employing the electroquasistatic approximation, a system of coupled first-order differential equations for the membrane electric field is derived which incorporates arbitrary time dependence in the external field and nonlinear membrane response (non-Ohmic conductivity). The behaviour of this model is investigated for a variety of applied fields in both the linear and highly nonlinear regimes. We find that peak membrane fields predicted by the nonlinear model are approximately twice as intense, for low-frequency electrical trauma conditions, as those of the linear theory.

  2. T-cell responses in malaria

    DEFF Research Database (Denmark)

    Hviid, L; Jakobsen, P H; Abu-Zeid, Y A;

    1992-01-01

    Malaria is caused by infection with protozoan parasites of the genus Plasmodium. It remains one of the most severe health problems in tropical regions of the world, and the rapid spread of resistance to drugs and insecticides has stimulated intensive research aimed at the development of a malaria...... vaccine. Despite this, no efficient operative vaccine is currently available. A large amount of information on T-cell responses to malaria antigens has been accumulated, concerning antigens derived from all stages of the parasite life cycle. The present review summarizes some of that information, and...... discusses factors affecting the responses of T cells to malaria antigens....

  3. Radiation response of human hematopoietic cells

    International Nuclear Information System (INIS)

    The radiosensitivity and capacity to accumulate and repair sub-lethal damage has been studied in hematopoietic cell lines of human origin and in stem cells derived from blood and bone narrow of normal human donors. The results were analysed in terms of the linear quadratic and multitarget models. For the cell lines intrinsic radiosensitivity varied widely with D/sub o/'s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed same capacity to accumulate sub-lethal damage and in three of these survival was enhanced by dose fractionation or reduction of dose rate. Among the cell lines of leukemic origin, several did not conform in one or more respects with the highly radiosensitive and repair deficient model associated with hematopoietic cells. There was no apparent correlation between radiation response and the phenotype (myeloid, lymphoid or undifferentiated) of the cell lines studied. Variability of radiation response and in some cases an unpredicted degree of radioresistance and capacity to repair sub-lethal damage has now been demonstrated for both cultured and primary explants of human leukemic cells. These observations have implications for the design of Total Body Irradiation protocols for use prior to bone narrow transplant

  4. Medical education, social responsibility and praxis: Responding to the needs of all children.

    Science.gov (United States)

    Martimianakis, Maria Athina

    2016-01-01

    While poverty is a recognized risk factor for ill health, directly intervening on the effects of poverty has traditionally been considered to fall outside the realm of a physician's daily practice. Yet, to appropriately respond to the health needs of all children, we have the social responsibility to help our trainees become competent health advocates. Experiential learning approaches can be used to aid students in developing identities and competencies as health advocates. Experiencing illness outside the sterility of the clinic, from the patient's point of view, encourages students to seek the knowledge they need to care for patients who are disenfranchised, socially vulnerable and/or marginalized. PMID:27441019

  5. Regulatory T cells in cutaneous immune responses.

    OpenAIRE

    Honda, Tetsuya; MIYACHI, YOSHIKI; Kabashima, Kenji

    2011-01-01

    Regulatory T cells (Treg) are a subset of T cells with strong immunosuppressive activity. In the skin, it has recently been revealed that Treg play important roles not only in the maintenance of skin homeostasis but also in the regulation of the immune responses, such as contact hypersensitivity and atopic dermatitis. Furthermore, the skin plays important roles in the induction of Treg in the periphery. In this review, we will provide an overview of the mechanism of Treg-mediated immunosuppre...

  6. Will specialized equipment and supplies needed for an oil spill response be available when you need them?

    International Nuclear Information System (INIS)

    As a consequence of recent and highly publicized oil spills, much effort and money has been expended on the development of new oil spill response technologies. Since medium to large size spills are infrequent events, however, it has historically been difficult to maintain a stable source of supplies for high-technology oil spill response methods. Examples of such methods include laser fluorosensors for spill detection, computer models for predicting spill trajectories, and bioremediation and in-situ burning of spills. Problems with spill response research is the duplication of research, relative inaccessiblity of the relevant literature, lack of continuity of staff who understand advanced spill response techniques, lack of training in new techniques, regulatory constraints on the use of new techniques, and lack of availability of the latest spill control equipment and materials. Rather than burden oil spill response funding groups with the responsibility for maintaining expensive systems for response to unlikely or infrequent events, it is suggested that oil spill technology research groups should investigate alternative users for their technologies. For example, if a chemical used for suppressing soot during oil spill burning were also applicable to pool burning of oil in sumps and test flares, there would be a commercial incentive to make it readily available. 22 refs

  7. Multidimensional evaluation of a mental health court: Adherence to the risk-need-responsivity model.

    Science.gov (United States)

    Campbell, Mary Ann; Canales, Donaldo D; Wei, Ran; Totten, Angela E; Macaulay, W Alex C; Wershler, Julie L

    2015-10-01

    The current study examined the impact of a mental health court (MHC) on mental health recovery, criminogenic needs, and recidivism in a sample of 196 community-based offenders with mental illness. Using a pre-post design, mental health recovery and criminogenic needs were assessed at the time of MHC referral and discharge. File records were reviewed to score the Level of Service/Risk-Need-Responsivity instrument (Andrews, Bonta, & Wormith, 2008) to capture criminogenic needs, and a coding guide was used to extract mental health recovery information at each time point. Only mental health recovery data were available at 12 months post-MHC involvement. Recidivism (i.e., charges) was recorded from police records over an average follow-up period of 40.67 months post-MHC discharge. Case management adherence to the Risk-Need-Responsivity (RNR) model of offender case management was also examined. Small but significant improvements were found for criminogenic needs and some indicators of mental health recovery for MHC completers relative to participants who were prematurely discharged or referred but not admitted to the program. MHC completers had a similar rate of general recidivism (28.6%) to cases not admitted to MHC and managed by the traditional criminal justice system (32.6%). However, MHC case plans only moderately adhered to the RNR model. Implications of these results suggest that the RNR model may be an effective case management approach for MHCs to assist with decision-making regarding admission, supervision intensity, and intervention targets, and that interventions in MHC contexts should attend to both criminogenic and mental health needs. PMID:25938859

  8. Mast cells as regulators of T cell responses

    Directory of Open Access Journals (Sweden)

    Silvia eBulfone-Paus

    2015-08-01

    Full Text Available Mast cells are recognized to participate in the regulation of innate and adaptive immune responses. Owing to their strategic location at the host-environment interface they control tissue homeostasis and are key cells for starting early host defence against intruders. Upon degranulation induced, e.g. by immunoglobulin E (IgE and allergen-mediated engagement of the high-affinity IgE receptor, complement or certain neuropeptide receptors, mast cells release a wide variety of preformed and newly synthesized products including proteases, lipid mediators, and many cytokines, chemokines, and growth factors. Interestingly, increasing evidence suggests a regulatory role for mast cells in inflammatory diseases via the regulation of T cell activities. Furthermore, rather than only serving as effector cells, mast cells are now recognized to induce T cell activation, recruitment, proliferation and cytokine secretion in an antigen-dependent manner and to impact on regulatory T cells. This review synthesizes recent developments in mast cell-T cell interactions, discusses their biological and clinical relevance, and explores recent controversies in this field of mast cell research.

  9. Radiation response in prostate cancer stem cells

    International Nuclear Information System (INIS)

    The full text of the publication follows. Introduction: Currently, there is no successful treatment for secondary prostate cancer. Resistance of secondary tumours and metastases to radiotherapy and chemotherapy might be explained by cancer stem cells (CSCs). Prostate (P) CSCs are rare cells defined by cell surface markers, CD133+, a2b1integrinhi and CD44+, and are capable of self-renewal, differentiation and invasion in vitro and tumour initiation in vivo. Hypothesis: PCSCs have an alternative DNA damage response following radiation and are resistant to radiation treatment. Methods: Primary prostate (benign and cancer) epithelial stem (SC) transit amplifying (TA, CD133-/a2b1integrinhi/CD44+) and committed basal (CB, CD133-/a2b1integrinlo/CD44+) cells were exposed to 2 Gy of radiation (IR) to induce a DNA damage response. Immunofluorescence was used to quantify nuclear foci, representative of DNA damage response proteins (g-H2AX, 53BP1, phosphorylated ATM/ATR substrates, phospho-Chk2Th68). Immunofluorescence was also used to co-stain for heterochromatin and DNA damage markers. Comet assays (neutral and alkaline) were used to directly assess DNA damage. Results: In benign and cancer cells, the SCs had a lower percentage of cells containing initial foci (30 min post-IR), compared to the TA and CB cells. At 24 h post-IR there was a reduced percentage of cells positive for foci in TA and CB cells suggesting repair. Whilst there were also signs of repair in benign SCs, in the PCSCs there was an increase in percentage of cells positive for foci at 24 h, indicative of a delayed damage response. Comet assays indicated that SCs sustain different kinds of DNA damage to TA and CB cells. Heterochromatin staining indicated that DNA damage foci preferentially formed in euchromatin. Future work: Further studies will include apoptosis and clonogenic assays to measure PCSC survival. In addition, PCSC chromatin status will be examined to elucidate DNA repair kinetics. If we are able

  10. Educate Together: an inclusive response to the needs of a pluralist Ireland?

    OpenAIRE

    Lalor, John P.

    2013-01-01

    Educate Together: An inclusive response to the needs of a Pluralist Ireland? Ireland has undergone profound changes over the last twenty years. These changes have impacted on all aspects of Irish life not least in the area of compulsory education. Irish classrooms, reflecting the conditions prevailing in the broader society, have become more diverse environments during this time. This thesis examines how one element of the Irish education system, Educate Together, reflects this diversity in h...

  11. Psychological need satisfaction, intrinsic motivation and affective response to exercise in adolescents

    OpenAIRE

    Schneider, Margaret L.; Kwan, Bethany M.

    2013-01-01

    ObjectivesTo further understanding of the factors influencing adolescents’ motivations for physical activity, the relationship of variables derived from Self-Determination Theory to adolescents’ affective response to exercise was examined.DesignCorrelational.MethodAdolescents (N = 182) self-reported psychological needs satisfaction (perceived competence, relatedness, and autonomy) and intrinsic motivation related to exercise. In two clinic visits, adolescents reported their affect before, dur...

  12. Emergency management in the Swedish electricity market: the need to challenge the responsibility gap

    OpenAIRE

    Palm, Jenny

    2008-01-01

    A secure energy supply is a basic need of society. Along with electricity market deregulation, a responsibility gap has arisen, where private energy companies lack economic incentives to invest in an electricity distribution grid that is secured to the level desired by society. This article discusses the emergency management strategies of municipal authorities for securing the electricity supply, according to a networked, or “governance”, control and direction structure, and how this influenc...

  13. Regulated cell death and adaptive stress responses.

    Science.gov (United States)

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Kepp, Oliver; Kroemer, Guido

    2016-06-01

    Eukaryotic cells react to potentially dangerous perturbations of the intracellular or extracellular microenvironment by activating rapid (transcription-independent) mechanisms that attempt to restore homeostasis. If such perturbations persist, cells may still try to cope with stress by activating delayed and robust (transcription-dependent) adaptive systems, or they may actively engage in cellular suicide. This regulated form of cell death can manifest with various morphological, biochemical and immunological correlates, and constitutes an ultimate attempt of stressed cells to maintain organismal homeostasis. Here, we dissect the general organization of adaptive cellular responses to stress, their intimate connection with regulated cell death, and how the latter operates for the preservation of organismal homeostasis. PMID:27048813

  14. Lawrence Livermore National Laboratory Emergency Response Capability Baseline Needs Assessment Requirement Document

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, J A

    2009-12-30

    This revision of the LLNL Fire Protection Baseline Needs Assessment (BNA) was prepared by John A. Sharry, LLNL Fire Marshal and LLNL Division Leader for Fire Protection and reviewed by Martin Gresho, Sandia/CA Fire Marshal. The document follows and expands upon the format and contents of the DOE Model Fire Protection Baseline Capabilities Assessment document contained on the DOE Fire Protection Web Site, but only address emergency response. The original LLNL BNA was created on April 23, 1997 as a means of collecting all requirements concerning emergency response capabilities at LLNL (including response to emergencies at Sandia/CA) into one BNA document. The original BNA documented the basis for emergency response, emergency personnel staffing, and emergency response equipment over the years. The BNA has been updated and reissued five times since in 1998, 1999, 2000, 2002, and 2004. A significant format change was performed in the 2004 update of the BNA in that it was 'zero based.' Starting with the requirement documents, the 2004 BNA evaluated the requirements, and determined minimum needs without regard to previous evaluations. This 2010 update maintains the same basic format and requirements as the 2004 BNA. In this 2010 BNA, as in the previous BNA, the document has been intentionally divided into two separate documents - the needs assessment (1) and the compliance assessment (2). The needs assessment will be referred to as the BNA and the compliance assessment will be referred to as the BNA Compliance Assessment. The primary driver for separation is that the needs assessment identifies the detailed applicable regulations (primarily NFPA Standards) for emergency response capabilities based on the hazards present at LLNL and Sandia/CA and the geographical location of the facilities. The needs assessment also identifies areas where the modification of the requirements in the applicable NFPA standards is appropriate, due to the improved fire protection

  15. Radiation response of rodent neural precursor cells

    International Nuclear Information System (INIS)

    Full text: Therapeutic irradiation of the brain can cause cognitive dysfunction that is not treatable or well understood. Several lines of evidence from our laboratory suggest that radiation induced inhibition of neurogenesis in the hippocampus may be involved. To understand the mechanisms underlying these observations, we initiated studies using neural precursor cells isolated from the adult rat hippocampus. Cells were cultured exponentially and analyzed for acute (0-24h) and chronic (3-33 day) changes in apoptosis and oxidative stress following exposure to X-rays. Oxidative stress was measured using a dye sensitive to reactive oxygen species (ROS) and apoptosis was measured using annexin V binding; each endpoint was quantified by fluorescent automated cell sorting (FACS). Following exposure to X-rays, neural precursor cells exhibit a dose-responsive increase in the level of ROS and apoptosis over acute and chronic time frames. ROS and apoptosis were maximal at 12h, increasing 35 and 37% respectively over that of unirradiated controls. ROS and apoptosis peaked again at 24h, increasing 31 and 21% respectively over controls. Chronic levels of ROS and apoptosis were persistently elevated in a dose-dependent manner. ROS showed significant increases (34-180%) over a 3-4 week interval, while increases in apoptosis were less dramatic, rising 45% by week one before dropping to background. Irradiation of rat neural precursor cells was associated with an increase in p53 protein levels, and the activation of G1/S and G2/M checkpoints. These data suggest that the apoptotic and ROS responses may be tied to p53 dependent regulation of cell cycle control and stress activated pathways. We propose that oxidative stress plays a critical role in the radiation response of neural precursor cells, and discuss how this might contribute to the inhibition of neurogenesis and the cognitive impairment observed in the irradiated CNS

  16. Response to DNA damage: why do we need to focus on protein phosphatases?

    Directory of Open Access Journals (Sweden)

    MidoriShimada

    2013-01-01

    Full Text Available Eukaryotic cells are continuously threatened by unavoidable errors during normal DNA replication or various sources of genotoxic stresses that cause DNA damage or stalled replication. To maintain genomic integrity, cells have developed a coordinated signaling network, known as the DNA damage response (DDR. Following DNA damage, sensor molecules detect the presence of DNA damage and transmit signals to downstream transducer molecules. This in turn conveys the signals to numerous effectors, which initiate a large number of specific biological responses, including transient cell cycle arrest mediated by checkpoints, DNA repair, and apoptosis. It is recently becoming clear that dephosphorylation events are involved in keeping DDR factors inactive during normal cell growth. Moreover, dephosphorylation is required to shut off checkpoint arrest following DNA damage and has been implicated in the activation of the DDR. Spatial and temporal regulation of phosphorylation events is essential for the DDR, and fine-tuning of phosphorylation is partly mediated by protein phosphatases. While the role of kinases in the DDR has been well documented, the complex roles of protein dephosphorylation have only recently begun to be investigated. Therefore, it is important to focus on the role of phosphatases and to determine how their activity is regulated upon DNA damage. In this work, we summarize current knowledge on the involvement of serine/threonine phosphatases, especially the protein phosphatase 1, protein phosphatase 2A, and protein phosphatase Mg2+/Mn2+-dependent families, in the DDR.

  17. Emergency management in the Swedish electricity market: The need to challenge the responsibility gap

    International Nuclear Information System (INIS)

    A secure energy supply is a basic need of society. Along with electricity market deregulation, a responsibility gap has arisen, where private energy companies lack economic incentives to invest in an electricity distribution grid that is secured to the level desired by society. This article discusses the emergency management strategies of municipal authorities for securing the electricity supply, according to a networked, or 'governance', control and direction structure, and how this influences the relationship between electricity companies and Swedish municipalities. The Swedish electricity system has traditionally developed in a monopoly context. Since electricity market deregulation, the responsibility for electricity supply security has become unclear; field studies of Swedish municipalities indicate that all actors still seem to be seeking to find their proper roles in the deregulated market. Municipalities still expect to exercise influence over private energy company decisions regarding prioritization of emergency power deliveries. Energy companies vacillate between emphasizing their need to regard economic factors and their sense of responsibility for providing a secure electricity supply to vital municipal functions (even though municipalities may lack contracts specifying this)

  18. Emergency management in the Swedish electricity market: The need to challenge the responsibility gap

    International Nuclear Information System (INIS)

    A secure energy supply is a basic need of society. Along with electricity market deregulation, a responsibility gap has arisen, where private energy companies lack economic incentives to invest in an electricity distribution grid that is secured to the level desired by society. This article discusses the emergency management strategies of municipal authorities for securing the electricity supply, according to a networked, or 'governance', control and direction structure, and how this influences the relationship between electricity companies and Swedish municipalities. The Swedish electricity system has traditionally developed in a monopoly context. Since electricity market deregulation, the responsibility for electricity supply security has become unclear; field studies of Swedish municipalities indicate that all actors still seem to be seeking to find their proper roles in the deregulated market. Municipalities still expect to exercise influence over private energy company decisions regarding prioritization of emergency power deliveries. Energy companies vacillate between emphasizing their need to regard economic factors and their sense of responsibility for providing a secure electricity supply to vital municipal functions (even though municipalities may lack contracts specifying this). (author)

  19. Metabolic Responses of Bacterial Cells to Immobilization.

    Science.gov (United States)

    Żur, Joanna; Wojcieszyńska, Danuta; Guzik, Urszula

    2016-01-01

    In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and biotransformation of xenobiotics in wastewater treatment plants. Although the literature data on the physiological changes and behaviour of cells in the immobilized state remain fragmentary, it is well documented that in natural settings microorganisms are mainly found in association with surfaces, which results in biofilm formation. Biofilms are characterized by genetic and physiological heterogeneity and the occurrence of altered microenvironments within the matrix. Microbial cells in communities display a variety of metabolic differences as compared to their free-living counterparts. Immobilization of bacteria can occur either as a natural phenomenon or as an artificial process. The majority of changes observed in immobilized cells result from protection provided by the supports. Knowledge about the main physiological responses occurring in immobilized cells may contribute to improving the efficiency of immobilization techniques. This paper reviews the main metabolic changes exhibited by immobilized bacterial cells, including growth rate, biodegradation capabilities, biocatalytic efficiency and plasmid stability. PMID:27455220

  20. Metabolic Responses of Bacterial Cells to Immobilization

    Directory of Open Access Journals (Sweden)

    Joanna Żur

    2016-07-01

    Full Text Available In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and biotransformation of xenobiotics in wastewater treatment plants. Although the literature data on the physiological changes and behaviour of cells in the immobilized state remain fragmentary, it is well documented that in natural settings microorganisms are mainly found in association with surfaces, which results in biofilm formation. Biofilms are characterized by genetic and physiological heterogeneity and the occurrence of altered microenvironments within the matrix. Microbial cells in communities display a variety of metabolic differences as compared to their free-living counterparts. Immobilization of bacteria can occur either as a natural phenomenon or as an artificial process. The majority of changes observed in immobilized cells result from protection provided by the supports. Knowledge about the main physiological responses occurring in immobilized cells may contribute to improving the efficiency of immobilization techniques. This paper reviews the main metabolic changes exhibited by immobilized bacterial cells, including growth rate, biodegradation capabilities, biocatalytic efficiency and plasmid stability.

  1. Responsiveness of Lebanon's primary healthcare centers to non-communicable diseases and related healthcare needs.

    Science.gov (United States)

    Yassoub, Rami; Hashimi, Suha; Awada, Siham; El-Jardali, Fadi

    2014-01-01

    Lebanon currently faces a rise in non-communicable diseases (NCD) that is stressing the population's health and financial well-being. Preventive care is recognized as the optimal health equitable, cost-effective solution. The study aims to assess the responsiveness of primary health care centers (PHCs) to NCD, and identify the needed health arrangements and responsibilities of PHCs, the Ministry Of Public Health and other healthcare system entities, for PHCs to purse a more preventive role against NCD. Single and group interviews were conducted via a semi-structured questionnaire with 10 PHCs from Lebanon's primary health care network that have undergone recent pilot accreditation and are recognized for having quality services and facilities. This manifested administrative aspects and NCD-related services of PHCs and generated information regarding the centers' deficiencies, strengths and areas needing improvement for fulfilling a more preventive role. Administrative features of PHCs varied according to number and type of health personnel employed. Variations and deficiencies within and among PHCs were manifested specifically at the level of cardiovascular and respiratory diseases and cancer. PHCs identified the pilot accreditation as beneficial at the administrative and clinical levels; however, various financial and non-financial resources, in addition to establishing a strong referral system with secondary care settings and further arrangements with MOPH, are necessary for PHCs to pursue a stronger preventive role. The generated results denote needed changes within the healthcare system's governance, financing and delivery. They involve empowering PHCs and increasing their breadth of services, allocating a greater portion of national budget to health and preventive care, and equipping PHCs with personnel skilled in conducting community-wide preventive activities. PMID:23729408

  2. Fostering an Adolescent-Centered Community Responsive to Student Needs: Lessons Learned and Suggestions for Middle Level Educators

    Science.gov (United States)

    Ellerbock, Cheryl R.; Kiefer, Sarah M.

    2014-01-01

    Young adolescents have unique basic and developmental needs. Middle level educators are best able to reach and teach young adolescents when they understand students' needs and when the school environment, including its organizational structures and teacher practices, are responsive to these needs. Findings from a recently conducted…

  3. Autophagic response to cell culture stress in pluripotent stem cells.

    Science.gov (United States)

    Gregory, Siân; Swamy, Sushma; Hewitt, Zoe; Wood, Andrew; Weightman, Richard; Moore, Harry

    2016-05-01

    Autophagy is an important conserved cellular process, both constitutively as a recycling pathway for long lived proteins and as an upregulated stress response. Recent findings suggest a fundamental role for autophagic processes in the maintenance of pluripotent stem cell function. In human embryonic stem cells (hESCS), autophagy was investigated by transfection of LC3-GFP to visualize autophagosomes and with an antibody to LC3B protein. The presence of the primary cilium (PC) in hESCs as the site of recruitment of autophagy-related proteins was also assessed. HESCs (mShef11) in vitro displayed basal autophagy which was upregulated in response to deprivation of culture medium replacement. Significantly higher levels of autophagy were exhibited on spontaneous differentiation of hESCs in vitro. The PC was confirmed to be present in hESCs and therefore may serve to coordinate autophagy function. PMID:26385182

  4. Regulatory T cells control immune responses through their nonredundant tissue specific features

    OpenAIRE

    Sari eLehtimäki; Riitta eLahesmaa

    2013-01-01

    Regulatory T cells (Treg) are needed to control immune responses and to maintain immune homeostasis. Most potent regulators are Foxp3 expressing CD4+ T cells which can be roughly divided in to two main groups, natural Treg cells (nTreg) developing in the thymus and induced or adaptive Treg cells (iTreg) developing in the periphery from naïve, conventional T cells. Both nTreg cells and iTreg cells have their own, nonredundant roles in the immune system, with nTreg cells mainly maintaining...

  5. Unmet Needs for Psychosocial Care in Hematologic Malignancies and Hematopoietic Cell Transplant.

    Science.gov (United States)

    Barata, Anna; Wood, William A; Choi, Sung Won; Jim, Heather S L

    2016-08-01

    Individuals diagnosed with hematologic malignancies experience significant unmet psychological, physical, informational, financial, and spiritual needs. The goal of the current review is to summarize and highlight recent research focused on these issues in the diagnosis and treatment periods and beyond. The review also describes the needs of adolescent and young adult (AYA) and pediatric patients. While a large body of research has reported on unmet needs among adult hematologic cancer patients, there is far less data regarding the challenges confronted by AYA and pediatric populations. Available data suggests that among all age groups, hematopoietic cell transplantation (HCT) is a risk factor for greater unmet needs. Recommendations for screening and evidence-based interventions to prevent or ameliorate unmet needs are provided. Future research is needed to develop additional evidence-based psychosocial interventions with a focus on hematologic cancer. PMID:27113094

  6. The need for a systematic approach to disaster psychosocial response: a suggested competency framework.

    Science.gov (United States)

    Cox, Robin S; Danford, Taryn

    2014-04-01

    Competency models attempt to define what makes expert performers "experts." Successful disaster psychosocial planning and the institutionalizing of psychosocial response within emergency management require clearly-defined skill sets. This necessitates anticipating both the short- and long-term psychosocial implications of a disaster or health emergency (ie, pandemic) by developing effective and sustained working relationships among psychosocial providers, programs, and other planning partners. The following article outlines recommended competencies for psychosocial responders to enable communities and organizations to prepare for and effectively manage a disaster response. Competency-based models are founded on observable performance or behavioral indicators, attitudes, traits, or personalities related to effective performance in a specific role or job. After analyzing the literature regarding competency-based frameworks, a proposed competency framework that details 13 competency domains is suggested. Each domain describes a series of competencies and suggests behavioral indicators for each competency and, where relevant, associated training expectations. These domains have been organized under three distinct categories or types of competencies: general competency domains; disaster psychosocial intervention competency domains; and disaster psychosocial program leadership and coordination competency domains. Competencies do not replace job descriptions nor should they be confused with performance assessments. What they can do is update and revise job descriptions; orient existing and new employees to their disaster/emergency roles and responsibilities; target training needs; provide the basis for ongoing self-assessment by agencies and individuals as they evaluate their readiness to respond; and provide a job- or role-relevant basis for performance appraisal dimensions or standards and review discussions. Using a modular approach to psychosocial planning, service

  7. Design principles for CANDU control centres in response to evolving utility business needs

    International Nuclear Information System (INIS)

    Nuclear generation operators are facing a challenging business environment at the beginning of the new millennium. Evolving changes in business context, competitive commercial pressures, and changes in technology have dictated recurring evaluation of operational practices and the adequacy of supporting tools, and the pursuit of opportunities for operational improvement. A key area of utility operations that has been impacted by these changes is the nuclear plant control centre. Changes to workspace layout, equipment provisions, staffing, and work organization are examples of some of the adjustments being introduced to improve operational and safety effectiveness. This paper discusses some of the key factors influencing these changes and identifies additional design principles for CANDU control centres that will enable new control centre designs and retrofits of existing control centres to remain relevant and responsive to utility needs. (author)

  8. Emergency management: e-learning as an immediate response to veterinary training needs.

    Science.gov (United States)

    Alessandrini, Barbara; D'Albenzio, Silvia; Turrini, Monica; Valerii, Lejla; Moretti, Michela; Pediconi, Ombretta; Callegari, Maria Luisa; Lelli, Rossella

    2012-01-01

    Veterinary training plays a crucial role in increasing effectiveness of veterinary response to epidemic and non-epidemic emergencies. Being able to assess learning needs and to deliver training is acknowledged as a strategic priority in veterinary public health activities. The validation of an e-learning system that is able to respond to the urgent needs of veterinary professionals to ensure the despatch of rapid teaching methods on emerging and re-emerging animal diseases and zoonoses was the core of a research project developed in the Mediterranean Basin between 2005 and 2009. The project validated a new transferable, sustainable and repeatable learning model, the main components of which are described. The model is applied to an emergency situation that occurred in Italy in 2008, when West Nile disease outbreaks were reported in northern Italy. Approximately 450 official veterinarians were trained, using an e-learning system that showed adaptability and effectiveness in transferring knowledge, skills and competence to face the situation. The case was used to validate the effectiveness of the model and proved that it can be applied in any emergency situation, i.e. every time that rapid dissemination of knowledge and skills is required. PMID:22718337

  9. Emergency management: e-learning as an immediate response to veterinary training needs

    Directory of Open Access Journals (Sweden)

    Barbara Alessandrini

    2012-06-01

    Full Text Available Veterinary training plays a crucial role in increasing effectiveness of veterinary response to epidemic and non-epidemic emergencies. Being able to assess learning needs and to deliver training is acknowledged as a strategic priority in veterinary public health activities. The validation of an e-learning system that is able to respond to the urgent needs of veterinary professionals to ensure the despatch of rapid teaching methods on emerging and re-emerging animal diseases and zoonoses was the core of a research project developed in the Mediterranean Basin between 2005 and 2009. The project validated a new transferable, sustainable and repeatable learning model, the main components of which are described. The model is applied to an emergency situation that occurred in Italy in 2008, when West Nile disease outbreaks were reported in northern Italy. Approximately 450 official veterinarians were trained, using an e-learning system that showed adaptability and effectiveness in transferring knowledge, skills and competence to face the situation. The case was used to validate the effectiveness of the model and proved that it can be applied in any emergency situation, i.e. every time that rapid dissemination of knowledge and skills is required.

  10. Silicon Carbide Optics for Space Situational Awareness and Responsive Space Needs

    Science.gov (United States)

    Robichaud, J.; Green, J.; Catropa, D.; Rider, B.; Ullathorne, C.

    Over the past 10 years the application of Silicon Carbide (SiC) materials to space based imaging systems has expanded. The aerospace community has long recognized the technical, cost, and schedule benefits associated with the material, and adoption of the technology is facilitated as more successful flight systems are demonstrated. SiC provides a number of technical advantages, as a result of superior material properties. The material can also be manufactured using near-net-shape fabrication processes which provide significant cost and schedule advantages compared with competing material technologies. These technical and manufacturing advantages make SiC uniquely well suited to address the needs associated with Space Situational Awareness (SSA) and Responsive Space (RS) applications. The material has a low coefficient of thermal expansion, and a high thermal conductivity, allowing visible quality imaging in the presence of stressing, and changing, thermal loads. The material's specific stiffness is high, approximately 70% of Beryllium, allowing stiff, lightweight optical systems to be produced. Passively athermal systems have been produced, demonstrating the ability of the material to provide visible quality imaging, without the need for actively controlled focus adjust mechanisms. In addition, SiC structural elements do not outgas, and have no issues with moisture absorption, allowing rapid on-orbit data acquisition. From the manufacturing perspective the material offers dramatic schedule benefits, these come primarily from L-3 SSG's near-net-shape manufacturing process which allows complex, lightweighted optical and structural elements to be produced without the need for costly/time-consuming machining processes. These schedule advantages become more dramatic as the aperture of the system increases, and/or as the number of units increases. In this paper we provide an overview of the technical and manufacturing advantages associated with SiC, provide background

  11. Lawrence Livermore National Laboratory Emergency Response Capability 2009 Baseline Needs Assessment Performance Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, J A

    2009-12-30

    This document was prepared by John A. Sharry, LLNL Fire Marshal and Division Leader for Fire Protection and was reviewed by Sandia/CA Fire Marshal, Martin Gresho. This document is the second of a two-part analysis of Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2009 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2004 BNA, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, fire department training records, and fire department policies and procedures. On October 1, 2007, LLNL contracted with the Alameda County Fire Department to provide emergency response services. The level of service called for in that contract is the same level of service as was provided by the LLNL Fire Department prior to that date. This Compliance Assessment will evaluate fire department services beginning October 1, 2008 as provided by the Alameda County Fire Department.

  12. Urgent Need to Orient Public Health Response to Rapid Nutrition Transition

    Directory of Open Access Journals (Sweden)

    Umesh Kapil

    2012-01-01

    Full Text Available India is currently undergoing a rapid transition on economic, demographic, epidemiologic, nutrition, and sociological fronts. There is evidence of a decline in undernutrition with a simultaneous escalation in overnutrition and associated non-communicable diseases (NCDs. However, the current concern and national policy response for tackling malnutrition in India is still primarily restricted to undernutrition diagnosed on the basis of body size (anthropometry. A complex range of interacting factors have been linked to the rising trend of overnutrition and associated NCDs from a global perspective. The burden of overnutrition and associated morbidities is rapidly escalating to alarming proportions, particularly in urban areas and high socio-economic status groups. The poor are not spared from this transition. It is predicted that a more rapid transition may occur amongst poor populations in future with higher economic development. The need of the hour is to launch an integrated public health response to the dual burden beginning from pregnancy and early life. This will obviously require careful deliberation of the strategy and interventions, and a multi-sectoral approach, especially involving the health, women and child development, nutrition, education, agriculture, food processing, trade, architecture, water supply and sanitation, community and non-governmental organizations.

  13. Culturally responsive middle school science: A case study of needs, demands, and challenges

    Science.gov (United States)

    Woodrow, Kelli Ellen

    2007-12-01

    Culturally responsive programming has been proposed as a remedy for the well-documented disconnect between schools and the ethnically and culturally diverse students who attend them. These programs often focus on creating instructional materials and pedagogical practices that are aligned with the knowledges, perspectives and practices of these students. This study builds on that literature and examines the needs, demands, and challenges of developing a culturally responsive health science program for ethnically and culturally diverse urban middle school students. I approached this problem through a content analysis of the intended curriculum and a microethnography of the enacted curriculum. In my analysis of the intended curriculum, I adapted a science textbook analysis instrument created by the American Association for the Advancement of Science (AAAS) to include criteria related to identified features of culturally responsive education. Using these modified analytic criteria, I found that the pilot drafts of the curricular materials excelled in the areas of engaging students in relevant phenomenon but lacked many of these specifically culturally responsive elements. Recommendations were made to redress these deficiencies. In my analysis of the enacted curriculum, I observed in five eighth grade classrooms where the program was being implemented. I used participant observation, audio and video tape recordings, artifacts, and interviews over a six-month period to investigate teacher/student interactions, the social organization of the classrooms, and students' culturally distinctive knowledge resources---or what is sometimes referred to as their "funds of knowledge." I found that the affective interactions between teachers and students were precursors to any reform, and that students and teachers similarly defined these interactions as "teacher care." In addition, I found that the social organization of the classroom often privileged official content and ways of

  14. Regulatory T Cells Control Immune Responses through Their Non-Redundant Tissue Specific Features

    OpenAIRE

    Lehtimäki, Sari; Lahesmaa, Riitta

    2013-01-01

    Regulatory T cells (Treg) are needed in the control of immune responses and to maintain immune homeostasis. Of this subtype of regulatory lymphocytes, the most potent are Foxp3 expressing CD4+ T cells, which can be roughly divided into two main groups; natural Treg cells (nTreg), developing in the thymus, and induced or adaptive Treg cells (iTreg), developing in the periphery from naïve, conventional T cells. Both nTreg cells and iTreg cells have their own, non-redundant roles in the immune s...

  15. Plant Cell Adaptive Responses to Microgravity

    Science.gov (United States)

    Kordyum, Elizabeth; Kozeko, Liudmyla; Talalaev, Alexandr

    simulated microgravity and temperature elevation have different effects on the small HSP genes belonging to subfamilies with different subcellular localization: cytosol/nucleus - PsHSP17.1-СІІ and PsHSP18.1-СІ, cloroplasts - PsHSP26.2-Cl, endoplasmatic reticulum - PsHSP22.7-ER and mitochondria - PsHSP22.9-M: unlike high temperature, clinorotation does not cause denaturation of cell proteins, that confirms the sHSP chaperone function. Dynamics of investigated gene expression in pea seedlings growing 5 days after seed germination under clinorotation was similar to that in the stationary control. Similar patterns in dynamics of sHSP gene expression in the stationary control and under clinorotation may be one of mechanisms providing plant adaptation to simulated microgravity. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in cell organelle functional load. Thus, next certain changes in the structure and function of plant cells may be considered as adaptive: 1) an increase in the unsaturated fatty acid content in the plasmalemma, 2) rearrangements of organelle ultrastructure and an increase in their functional load, 3) an increase in cortical F-actin under destabilization of tubulin microtubules, 4) the level of gene expression and synthesis of heat shock proteins, 5) alterations of the enzyme and antioxidant system activity. The dynamics of these patterns demonstrated that the adaptation occurs on the principle of self-regulating systems in the limits of physiological norm reaction. The very importance of changed expression of genes involved in different cellular processes, especially HSP genes, in cell adaptation to altered gravity is discussed.

  16. The management of infant developmental needs by community nurses - Part 1: Description of the responsibilities of community nurses with regard to the management of infant developmental needs

    Directory of Open Access Journals (Sweden)

    R. Leech

    2007-09-01

    Full Text Available This article is one of two that describes the responsibilities of community nurses, according to their legal scope of practice, with regard to the management of developmental needs of infants in primary health care clinics in South Africa. A subsequent article describes the development of guidelines for the support of community nurses to address the developmental needs of infants 0 - 2 years. While evidence confirms that developmental surveillance should be incorporated into the ongoing health care of the infant, such services are not consistently provided in health care settings and, if provided, the delivery thereof suffers from significant inadequacies. A case study strategy was used to investigate the phenomenon and content analysis utilised to analyze the data. The Transactional Model of Development was selected to interpret the data obtained in the study. Findings of the study show that infant developmental care is not included to its fullest potential in the health care delivered to infants and their families, thereby indicating that community nurses do not meet the standards of the profession with regard to the management of infant developmental needs. Health service managers need to review their commitment and type of support to community nurses, if infant developmental care, as part of community nurses’ responsibilities, is to be effective and of high quality. Furthermore, community nurses and other health care professionals must recognize the nature and potential of inter-professional collaboration to ensure positive outcomes for infants with developmental delays and disabilities.

  17. The Interplay between Adolescent Needs and Secondary School Structures: Fostering Developmentally Responsive Middle and High School Environments across the Transition

    Science.gov (United States)

    Ellerbrock, Cheryl R.; Kiefer, Sarah M.

    2013-01-01

    Understanding the developmental responsiveness of secondary school environments may be an important factor in supporting students as they make the transition from one school to the next. Students' needs may or may not be met depending on the nature of the fit between their basic and developmental needs and secondary school structures at the…

  18. Occupational safety and health's role in sustainable, responsible nanotechnology: gaps and needs.

    Science.gov (United States)

    Iavicoli, S; Rondinone, B M; Boccuni, F

    2009-06-01

    The newly fledged nanotechnologies offer opportunities for social development, but uncertainties prevail about their impact on human and environmental health. There is still a huge gap between technological progress and research into the health and safety aspects of nanomaterials. This is clear from the quantity of nanoproducts already on the market--more than 600--and the public and private funds dedicated to the development of nanotechnologies, which are almost a hundred times those available for research into their effects on health and safety. Estimates have it that by 2014, nanotechnologies will be widely used in our society and ten million new jobs will be created. Therefore, it becomes essential to plan an integrated approach to specific risk analysis at work. The following gaps and needs come to light: limited information, difficulties in relating nanotechnologies and production of nanomaterials to specific areas of application, efforts required to assess the hazards posed by nanomaterials in realistic exposure conditions, ethical issues about nanotechnology in the workplace likely to arise from today's knowledge about the hazards of nanomaterials and the risks they may pose to workers. An integrated approach to research, cooperation, and communication strategies is essential if we are to direct our efforts toward responsible and sustainable growth of nanotechnologies. PMID:19755456

  19. Epilepsy in India II: Impact, burden, and need for a multisectoral public health response.

    Science.gov (United States)

    Amudhan, Senthil; Gururaj, Gopalkrishna; Satishchandra, Parthasarathy

    2015-01-01

    Epilepsy is a common neurological disorder whose consequences are influenced socially and culturally, especially in India. This review (second of the two part series) was carried out to understand the social impact and economic burden to develop comprehensive program for control and prevention of epilepsy. Epilepsy is known to have adverse effect on education, employment, marriage, and other essential social opportunities. Economic burden associated with epilepsy is very high with treatment and travel costs emerging as an important contributing factor. A vicious cycle between economic burden and poor disease outcome is clear. There is no significant change in the perception, stigma, and discrimination of epilepsy across the country despite improvement in educational and social parameters over the time. The huge treatment gap and poor quality of life is further worsened by the associated comorbidities and conditions. Thus, a multidisciplinary response is needed to address the burden and impact of epilepsy which calls for an integrated and multipronged approach for epilepsy care, prevention, and rehabilitation. Service delivery, capacity building, integration into the existing program, mobilizing public support, and increasing public awareness will be the hallmarks of such an integrated approach in a public health model. PMID:26713005

  20. Epilepsy in India II: Impact, burden, and need for a multisectoral public health response

    Directory of Open Access Journals (Sweden)

    Senthil Amudhan

    2015-01-01

    Full Text Available Epilepsy is a common neurological disorder whose consequences are influenced socially and culturally, especially in India. This review (second of the two part series was carried out to understand the social impact and economic burden to develop comprehensive program for control and prevention of epilepsy. Epilepsy is known to have adverse effect on education, employment, marriage, and other essential social opportunities. Economic burden associated with epilepsy is very high with treatment and travel costs emerging as an important contributing factor. A vicious cycle between economic burden and poor disease outcome is clear. There is no significant change in the perception, stigma, and discrimination of epilepsy across the country despite improvement in educational and social parameters over the time. The huge treatment gap and poor quality of life is further worsened by the associated comorbidities and conditions. Thus, a multidisciplinary response is needed to address the burden and impact of epilepsy which calls for an integrated and multipronged approach for epilepsy care, prevention, and rehabilitation. Service delivery, capacity building, integration into the existing program, mobilizing public support, and increasing public awareness will be the hallmarks of such an integrated approach in a public health model.

  1. Thomas Alva Edison—battery and device innovation in response to application's needs

    Science.gov (United States)

    Salkind, Alvin J.; Israel, Paul

    Thomas Alva Edison, the most prolific inventor in North America, with over 1000 patents, was the descendant of early settlers from the Netherlands to the Hudson Valley region of New York/New Jersey. However, his genealogical trail encompasses many cities, provinces, states, and countries, including Holland, France, Scotland, New Amsterdam, New York, New Jersey, Nova Scotia, Ontario, Ohio, and Michigan. He was motivated to develop and invent in response to perceived needs of commercial devices and was the creator of the concept of an industrial research laboratory. His activities covered a wide-range of chemical, electrical, medical, metallurgical, entertainment, and communication devices and led to the creation of major worldwide industries. However, his expressed underlying concern was the "service it might give others". This presentation reviews commercial developments in comparison with the technologies and motivations of the time and is illustrated by material from the Rutgers University 'Edison Papers Project', Edison's personal notes found in the Edison Battery Factory and preserved by Professor Salkind, and records of The Electrochemical Society.

  2. Natural killer cell mediated cytotoxic responses in the Tasmanian devil.

    Science.gov (United States)

    Brown, Gabriella K; Kreiss, Alexandre; Lyons, A Bruce; Woods, Gregory M

    2011-01-01

    The Tasmanian devil (Sarcophilus harrisii), the world's largest marsupial carnivore, is under threat of extinction following the emergence of an infectious cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils during biting. The disease is consistently fatal and devils succumb without developing a protective immune response. The aim of this study was to determine if Tasmanian devils were capable of forming cytotoxic antitumour responses and develop antibodies against DFTD cells and foreign tumour cells. The two Tasmanian devils immunised with irradiated DFTD cells did not form cytotoxic or humoral responses against DFTD cells, even after multiple immunisations. However, following immunisation with xenogenic K562 cells, devils did produce cytotoxic responses and antibodies against this foreign tumour cell line. The cytotoxicity appeared to occur through the activity of natural killer (NK) cells in an antibody dependent manner. Classical NK cell responses, such as innate killing of DFTD and foreign cancer cells, were not observed. Cells with an NK-like phenotype comprised approximately 4 percent of peripheral blood mononuclear cells. The results of this study suggest that Tasmanian devils have NK cells with functional cytotoxic pathways. Although devil NK cells do not directly recognise DFTD cancer cells, the development of antibody dependent cell-mediated cytotoxicity presents a potential pathway to induce cytotoxic responses against the disease. These findings have positive implications for future DFTD vaccine research. PMID:21957452

  3. The care of Filipino juvenile offenders in residential facilities evaluated using the risk-need-responsivity model.

    Science.gov (United States)

    Spruit, Anouk; Wissink, Inge B; Stams, Geert Jan J M

    2016-01-01

    According to the risk-need-responsivity model of offender, assessment and rehabilitation treatment should target specific factors that are related to re-offending. This study evaluates the residential care of Filipino juvenile offenders using the risk-need-responsivity model. Risk analyses and criminogenic needs assessments (parenting style, aggression, relationships with peers, empathy, and moral reasoning) have been conducted using data of 55 juvenile offenders in four residential facilities. The psychological care has been assessed using a checklist. Statistical analyses showed that juvenile offenders had a high risk of re-offending, high aggression, difficulties in making pro-social friends, and a delayed socio-moral development. The psychological programs in the residential facilities were evaluated to be poor. The availability of the psychological care in the facilities fitted poorly with the characteristics of the juvenile offenders and did not comply with the risk-need-responsivity model. Implications for research and practice are discussed. PMID:27137741

  4. Light-trapping in solar cells by photonic nanostructures. The need for benchmarking and fabrication assessments

    Energy Technology Data Exchange (ETDEWEB)

    Lenzmann, F.O.; Salpakari, J.; Weeber, A.W.; Olson, C.L. [ECN Solar Energy, Petten (Netherlands)

    2013-07-15

    Light-trapping in solar cells by photonic nanostructures, e.g., nano-textured surfaces or metallic and nonmetallic nanoparticles is a research area of great promise. A large multitude of configurations is being explored and there is a rising need for (a set of) assessment elements that help to narrow in on the most viable ones. This paper discusses two examples: benchmark devices and the assessment of fabrication aspects for the nanostructures.

  5. Aging impairs recipient T cell intrinsic and extrinsic factors in response to transplantation.

    Directory of Open Access Journals (Sweden)

    Hua Shen

    Full Text Available BACKGROUND: As increasing numbers of older people are listed for solid organ transplantation, there is an urgent need to better understand how aging modifies alloimmune responses. Here, we investigated whether aging impairs the ability of donor dendritic cells or recipient immunity to prime alloimmune responses to organ transplantation. PRINCIPAL FINDINGS: Using murine experimental models, we found that aging impaired the host environment to expand and activate antigen specific CD8(+ T cells. Additionally, aging impaired the ability of polyclonal T cells to induce acute allograft rejection. However, the alloimmune priming capability of donor dendritic cells was preserved with aging. CONCLUSION: Aging impairs recipient responses, both T cell intrinsic and extrinsic, in response to organ transplantation.

  6. What Response Rates Are Needed to Make Reliable Inferences from Student Evaluations of Teaching?

    Science.gov (United States)

    Zumrawi, Abdel Azim; Bates, Simon P.; Schroeder, Marianne

    2014-01-01

    This paper addresses the determination of statistically desirable response rates in students' surveys, with emphasis on assessing the effect of underlying variability in the student evaluation of teaching (SET). We discuss factors affecting the determination of adequate response rates and highlight challenges caused by non-response and lack…

  7. An Analysis of Valencia Community College's Policy Response to Local Community Agencies' Need for Student Volunteers.

    Science.gov (United States)

    Bennett, Lula M.

    A study was conducted at Valencia Community College (VCC) to evaluate VCC's success in meeting the community's need for volunteers, to determine the needs of student volunteers, and to discover what kinds of students were participating in the student volunteer program. Results of a questionnaire completed by 72 student volunteers indicated that…

  8. Practitioner Response to Parental Need in Email Consultation: How Do They Match? A Content Analysis

    Science.gov (United States)

    Nieuwboer, Christa C.; Fukkink, Ruben G.; Hermanns, Jo M. A.

    2014-01-01

    Background: Single session email consultations in web-based parenting support may be used for a variety of reasons. Parents may be looking for information on developmental needs of children, for suggestions to improve their parenting skills, or for referrals to helpful resources. The way the practitioner meets the needs of parents, choosing a…

  9. Fuel cell-based cogeneration system covering data centers’ energy needs

    International Nuclear Information System (INIS)

    The Information and Communication Technology industry has gone in the recent years through a dramatic expansion, driven by many new online (local and remote) applications and services. Such growth has obviously triggered an equally remarkable growth in energy consumption by data centers, which require huge amounts of power not only for IT devices, but also for power distribution units and for air-conditioning systems needed to cool the IT equipment. This paper is dedicated to the economic and energy performance assessment of a cogeneration system based on a natural gas membrane steam reformer producing a pure hydrogen flow for electric power generation in a polymer electrolyte membrane fuel cell. Heat is recovered from both the reforming unit and the fuel cell in order to supply the needs of an office building located near the data center. In this case, the cooling energy needs of the data center are covered by means of a vapor-compression chiller equipped with a free-cooling unit. Since the fuel cell’s output is direct current rather than alternate current, the possibility of further improving data centers’ energy efficiency adopting DC-powered data center equipment is also discussed. -- Highlights: ► Data centers' energy needs are discussed and possible savings from advanced energy management techniques are estimated. ► The thermal energy requirements of an office building close to the data center are added to the energy scenario. ► Significant energy and cost savings can be obtained by means of free-cooling, high-voltage direct current, and a cogeneration facility. ► The cogeneration system is based on a natural gas membrane reformer and a PEM fuel cell. ► Energy flows in the membrane reformer are analyzed and an optimal value of steam-to-carbon ratio is found in order to minimize the required membrane area.

  10. Sensor Needs and Requirements for Fuel Cells and CIDI/SIDI Engines

    Energy Technology Data Exchange (ETDEWEB)

    Glass, R.S.

    2000-03-01

    To reduce U.S. dependence on imported oil, improve urban air quality, and decrease greenhouse gas emissions, the Department of Energy (DOE) is developing advanced vehicle technologies and fuels. Enabling technologies for fuel cell power systems and direct-injection engines are being developed by DOE through the Partnership for a New Generation of Vehicles (PNGV), a government-industry collaboration to produce vehicles having up to three times the fuel economy of conventional mid-size automobiles. Sensors have been identified as a research and development need for both fuel cell and direct-injection systems, because current sensor technologies do not adequately meet requirements. Sensors are needed for emission control, for passenger safety and comfort, to increase system lifetime, and for system performance enhancement through feedback and control. These proceedings document the results of a workshop to define sensor requirements for proton exchange membrane (PEM) fuel cell systems and direct-injection engines for automotive applications. The recommendations from this workshop will be incorporated into the multi-year R&D plan of the DOE Office of Advanced Automotive Technologies. The objectives of the workshop were to: define the requirements for sensors; establish R&D priorities; identify the technical targets and technical barriers; and facilitate collaborations among participants. The recommendations from this workshop will be incorporated into the multi-year R&D plan of the DOE Office of Advanced Automotive Technologies.

  11. Understanding responses to political conflict: interactive effects of the need for closure and salient conflict schemas.

    OpenAIRE

    Golec de Zavala, Agnieszka; Federico, Christopher

    2004-01-01

    Two studies examined the relationship between the need for cognitive closure and preferences for conflict-resolution strategies in two different samples of elite political actors. While research suggests that the high need for closure should be associated with competitiveness, we argue that this relationship should be strongest among political actors with a hostile “conflict schema,” or representation of what a conflict is and how it should be dealt with. We provide evidence for this hypothe...

  12. A NEW VISION IN SALES: SATISFYING CUSTOMER NEEDS AND SOCIAL RESPONSIBILITY

    OpenAIRE

    Ion Stancu

    2015-01-01

    The new vision in sales requires, among other things, changing the salespeople's position towards the potential client by applying a philosophy that involves taking into consideration the people they come into contact with and providing solutions to address their needs in a disinterested manner, without having to pretend reciprocity. All this must be based on the concept of total sales utility, solutions to solve clients' immediate needs: the urgent ones, those who are direc...

  13. Teachers’ Pastoral Role in Response to the Needs of Orphaned Learners

    Directory of Open Access Journals (Sweden)

    Teresa Auma Ogina

    2010-12-01

    Full Text Available This article discusses a study that explored the way teachers perceive and describe their roles in responding to the needs of orphaned learners. The participants in the study comprised three secondary and two primary school teachers. The data on the teachers’ experiences were collected through semi-structured interviews, and the findings revealed that, although some of the teachers attempted to fulfill some of the orphaned learners’ needs, most were unable to cope with the combined roles of teaching and learning and care giving. The study identified a lack of material, social, and emotional support for grieving learners. The findings indicate that there is a need for teacher development in terms of preparing teachers to provide pastoral care for orphaned learners. For the teachers’ efforts to be more fruitful, there is also an urgent need for supportive school leadership. In addition, the study highlights the need for counsellors and social workers to be appointed to work in collaboration with the teachers in providing for the needs of the learners.

  14. Fluoride inhibits the response of bone cells to mechanical loading

    NARCIS (Netherlands)

    H.M.E. Willems; E.G.H.M. van den Heuvel; S. Castelein; J. Keverling Buisman; A.L.J.J. Bronckers; A.D. Bakker; J. Klein-Nulend

    2011-01-01

    The response of bone cells to mechanical loading is mediated by the cytoskeleton. Since the bone anabolic agent fluoride disrupts the cytoskeleton, we investigated whether fluoride affects the response of bone cells to mechanical loading, and whether this is cytoskeleton mediated. The mechano-respon

  15. B-Cell Response during Protozoan Parasite Infections

    OpenAIRE

    Amezcua Vesely, María C; Bermejo, Daniela A.; Montes, Carolina L.; Acosta-Rodríguez, Eva V.; Adriana Gruppi

    2012-01-01

    In this review, we discuss how protozoan parasites alter immature and mature B cell compartment. B1 and marginal zone (MZ) B cells, considered innate like B cells, are activated during protozoan parasite infections, and they generate short lived plasma cells providing a prompt antibody source. In addition, protozoan infections induce massive B cell response with polyclonal activation that leads to hypergammaglobulnemia with serum antibodies specific for the parasites and self and/or non relat...

  16. Reticence vs. Responsibility: Why Climate Scientists Sometimes Need to Think Like Emergency Room Doctors

    Science.gov (United States)

    Peacock, K.

    2013-12-01

    Hansen (2007), Brysse et al (2012), and Oreskes (2013) have drawn attention to the too-frequent reticence of climate scientists---the unwillingness to err on the side of predicting extreme outcomes or recommend strong action to prevent those outcomes. In Hansen's words, this may hinder 'communication with the public about dangers of global warming' and thereby lessen the chance of effective responses to this urgent threat. Scientists may be reticent about the kinds of extreme outcomes that could occur (ice sheet collapse, oceanic anoxia, killer heat waves, etc.), the probabilities of such outcomes, or the options for preventing or mitigating such outcomes. I will review the reasons, some understandable and some regrettable, for such reticence. (The latter could include the 'seepage' into professional discourse of the often-poisonous atmosphere of climate science denialism; Lewandowsky 2013.) My major aim will be to argue that scientists need a clearly defined ethical framework that coheres with the scientific ethos, and I will suggest that the place to look for such an ethical framework is in the realm of professional ethics. I will review key features of the learned professions such as medicine and engineering, where practitioners (such as emergency room physicians) are necessarily attuned to the imperative of making life-or-death decisions and recommendations in real time, under conditions of uncertainty. I hardly mean to suggest that pure science does not have a professional ethos of its own, but research science as such is not a legally constituted profession (like medicine) and it is focussed on the disinterested search for reliable knowledge above all other goals. Medicine and engineering depend upon and contribute to scientific knowledge but they are aimed at practical ends as well---the welfare of patients or protection of the public as a whole. Also, it is in the nature of engineering and other learned professions that (like pure science) they often

  17. B Cells Promote Th1- Skewed NKT Cell Response by CD1d-TCR Interaction

    OpenAIRE

    Shin, Jung Hoon; Park, Se-Ho

    2013-01-01

    CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although α-galactosylceramide (α-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-γ by NKT cells, concomitant with a d...

  18. Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies

    Directory of Open Access Journals (Sweden)

    Rishi Raj Rikhi

    2016-03-01

    Full Text Available Limited research exists regarding the most aggressive forms of hepatoblastoma. Cell lines of the rare subtypes of hepatoblastoma with poor prognosis are not only difficult to attain, but are challenging to characterize histologically. A community approach to educating parents and families of the need for donated tissue is necessary for scientists to have access to resources for murine models and drug discovery. Herein we describe the currently available resources, the today’s existing gaps in research, and the path to move forward for uniform cure of hepatoblastoma.

  19. Status and research needs for prediction of seismic response in liquid containers

    International Nuclear Information System (INIS)

    Current methods for seismic design of liquid storage tanks and steam suppression pools are reviewed to establish requirements for future research. The use of a transfer function and response spectrum method is emphasized for prediction of slosh response and impulsive loading. The method is also applicable to operating transient loads that occur in nuclear power plants. Direct applicability is noted for much of the available design data that had previously been developed for aerospace launch vehicles. (orig.)

  20. CD83 Modulates B Cell Activation and Germinal Center Responses.

    Science.gov (United States)

    Krzyzak, Lena; Seitz, Christine; Urbat, Anne; Hutzler, Stefan; Ostalecki, Christian; Gläsner, Joachim; Hiergeist, Andreas; Gessner, André; Winkler, Thomas H; Steinkasserer, Alexander; Nitschke, Lars

    2016-05-01

    CD83 is a maturation marker for dendritic cells. In the B cell lineage, CD83 is expressed especially on activated B cells and on light zone B cells during the germinal center (GC) reaction. The function of CD83 during GC responses is unclear. CD83(-/-) mice have a strong reduction of CD4(+) T cells, which makes it difficult to analyze a functional role of CD83 on B cells during GC responses. Therefore, in the present study we generated a B cell-specific CD83 conditional knockout (CD83 B-cKO) model. CD83 B-cKO B cells show defective upregulation of MHC class II and CD86 expression and impaired proliferation after different stimuli. Analyses of GC responses after immunization with various Ags revealed a characteristic shift in dark zone and light zone B cell numbers, with an increase of B cells in the dark zone of CD83 B-cKO mice. This effect was not accompanied by alterations in the level of IgG immune responses or by major differences in affinity maturation. However, an enhanced IgE response was observed in CD83 B-cKO mice. Additionally, we observed a strong competitive disadvantage of CD83-cKO B cells in GC responses in mixed bone marrow chimeras. Furthermore, infection of mice with Borrelia burgdorferi revealed a defect in bacterial clearance of CD83 B-cKO mice with a shift toward a Th2 response, indicated by a strong increase in IgE titers. Taken together, our results show that CD83 is important for B cell activation and modulates GC composition and IgE Ab responses in vivo. PMID:26983787

  1. Is Singapore's School Geography Becoming Too Responsive to the Changing Needs of Society?

    Science.gov (United States)

    Chang, Chew-Hung

    2014-01-01

    In understanding the divergences and commonalities in the representations of geography across different national settings, the case of Singapore is examined through the notion of politicisation of school curricula to meet the needs of "significant power groups". In particular, the development of school geography in Singapore and its…

  2. Fathers of Children with Autism: Perceived Roles, Responsibilities, and Support Needs

    Science.gov (United States)

    Meadan, Hedda; Stoner, Julia B.; Angell, Maureen E.

    2015-01-01

    Emphasis on families' involvement in the education of children with disabilities is evident in the Individuals with Disabilities Education Act (IDEA) and in published best practices. However, most of the research related to families of children with disabilities has focused on mothers' experiences, involvement, and needs. There is limited…

  3. All Work and No Play? Understanding the Needs of Children with Caring Responsibilities

    Science.gov (United States)

    Aldridge, Jo

    2008-01-01

    This article draws on research with children who provide care for parents with serious mental health problems and signals ongoing research that uses photographic participation methods with these groups of vulnerable children. The intention of this article is to highlight the need to move away from popular and simplistic representations of children…

  4. The Foreign Language Needs of British Business: A CTC Response. CTC Trust Publication Number 3.

    Science.gov (United States)

    Hagen, Stephen

    The need for second language training in the United Kingdom for trade and industry is examined, and the role of City Technology Colleges (CTCs) in providing such training is discussed. It is argued that reliance on English is no longer sufficient for trade in the world market, since the most important markets for British goods and services are…

  5. Safety features designed to eliminate the need for off-site emergency response

    International Nuclear Information System (INIS)

    Conclusions: • DiD failure mainly because of design flaws and human factors. • For SFR, large radioactive releases could be eliminated by reduction of human errors, control of the coolant system and containment conditions. • Codes and standards for DECs need to be updated

  6. A Survey of Teachers of Students with Visual Impairments: Responsibilities, Satisfactions, and Needs

    Science.gov (United States)

    Griffin-Shirley, Nora; Koenig, Alan K.; Layton, Carol A.; Davidson, Roseanna C.; Siew, Lai Keun; Edmonds, Amy R.; Robinson, Margaret C.

    2004-01-01

    For all children with visual impairments to receive services from qualified teachers is important. The roles of teachers of students with visual impairments change, influenced by such factors as the changing demographics of children with visual impairments, the types of services needed by the students on their caseloads, caseload sizes and work…

  7. Most oxidative stress response in water samples comes from unknown chemicals: the need for effect-based water quality trigger values.

    Science.gov (United States)

    Escher, Beate I; van Daele, Charlotte; Dutt, Mriga; Tang, Janet Y M; Altenburger, Rolf

    2013-07-01

    The induction of adaptive stress response pathways is an early and sensitive indicator of the presence of chemical and non-chemical stressors in cells. An important stress response is the Nrf-2 mediated oxidative stress response pathway where electrophilic chemicals or chemicals that cause the formation of reactive oxygen species initiate the production of antioxidants and metabolic detoxification enzymes. The AREc32 cell line is sensitive to chemicals inducing oxidative stress and has been previously applied for water quality monitoring of organic micropollutants and disinfection byproducts. Here we propose an algorithm for the derivation of effect-based water quality trigger values for this end point that is based on the combined effects of mixtures of regulated chemicals. Mixture experiments agreed with predictions by the mixture toxicity concept of concentration addition. The responses in the AREc32 and the concentrations of 269 individual chemicals were quantified in nine environmental samples, ranging from treated effluent, recycled water, stormwater to drinking water. The effects of the detected chemicals could explain less than 0.1% of the observed induction of the oxidative stress response in the sample, affirming the need to use effect-based trigger values that account for all chemicals present. PMID:23432033

  8. Stem Cells Matter in Response to Fasting

    Directory of Open Access Journals (Sweden)

    Badi Sri Sailaja

    2015-12-01

    Full Text Available The molecular processes underlying intestinal adaptation to fasting and re-feeding remain largely uncharacterized. In this issue of Cell Reports, Richmond et al. report that dormant intestinal stem cells are regulated by PTEN and nutritional status.

  9. Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells.

    Science.gov (United States)

    Jyotaki, Masafumi; Sanematsu, Keisuke; Shigemura, Noriatsu; Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-09-22

    Leptin is an important hormone that regulates food intake and energy homeostasis by acting on central and peripheral targets. In the gustatory system, leptin is known to selectively suppress sweet responses by inhibiting the activation of sweet sensitive taste cells. Sweet taste receptor (T1R2+T1R3) is also expressed in gut enteroendocrine cells and contributes to nutrient sensing, hormone release and glucose absorption. Because of the similarities in expression patterns between enteroendocrine and taste receptor cells, we hypothesized that they may also share similar mechanisms used to modify/regulate the sweet responsiveness of these cells by leptin. Here, we used mouse enteroendocrine cell line STC-1 and examined potential effect of leptin on Ca(2+) responses of STC-1 cells to various taste compounds. Ca(2+) responses to sweet compounds in STC-1 cells were suppressed by a rodent T1R3 inhibitor gurmarin, suggesting the involvement of T1R3-dependent receptors in detection of sweet compounds. Responses to sweet substances were suppressed by ⩾1ng/ml leptin without affecting responses to bitter, umami and salty compounds. This effect was inhibited by a leptin antagonist (mutant L39A/D40A/F41A) and by ATP gated K(+) (KATP) channel closer glibenclamide, suggesting that leptin affects sweet taste responses of enteroendocrine cells via activation of leptin receptor and KATP channel expressed in these cells. Moreover, leptin selectively inhibited sweet-induced but not bitter-induced glucagon-like peptide-1 (GLP-1) secretion from STC-1 cells. These results suggest that leptin modulates sweet taste responses of enteroendocrine cells to regulate nutrient sensing, hormone release and glucose absorption in the gut. PMID:27353597

  10. T cell immune responses in psoriasis.

    Directory of Open Access Journals (Sweden)

    Zohre Jadali

    2014-08-01

    Full Text Available A central role for T cells and their cytokines in the pathogenesis of psoriasis has been proposed; however, there are controversies over the details of this issue. The goal of this study is to summarise currently available data on the importance of T cells in psoriasis pathogenesis. A systematic review of the English medical literature was conducted by searching PubMed, Embase, ISI Web of Knowledge, and Iranian databases including Iranmedex, and SID for studies on associations between the involvement of T cell subsets and psoriasis. The results of the present study indicate that alterations in the number and function of different subsets of T-cells are associated with psoriasis. It appears that studies on T cell subsets contributed to understanding the immunopathogenesis of psoriasis. In addition, it may have provided novel therapeutic opportunities in ameliorating immunopathologies.

  11. Investigation of the response of low-dose irradiated cells. Pt. 2. Radio-adaptive response of human embryonic cells is related to cell-to-cell communication

    International Nuclear Information System (INIS)

    To clarify the radio-adaptive response of normal cells to low-dose radiation, we irradiated human embryonic cells and HeLa cells with low-dose X-ray and examined the changes in sensitivity to subsequent high-dose X-irradiation. The results obtained were as follows; (1) When HE cells were irradiated by a high-dose of 200 cGy, the growth ratio of the living cells five days after the irradiation decreased to 37% of that of the cells which received no X-irradiation. When the cells received a preliminary irradiation of 10 to 20 cGy four hours before the irradiation of 200 cGy, the relative growth ratios increased significantly to 45-53%. (2) This preliminary irradiation effect was not observed in HeLa cells, being cancer cells. (3) When the HE cells suspended in a Ca2+ iron-free medium or TPA added medium while receiving the preliminary irradiation of 13 cGy, the effect of the preliminary irradiation in increasing the relative growth ratio of living cells was not observed. (4) This indicates that normal cells shows an adaptive response to low-dose radiation and become more radioresistant. This phenomenon is considered to involve cell-to-cell communication maintained in normal cells and intracellular signal transduction in which Ca2+ ion plays a role. (author)

  12. Suppression of T cell responses in the tumor microenvironment.

    Science.gov (United States)

    Frey, Alan B

    2015-12-16

    The immune system recognizes protein antigens expressed in transformed cells evidenced by accumulation of antigen-specific T cells in tumor and tumor draining lymph nodes. However, despite demonstrable immune response, cancers grow progressively suggesting that priming of antitumor immunity is insufficiently vigorous or that antitumor immunity is suppressed, or both. Compared to virus infection, antitumor T cells are low abundance that likely contributes to tumor escape and enhancement of priming is a long-sought goal of experimental vaccination therapy. Furthermore, patient treatment with antigen-specific T cells can in some cases overcome deficient priming and cause tumor regression supporting the notion that low numbers of T cells permits tumor outgrowth. However, tumor-induced suppression of antitumor immune response is now recognized as a significant factor contributing to cancer growth and reversal of the inhibitory influences within the tumor microenvironment is a major research objective. Multiple cell types and factors can inhibit T cell functions in tumors and may be grouped in two general classes: T cell intrinsic and T cell extrinsic. T cell intrinsic factors are exemplified by T cell expression of cell surface inhibitory signaling receptors that, after contact with cells expressing a cognate ligand, inactivate proximal T Cell Receptor-mediated signal transduction therein rendering T cells dysfunctional. T cell extrinsic factors are more diverse in nature and are produced by tumors and various non-tumor cells in the tumor microenvironment. These include proteins secreted by tumor or stromal cells, highly reactive soluble oxygen and nitrogen species, cytokines, chemokines, gangliosides, and toxic metabolites. These factors may restrict T cell entrance into the tumor parenchyma, cause inactivation of effector phase T cell functions, or induce T cell apoptosis ultimately causing diminished cancer elimination. Here, we review the contributions of inhibitory

  13. Response to Intervention (RTI): What Teachers of Reading Need to Know

    Science.gov (United States)

    Mesmer, Eric M.; Mesmer, Heidi Anne E.

    2008-01-01

    Since the reauthorization of the Individuals With Disabilities Education Act (2004), the use of Response to Intervention (RTI) in the identification of students suspected of having learning disabilities has been legitimized. Several professional organizations, including the International Reading Association (IRA), have recognized the importance of…

  14. Fidelity of Implementation Framework: A Critical Need for Response to Intervention Models

    Science.gov (United States)

    Keller-Margulis, Milena A.

    2012-01-01

    Response to Intervention (RtI) has gained increased attention with the reauthorization of the Individuals with Disabilities Education Improvement Act. Since RtI was introduced at the policy level as a mechanism for use in the learning disability identification process, much of the implementation work has focused on this application. School-based…

  15. Special Education Administrators' Response to the Educational Needs of Foster Care Youth: Collaborative or Disjointed?

    Science.gov (United States)

    Palladino, John; Haar, Jean

    2011-01-01

    Although the literature discusses the deleterious educational outcomes that foster care students endure, little attention has focused on school personnel's responses to the phenomenon. Despite the documented relationship between foster care and special education, a missing contribution is the voice of special education administrators. In turn, the…

  16. Why do we need international standards on responsible research publication for authors and editors?

    Directory of Open Access Journals (Sweden)

    Elizabeth Wager

    2013-12-01

    Full Text Available Delivering the best possible healthcare requires a reliable evidence-base of research publications. Both authors and editors have responsibilities when publishing research yet it can be hard to find guidance on these. Most journal instructions concentrate on style and formatting but give little or no information about research and publication ethics.

  17. Rearing Adolescents in Contemporary Society: A Conceptual Framework for Understanding the Responsibilities and Needs of Parents.

    Science.gov (United States)

    Small, Stephen A.; Eastman, Gay

    1991-01-01

    Examines parental responsibilities of rearing adolescent children as well as the factors that can support or undermine a parent's ability to perform them. Integrates current research and theory on child rearing, adolescent and adult development, and parent adolescent relations to present a conceptual framework for parenting adolescents. Discusses…

  18. Aligning Cultural Responsiveness in Evaluation and Evaluation Capacity Building: A Needs Assessment with Family Support Programs

    OpenAIRE

    Cook, Natalie Ebony

    2016-01-01

    Family support programs serve vulnerable families by providing various forms of support, such as education, health services, financial assistance, and referrals to community resources. A major feature of evaluation involves assessing program effectiveness and learning from evaluation findings (Mertens and Wilson, 2012). Collaboration and cultural responsiveness are important topics in evaluation which remain largely distinct in the literature. However, evaluation capacity building provides a...

  19. Characterization of Virus-Responsive Plasmacytoid Dendritic Cells in the Rhesus Macaque

    OpenAIRE

    Chung, Eugene; Amrute, Sheela B.; Abel, Kristina; Gupta, Gunjan; Wang, Yichuan; Miller, Christopher J.; Fitzgerald-Bocarsly, Patricia

    2005-01-01

    Plasmacytoid dendritic cells (PDC) are potent producers of alpha interferon (IFN-α) in response to enveloped viruses and provide a critical link between the innate and adaptive immune responses. Although the loss of peripheral blood PDC function and numbers has been linked to human immunodeficiency virus (HIV) progression in humans, a suitable animal model is needed to study the effects of immunodeficiency virus infection on PDC function. The rhesus macaque SIV model closely mimics human HIV ...

  20. Responses of primate spinomesencephalic tract cells to intradermal capsaicin.

    Science.gov (United States)

    Dougherty, P M; Schwartz, A; Lenz, F A

    1999-01-01

    The responses of 32 spinomesencephalic tract cells to intradermal capsaicin were examined in anesthetized monkeys. Wide dynamic range (n = 20) and nociceptive specific (n = 6) cells showed two types of excitatory responses to intradermal injection of capsaicin. The first excitatory response shown by the majority of wide dynamic range (n = 13) and nociceptive specific (n = 4) cells was consistent with their sensitization by capsaicin. The cells showed an acute and prolonged increase in ongoing activity with capsaicin injection. Responses to mechanical stimuli were substantially increased after capsaicin and an expansion of receptive field was often observed. The responses of the same cells to excitatory amino acid agonists applied locally by iontophoresis also increased. All cells showing sensitization were antidromically activated from periaqueductal gray regions dorsal to the sulcus limitans. Electrical stimulation at these sites did not affect the ongoing or evoked discharges of these cells. The second excitatory response of wide dynamic range (n = 5) and nociceptive specific (n = 1) cells was a novel pattern not consistent with sensitization. These cells nevertheless showed an acute and prolonged increase in background activity after capsaicin injection. Yet, there was no change or a decrease in responses to cutaneous stimuli, no evidence for change in receptive field size and no increase in responses to locally released excitatory amino acids. These cells projected to regions in the periaqueductal gray ventral to the sulcus limitans. Electrical stimulation at these sites produced a decrease in spontaneous activity of the same cell. Low threshold mesencephalic-projecting neurons (n = 6) showed a single inhibitory pattern (n = 4) of responses to capsaicin. The injection produced an acute decrease in spontaneous activity that was sustained for at least 30 min after injection. The responses to cutaneous stimuli and to excitatory amino acids were also substantially

  1. Children With Special Health Care Needs: Acknowledging the Dilemma of Difference in Policy Responses to Obesity

    OpenAIRE

    Minihan, Paula M.; Must, Aviva; Anderson, Betsy; Popper, Barbara; Dworetzky, Beth

    2011-01-01

    Children with special health care needs (SHCN) account for part of the increasing prevalence of childhood obesity in the general population and can face an elevated risk for obesity. The federal government, in partnership with states, has assumed the role of steward for this vulnerable population and supports a network of services designed to promote their health through increased access to quality health services. Addressing obesity-related health risks among children with SHCN requires poli...

  2. A Comprehensive Medical Education Program Response to Rural Primary Care Needs

    OpenAIRE

    Glasser, Michael; Hunsaker, Matthew; Sweet, Kimberly; MacDowell, Martin; Meurer, Mark

    2008-01-01

    This article presents the characteristics and results of the Rural Medical Education (RMED) Program which addresses medical workforce needs focused on reducing rural health disparities. The program is comprehensive in implementing a system of recruitment of candidates from rural backgrounds, offering a rural-focused curriculum, and instituting evaluative components to track outcomes. Distinctive program features include a Recruitment and Retention Committee of rural community members; special...

  3. Cellular automaton model of cell response to targeted radiation

    International Nuclear Information System (INIS)

    It has been shown that the response of cells to low doses of radiation is not linear and cannot be accurately extrapolated from the high dose response. To investigate possible mechanisms involved in the behaviour of cells under very low doses of radiation, a cellular automaton (CA) model was created. The diffusion and consumption of glucose in the culture dish were computed in parallel to the growth of cells. A new model for calculating survival probability was introduced; the communication between targeted and non-targeted cells was also included. Early results on the response of non-confluent cells to targeted irradiation showed the capability of the model to take account for the non-linear response in the low-dose domain

  4. In vitro mesenchymal stem cell response to a CO2 laser modified polymeric material.

    Science.gov (United States)

    Waugh, D G; Hussain, I; Lawrence, J; Smith, G C; Cosgrove, D; Toccaceli, C

    2016-10-01

    With an ageing world population it is becoming significantly apparent that there is a need to produce implants and platforms to manipulate stem cell growth on a pharmaceutical scale. This is needed to meet the socio-economic demands of many countries worldwide. This paper details one of the first ever studies in to the manipulation of stem cell growth on CO2 laser surface treated nylon 6,6 highlighting its potential as an inexpensive platform to manipulate stem cell growth on a pharmaceutical scale. Through CO2 laser surface treatment discrete changes to the surfaces were made. That is, the surface roughness of the nylon 6,6 was increased by up to 4.3μm, the contact angle was modulated by up to 5° and the surface oxygen content increased by up to 1atom %. Following mesenchymal stem cell growth on the laser treated samples, it was identified that CO2 laser surface treatment gave rise to an enhanced response with an increase in viable cell count of up to 60,000cells/ml when compared to the as-received sample. The effect of surface parameters modified by the CO2 laser surface treatment on the mesenchymal stem cell response is also discussed along with potential trends that could be identified to govern the mesenchymal stem cell response. PMID:27287173

  5. Who Needs a Fracking Education? The Educational Response to Low-Skill Biased Technological Change

    OpenAIRE

    Cascio, Elizabeth U.; Ayushi Narayan

    2015-01-01

    Over the past decade, a technological breakthrough – hydraulic fracturing or “fracking” – has fueled a boom in oil and natural gas extraction by reaching shale reserves inaccessible through conventional technologies. We explore the educational response to fracking, taking advantage of the timing of its widespread introduction and the spatial variation in shale oil and gas reserves. We show that local labor demand shocks from fracking have been biased toward low-skilled labor and males, reduci...

  6. Inhibition of host cell translation elongation by Legionella pneumophila blocks the host cell unfolded protein response

    Science.gov (United States)

    Hempstead, Andrew D.; Isberg, Ralph R.

    2015-01-01

    Cells of the innate immune system recognize bacterial pathogens by detecting common microbial patterns as well as pathogen-specific activities. One system that responds to these stimuli is the IRE1 branch of the unfolded protein response (UPR), a sensor of endoplasmic reticulum (ER) stress. Activation of IRE1, in the context of Toll-like receptor (TLR) signaling, induces strong proinflammatory cytokine induction. We show here that Legionella pneumophila, an intravacuolar pathogen that replicates in an ER-associated compartment, blocks activation of the IRE1 pathway despite presenting pathogen products that stimulate this response. L. pneumophila TLR ligands induced the splicing of mRNA encoding XBP1s, the main target of IRE1 activity. L. pneumophila was able to inhibit both chemical and bacterial induction of XBP1 splicing via bacterial translocated proteins that interfere with host protein translation. A strain lacking five translocated translation elongation inhibitors was unable to block XBP1 splicing, but this could be rescued by expression of a single such inhibitor, consistent with limitation of the response by translation elongation inhibitors. Chemical inhibition of translation elongation blocked pattern recognition receptor-mediated XBP1 splicing, mimicking the effects of the bacterial translation inhibitors. In contrast, host cell-promoted inhibition of translation initiation in response to the pathogen was ineffective in blocking XBP1 splicing, demonstrating the need for the elongation inhibitors for protection from the UPR. The inhibition of host translation elongation may be a common strategy used by pathogens to limit the innate immune response by interfering with signaling via the UPR. PMID:26598709

  7. The radiation response of cells recovering after chronic hypoxia

    International Nuclear Information System (INIS)

    Experiments were performed to study the influence of hypoxic pretreatment on the radiation response of A431 human squamous carcinoma cells. Reaeration for 10 min after chronic hypoxia (greater than 2 h) was found to enhance the radiosensitivity of A431 cells, and the maximal effect was seen for those cells reaerated after 12 h of hypoxia. The radiosensitivity enhancement for reaerated cells after 12 h of hypoxia was maximized by 5 min after the return to aerobic conditions and reached the control level by 12 h of reaeration. This enhanced radiosensitive state was characterized by a reduced shoulder region and increased slope of the radiation dose-response curve for cells in both the exponential and plateau phases of growth. There was a slight increase in the number of G1 and decrease in the number of S and G2 + M cells for both exponential- and plateau-phase cultures following 12 h hypoxic treatment. Although growth inhibition induced by 12 h of hypoxia was seen for cells in the exponential phase, there was no cell number change in the plateau-phase culture after hypoxia. Plating efficiency (PE) of cells in both growth phases was reduced by 30% after hypoxia. Furthermore, in the exponential-phase culture, the extent of reduction in PE after hypoxia was similar among cells in different phases of the cell cycle. Although S-phase cells in exponentially growing cultures were relatively more resistant to radiation than G1 and G2 + M cells, the cell age-response pattern was the same whether the cells had been aerobic or hypoxic before reaeration and irradiation. Furthermore, the enhancement ratio associated with reaeration after 12 h of hypoxia for these three subpopulations of cells was 1.3. Our results indicate that the increase in radiosensitivity due to reaeration after chronic hypoxia is unlikely to be related to the changes of cell cycle stage and growth phase during hypoxic treatment

  8. Epidermal stem cells response to radiative genotoxic stress

    International Nuclear Information System (INIS)

    Human skin is the first organ exposed to various environmental stresses, which requires the development by skin stem cells of specific mechanisms to protect themselves and to ensure tissue homeostasis. As stem cells are responsible for the maintenance of epidermis during individual lifetime, the preservation of genomic integrity in these cells is essential. My PhD aimed at exploring the mechanisms set up by epidermal stem cells in order to protect themselves from two genotoxic stresses, ionizing radiation (Gamma Rays) and ultraviolet radiation (UVB). To begin my PhD, I have taken part of the demonstration of protective mechanisms used by keratinocyte stem cells after ionizing radiation. It has been shown that these cells are able to rapidly repair most types of radiation-induced DNA damage. Furthermore, we demonstrated that this repair is activated by the fibroblast growth factor 2 (FGF2). In order to know if this protective mechanism is also operating in cutaneous carcinoma stem cells, we investigated the response to gamma Rays of carcinoma stem cells isolated from a human carcinoma cell line. As in normal keratinocyte stem cells, we demonstrated that cancer stem cells could rapidly repair radio-induced DNA damage. Furthermore, fibroblast growth factor 2 also mediates this repair, notably thanks to its nuclear isoforms. The second project of my PhD was to study human epidermal stem cells and progenitors responses to UVB radiation. Once cytometry and irradiation conditions were set up, the toxicity of UVB radiation has been evaluate in the primary cell model. We then characterized UVB photons effects on cell viability, proliferation and repair of DNA damage. This study allowed us to bring out that responses of stem cells and their progeny to UVB are different, notably at the level of part of their repair activity of DNA damage. Moreover, progenitors and stem cells transcriptomic responses after UVB irradiation have been study in order to analyze the global

  9. Innate response activator B cells: origins and functions.

    Science.gov (United States)

    Chousterman, Benjamin G; Swirski, Filip K

    2015-10-01

    Innate response activator (IRA) B cells are a subset of B-1a derived B cells that produce the growth factors granulocyte macrophage colony stimulating factor and IL-3. In mouse models of sepsis and pneumonia, B-1a B cells residing in serosal sites recognize bacteria, migrate to the spleen or lung, and differentiate to IRA B cells that then contribute to the host response by amplifying inflammation and producing polyreactive IgM. In atherosclerosis, IRA B cells accumulate in the spleen, where they promote extramedullary hematopoiesis and activate classical dendritic cells. In this review, we focus on the ontogeny and function of IRA B cells in acute and chronic inflammation. PMID:25957266

  10. Response of T cells in vivo Induced by Repeated Superantigen Treatments at Different Time Intervals

    Institute of Scientific and Technical Information of China (English)

    Yang HUANG; Yanfang SUI; Xiumin ZHANG; Shaoyan SI; Wei GE; Peizhen HU; Xia LI; Bin MA

    2007-01-01

    We have investigated the response of T cells to staphylococcal enterotoxin A (SEA) injections in vivo. We found that a single injection of SEA with an optimal dose of 10 μg increased the expression of both CD4 and CD8 significantly. There was expansion of SEA-reactive T cells in vivo after SEA re-injection and the time interval between injections strongly influenced the responsiveness of CD4+ and CD8+ T cells.Anergy of T cells was observed after three SEA treatments. The time interval between injections mainly affected the unresponsiveness of CD4+ T cells, not CD8+ T cells. Marked deletion followed by anergy of CD4+ T cells was induced at short intervals, and anergy without obvious deletion of CD4+ T cells was induced at long intervals. We also found that the anergic state was reversible in vivo. Repeated SEA stimulation led to down-regulation of interleukin (IL)-2, and high levels of IL-10. This study showed that both CD4+ and CD8+ SEA-primed T cells were responsive to SEA rechallenge in vivo, and a third injection was needed to induce the anergy of T cells.

  11. Hematopoietic Stem Cell Transplantation: Need for Research & Potential Applications. It’s status in India

    OpenAIRE

    Banavali, Shripad D

    2009-01-01

    Stem cells are undifferentiated cells that through replications have the capabilities of both self-renewal and differentiation into mature specialized cells. Broadly, there are two types of stem cells, embryonic stem cells and adult stem cells. Embryonic stem cell biology has been associated with ethical controversy and also their growth is difficult to control. Adult stem cells are located in tissues throughout the body and function as a reservoir to replace damaged or aging cells. Embryonic...

  12. Pacer cell response to periodic Zeitgebers

    Science.gov (United States)

    Beersma, D. G. M.; Broer, H. W.; Efstathiou, K.; Gargar, K. A.; Hoveijn, I.

    2011-09-01

    Almost all organisms show some kind of time periodicity in their behavior. In mammals, the neurons of the suprachiasmatic nucleus form a biological clock regulating the activity-inactivity cycle of the animal. The main question is how this clock is able to entrain to the natural 24 h light-dark cycle by which it is stimulated. Such a system is usually modeled as a collection of mutually coupled two-state (active-inactive) phase oscillators with an external stimulus (Zeitgeber). In this article however, we investigate the entrainment of a single pacer cell to the ensemble of other pacer cells. Moreover the stimulus of the ensemble is taken to be periodic. The pacer cell interacts with its environment by phase delay at the end of its activity interval and phase advance at the end of its inactivity interval. We develop a mathematical model for this system, naturally leading to a circle map depending on parameters like the intrinsic period and phase delay and advance. The existence of resonance tongues in a circle map shows that an individual pacer cell is able to synchronize with the ensemble. We furthermore show how the parameters in the model can be related to biological observable quantities. Finally we give several directions of further research.

  13. Invariant NKT Cell Response to Dengue Virus Infection in Human

    OpenAIRE

    Matangkasombut, Ponpan; Chan-in, Wilawan; Opasawaschai, Anunya; Pongchaikul, Pisut; Tangthawornchaikul, Nattaya; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Duangchinda, Thaneeya; Screaton, Gavin; Mongkolsapaya, Juthathip

    2014-01-01

    Background Dengue viral infection is a global health threat without vaccine or specific treatment. The clinical outcome varies from asymptomatic, mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune responses were found to be detrimental in the dengue pathogenesis, the roles of earlier innate events remain largely uninvestigated. Invariant natural killer T (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive response but their rol...

  14. Dendritic Cell Responses to Surface Properties of Clinical Titanium Surfaces

    OpenAIRE

    Kou, Peng Meng; Schwartz, Zvi; Boyan, Barbara D; Babensee, Julia E.

    2010-01-01

    Dendritic cells (DCs) play pivotal roles in responding to foreign entities during an innate immune response and initiating effective adaptive immunity as well as maintaining immune tolerance. The sensitivity of DCs to foreign stimuli also makes them useful cells to assess the inflammatory response to biomaterials. Elucidating the material property-DC phenotype relationships using a well-defined biomaterial system is expected to provide criteria for immuno-modulatory biomaterial design. Clinic...

  15. Regulation of immune cell responses by semaphorins and their receptors

    OpenAIRE

    Takamatsu, Hyota; Okuno, Tatsusada; Kumanogoh, Atsushi

    2010-01-01

    Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called ‘immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins ...

  16. Bystander responses in cells models; targets, dosimetry and mechanisms

    International Nuclear Information System (INIS)

    The use of microbeam approaches has been a major advance in probing the relevance of bystander responses in cell and tissue models. Our own studies at the Gray Cancer Institute have used both a charged particle microbeam, producing protons and helium ions and a soft X-ray microprobe, delivering focused carbon-K, aluminium-K and titanium-K soft X-rays. Using these techniques we have been able to build up a comprehensive picture of the underlying differences between bystander responses and direct effects in cell and tissue-like models. What is now clear is that bystander dose-response relationships, the underlying mechanisms of action and the targets involved are not the same as those observed for direct irradiation of DNA in the nucleus. Our recent studies have shown bystander responses induced in human or hamster cells even when radiation is deposited away from the nucleus in cytoplasmic targets either after charged particle or soft X-ray exposure. Importantly, the level of bystander effect, measured as cell killing was similar to that observed when the same amount of energy was deposited but targeted to the nucleus. In other studies, we have shown that underlying determination of the level of response is the energy deposited in a single cell rather than the number of cells hit. Also the overall response at low doses may be dominated by bystander signaling. These observations have significance for our understanding of radiation risk at low doses including those of environmental exposures and the applicability of the Linear Non Threshold model. The realization that cell to cell signaling is important for radiation response may also open up new therapeutic opportunities to either improve tumor cell kill or protect normal tissues if the pathways underpinning bystander signaling can be elucidated and controlled

  17. EU emissions trading. The need for cap adjustment in response to external shocks and unexpected developments?

    Energy Technology Data Exchange (ETDEWEB)

    Diekmann, Jochen [DIW, Berlin (Germany)

    2012-11-15

    In this paper the advantages and disadvantages of the various adaptation options will be discussed from an economic perspective. Firstly, the criteria for identifying a need for potentially legitimate adaptation should be investigated. Furthermore, the issue of appropriate timely intervention points prior to or within the trading period will be discussed. In what periods and scenarios are adjustments to the cap worthwhile from an economic perspective? To what extent could minimum prices or price ranges make sense? What role could a strategic reserve play? By addressing these issues, it will be fundamentally discussed as to how the emissions trading scheme could be further developed and strengthened by greater flexibility. After a brief characterisation of emissions trading in theory and practice in Chapter 2, Chapter 3 will identify potential external shocks and unexpected developments which may impair the functioning of an emissions trading scheme. The current problems of cap setting for the third trading period of the EU ETS will be described in Chapter 4. Against this background, cap adjustments will be discussed in Chapter 5, minimum and maximum prices in Chapter 6 and strategic reserves in emissions trading in Chapter 7. The conclusions are summarised in Chapter 8.

  18. Understanding and Meeting the Needs of Space Scientists in EPO—Survey Results, Responses, and Strategies

    Science.gov (United States)

    Grier, J.; Buxner, S.; Schneider, N.

    2015-11-01

    As science literacy is falling in the United States, our world continues to become more complex. Everyone now requires an understanding of science, technology, and the relationship of interconnected systems in order to successfully navigate the complex issues facing us. Scientists are a critical resource, bringing to the table an understanding of the nature of science as a process, as well as up-to-the-minute scientific content. They can function in a wide range of capacities in education and public outreach (EPO) to meet some of the learning challenges of teachers, students, and the general public. Societies that work directly with scientists, such as the American Astronomical Society (AAS) and the Division for Planetary Sciences (DPS) are interested in understanding how their member scientists view the act of reaching out, how they do it, and how the DPS can continue to support them as they engage with a variety of audiences in an EPO capacity. To this end, we (the NASA Science Mission Directorate Planetary Science Forum and DPS leadership) conducted a series of semi-structured interviews with a subsection of DPS members to learn more about their attitudes and needs, and to begin to pinpoint opportunities and strategies for future consideration. Presented here are our preliminary results and the ideas generated for further conversations.

  19. Squamous cell carcinoma of the skin: Emerging need for novel biomarkers

    Directory of Open Access Journals (Sweden)

    Atte Kivisaari

    2013-01-01

    Full Text Available The incidence of non-melanoma skin cancers (NMSC is rising worldwide resulting in demand for clinically useful prognostic biomarkers for these malignant tumors, especially for invasive and metastatic cutaneous squamous cell carcinoma (cSCC. Important risk factors for the development and progression of cSCC include ultraviolet radiation, chronic skin ulcers and immunosuppression. Due to the role of cumulative long-term sun exposure, cSCC is usually a disease of the elderly, but the incidence is also growing in younger individuals due to increased recreational exposure to sunlight. Although clinical diagnosis of cSCC is usually easy and treatment with surgical excision curable, it is responsible for the majority of NMSC related deaths. Clinicians treating skin cancer patients are aware that certain cSCCs grow rapidly and metastasize, but the underlying molecular mechanisms responsible for the aggressive progression of a subpopulation of cSCCs remain incompletely understood. Recently, new molecular markers for progression of cSCC have been identified.

  20. T Cell Responses: Naive to Memory and Everything in Between

    Science.gov (United States)

    Pennock, Nathan D.; White, Jason T.; Cross, Eric W.; Cheney, Elizabeth E.; Tamburini, Beth A.; Kedl, Ross M.

    2013-01-01

    The authors describe the actions that take place in T cells because of their amazing capacity to proliferate and adopt functional roles aimed at clearing a host of an infectious agent. There is a drastic decline in the T cell population once the primary response is over and the infection is terminated. What remains afterward is a population of T…

  1. Science and Society Under Attack: The Need for Political As Well As Scientific Responses

    Science.gov (United States)

    Berman, Marshall

    2006-03-01

    Today science and scientists are under attack. This is not new in human history. Copernicus delayed publishing for fear of possible persecution. Bruno was burned at the stake. Galileo was forced to recant. Darwin worked for 20 years without publishing his ideas, perhaps out of fear of possible consequences. In the US today, fundamentalist evangelicals have launched an attack on science, from intelligent design creationism, to stem cell research, global warming, vaccines to prevent cervical cancer, even museums that show exhibits on evolution. In the 21^st century, this medieval mentality must be strenuously resisted. Rational thought can co-exist with religious faith, unless extremism becomes the norm. Scientists have often ignored politics in their pursuit of new knowledge. But they must understand that public opinion is strongly influenced by non-scientific elements of society, from the pulpit, from politicians and bureaucrats, from a scientifically illiterate public, and from a media that frequently treats all points of view as equal, when they are most certainly not. Will science eventually be required to pass muster for religious fundamentalists in the near future?

  2. Analysis of the memory B cell response against glycoconjugate vaccines

    OpenAIRE

    Faenzi, Elisa

    2012-01-01

    The development of vaccines directed against polysaccharide capsules of S. pneumoniae, H. influenzae and N. meningitidis have been of great importance in preventing potentially fatal infections. Bacterial capsular polysaccharides are T-cell-independent antigens that induce specific antibody response characterized by IgM immunoglobulins, with a very low IgG class switched response and lack of capability of inducing a booster response. The inability of pure polysaccharides to induce sustained i...

  3. Macrophages in cardiac homeostasis, injury responses and progenitor cell mobilisation

    OpenAIRE

    Pinto, Alexander R.; Godwin, James W.; Rosenthal, Nadia A.

    2014-01-01

    Macrophages are an immune cell type found in every organ of the body. Classically, macrophages are recognised as housekeeping cells involved in the detection of foreign antigens and danger signatures, and the clearance of tissue debris. However, macrophages are increasingly recognised as a highly versatile cell type with a diverse range of functions that are important for tissue homeostasis and injury responses. Recent research findings suggest that macrophages contribute to tissue regenerati...

  4. Itch expression by Treg cells controls Th2 inflammatory responses

    OpenAIRE

    Jin, Hyung-Seung; Park, Yoon; Elly, Chris; Liu, Yun-Cai

    2013-01-01

    Regulatory T (Treg) cells maintain immune homeostasis by limiting autoimmune and inflammatory responses. Treg differentiation, maintenance, and function are controlled by the transcription factor Foxp3. However, the exact molecular mechanisms underlying Treg cell regulation remain elusive. Here, we show that Treg cell–specific ablation of the E3 ubiquitin ligase Itch in mice caused massive multiorgan lymphocyte infiltration and skin lesions, chronic T cell activation, and the development of s...

  5. Tissue specific heterogeneity in effector immune cell response

    Directory of Open Access Journals (Sweden)

    Saba eTufail

    2013-08-01

    Full Text Available Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct ‘homing codes’ (adhesion molecules and chemokine receptors during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A and sunlight (vitamin D3 prime dendritic cells, imprinting them to play centrestage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues alongwith giving an overview of tissue tropism in B cells.

  6. Studies on adaptive responses in Chinese hamster cells

    International Nuclear Information System (INIS)

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

  7. Evolution of the Data Access Protocol in Response to Community Needs

    Science.gov (United States)

    Gallagher, J.; Caron, J. L.; Davis, E.; Fulker, D.; Heimbigner, D.; Holloway, D.; Howe, B.; Moe, S.; Potter, N.

    2012-12-01

    Under the aegis of the OPULS (OPeNDAP-Unidata Linked Servers) Project, funded by NOAA, version 2 of OPeNDAP's Data Access Protocol (DAP2) is being updated to version 4. DAP4 is the first major upgrade in almost two decades and will embody three main areas of advancement. First, the data-model extensions developed by the OPULS team focus on three areas: Better support for coverages, access to HDF5 files and access to relational databases. DAP2 support for coverages (defined as a sampled functions) was limited to simple rectangular coverages that work well for (some) model outputs and processed satellite data but that cannot represent trajectories or satellite swath data, for example. We have extended the coverage concept in DAP4 to remove these limitations. These changes are informed by work at Unidata on the Common Data Model and also by the OGC's abstract coverages specification. In a similar vein, we have extended DAP2's support for relations by including the concept of foreign keys, so that tables can be explicitly related to one another. Second, the web interfaces - web services - that provides access to data using via DAP will be more clearly defined and use other (, orthogonal), standards where they are appropriate. An important case is the XML interface, which provides a cleaner way to build other response media types such as JSON and RDF (for metadata) and to build support for Atom, thus simplify the integration of DAP servers with tools that support OpenSearch. Input from the ESIP federation and work performed with IOOS have informed our choices here. Last, DAP4-compliant servers will support richer data-processing capabilities than DAP2, enabling a wider array of server functions that manipulate data before returning values. Two projects currently are exploring just what can be done even with DAP2's server-function model: The MIIC project at LARC and OPULS itself (with work performed at the University of Washington). Both projects have demonstrated that

  8. CD4+ T cell responses in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Nasser Semmo; Paul Klenerman

    2007-01-01

    Hepatitis C virus (HCV) infection is a major cause of liver damage, with virus-induced end-stage disease such as liver cirrhosis and hepatocellular carcinoma resulting in a high rate of morbidity and mortality worldwide. Evidence that CD4+ T cell responses to HCV play an important role in the outcome of acute infection has been shown in several studies. However, the mechanisms behind viral persistence and the failure of CD4+ T cell responses to contain virus are poorly understood. During chronic HCV infection, HCV-specific CD4+ T cell responses are relatively weak or absent whereas in resolved infection these responses are vigorous and multispecific. Persons with a T-helper type Ⅰ profile, which promotes cellular effector mechanisms are thought to be more likely to experience viral clearance, but the overall role of these cells in the immunopathogenesis of chronic liver disease is not known. To define this, much more data is required on the function and specificity of virus-specific CD4+ T cells,especially in the early phases of acute disease and in the liver during chronic infection. The role and possible mechanisms of action of CD4+ T cell responses in determining the outcome of acute and chronic HCV infection will be discussed in this review.

  9. Temporal Analyses of the Response of Intervertebral Disc Cells and Mesenchymal Stem Cells to Nutrient Deprivation

    Directory of Open Access Journals (Sweden)

    Sarah A. Turner

    2016-01-01

    Full Text Available Much emphasis has been placed recently on the repair of degenerate discs using implanted cells, such as disc cells or bone marrow derived mesenchymal stem cells (MSCs. This study examines the temporal response of bovine and human nucleus pulposus (NP cells and MSCs cultured in monolayer following exposure to altered levels of glucose (0, 3.15, and 4.5 g/L and foetal bovine serum (0, 10, and 20% using an automated time-lapse imaging system. NP cells were also exposed to the cell death inducers, hydrogen peroxide and staurosporine, in comparison to serum starvation. We have demonstrated that human NP cells show an initial “shock” response to reduced nutrition (glucose. However, as time progresses, NP cells supplemented with serum recover with minimal evidence of cell death. Human NP cells show no evidence of proliferation in response to nutrient supplementation, whereas MSCs showed greater response to increased nutrition. When specifically inducing NP cell death with hydrogen peroxide and staurosporine, as expected, the cell number declined. These results support the concept that implanted NP cells or MSCs may be capable of survival in the nutrient-poor environment of the degenerate human disc, which has important clinical implications for the development of IVD cell therapies.

  10. Natural killer cells promote early CD8 T cell responses against cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Scott H Robbins

    2007-08-01

    Full Text Available Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs for cytokine production, preserves the conventional dendritic cell (cDC compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate

  11. DNA damage responses in cancer stem cells: Implications for cancer therapeutic strategies

    Institute of Scientific and Technical Information of China (English)

    Qi-En; Wang

    2015-01-01

    The identification of cancer stem cells(CSCs) that are responsible for tumor initiation, growth, metastasis, and therapeutic resistance might lead to a new thinking on cancer treatments. Similar to stem cells,CSCs also display high resistance to radiotherapy and chemotherapy with genotoxic agents. Thus, conventional therapy may shrink the tumor volume but cannot eliminate cancer. Eradiation of CSCs represents a novel therapeutic strategy. CSCs possess a highly efficient DNA damage response(DDR) system, which is considered as a contributor to the resistance of these cells from exposures to DNA damaging agents. Targeting of enhanced DDR in CSCs is thus proposed to facilitate the eradication of CSCs by conventional therapeutics. To achieve this aim, a better understanding of the cellular responses to DNA damage in CSCs is needed. In addition to the protein kinases and enzymes that are involved in DDR, other processes that affect the DDR including chromatin remodeling should also be explored.

  12. Classroom Behaviour Management Strategies in Response to Problematic Behaviours of Primary School Children with Special Educational Needs: Views of Special Educational Needs Coordinators

    Science.gov (United States)

    Nye, Elizabeth; Gardner, Frances; Hansford, Lorraine; Edwards, Vanessa; Hayes, Rachel; Ford, Tamsin

    2016-01-01

    Children identified with special educational needs (SEN) and behavioural difficulties present extra challenges to educators and require additional supports in school. This paper presents views from special educational needs coordinators (SENCos) on various strategies used by educators to support children identified with SEN and problematic…

  13. The Role of Treg Cells in the Cancer Immunological Response

    Directory of Open Access Journals (Sweden)

    Stephen M. Ansell

    2009-01-01

    Full Text Available Problem statement: T cell-mediated immunosuppression has been observed for decades without clarification as to which factor was responsible for this observation. The identification of CD4+CD25+ regulatory T (Treg cells represents a milestone in the filed of immunology and provides an explanation for T-cell-mediated immunosuppression. Although Treg cells were originally identified for their ability to prevent organ-specific autoimmune disease in mice, emerging evidence suggests that Treg cells play a pivotal role in tumor immunity and contribute to tumor growth and progression, thereby having an important impact on the outcome of cancer patients. Approach: This article reviewed the medical literature to describe how Treg cells affect anti-tumor immunity. Results: Treg cells suppressed anti-tumor immunity by inhibiting the effector functions of tumor-specific T cells and NK cells. Importantly, tumor cells played an active role in recruiting and generating Treg cells and creating a suppressive tumor microenvironment. Strategies to deplete Treg cells or inhibit their function had yielded promising results by enhancing anti-tumor immunity in experimental studies as well as clinical practice. Conclusion: A better understanding of the pathophysiology of Treg cells not only increased our knowledge in a variety of aspects of immunology but also potentially benefited cancer patients.

  14. Experimental investigation of dynamic responses of a transparent PEM fuel cell to step changes in cell current density with operating temperature

    International Nuclear Information System (INIS)

    The dynamic responses of a proton exchange membrane fuel cell (PEMFC) are closely related to the novel water management technique used for the efficient operation of automotive PEMFCs. In order to better understand the dynamic water transport during cell transients, this paper presents an experimental investigation of the transient response of a cell under fully humidified conditions. The cell dynamic performance was measured by employing a transparent cell and investigated with visualization images of the water distribution in the flow channels. Furthermore, the effect of the operating temperature on the cell transients was examined. The results show that the cell dynamic behavior for the tested operating temperature (30-50 .deg. C) conditions is mainly governed by water transport characteristics related to cathode flooding. Also, we show that the time needed for the cell to reach steady-state after a current density step increase is retarded due to excessive water accumulation inside the cell at lower operating temperatures

  15. B Cells Regulate CD4+ T cell Responses to Papain Following BCR-Independent Papain Uptake

    OpenAIRE

    Dwyer, Daniel F.; Woodruff, Matthew C.; Carroll, Michael C.; Austen, K. Frank; Gurish, Michael F.

    2014-01-01

    Papain, a cysteine protease allergen with inherent adjuvant activity, induces potent IL4 expression by T cells in the popliteal lymph nodes (PLN) of mice following footpad immunization. Here we identify a novel, non-BCR mediated capacity for B cells to rapidly bind and internalize papain. B cells subsequently regulate the adaptive immune response by enhancing Inducible T cell Costimulator (ICOS) expression on CD4+ T cells and amplifying Th2 and T follicular helper induction. Antibody blockade...

  16. Nanosecond electric pulses trigger actin responses in plant cells

    International Nuclear Information System (INIS)

    We have analyzed the cellular effects of nanosecond pulsed electrical fields on plant cells using fluorescently tagged marker lines in the tobacco cell line BY-2 and confocal laser scanning microscopy. We observe a disintegration of the cytoskeleton in the cell cortex, followed by contraction of actin filaments towards the nucleus, and disintegration of the nuclear envelope. These responses are accompanied by irreversible permeabilization of the plasma membrane manifest as uptake of Trypan Blue. By pretreatment with the actin-stabilizing drug phalloidin, the detachment of transvacuolar actin from the cell periphery can be suppressed, and this treatment can also suppress the irreversible perforation of the plasma membrane. We discuss these findings in terms of a model, where nanosecond pulsed electric fields trigger actin responses that are key events in the plant-specific form of programmed cell death.

  17. Nanosecond electric pulses trigger actin responses in plant cells

    Energy Technology Data Exchange (ETDEWEB)

    Berghoefer, Thomas; Eing, Christian; Flickinger, Bianca [Institute for Pulsed Power and Microwave Technology (IHM), Forschungszentrum Karlsruhe GmbH, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen (Germany); Hohenberger, Petra [Botanical Institute I, University of Karlsruhe, Karlsruhe Institute of Technology, Kaiserstr. 2, 76128 Karlsruhe (Germany); Wegner, Lars H. [Institute for Pulsed Power and Microwave Technology (IHM), Forschungszentrum Karlsruhe GmbH, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen (Germany); Botanical Institute I, University of Karlsruhe, Karlsruhe Institute of Technology, Kaiserstr. 2, 76128 Karlsruhe (Germany); Frey, Wolfgang [Institute for Pulsed Power and Microwave Technology (IHM), Forschungszentrum Karlsruhe GmbH, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen (Germany); Nick, Peter, E-mail: peter.nick@bio.uni-karlsruhe.de [Botanical Institute I, University of Karlsruhe, Karlsruhe Institute of Technology, Kaiserstr. 2, 76128 Karlsruhe (Germany)

    2009-09-25

    We have analyzed the cellular effects of nanosecond pulsed electrical fields on plant cells using fluorescently tagged marker lines in the tobacco cell line BY-2 and confocal laser scanning microscopy. We observe a disintegration of the cytoskeleton in the cell cortex, followed by contraction of actin filaments towards the nucleus, and disintegration of the nuclear envelope. These responses are accompanied by irreversible permeabilization of the plasma membrane manifest as uptake of Trypan Blue. By pretreatment with the actin-stabilizing drug phalloidin, the detachment of transvacuolar actin from the cell periphery can be suppressed, and this treatment can also suppress the irreversible perforation of the plasma membrane. We discuss these findings in terms of a model, where nanosecond pulsed electric fields trigger actin responses that are key events in the plant-specific form of programmed cell death.

  18. Lactobacilli Modulate Natural Killer Cell Responses In Vitro

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Christensen, Hanne Risager; Frøkiær, Hanne

    of certain lactic acid bacteria has been shown to increase in vivo NK cytotoxicity. Here, we investigated how human gut flora-derived lactobacilli affect NK cells in vitro, by measuring proliferation and IFN-gamma production of human NK cells upon bacterial stimulation. CD3-CD56+ NK cells were...... isolated from buffy coats by negative isolation using non-NK lineage specific antibodies and magnetic beads. NK cells were incubated with 10 microg/ml UV-inactivated bacteria or 10 microg/ml phytohemagglutinin (PHA) for four days. Proliferation was assessed by incorporation of radioactive thymidine into NK...... cell DNA. The IFN-gamma concentration was measured by ELISA. Incubation of NK cells with a Lactobacillus acidophilus strain increased the proliferation of the NK cells and induced IFN-gamma production, both to levels comparable to PHA stimulation. The proliferative response was further enhanced with...

  19. The public costs of mental health response: Lessons from the New York City post-9/11 needs assessment

    OpenAIRE

    Jack, Kathrine; Glied, Sherry

    2002-01-01

    There is evidence of increased rates of psychiatric disorder in New York City in the period following September 11th. Public mental health services need to develop plans to respond to these higher rates of disorder. This article describes what we know and do not know with respect to the costs of such response. We examine evidence on the demand for mental health services, the nature of services to be provided, the characteristics of providers, and the likely sources of payment for care in the ...

  20. Intracellular Ca2+ responses and cell volume regulation upon cholinergic and purinergic stimulation in an immortalized salivary cell line.

    Science.gov (United States)

    Aure, Marit H; Røed, Asbjørn; Galtung, Hilde Kanli

    2010-06-01

    The water channel aquaporin 5 (AQP5) seems to play a key role in salivary fluid secretion and appears to be critical in the cell volume regulation of acinar cells. Recently, the cation channel transient potential vanilloid receptor 4 (TRPV4) was shown to be functionally connected to AQP5 and also to cell volume regulation in salivary glands. We used the Simian virus 40 (SV40) immortalized cell line SMG C10 from the rat submandibular salivary gland to investigate the effect of ATP and the neurotransmitter analogue carbachol on Ca(2+) signalling and cell volume regulation, as well as the involvement of TRPV4 in the responses. We used fura-2-AM imaging, cell volume measurements, and western blotting. Both carbachol and ATP increased the concentration of intracellular Ca(2+), but no volume changes could be measured. Inhibition of TRPV4 with ruthenium red impaired both ATP- and carbachol-stimulated Ca(2+) signals. Peak Ca(2+) signalling during hyposmotic exposure was significantly decreased following inhibition of TRPV4, while the cells' ability to volume regulate appeared to be unaffected. These results show that in the SMG C10 cells, simulation of nervous stimulation did not induce cell swelling, although the cells had intact volume regulatory mechanisms. Furthermore, even though Ca(2+) signals were not needed for this volume regulation, TRPV4 seems to play a role during ATP and carbachol stimulation. PMID:20572856

  1. Divergent Immunomodulating Effects of Probiotics on T Cell Responses to Oral Attenuated Human Rotavirus Vaccine and Virulent Human Rotavirus Infection in a Neonatal Gnotobiotic Piglet Disease Model

    OpenAIRE

    Chattha, Kuldeep S; Vlasova, Anastasia N.; Kandasamy, Sukumar; Rajashekara, Gireesh; Saif, Linda J.

    2013-01-01

    Rotaviruses (RVs) are a leading cause of childhood diarrhea. Current oral vaccines are not effective in impoverished countries where the vaccine is needed most. Therefore, alternative affordable strategies are urgently needed. Probiotics can alleviate diarrhea in children and enhance specific systemic and mucosal Ab responses, but the T cell responses are undefined. In this study, we elucidated the T cell and cytokine responses to attenuated human RV (AttHRV) and virulent human RV (HRV) in gn...

  2. Single-cell bioelectrical impedance platform for monitoring cellular response to drug treatment

    International Nuclear Information System (INIS)

    The response of cells to a chemical or biological agent in terms of their impedance changes in real-time is a useful mechanism that can be utilized for a wide variety of biomedical and environmental applications. The use of a single-cell-based analytical platform could be an effective approach to acquiring more sensitive cell impedance measurements, particularly in applications where only diminutive changes in impedance are expected. Here, we report the development of an on-chip cell impedance biosensor with two types of electrodes that host individual cells and cell populations, respectively, to study its efficacy in detecting cellular response. Human glioblastoma (U87MG) cells were patterned on single- and multi-cell electrodes through ligand-mediated natural cell adhesion. We comparatively investigated how these cancer cells on both types of electrodes respond to an ion channel inhibitor, chlorotoxin (CTX), in terms of their shape alternations and impedance changes to exploit the fine detectability of the single-cell-based system. The detecting electrodes hosting single cells exhibited a significant reduction in the real impedance signal, while electrodes hosting confluent monolayer of cells showed little to no impedance change. When single-cell electrodes were treated with CTX of different doses, a dose-dependent impedance change was observed. This enables us to identify the effective dose needed for this particular treatment. Our study demonstrated that this single-cell impedance system may potentially serve as a useful analytical tool for biomedical applications such as environmental toxin detection and drug evaluation

  3. Classroom behaviour management strategies in response to problematic behaviours of primary school children with special educational needs: views of special educational needs coordinators

    OpenAIRE

    Nye, E.; Gardner, F.; Hansford, L; Edwards, V.; Hayes, R; Ford, T.

    2015-01-01

    Children identified with special educational needs (SEN) and behavioural difficulties present extra challenges to educators and require additional supports in school. This paper presents views from special educational needs coordinators (SENCos) on various strategies used by educators to support children identified with SEN and problematic behaviours. The data were collected from telephone interviews with six SENCos from the UK’s South West Peninsula. The SENCos were invited to participate be...

  4. Biomedical Applications of the Cold Atmospheric Plasma: Cell Responses

    Science.gov (United States)

    Volotskova, Olga

    Current breakthrough research on cold atmospheric plasma (CAP) demonstrates that CAP has great potential in various areas, including medicine and biology, thus providing a new tool for living tissue treatment. Depending on the configuration the cold plasma sources can be used in the following areas: wound healing, skin diseases, hospital hygiene, sterilization, antifungal treatments, dental care, cosmetics targeted cell/tissue removal, and cancer treatments. This dissertation is focused on the studies of biomedical applications of cold atmospheric plasma jet based on helium flow and resultant cell responses to the cold plasma treatment. The studies were carried out on extra-cellular and intra-cellular levels in vitro. The main practical applications are wound healing and alternative to existing cancer therapy methods, areas of great interest and significant challenges. The CAP jet was built in the Micropropulsion and Nanotechnology Laboratory of Dr. Michael Keidar, as a part of multidisciplinary collaboration with the GW Medical School (Dr. M.A. Stepp) concerned with plasma medicine and bioengineering studies. Normal and cancer cells have two fundamental behavioral properties, proliferation and motility, which can be evaluated through cell migration rates and cell cycle progression. Various microscopic, spectroscopic and flow cytometry techniques were used to characterize cell responses to the cold plasma treatment. It was found that CAP effect on the cells is localized within the area of the treatment (of around ˜ 5mm in diameter). The migration rates of the normal skin cells can be reduced up to ˜ 40%. However, depending on the cell type the required treatment time is different, thus differential treatment of various cells presented in tissue is possible. The CAP effect on the migration was explained through the changes of the cell surface proteins/integrins. It was also found that normal and cancer cells respond differently to the CAP treatment under the same

  5. The DNA damage-induced cell death response: a roadmap to kill cancer cells.

    Science.gov (United States)

    Matt, Sonja; Hofmann, Thomas G

    2016-08-01

    Upon massive DNA damage cells fail to undergo productive DNA repair and trigger the cell death response. Resistance to cell death is linked to cellular transformation and carcinogenesis as well as radio- and chemoresistance, making the underlying signaling pathways a promising target for therapeutic intervention. Diverse DNA damage-induced cell death pathways are operative in mammalian cells and finally culminate in the induction of programmed cell death via activation of apoptosis or necroptosis. These signaling routes affect nuclear, mitochondria- and plasma membrane-associated key molecules to activate the apoptotic or necroptotic response. In this review, we highlight the main signaling pathways, molecular players and mechanisms guiding the DNA damage-induced cell death response. PMID:26791483

  6. Relation between radio-adaptive response and cell to cell communication

    International Nuclear Information System (INIS)

    Ionizing radiation has been considered to cause severe damages to DNA and do harm to cells in proportion to the dose, however low it might be. In 1984, Wolff et al. showed that human peripheral lymphocytes adapted to the low-dose radiation from 3H-TdR added in culture medium and became resistant to the subsequent irradiation with high-doses of X-rays. This response, which is called radio-adaptive response, is also induced by X-rays and gamma-rays in human lymphocytes and Chinese hamster V79 cells. However, the mechanisms of and conditions for adaptive responses to radiation have not been clarified. With an objective of clarifying the conditions for adaptive responses of cells to radiation, we examined how the cell to cell communication is involved in the adaptive responses. We irradiated normal human embryo-derived (HE) cells and cancer cells (HeLa) in culture at high density with low-dose X-ray and examined their radio-adaptive responses by measuring the changes in sensitivity to subsequent high-dose X-ray irradiation using the Trypan Blue dye-exclusion test method. We also conducted experiments to examine the effects of Ca2+ ions and Phorbol 12-Myristate 13-Acetate (TPA) which are supposed to be involved in cell to cell communication. (author)

  7. Aggressive B-cell lymphomas: how many categories do we need?

    OpenAIRE

    Said, Jonathan W.

    2012-01-01

    Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. The aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma and its blastoid variant, and B lymphoblastic lymphoma. Differences in histology, cytogenetic and molecular abnormalities, as well as the relationship with the tumor mic...

  8. T cell regulation of the thymus-independent antibody response to trinitrophenylated-Brucella abortus (TNP-BA)

    Energy Technology Data Exchange (ETDEWEB)

    Tanay, A.; Strober, S.

    1985-06-01

    The authors have previously observed a reduction of the T cell-dependent primary antibody response to dinitrophenylated keyhole limpet hemocyanin, and an enhancement of the T cell-independent response to trinitrophenylated Brucella abortus (TNP-BA) in BALB/c mice after treatment with total lymphoid irradiation (TLI). To elucidate the relative contribution of T and B cells to the enhanced T cell-independent antibody responses after TLI, a syngeneic primary adoptive transfer system was utilized whereby irradiated hosts were reconstituted with unfractionated spleen cells or a combination of purified T and B cells from TLI-treated and untreated control mice. Antibody responses of purified splenic B cells from TLI-treated BALB/c mice (TLI/B) to TNP-BA were enhanced 10-fold as compared with those of unfractionated (UF) spleen cells or B cells from normal (NL) BALB/c mice (NL/UF and NL/B, respectively). Splenic T cells from normal animals (NL/T) suppressed the anti-TNP-BA response of TLI/B by more than 100-fold. NL/T neither suppressed nor enhanced the response of NL/B. On the other hand, T cells from TLI-treated mice (TLI/T) enhanced by 100-fold the anti-TNP-BA response of NL/B, but neither suppressed nor enhanced the response of TLI/B. Thus, T cells can regulate the T cell-independent antibody response to TNP-BA. However, experimental manipulation of the T and B cell populations is needed to demonstrate the regulatory functions.

  9. Increase in collagen production with loss of androgen responsiveness in cultured androgen-responsive Shionogi carcinoma 115 cells.

    Science.gov (United States)

    Terada, N; Wakimoto, H; Yamamoto, R; Uchida, N; Takatsuka, D; Takada, T; Taniguchi, H; Li, W; Kitamura, Y; Matsumoto, K

    1988-05-01

    The collagen production of androgen-responsive and -unresponsive Shionogi carcinoma 115 cells was investigated by culturing them in a medium with or without testosterone. Androgen-unresponsive cells were obtained by culturing a cloned androgen-responsive cell in a testosterone-free medium for 12 weeks. The collagen production of androgen-responsive cells slightly increased in the absence of testosterone, whereas testosterone did not affect the collagen production of androgen-unresponsive cells. Androgen-unresponsive cells produced 3-4 times more collagen than androgen-responsive cells. The major collagen produced by both androgen-responsive and - unresponsive cells migrated to the same position in sodium dodecylsulfate:polyacylamide gel electrophoresis. The present results indicate that the collagen production of androgen-responsive Shionogi carcinoma 115 cells increases with the loss of androgen responsiveness in culture. PMID:3169094

  10. Functional genomics of UV radiation responses in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Koch-Paiz, Christine A.; Amundson, Sally A.; Bittner, Michael L.; Meltzer, Paul S.; Fornace, Albert J

    2004-05-18

    The gene expression responses of MCF-7, a p53 wild-type (wt) human cell line, were monitored by cDNA microarray hybridization after exposure to different wavelengths of UV irradiation. Equitoxic doses of UVA, UVB, and UVC radiation were used to reduce survival to 37%. The effects of suramin, a signal pathway inhibitor, on the gene expression responses to the three UV wavelengths were also compared in this model system. UVB radiation triggered the broadest gene expression responses, and 172 genes were found to be consistently responsive in at least two-thirds of independent UVB experiments. These UVB radiation-responsive genes encode proteins with diverse cellular roles including cell cycle control, DNA repair, signaling, transcription, protein synthesis, protein degradation, and RNA metabolism. The set of UVB-responsive genes included most of the genes responding to an equitoxic dose of UVC radiation, plus additional genes that were not strongly triggered by UVC radiation. There was also some overlap with genes responding to an equitoxic dose of UVA radiation, although responses to this lower energy UV radiation were overall weaker. Signaling through growth factor receptors and other cytokine receptors was shown to have a major role in mediating UV radiation stress responses, as suramin, which inhibits such receptors, attenuated responses to UV radiation in nearly all the cases. Inhibition by suramin was greater for UVC than for UVB irradiation. This probably reflects the more prominent role in UVB damage response of signaling by reactive oxygen species, which would not be affected by suramin. Our results with suramin demonstrate the power of cDNA microarray hybridization to illuminate the global effects of a pharmacologic inhibitor on cell signaling.

  11. Cancer cell response to nanoparticles: criticality and optimality.

    Science.gov (United States)

    Patra, Hirak Kumar; Dasgupta, Anjan Kr

    2012-08-01

    A stochastic variation in size and electrical parameters is common in nanoparticles. Synthesizing gold nanoparticles with a varying range of size and zeta potential, we show that there is clustering at certain regions of hydrodynamic diameter and zeta potentials that can be classified using k-clustering technique. A cluster boundary was observed around 50 nm, a size known for its optimal response to cells. However, neither size nor zeta potential alone determined the optimal cellular response (e.g., percentage cell survival) induced by such nanoparticles. A complex interplay prevails between size, zeta potential, nature of surface functionalization, and extent of adhesion of the cell to a solid matrix. However, it follows that the ratio of zeta potential to surface area, which scales as the electrical field (by Gaussian law), serves as an appropriate indicator for optimal cellular response. The phase plot spanned by fractional survival and effective electric field (charge density) indicates a positive correlation between mean cell survival and the magnitude of the electric field. The phase plot spanned by fractional survival and effective electric field (charge density) associated with the nanosurface shows a bifurcation behavior. Wide variation of cell survival response is observed at certain critical values of the surface charge density, whereas in other ranges the cellular response is well behaved and more predictable. Existence of phase points near the critical region corresponds to wide fluctuation of nanoparticle-induced response, for small changes in the nanosurface property. Smaller nanoparticles with low zeta potential (e.g., those conjugated with arginine) can have such an attribute (i.e., higher electrical field strength), and eventually they cause more cell death. The study may help in optimal design of nanodrugs. PMID:22094123

  12. Hematopoietic Stem Cell Transplantation: Need for Research & Potential Applications. It’s status in India

    Directory of Open Access Journals (Sweden)

    Shripad D. Banavali

    2009-01-01

    Full Text Available Stem cells are undifferentiated cells that through replications have the capabilities of both self-renewal and differentiation into mature specialized cells. Broadly, there are two types of stem cells, embryonic stem cells and adult stem cells. Embryonic stem cell biology has been associated with ethical controversy and also their growth is difficult to control. Adult stem cells are located in tissues throughout the body and function as a reservoir to replace damaged or aging cells. Embryonic stem cells are by definitions, the master cells capable of differentiating into every type of cells either in-vitro or in-vivo. Several lines of evidence suggests, however, that adult stem cells and even terminally differentiated somatic cells under appropriate micro-environmental cues are able to be reprogrammed and contribute to a much wider spectrum of differentiated progeny than previously anticipated. Hematopoietic Stem Cells (HSCs, for example, from different sources have been shown to cross the tissue boundaries and give rise to the cells of the other germ layers.In the past few years, the plasticity of adult cells in several post-natal tissues has attracted special attention in regenerative medicine. Stem cell therapies represent a new field of biomedical science which could provide in the future the cure for diseases until now considered incurable. The reconstitution of adult stem cells may be promising source for the regeneration of damaged tissues and for the resolution of organ dysfunction. However, there are two major limitations to the use of such cells:- (i They are rare and (ii Only a few types exist that can be isolated without harming the patient.Due to the inability to efficiently and safely harvest or expand stem cells from most adult organs (e.g. liver, gastrointestinal tract, heart, brain, the majority of human stem cell trials have focused on clinical applications for HSCs, mesenchymal stem cells (MSCs, or both, which can be easily

  13. T cell Bim levels reflect responses to anti–PD-1 cancer therapy

    Science.gov (United States)

    Dronca, Roxana S.; Liu, Xin; Harrington, Susan M.; Chen, Lingling; Cao, Siyu; Kottschade, Lisa A.; McWilliams, Robert R.; Block, Matthew S.; Nevala, Wendy K.; Thompson, Michael A.; Mansfield, Aaron S.; Park, Sean S.; Markovic, Svetomir N.; Dong, Haidong

    2016-01-01

    Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+ T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility. PMID:27182556

  14. Intestinal stem cell response to injury: lessons from Drosophila.

    Science.gov (United States)

    Jiang, Huaqi; Tian, Aiguo; Jiang, Jin

    2016-09-01

    Many adult tissues and organs are maintained by resident stem cells that are activated in response to injury but the mechanisms that regulate stem cell activity during regeneration are still poorly understood. An emerging system to study such problem is the Drosophila adult midgut. Recent studies have identified both intrinsic factors and extrinsic niche signals that control the proliferation, self-renewal, and lineage differentiation of Drosophila adult intestinal stem cells (ISCs). These findings set up the stage to interrogate how niche signals are regulated and how they are integrated with cell-intrinsic factors to control ISC activity during normal homeostasis and regeneration. Here we review the current understanding of the mechanisms that control ISC self-renewal, proliferation, and lineage differentiation in Drosophila adult midgut with a focus on the niche signaling network that governs ISC activity in response to injury. PMID:27137186

  15. Macrophages in cardiac homeostasis, injury responses and progenitor cell mobilisation

    Directory of Open Access Journals (Sweden)

    Alexander R. Pinto

    2014-11-01

    Full Text Available Macrophages are an immune cell type found in every organ of the body. Classically, macrophages are recognised as housekeeping cells involved in the detection of foreign antigens and danger signatures, and the clearance of tissue debris. However, macrophages are increasingly recognised as a highly versatile cell type with a diverse range of functions that are important for tissue homeostasis and injury responses. Recent research findings suggest that macrophages contribute to tissue regeneration and may play a role in the activation and mobilisation of stem cells. This review describes recent advances in our understanding of the role played by macrophages in cardiac tissue maintenance and repair following injury. We examine the involvement of exogenous and resident tissue macrophages in cardiac inflammatory responses and their potential activity in regulating cardiac regeneration.

  16. Radiation response of spermatogonial stem cells in the mouse

    International Nuclear Information System (INIS)

    Spermatogonial stem cells are able to repopulate the testis by forming clones that elongate along the walls of the seminiferous tubules depleted of spermatogenetic cells as a result of an irradiation. The surviving number of stem cells after irradiation was estimated by determining the fraction of repopulated tubules in cross-sections of the testis 11 weeks after irradiation. This fraction, called the 'repopulation index', is assumed to be directly proportional to the number of surviving stem cells. The response of spermatogonial stem cells in the CBA mouse to 1-MeV fission neutrons was investigated. Radioresistant, colony forming stem cells in the mouse testis move into a much more radiosensitive phase of their cell cycle shortly after irradiation. This is demonstrated in publication II in experiments in which total doses of 300 rad of neutrons and 1200 rad of X-rays were split into two equal fractions. The radiation response of spermatogonial stem cells in the mouse which survived various doses of fission neutrons 24 hours before was studied in publication III. Twenty four hours after a dose of 150 rad of fission neutrons all first-dose survivors have moved from a radioresistant (D0 89+-4 rad in this study) towards a radiosensitive phase of their cell cycle. Spermatogonial stem cells which survive a neutron dose of 150 rad all belong to a radioresistant stem cell population in the seminiferous epithelium. The data in publication IV show that during the first 26 days after a dose of 150 rad of neutrons the stem cell population first increases and then slowly decreases its radiosensitivity, to stay fixed at a relatively high level. (Auth.)

  17. T cell responses in psoriasis and psoriatic arthritis.

    Science.gov (United States)

    Diani, Marco; Altomare, Gianfranco; Reali, Eva

    2015-04-01

    According to the current view the histological features of psoriasis arise as a consequence of the interplay between T cells, dendritic cells and keratinocytes giving rise to a self-perpetuating loop that amplifies and sustains inflammation in lesional skin. In particular, myeloid dendritic cell secretion of IL-23 and IL-12 activates IL-17-producing T cells, Th22 and Th1 cells, leading to the production of inflammatory cytokines such as IL-17, IFN-γ, TNF and IL-22. These cytokines mediate effects on keratinocytes thus establishing the inflammatory loop. Unlike psoriasis the immunopathogenic features of psoriatic arthritis are poorly characterized and there is a gap in the knowledge of the pathogenic link between inflammatory T cell responses arising in the skin and the development of joint inflammation. Here we review the knowledge accumulated over the years from the early evidence of autoreactive CD8 T cells that was studied mainly in the years 1990s and 2000s to the recent findings of the role of Th17, Tc17 cells and γδ T cells in psoriatic disease pathogenesis. The review will also focus on common and distinguishing features of T cell responses in psoriatic plaques and in synovial fluid of patients with psoriatic arthritis. The integration of this information could help to distinguish the role played by T cells in the initiation phase of the disease from the role of T cells as downstream effectors sustaining inflammation in psoriatic plaques and potentially leading to disease manifestation in distant joints. PMID:25445403

  18. Response of human hair cortical cells to fractionated radiotherapy

    International Nuclear Information System (INIS)

    Hair cortical cell counting (HCCC) represents a non-invasive, in-vivo measure of cell kill in the human integument. Sixty-six patients undergoing conventionally fractionated, external beam radiotherapy for early stage carcinoma of the prostate had groin hair samples counted. This technique is a sensitive and reproducible measure of radiation effect and may have applicability as an in-vivo prediction tool or in the field of biological dosimetry. A repopulative follicular response occurring at 3-4 weeks may explain flattening of the dose response curve

  19. Use of comparative genomics approaches to characterize interspecies differences in response to environmental chemicals: Challenges, opportunities, and research needs

    International Nuclear Information System (INIS)

    A critical challenge for environmental chemical risk assessment is the characterization and reduction of uncertainties introduced when extrapolating inferences from one species to another. The purpose of this article is to explore the challenges, opportunities, and research needs surrounding the issue of how genomics data and computational and systems level approaches can be applied to inform differences in response to environmental chemical exposure across species. We propose that the data, tools, and evolutionary framework of comparative genomics be adapted to inform interspecies differences in chemical mechanisms of action. We compare and contrast existing approaches, from disciplines as varied as evolutionary biology, systems biology, mathematics, and computer science, that can be used, modified, and combined in new ways to discover and characterize interspecies differences in chemical mechanism of action which, in turn, can be explored for application to risk assessment. We consider how genetic, protein, pathway, and network information can be interrogated from an evolutionary biology perspective to effectively characterize variations in biological processes of toxicological relevance among organisms. We conclude that comparative genomics approaches show promise for characterizing interspecies differences in mechanisms of action, and further, for improving our understanding of the uncertainties inherent in extrapolating inferences across species in both ecological and human health risk assessment. To achieve long-term relevance and consistent use in environmental chemical risk assessment, improved bioinformatics tools, computational methods robust to data gaps, and quantitative approaches for conducting extrapolations across species are critically needed. Specific areas ripe for research to address these needs are recommended

  20. Use of comparative genomics approaches to characterize interspecies differences in response to environmental chemicals: Challenges, opportunities, and research needs

    Energy Technology Data Exchange (ETDEWEB)

    Burgess-Herbert, Sarah L., E-mail: sarah.burgess@alum.mit.edu [American Association for the Advancement of Science (AAAS) Science and Technology Policy Fellow at the US Environmental Protection Agency (EPA), 2009–10 (United States); Euling, Susan Y. [National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Washington, DC 20460 (United States)

    2013-09-15

    A critical challenge for environmental chemical risk assessment is the characterization and reduction of uncertainties introduced when extrapolating inferences from one species to another. The purpose of this article is to explore the challenges, opportunities, and research needs surrounding the issue of how genomics data and computational and systems level approaches can be applied to inform differences in response to environmental chemical exposure across species. We propose that the data, tools, and evolutionary framework of comparative genomics be adapted to inform interspecies differences in chemical mechanisms of action. We compare and contrast existing approaches, from disciplines as varied as evolutionary biology, systems biology, mathematics, and computer science, that can be used, modified, and combined in new ways to discover and characterize interspecies differences in chemical mechanism of action which, in turn, can be explored for application to risk assessment. We consider how genetic, protein, pathway, and network information can be interrogated from an evolutionary biology perspective to effectively characterize variations in biological processes of toxicological relevance among organisms. We conclude that comparative genomics approaches show promise for characterizing interspecies differences in mechanisms of action, and further, for improving our understanding of the uncertainties inherent in extrapolating inferences across species in both ecological and human health risk assessment. To achieve long-term relevance and consistent use in environmental chemical risk assessment, improved bioinformatics tools, computational methods robust to data gaps, and quantitative approaches for conducting extrapolations across species are critically needed. Specific areas ripe for research to address these needs are recommended.

  1. The Inflammation Response to DEHP through PPARγ in Endometrial Cells

    Directory of Open Access Journals (Sweden)

    Qiansheng Huang

    2016-03-01

    Full Text Available Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa were recruited to investigate the effects of di-(2-ethylhexyl phthalate (DEHP at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

  2. The stringent response and cell cycle arrest in Escherichia coli.

    OpenAIRE

    Daniel J Ferullo; Lovett, Susan T.

    2008-01-01

    The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes...

  3. The Stringent Response and Cell Cycle Arrest in Escherichia coli

    OpenAIRE

    Daniel J Ferullo; Lovett, Susan T.

    2008-01-01

    The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes...

  4. Human CD4+ T Cell Response to Human Herpesvirus 6

    OpenAIRE

    Nastke, Maria-D.; Becerra, Aniuska; Yin, Liusong; Dominguez-Amorocho, Omar; Gibson, Laura; Stern, Lawrence J.; Calvo-Calle, J. Mauricio

    2012-01-01

    Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent infection for life. HHV-6 reactivation has been associated with transplant rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug-induced hypersensitivity syndrome. The poor understanding of the targets and outcome of the cellular immune response to HHV-6 makes it difficult to outline the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T cell responses to HHV-6 using...

  5. Oral microbial biofilm stimulation of epithelial cell responses

    OpenAIRE

    Peyyala, Rebecca; Kirakodu, Sreenatha S.; Novak, Karen F.; Ebersole, Jeffrey L.

    2012-01-01

    Oral bacterial biofilms trigger chronic inflammatory responses in the host that can result in the tissue destructive events of periodontitis. However, the characteristics of the capacity of specific host cell types to respond to these biofilms remain ill-defined. This report describes the use of a novel model of bacterial biofilms to stimulate oral epithelial cells and profile select cytokines and chemokines that contribute to the local inflammatory environment in the periodontium. Monoinfect...

  6. Bisphosphonates target B cells to enhance humoral immune responses

    OpenAIRE

    Tonti, Elena; Jiménez de Oya, Nereida; Galliverti, Gabriele; Moseman, E. Ashley; Di Lucia, Pietro; Amabile, Angelo; Sammicheli, Stefano; De Giovanni, Marco; Sironi, Laura; Chevrier, Nicolas; Sitia, Giovanni; Gennari, Luigi; Guidotti, Luca G.; von Andrian, Ulrich H.; Iannacone, Matteo

    2013-01-01

    Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4+ and γδ T cells, neutrophils or dendritic cells and their effect does not rely on local macrophage depletion ...

  7. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria.

    Science.gov (United States)

    Hepworth, Matthew R; Monticelli, Laurel A; Fung, Thomas C; Ziegler, Carly G K; Grunberg, Stephanie; Sinha, Rohini; Mantegazza, Adriana R; Ma, Hak-Ling; Crawford, Alison; Angelosanto, Jill M; Wherry, E John; Koni, Pandelakis A; Bushman, Frederic D; Elson, Charles O; Eberl, Gérard; Artis, David; Sonnenberg, Gregory F

    2013-06-01

    Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in cytokine-mediated regulation of intestinal epithelial cell barrier integrity. Alterations in ILC responses are associated with multiple chronic human diseases, including inflammatory bowel disease, implicating a role for ILCs in disease pathogenesis. Owing to an inability to target ILCs selectively, experimental studies assessing ILC function have predominantly used mice lacking adaptive immune cells. However, in lymphocyte-sufficient hosts ILCs are vastly outnumbered by CD4(+) T cells, which express similar profiles of effector cytokines. Therefore, the function of ILCs in the presence of adaptive immunity and their potential to influence adaptive immune cell responses remain unknown. To test this, we used genetic or antibody-mediated depletion strategies to target murine ILCs in the presence of an adaptive immune system. We show that loss of retinoic-acid-receptor-related orphan receptor-γt-positive (RORγt(+)) ILCs was associated with dysregulated adaptive immune cell responses against commensal bacteria and low-grade systemic inflammation. Remarkably, ILC-mediated regulation of adaptive immune cells occurred independently of interleukin (IL)-17A, IL-22 or IL-23. Genome-wide transcriptional profiling and functional analyses revealed that RORγt(+) ILCs express major histocompatibility complex class II (MHCII) and can process and present antigen. However, rather than inducing T-cell proliferation, ILCs acted to limit commensal bacteria-specific CD4(+) T-cell responses. Consistent with this, selective deletion of MHCII in murine RORγt(+) ILCs resulted in dysregulated commensal bacteria-dependent CD4(+) T-cell responses that promoted spontaneous intestinal inflammation. These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4(+) T cells that limit pathological adaptive immune cell responses to commensal

  8. A stimulating way to improve T cell responses to poxvirus-vectored vaccines

    OpenAIRE

    Isaacs, Stuart N.

    2010-01-01

    Vaccines remain one of the most cost-effective public health measures. Despite ongoing efforts, protective vaccines against cancer and many infectious diseases, including malaria, tuberculosis, and HIV/AIDS, are still not in hand. Most investigators believe that to succeed against these difficult targets, vaccines that generate potent T cell responses are needed. In this issue of the JCI, Salek-Ardakani et al. show how the relative virulence of a virus/vaccine vector affects the memory CD8+ T...

  9. Sensory Transduction of the CO2 Response of Guard Cells

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Eduardo Zeiger

    2003-06-30

    Stomata have a key role in the regulation of gas exchange and intercellular CO2 concentrations of leaves. Guard cells sense internal and external signals in the leaf environment and transduce these signals into osmoregulatory processes that control stomatal apertures. This research proposal addresses the characterization of the sensory transduction of the CO2 signal in guard cells. Recent studies have shown that in Vicia leaves kept at constant light and temperature in a growth chamber, changes in ambient CO2 concentrations cause large changes in guard cell zeaxanthin that are linear with CO2-dependent changes in stomatal apertures. Research proposed here will test the hypothesis that zeaxanthin function as a transducer of CO2 signals in guard cells. Three central aspects of this hypothesis will be investigated: CO2 sensing by the carboxylation reaction of Rubisco in the guard cell chloroplast, which would modulate zeaxanthin concentrations via changes in lumen pH; transduction of the CO2 signal by zeaxanthin via a transducing cascade that controls guard cell osmoregulation; and blue light dependence of the CO2 signal transduction by zeaxanthin, required for the formation of an isomeric form of zeaxanthin that is physiologically active as a transducer. The role of Rubisco in CO2 sensing will be investigated in experiments characterizing the stomatal response to CO2 in the Arabidopsis mutants R100 and rca-, which have reduced rates of Rubisco-dependent carboxylation. The role of zeaxanthin as a CO2 transducer will be studied in npq1, a zeaxanthin-less mutant. The blue light-dependence of CO2 sensing will be studied in experiments characterizing the stomatal response to CO2 under red light. Arabidopsis mutants will also be used in further studies of an acclimation of the stomatal response to CO2, and a possible role of the xanthophyll cycle of the guard cell chloroplast in acclimations of the stomatal response to CO2. Studies on the osmoregulatory role of sucrose in

  10. Bystander T cells in human immune responses to dengue antigens

    Directory of Open Access Journals (Sweden)

    Suwannasaen Duangchan

    2010-09-01

    Full Text Available Abstract Background Previous studies of T cell activation in dengue infection have focused on restriction of specific T cell receptors (TCRs and classical MHC molecules. However, bystander T cell activation, which is TCR independent, occurs via cytokines in other viral infections, both in vitro and in vivo, and enables T cells to bypass certain control checkpoints. Moreover, clinical and pathological evidence has pointed to cytokines as the mediators of dengue disease severity. Therefore, we investigated bystander T cell induction by dengue viral antigen. Results Whole blood samples from 55 Thai schoolchildren aged 13-14 years were assayed for in vitro interferon-gamma (IFN-γ induction in response to inactivated dengue serotype 2 antigen (Den2. The contribution of TCR-dependent and independent pathways was tested by treatment with cyclosporin A (CsA, which inhibits TCR-dependent activation of T cells. ELISA results revealed that approximately 72% of IFN-γ production occurred via the TCR-dependent pathway. The major IFN-γ sources were natural killer (NK (mean ± SE = 55.2 ± 3.3, CD4+T (24.5 ± 3.3 and CD8+T cells (17.9 ± 1.5, respectively, as demonstrated by four-color flow cytometry. Interestingly, in addition to these cells, we found CsA-resistant IFN-γ producing T cells (CD4+T = 26.9 ± 3.6% and CD8+T = 20.3 ± 2.1% implying the existence of activated bystander T cells in response to dengue antigen in vitro. These bystander CD4+ and CD8+T cells had similar kinetics to NK cells, appeared after 12 h and were inhibited by anti-IL-12 neutralization indicating cytokine involvement. Conclusions This study described immune cell profiles and highlighted bystander T cell activation in response to dengue viral antigens of healthy people in an endemic area. Further studies on bystander T cell activation in dengue viral infection may reveal the immune mechanisms that protect or enhance pathogenesis of secondary dengue infection.

  11. Responses of macaque ganglion cells to far violet lights

    International Nuclear Information System (INIS)

    In a sample of 487 colour-opponent ganglion cells recorded in the central retina of the rhesus and cynomolgus monkeys, 9% of these neurones were found to have responses with the same sign at both ends of the visible spectrum mediated by red-sensitive cones and mid-spectral responses of opposite sign mediated by green-sensitive cones. Selective chromatic adaptation showed that the responses to far violet lights (400 to 420 nm) were due to input from red- and not blue-sensitive cones. These responses were enhanced by backgrounds depressing the sensitivity of blue- and green-sensitive cones and they were depressed by backgrounds depressing the sensitivity of red-sensitive cones; the sensitivity of these responses was yoked to that of responses to far red lights. The relative incidence of these ganglion cells was maximal at the foveal region and decreased towards the peripheral retina. The properties of these cells are consistent with some psychophysical observations of human vision at the short wave-lengths. (author)

  12. Assessing the readiness and training needs of non-urban physicians in public health emergency and response.

    Science.gov (United States)

    Hsu, Chiehwen Ed; Mas, Francisco Soto; Jacobson, Holly; Papenfuss, Richard; Nkhoma, Ella T; Zoretic, James

    2005-01-01

    Emergency readiness has become a public health priority for United States communities after the 9/11 attacks. Communities that have a less developed public health infrastructure are challenged to organize preparedness and response efforts and to ensure that health care providers are capable of caring for victims of terrorist acts. A survey was used to assess non-urban physicians' prior experience with and self-confidence in treating, and preferred training needs for responding to chemical, biologic, radiologic, nuclear, and explosive (CBRNE) cases. Data were collected through a mailed and Web-based survey. Although the response rate was calculated at 30%, approximately one third of the surveys were not able to be delivered. Most respondents reported never having seen or treated CBRNE-inflicted cases and were not confident in their ability to diagnose or treat CBRNE cases, but many were willing to participate in a state-led response plan. Almost half of the individuals had not participated in any related training but expressed interest in receiving training in small group workshops or through CD-ROM. These results provide potential direction for strategic preparedness planning for non-urban health care providers. PMID:16216794

  13. Cell response of Chlamydomonas actinochloris culture to repeated microwave irradiation

    Directory of Open Access Journals (Sweden)

    OLESIA O. GRYGORIEVA

    2015-05-01

    Full Text Available Abstract. Grygorieva OO, Berezovsjka MA, Dacenko OI. 2015. Cell response of Chlamydomonas actinochloris culture to repeated microwave irradiation. Nusantara Bioscience 7: 38-42. Two cultures of Chlamydomonas actinochloris Deason et Bold in the lag-phase were exposed to the microwave irradiation. One of them (culture 1 was not treated beforehand, whereas the other (culture 2 was irradiated by microwaves 2 years earlier. The measurement of cell quantity as well as measurement of change of intensities and spectra of cultures photoluminescence (PL in the range of chlorophyll a emission was regularly conducted during the cell cultures development. Cell concentration of culture 1 exposed to the microwave irradiation for the first time has quickly restored while cell concentration of culture 2 which was irradiated repeatedly has fallen significantly. The following increasing of cell concentration of culture 2 is negligible. Cell concentration reaches the steady-state level that is about a half of the cell concentration of control culture. Initially the PL efficiency of cells of both cultures decreases noticeable as a result of irradiation. Then there is the monotonic increase to the values which are significantly higher than the corresponding values in the control cultures. The ratio of the intensities at the maxima of the main emission bands of chlorophyll for control samples of both cultures remained approximately at the same level. At the same time effect of irradiation on the cell PL spectrum appears as a temporary reduction of this magnitude.

  14. Involvement of LSECtin in the hepatic natural killer cell response.

    Science.gov (United States)

    Yang, Juntao; Wang, He; Wang, Min; Liu, Biao; Xu, Hui; Xu, Feng; Zhao, Dianyuan; Hu, Bin; Zhao, Na; Wang, Junyi; Liu, Di; Tang, Li; He, Fuchu

    2016-07-15

    Accumulating evidence has indicated that natural killer cells (NK cells) play an important role in immune responses generated in the liver. However, the underlying molecular basis for local immune regulation is poorly understood. Mice were intraperitoneally injected with polyinosinic-polycytidylic acid (PolyI:C) at a dose of 20 mg/kg body wt. The percentage and absolute number of NK cells in the liver were analysed with flow cytometry. LSECtin knockout mice and LSECtin cDNA plasmids were used for analyze the role of LSECtin in hepatic NK cell regulation in vivo. Here, we show that the C-type lectin LSECtin, a member of the DC-SIGN family, is a novel liver regulator for NK cells. LSECtin could bind to NK cells in a carbohydrate-dependent manner and could regulate the number of hepatic NK cells. In the NK cell-mediated acute liver injury model induced with PolyI:C, the exogenous expression of LSECtin accelerated NK cell-induced liver injury, whereas the absence of LSECtin ameliorated this condition. Our results reveal that LSECtin is a novel, liver-specific NK cell regulator that may be a target for the treatment of inflammatory diseases in the liver. PMID:27184407

  15. Biomechanical changes in endothelial cells result from an inflammatory response

    Science.gov (United States)

    Vaitkus, Janina; Stroka, Kimberly; Aranda-Espinoza, Helim

    2012-02-01

    During periods of infection and disease, the immune system induces the release of TNF-α, an inflammatory cytokine, from a variety of cell types, such as macrophages. TNF-α, while circulating in the vasculature, binds to the apical surface of endothelial cells and causes a wide range of biological and mechanical changes to the endothelium. While the biological changes have been widely studied, the biomechanical aspects have been largely unexplored. Here, we investigated the biomechanical changes of the endothelium as a function of TNF-α treatment. First, we studied the traction forces applied by the endothelium, an effect that is much less studied than others. Through the use of traction force microscopy, we found that TNF-α causes an increase in traction forces applied by the endothelial cells as compared to non-treated cells. Then, we investigated cell morphology, cell mechanics, migration, and cytoskeletal dynamics. We found that in addition to increasing applied traction forces, TNF-α causes an increase in cell area and aspect ratio on average, as well as a shift in the organization of F-actin filaments within the cell. Combining these findings together, our results show that an inflammatory response heavily impacts the morphology, cell mechanics, migration, cytoskeletal dynamics, and applied traction forces of endothelial cells.

  16. Nutritional lipid supply can control the heat shock response of B16 melanoma cells in culture.

    Science.gov (United States)

    Péter, Mária; Balogh, Gábor; Gombos, Imre; Liebisch, Gerhard; Horváth, Ibolya; Török, Zsolt; Nagy, Enikő; Maslyanko, Andriy; Benkő, Sándor; Schmitz, Gerd; Harwood, John L; Vígh, László

    2012-11-01

    The in vitro culture of cells offers an extremely valuable method for probing biochemical questions and many commonly-used protocols are available. For mammalian cells a source of lipid is usually provided in the serum component. In this study we examined the question as to whether the nature of the lipid could become limiting at high cell densities and, therefore, prospectively influence the metabolism and physiology of the cells themselves. When B16 mouse melanoma cells were cultured, we noted a marked decrease in the proportions of n-3 and n-6 polyunsaturated fatty acids (PUFAs) with increasing cell density. This was despite considerable quantities of these PUFAs still remaining in the culture medium and seemed to reflect the preferential uptake of unesterified PUFA rather than other lipid classes from the media. The reduction in B16 total PUFA was reflected in changes in about 70% of the molecular species of membrane phosphoglycerides which were analysed by mass spectrometry. The importance of this finding lies in the need for n-3 and n-6 PUFA in mammalian cells (which cannot synthesize their own). Although the cholesterol content of cells was unchanged the amount of cholesterol enrichment in membrane rafts (as assessed by fluorescence) was severely decreased, simultaneous with a reduced heat shock response following exposure to 42°C. These data emphasize the pivotal role of nutrient supply (in this case for PUFAs) in modifying responses to stress and highlight the need for the careful control of culture conditions when assessing cellular responses in vitro. PMID:22583025

  17. Interstitial cells of Cajal mediate mechanosensitive responses in the stomach

    Science.gov (United States)

    Won, Kyung-Jong; Sanders, Kenton M.; Ward, Sean M.

    2005-10-01

    Changes in motor activity are a basic response to filling of smooth muscle organs. Responses to gastric filling, for example, are thought to be regulated by neural reflexes. Here, we demonstrate a previously uncharacterized aspect of stretch-dependent responses in visceral smooth muscles that is mediated by mechanosensitive interstitial cells of Cajal. Length ramps were applied to the murine antral muscles while recording intracellular electrical activity and isometric force. Stretching muscles by an average of 27 ± 1% of resting length resulted in 5 mN of force. Increasing length caused membrane depolarization and increased slow-wave frequency. The responses were dependent on the rate of stretch. Stretch-dependent responses were not inhibited by neuronal antagonists or nifedipine. Increases in slow-wave frequency, but not membrane depolarization, were inhibited by reducing external Ca2+ (100 μM) and by Ni2+ (250 μM). Responses to stretch were inhibited by indomethacin (1 μM) and were absent in cyclooxygenase II-deficient mice, suggesting that cyclooxygenase II-derived eicosanoids may mediate these responses. Dual microelectrode impalements of muscle cells within the corpus and antrum showed that stretch-induced changes in slow-wave frequency uncoupled proximal-to-distal propagation of slow waves. This uncoupling could interfere with gastric peristalsis and impede gastric emptying. Stretch of antral muscles of W/WV mice, which lack intramuscular interstitial cells of Cajal, did not affect membrane depolarization or slow-wave frequency. These data demonstrate a previously uncharacterized nonneural stretch reflex in gastric muscles and provide physiological evidence demonstrating a mechanosensitive role for interstitial cells of Cajal in smooth muscle tissues. gastric compliance | pacemaker | stretch | slow waves | propagation

  18. Mechanical Response of Single Plant Cells to Cell Poking: A Numerical Simulation Model

    Institute of Scientific and Technical Information of China (English)

    Rong Wang; Qun-Ying Jiao; De-Qiang Wei

    2006-01-01

    Cell poking is an experimental technique that is widely used to study the mechanical properties of plant cells. A full understanding of the mechanical responses of plant cells to poking force is helpful for experimental work. The aim of this study was to numerically investigate the stress distribution of the cell wall,cell turgor, and deformation of plant cells in response to applied poking force. Furthermore, the locations damaged during poking were analyzed. The model simulates cell poking, with the cell treated as a spherical,homogeneous, isotropic elastic membrane, filled with incompressible, highly viscous liquid. Equilibrium equations for the contact region and the non-contact regions were determined by using membrane theory.The boundary conditions and continuity conditions for the solution of the problem were found. The forcedeformation curve, turgor pressure and tension of the cell wall under cell poking conditions were obtained.The tension of the cell wall circumference was larger than that of the meridian. In general, maximal stress occurred at the equator around. When cell deformation increased to a certain level, the tension at the poker tip exceeded that of the equator. Breakage of the cell wall may start from the equator or the poker tip,depending on the deformation. A nonlinear model is suitable for estimating turgor, stress, and stiffness,and numerical simulation is a powerful method for determining plant cell mechanical properties.

  19. Plasticity of airway epithelial cell transcriptome in response to flagellin.

    Directory of Open Access Journals (Sweden)

    Joan G Clark

    Full Text Available Airway epithelial cells (AEC are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using whole-genome microarrays and RNA sequencing. We exposed monolayer and ALI AEC cultures to flagellin in vitro and analyzed the transcriptional response by microarray and RNA-sequencing. ELISA and RT-PCR were used to validate changes in select candidates. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. We conclude that in vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium.

  20. Plasticity of airway epithelial cell transcriptome in response to flagellin.

    Science.gov (United States)

    Clark, Joan G; Kim, Kyoung-Hee; Basom, Ryan S; Gharib, Sina A

    2015-01-01

    Airway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using whole-genome microarrays and RNA sequencing. We exposed monolayer and ALI AEC cultures to flagellin in vitro and analyzed the transcriptional response by microarray and RNA-sequencing. ELISA and RT-PCR were used to validate changes in select candidates. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. We conclude that in vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium. PMID:25668187

  1. Enabling Responsible Energy Decisions: What People Know, Want to Know, and Need to Know about Climate Change

    Science.gov (United States)

    PytlikZillig, L. M.; Tomkins, A. J.; Harrington, J. A.

    2012-12-01

    As part of a broader regional effort focused on climate change education and rural communities, this paper focuses on a specific effort to understand effective approaches to two presumably complementary goals: The goal of increasing knowledge about climate change and climate science in a community, and the goal of having communities use climate change and climate science information when making decisions. In this paper, we explore the argument that people do not need or want to know about climate change, in order to make responsible and sustainable energy decisions. Furthermore, we hypothesize that involvement in making responsible and sustainable energy decisions will increase openness and readiness to process climate science information, and thus increase learning about climate change in subsequent exposures to such information. Support for these hypotheses would suggest that rather than encouraging education to enable action (including engagement in attempts to make responsible decisions), efforts should focus on encouraging actions first and education second. To investigate our hypotheses, we will analyze and report results from efforts to engage residents from a medium-sized Midwestern city to give input on future programs involving sustainable energy use. The engagement process (which will not be complete until after the AGU deadline) involves an online survey and an optional face-to-face discussion with city officials and experts in energy-related areas. The online survey includes brief information about current local energy programs, questions assessing knowledge of climate change, and an open-ended question asking what additional information residents need in order to make good decisions and recommendations concerning the energy programs. To examine support for our hypotheses, we will report (1) relationships between subjective and objective knowledge of climate science and willingness to attend the face-to-face discussion about the city's energy decisions

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

    CERN Document Server

    Liu, Longjian

    2012-01-01

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

  3. Cell responses to FGFR3 signalling: growth, differentiation and apoptosis

    International Nuclear Information System (INIS)

    FGFR3 is a receptor tyrosine kinase (RTK) of the FGF receptor family, known to have a negative regulatory effect on long bone growth. Fgfr3 knockout mice display longer bones and, accordingly, most germline-activating mutations in man are associated with dwarfism. Somatically, some of the same activating mutations are associated with the human cancers multiple myeloma, cervical carcinoma and carcinoma of the bladder. How signalling through FGFR3 can lead to either chondrocyte apoptosis or cancer cell proliferation is not fully understood. Although FGFR3 can be expressed as two main splice isoforms (IIIb or IIIc), there is no apparent link with specific cell responses, which may rather be associated with the cell type or its differentiation status. Depending on cell type, differential activation of STAT proteins has been observed. STAT1 phosphorylation seems to be involved in inhibition of chondrocyte proliferation while activation of the ERK pathway inhibits chondrocyte differentiation and B-cell proliferation (as in multiple myeloma). The role of FGFR3 in epithelial cancers (bladder and cervix) is not known. Some of the cell specificity may arise via modulation of signalling by crosstalk with other signalling pathways. Recently, inhibition of the ERK pathway in achondroplastic mice has provided hope for an approach to the treatment of dwarfism. Further understanding of the ability of FGFR3 to trigger different responses depending on cell type and cellular context may lead to treatments for both skeletal dysplasias and cancer

  4. A response calculus for immobilized T cell receptor ligands

    DEFF Research Database (Denmark)

    Andersen, P S; Menné, C; Mariuzza, R A;

    2001-01-01

    To address the molecular mechanism of T cell receptor (TCR) signaling, we have formulated a model for T cell activation, termed the 2D-affinity model, in which the density of TCR on the T cell surface, the density of ligand on the presenting surface, and their corresponding two-dimensional affini...... affinity in solution, are of optimal two-dimensional affinity thereby allowing effective TCR binding under physiological conditions, i.e. at low ligand densities in cellular interfaces....... determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated the...

  5. Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines.

    Science.gov (United States)

    Good, Michael F; Hawkes, Michael T; Yanow, Stephanie K

    2015-11-01

    Malaria vaccine development is hampered by the lack of small animal models that recapitulate human immune responses to Plasmodium falciparum. We review the burgeoning literature on humanized mice for P. falciparum infection, including challenges in engraftment of human immune cells, hepatocytes, and erythrocytes. Recent advances in immune-compromised mouse models and stem cell technology have already enabled proof of concept that the entire parasite life cycle can be sustained in a murine model and that adaptive human immune responses to several parasite stages can be measured. Nonetheless, optimization is needed to achieve a reproducible and relevant murine model for malaria vaccine development. This review is focused on the complexities of T cell development in a mouse humanized with both a lymphoid system and hepatocytes. An understanding of this will facilitate the use of humanized mice in the development of liver-stage vaccines. PMID:26458783

  6. The Role of the Immune Response in Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Triozzi, Pierre L., E-mail: triozzp@ccf.org [Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Fernandez, Anthony P. [Departments of Dermatology and Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States)

    2013-02-28

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

  7. The Role of the Immune Response in Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies

  8. Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy.

    Directory of Open Access Journals (Sweden)

    Adam Szulkin

    Full Text Available BACKGROUND: Malignant mesothelioma cells have an epithelioid or sarcomatoid morphology, both of which may be present in the same tumor. The sarcomatoid phenotype is associated with worse prognosis and heterogeneity of mesothelioma cells may contribute to therapy resistance, which is often seen in mesothelioma. This study aimed to investigate differences in sensitivity between mesothelioma cell lines to anti-cancer drugs. We studied two novel drugs, selenite and bortezomib and compared their effect to four conventional drugs. We also investigated the immunoreactivity of potential predictive markers for drug sensitivity; Pgp, MRP-1, ERCC1, RRM1, TS, xCT and proteasome 20S subunit. MATERIALS AND METHODS: We treated six mesothelioma cell lines with selenite, bortezomib, carboplatin, pemetrexed, doxorubicin or gemcitabine as single agents and in combinations. Viability was measured after 24 and 48 hours. Immunocytochemistry was used to detect predictive markers. RESULTS: As a single agent, selenite was effective on four out of six cell lines, and in combination with bortezomib yielded the greatest response in the studied mesothelioma cell lines. Cells with an epithelioid phenotype were generally more sensitive to the different drugs than the sarcomatoid cells. Extensive S-phase arrest was seen in pemetrexed-sensitive cell lines. MRP-1 predicted sensitivity of cell lines to treatment with carboplatin and xCT predicted pemetrexed effect. CONCLUSIONS: The observed heterogeneity in sensitivity of mesothelioma cell lines with different morphology highlights the need for more individualized therapy, requiring development of methods to predict drug sensitivity of individual tumors. Selenite and bortezomib showed a superior effect compared to conventional drugs, motivating clinical testing of these agents as future treatment regime components for patients with malignant mesothelioma.

  9. Human T cell responses to dengue virus antigens. Proliferative responses and interferon gamma production.

    OpenAIRE

    Kurane, I; Innis, B L; Nisalak, A; Hoke, C; Nimmannitya, S; Meager, A.; Ennis, F A

    1989-01-01

    The severe complications of dengue virus infections, hemorrhagic manifestations and shock, are more commonly observed during secondary dengue virus infections than during primary infections. It has been speculated that these complications are mediated by cross-reactive host-immune responses. We have begun to analyze human T cell responses to dengue antigens in vitro to explain the possible role of T lymphocytes in the pathogenesis of these complications. Dengue antigens induce proliferative r...

  10. Clinicopathological prognostic implicators of oral squamous cell carcinoma: Need to understand and revise

    OpenAIRE

    Jadhav, Kiran B; Nidhi Gupta

    2013-01-01

    In spite of the vast amount of research and the advances, oral squamous cell carcinoma implies quite significant mortality and morbidity rates. This has motivated the search of factors with prognostic relevance. A web based search was initiated for all published articles by using Medline/PubMed, Google Scholar with key words such as prognosis, survival rate, risk factors associated with oral squamous cell carcinoma, prognosis of oral squamous cell carcinoma. The search was restricted to artic...

  11. Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

    Directory of Open Access Journals (Sweden)

    Klier Ulrike

    2011-09-01

    Full Text Available Abstract Background Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells. Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells. Methods We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays. Results The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4+, activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested could be observed. Conclusion Cellular fusions of MSI+ carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These

  12. Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

    International Nuclear Information System (INIS)

    Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells. Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells. We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays. The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4+, activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested) could be observed. Cellular fusions of MSI+ carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These hybrid cells may have great potential for cellular immunotherapy and

  13. The stringent response and cell cycle arrest in Escherichia coli.

    Science.gov (United States)

    Ferullo, Daniel J; Lovett, Susan T

    2008-12-01

    The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes upon arrest. Nucleoids of these cells are decondensed; in the absence of the ability to synthesize ppGpp, nucleoids become highly condensed, similar to that seen after treatment with the translational inhibitor chloramphenicol. After induction of the stringent response, while regions corresponding to the origins of replication segregate, the termini remain colocalized in wild-type cells. In contrast, cells arrested by rifampicin and cephalexin do not show colocalized termini, suggesting that the stringent response arrests chromosome segregation at a specific point. Release from starvation causes rapid nucleoid reorganization, chromosome segregation, and resumption of replication. Arrest of replication and inhibition of colony formation by ppGpp accumulation is relieved in seqA and dam mutants, although other aspects of the stringent response appear to be intact. We propose that DNA methylation and SeqA binding to non-origin loci is necessary to enforce a full stringent arrest, affecting both initiation of replication and chromosome segregation. This is the first indication that bacterial chromosome segregation, whose mechanism is not understood, is a step that may be regulated in response to environmental conditions. PMID:19079575

  14. The stringent response and cell cycle arrest in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Daniel J Ferullo

    2008-12-01

    Full Text Available The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes upon arrest. Nucleoids of these cells are decondensed; in the absence of the ability to synthesize ppGpp, nucleoids become highly condensed, similar to that seen after treatment with the translational inhibitor chloramphenicol. After induction of the stringent response, while regions corresponding to the origins of replication segregate, the termini remain colocalized in wild-type cells. In contrast, cells arrested by rifampicin and cephalexin do not show colocalized termini, suggesting that the stringent response arrests chromosome segregation at a specific point. Release from starvation causes rapid nucleoid reorganization, chromosome segregation, and resumption of replication. Arrest of replication and inhibition of colony formation by ppGpp accumulation is relieved in seqA and dam mutants, although other aspects of the stringent response appear to be intact. We propose that DNA methylation and SeqA binding to non-origin loci is necessary to enforce a full stringent arrest, affecting both initiation of replication and chromosome segregation. This is the first indication that bacterial chromosome segregation, whose mechanism is not understood, is a step that may be regulated in response to environmental conditions.

  15. Temperature-Responsive Polymer Modified Surface for Cell Sheet Engineering

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    Teruo Okano

    2012-08-01

    Full Text Available In the past two decades, as a novel approach for tissue engineering, cell sheet engineering has been proposed by our laboratory. Poly(N-isopropylacrylamide (PIPAAm, which is a well-known temperature-responsive polymer, has been grafted on tissue culture polystyrene (TCPS surfaces through an electron beam irradiated polymerization. At 37 °C, where the PIPAAm modified surface is hydrophobic, cells can adhere, spread on the surface and grow to confluence. By decreasing temperature to 20 °C, since the surface turns to hydrophilic, cells can detach themselves from the surface spontaneously and form an intact cell sheet with extracellular matrix. For obtaining a temperature-induced cell attachment and detachment, it is necessary to immobilize an ultra thin PIPAAm layer on the TCPS surfaces. This review focuses on the characteristics of PIAPAm modified surfaces exhibiting these intelligent properties. In addition, PIPAAm modified surfaces giving a rapid cell-sheet recovery has been further developed on the basis of the characteristic of the PIPAAm surface. The designs of temperature-responsive polymer layer have provided an enormous potential to fabricate clinically applicable regenerative medicine.

  16. Cell response to quasi-monochromatic light with different coherence

    Science.gov (United States)

    Budagovsky, A. V.; Solovykh, N. V.; Budagovskaya, O. N.; Budagovsky, I. A.

    2015-04-01

    The problem of the light coherence effect on the magnitude of the photoinduced cell response is discussed. The origins of ambiguous interpretation of the known experimental results are considered. Using the biological models, essentially differing in anatomy, morphology and biological functions (acrospires of radish, blackberry microsprouts cultivated in vitro, plum pollen), the effect of statistical properties of quasi-monochromatic light (λmax = 633 nm) on the magnitude of the photoinduced cell response is shown. It is found that for relatively low spatial coherence, the cell functional activity changes insignificantly. The maximal enhancement of growing processes (stimulating effect) is observed when the coherence length Lcoh and the correlation radius rcor are greater than the cell size, i.e., the entire cell fits into the field coherence volume. In this case, the representative indicators (germination of seeds and pollen, the spears length) exceeds those of non-irradiated objects by 1.7 - 3.9 times. For more correct assessment of the effect of light statistical properties on photocontrol processes, it is proposed to replace the qualitative description (coherent - incoherent) with the quantitative one, using the determination of spatial and temporal correlation functions and comparing them with the characteristic dimensions of the biological structures, e.g., the cell size.

  17. Inclusive Education Reform in Bangladesh: Pre-Service Teachers’ Responses to Include Students with Special Educational Needs in Regular Classrooms

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    Md. Saiful Malak

    2013-01-01

    Full Text Available Inclusive education (IE has been recognized as a key strategy to ensure education for all in the developing world for the last two decades. As a developing country, Bangladesh is striving to address IE by undergoing various initiatives such as policy reform, awareness creation and teacher development. This paper based on a qualitative approach attempts to explore pre-service teachers’ responses to include students with special educational needs (SEN in regular classrooms in primary schools. A one-on-one interview was conducted with 20 pre-service teachers who were enrolled in a teacher education program of one public university in Bangladesh. The findings revealed from the study indicate that majority of the pre-service teachers have unfavourable attitudes to include students with SEN in regular classrooms. Misconception and lack of knowledge about disabilities are revealed from most of the pre-service teachers’ responses. Further large class size, high workloads, inflexible curriculum policy of primary education and inadequate experiential learning facilities of teacher education program are identified as barriers to IE reform. Several issues are discussed as implications in order to promote better inclusive practices in regular primary education.

  18. Human neuronal cell protein responses to Nipah virus infection

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    Hassan Sharifah

    2007-06-01

    Full Text Available Abstract Background Nipah virus (NiV, a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. Results Method for separation of the NiV-infected human neuronal cell proteins using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE was established. At least 800 protein spots were resolved of which seven were unique, six were significantly up-regulated and eight were significantly down-regulated. Six of these altered proteins were identified using mass spectrometry (MS and confirmed using MS/MS. The heterogenous nuclear ribonucleoprotein (hnRNP F, guanine nucleotide binding protein (G protein, voltage-dependent anion channel 2 (VDAC2 and cytochrome bc1 were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs H and H2 that were significantly down-regulated. Conclusion Several human neuronal cell proteins that are differentially expressed following NiV infection are identified. The proteins are associated with various cellular functions and their abundance reflects their significance in the cytopathologic responses to the infection and the regulation of NiV replication. The potential importance of the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the association of the mitochondrial protein with the cytopathologic responses to the infection and induction of apoptosis are highlighted.

  19. Monitoring the cytoskeletal EGF response in live gastric carcinoma cells.

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    Marco Felkl

    Full Text Available Altered cell motility is considered to be a key factor in determining tumor invasion and metastasis. Epidermal growth factor (EGF signaling has been implicated in this process by affecting cytoskeletal organization and dynamics in multiple ways. To sort the temporal and spatial regulation of EGF-dependent cytoskeletal re-organization in relation to a cell's motile behavior time-lapse microscopy was performed on EGF-responsive gastric carcinoma-derived MKN1 cells co-expressing different fluorescently labeled cytoskeletal filaments and focal adhesion components in various combinations. The experiments showed that EGF almost instantaneously induces a considerable increase in membrane ruffling and lamellipodial activity that can be inhibited by Cetuximab EGF receptor antibodies and is not elicited in non-responsive gastric carcinoma Hs746T cells. The transient cell extensions are rich in actin but lack microtubules and keratin intermediate filaments. We show that this EGF-induced increase in membrane motility can be measured by a simple image processing routine. Microtubule plus-ends subsequently invade growing cell extensions, which start to accumulate focal complexes at the lamellipodium-lamellum junction. Such paxillin-positive complexes mature into focal adhesions by tyrosine phosphorylation and recruitment of zyxin. These adhesions then serve as nucleation sites for keratin filaments which are used to enlarge the neighboring peripheral keratin network. Focal adhesions are either disassembled or give rise to stable zyxin-rich fibrillar adhesions which disassemble in the presence of EGF to support formation of new focal adhesion sites in the cell periphery. Taken together the results serve as a basis for modeling the early cytoskeletal EGF response as a tightly coordinated and step-wise process which is relevant for the prediction of the effectiveness of anti-EGF receptor-based tumor therapy.

  20. Marrow fat cell: response to x-ray induced aplasia

    International Nuclear Information System (INIS)

    Adipose tissue is an integral structural component of normal rabbit marrow and is believed to behave primarily as a cushion in response to hemopoietic proliferation, accommodating to changes in hemopoiesis by change in either size or number or both of the fat cells in order to maintain constancy of the marrow volume. To test this hypothesis, aplasia of the right femur of New Zealand white rabbits was induced by x irradiation with 8000 rads; the left unirradiated limb served as control. Twenty-four hours before sacrifice 50 μCi of palmitate-114C was administered intravenously and the marrow of both femurs removed. Samples of perinephric fat were taken for comparison. Fat cell volume, C14 palmitate turnover and fatty acid composition were determined. The total number of fat cells in the entire marrow of both femurs was calculated. The measurements showed no difference in size or fatty acid turnover of the fat cells in the irradiated aplastic marrow from the cells of the control marrow. The number of fat cells in both the irradiated and the unirradiated control femurs was essentially the same. These findings do not support the view that marrow fat cells respond to diminished hematopoiesis by either increase in their volume or number. In addition, the findings suggest that both marrow and subcutaneous fat cells are fairly resistant to high doses of x-ray irradiation

  1. Cyclic dinucleotides modulate human T-cell response through monocyte cell death.

    Science.gov (United States)

    Tosolini, Marie; Pont, Frédéric; Verhoeyen, Els; Fournié, Jean-Jacques

    2015-12-01

    Cyclic dinucleotides, a class of microbial messengers, have been recently identified in bacteria, but their activity in humans remains largely unknown. Here, we have studied the function of cyclic dinucleotides in humans. We found that c-di-AMP and cGAMP, two adenosine-based cyclic dinucleotides, activated T lymphocytes in an unusual manner through monocyte cell death. c-di-AMP and cGAMP induced the selective apoptosis of human monocytes, and T lymphocytes were activated by the direct contact with these dying monocytes. The ensuing T-cell response comprised cell-cycle exit, phenotypic maturation into effector memory cells and proliferation arrest, but not cell death. This quiescence was transient since T cells remained fully responsive to further restimulation. Together, our results depict a novel activation pattern for human T lymphocytes: a transient quiescence induced by c-di-AMP- or cGAMP-primed apoptotic monocytes. PMID:26460927

  2. Rat Sertoli cells acquire a β-adrenergic response during primary culture

    International Nuclear Information System (INIS)

    Two-dimensional polyacrylamide gel electrophoresis and the radioligand (-)-[125I]iodopindolol (125I-Pin) have been used to study isoproterenol-dependent protein phosphorylation and β-adrenergic receptor availability, respectively, in cultured Sertoli cells and freshly isolated seminiferous tubular segments of sexually immature and mature rats. Sertoli cells prepared from sexually immature rats show progressive 125I-Pin binding in primary cultures that correlates with isoproterenol-induced cell shape changes, redistribution of immunoreactive vimentin, and phosphorylation of this intermediate filament protein. Seminiferous tubules do not show significant isoproterenol-dependent vimentin phosphorylation nor 125I-Pin binding. However, vimentin phosphorylation can be induced by follicle-stimulating hormone or a cyclic nucleotide analog. This study stresses the need for correlating pharmacological-induced responses observed in Sertoli cell primary cultures with those in the intact seminiferous tubule

  3. Epithelial cells, the "switchboard" of respiratory immune defense responses: effects of air pollutants.

    Science.gov (United States)

    Müller, Loretta; Jaspers, Ilona

    2012-01-01

    "Epimmunome", a term introduced recently by Swamy and colleagues, describes all molecules and pathways used by epithelial cells (ECs) to instruct immune cells. Today, we know that ECs are among the first sites within the human body to be exposed to pathogens (such as influenza viruses) and that the release of chemokine and cytokines by ECs is influenced by inhaled agents. The role of the ECs as a switchboard to initiate and regulate immune responses is altered through air pollutant exposure, such as ozone, tobacco smoke and diesel exhaust emissions. The details of the interplay between ECs and immune cells are not yet fully understood and need to be investigated further. Co-culture models, cell specific genetically-modified mice and the analysis of human biopsies provide great tools to gain knowledge about potential mechanisms. Increasing our understanding about the role of ECs in respiratory immunity may yield novel therapeutic targets to modulate downstream diseases. PMID:22851042

  4. New Modeling Approaches to Investigate Cell Signaling in Radiation Response

    Science.gov (United States)

    Plante, Ianik; Cucinotta, Francis A.; Ponomarev, Artem L.

    2011-01-01

    Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine

  5. Oral microbial biofilm stimulation of epithelial cell responses.

    Science.gov (United States)

    Peyyala, Rebecca; Kirakodu, Sreenatha S; Novak, Karen F; Ebersole, Jeffrey L

    2012-04-01

    Oral bacterial biofilms trigger chronic inflammatory responses in the host that can result in the tissue destructive events of periodontitis. However, the characteristics of the capacity of specific host cell types to respond to these biofilms remain ill-defined. This report describes the use of a novel model of bacterial biofilms to stimulate oral epithelial cells and profile select cytokines and chemokines that contribute to the local inflammatory environment in the periodontium. Monoinfection biofilms were developed with Streptococcus sanguinis, Streptococcus oralis, Streptococcus gordonii, Actinomyces naeslundii, Fusobacterium nucleatum, and Porphyromonas gingivalis on rigid gas-permeable contact lenses. Biofilms, as well as planktonic cultures of these same bacterial species, were incubated under anaerobic conditions with a human oral epithelial cell line, OKF4, for up to 24h. Gro-1α, IL1α, IL-6, IL-8, TGFα, Fractalkine, MIP-1α, and IP-10 were shown to be produced in response to a range of the planktonic or biofilm forms of these species. P. gingivalis biofilms significantly inhibited the production of all of these cytokines and chemokines, except MIP-1α. Generally, the biofilms of all species inhibited Gro-1α, TGFα, and Fractalkine production, while F. nucleatum biofilms stimulated significant increases in IL-1α, IL-6, IL-8, and IP-10. A. naeslundii biofilms induced elevated levels of IL-6, IL-8 and IP-10. The oral streptococcal species in biofilms or planktonic forms were poor stimulants for any of these mediators from the epithelial cells. The results of these studies demonstrate that oral bacteria in biofilms elicit a substantially different profile of responses compared to planktonic bacteria of the same species. Moreover, certain oral species are highly stimulatory when in biofilms and interact with host cell receptors to trigger pathways of responses that appear quite divergent from individual bacteria. PMID:22266273

  6. Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type

    Science.gov (United States)

    Im, Maesoon; Fried, Shelley I.

    2016-04-01

    Objective. To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates. Approach. We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10-1000 ms). Each stimulus was a 4 ms long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode. Main results. ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported ‘reset’ behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4-7 Hz) that maximized the ratio of the responses arising in ON versus OFF cells. Significance. Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5-7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (> ˜7 Hz) due to the reset while responses of OFF cells are strong at low rates (< ˜4 Hz) due to reduced desensitization, both reducing the ratio

  7. Killing of Brain Tumor Cells by Hypoxia-Responsive Element Mediated Expression of BAX1

    Science.gov (United States)

    Ruan, Hangjun; Wang, Jingli; Hu, Lily; Lin, Ching-Shwun; Lamborn, Kathleen R; Deen, Dennis F

    1999-01-01

    Abstract The presence of radioresistant hypoxic cells in human brain tumors limits the overall effectiveness of conventional fractionated radiation therapy. Tumor-specific therapies that target hypoxic cells are clearly needed. We have investigated the expression of suicide genes under hypoxia by a hypoxia-responsive element (HRE), which can be activated through hypoxia-inducible factor-1 (HIF-1). We transfected plasmids containing multiple copies of HRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ gene expression under anoxia. Gene expression under anoxia versus oxia was increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87 MG cells was induced by the plasmid that contained three HREs, but not by the plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the control of HREs, cells transfected with the BAX plasmids were preferentially killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated gene expression is active in brain tumor cells, and that the amount of increased gene expression obtained is dependent on the cell line, the HRE copy number, and the degree of hypoxia. PMID:10933058

  8. Killing of Brain Tumor Cells by Hypoxia-Responsive Element Mediated Expression of BAX

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    Hangjun Ruan

    1999-11-01

    Full Text Available The presence of radioresistant hypoxic cells in human brain tumors limits the overall effectiveness of conventional fractionated radiation therapy. Tumor-specific therapies that target hypoxic cells are clearly needed. We have investigated the expression of suicide genes under hypoxia by a hypoxia-responsive element (HRE, which can be activated through hypoxia-inducible factor-1 (HIF-1. We transfected plasmids containing multiple copies of HIRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ gene expression under anoxia. Gene expression under anoxia versus oxia was increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87 MG cells was induced by the plasmid that contained three HREs, but not by the plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the control of HREs, cells transfected with the BAX plasmids were preferentially killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated gene expression is active in brain tumor cells, and that the amount of increased gene expression obtained is dependent on the cell line, the HIRE copy number, and the degree of hypoxia.

  9. Nitric Oxide And Hypoxia Response In Pluripotent Stem Cells

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    Estefanía Caballano Infantes

    2015-08-01

    Full Text Available The expansion of pluripotent cells (ESCs and iPSCs under conditions that maintain their pluripotency is necessary to implement a cell therapy program. Previously, we have described that low nitric oxide (NO donor diethylenetriamine/nitric oxide adduct (DETA-NO added to the culture medium, promote the expansion of these cell types. The molecular mechanisms are not yet known. We present evidences that ESC and iPSCs in normoxia in presence of low NO triggers a similar response to hypoxia, thus maintaining the pluripotency. We have studied the stability of HIF-1α (Hypoxia Inducible Factor in presence of low NO. Because of the close relationship between hypoxia, metabolism, mitochondrial function and pluripotency we have analyzed by q RT-PCR the expression of genes involved in the glucose metabolism such as: HK2, LDHA and PDK1; besides other HIF-1α target gene. We further analyzed the expression of genes involved in mitochondrial biogenesis such as PGC1α, TFAM and NRF1 and we have observed that low NO maintains the same pattern of expression that in hypoxia. The study of the mitochondrial membrane potential using Mito-Tracker dye showed that NO decrease the mitochondrial function. We will analyze other metabolic parameters, to determinate if low NO regulates mitochondrial function and mimics Hypoxia Response. The knowledge of the role of NO in the Hypoxia Response and the mechanism that helps to maintain self-renewal in pluripotent cells in normoxia, can help to the design of culture media where NO could be optimal for stem cell expansion in the performance of future cell therapies.

  10. Cell wall modification in grapevine cells in response to UV stress investigated by atomic force microscopy

    International Nuclear Information System (INIS)

    Despite cell wall reinforcement being a well-known defence mechanism of plants, it remains poorly characterized from a physical point of view. The objective of this work was to further describe this mechanism. Vitis vinifera cv Gamay cells were treated with UV-light (254 nm), a well-known elicitor of defence mechanisms in grapevines, and physical cell wall modifications were observed using the atomic force microscopy (AFM) under native conditions. The grapevine cell suspensions were continuously observed in their culture medium from 30 min to 24 h after elicitation. In the beginning, cellulose fibrils covered by a matrix surrounded the control and treated cells. After 3 h, the elicited cells displayed sprouted expansions around the cell wall that correspond to pectin chains. These expansions were not observed on untreated grapevine cells. The AFM tip was used to determine the average surface elastic modulus of cell wall that account for cell wall mechanical properties. The elasticity is diminished in UV-treated cells. In a comparative study, grapevine cells showed the same decrease in cell wall elasticity when treated with a fungal biotic elicitor of defence response. These results demonstrate cell wall strengthening by UV stress

  11. IL-22 dampens the T cell response in experimental malaria

    Science.gov (United States)

    Sellau, Julie; Alvarado, Catherine Fuentes; Hoenow, Stefan; Mackroth, Maria Sophie; Kleinschmidt, Dörte; Huber, Samuel; Jacobs, Thomas

    2016-01-01

    A tight regulation between the pro– and anti–inflammatory immune responses during plasmodial infection is of crucial importance, since a disruption leads to severe malaria pathology. IL-22 is a member of the IL-10 cytokine family, which is known to be highly important in immune regulation. We could detect high plasma levels of IL-22 in Plasmodium falciparum malaria as well as in Plasmodium berghei ANKA (PbA)-infected C57BL/6J mice. The deficiency of IL-22 in mice during PbA infection led to an earlier occurrence of cerebral malaria but is associated with a lower parasitemia compared to wt mice. Furthermore, at an early time point of infection T cells from PbA-infected Il22−/− mice showed an enhanced IFNγ but a diminished IL-17 production. Moreover, dendritic cells from Il22−/− mice expressed a higher amount of the costimulatory ligand CD86 upon infection. This finding can be corroborated in vitro since bone marrow-derived dendritic cells from Il22−/− mice are better inducers of an antigen-specific IFNγ response by CD8+ T cells. Even though there is no IL-22 receptor complex known on hematopoietic cells, our data suggest a link between IL-22 and the adaptive immune system which is currently not identified. PMID:27311945

  12. DNA Damage Response in Hematopoietic Stem Cell Ageing.

    Science.gov (United States)

    Li, Tangliang; Zhou, Zhong-Wei; Ju, Zhenyu; Wang, Zhao-Qi

    2016-06-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing. PMID:27221660

  13. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Institute of Scientific and Technical Information of China (English)

    Tangliang Li; Zhong-Wei Zhou; Zhenyu Ju; Zhao-Qi Wang

    2016-01-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employ-ing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically reg-ulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  14. Radiation Response of Cultured Human Cells Is Unaffected by Johrei

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    Zach Hall

    2007-01-01

    Full Text Available Johrei has been credited with healing thousands from radiation wounds after the Hiroshima and Nagasaki bombs in 1945. This alternative medical therapy is becoming increasingly popular in the United States, as are other Energy Medicine modalities that purport to influence a universal healing energy. Human brain cells were cultured and exposed to increasing doses of ionizing radiation. Experienced Johrei practitioners directed healing intentionality toward the cells for 30 min from a distance of 20 cm and the fate of the cells was observed by computerized time-lapse microscopy. Cell death and cell divisions were tallied every 30 min before, during and after Johrei treatment for a total of 22.5 h. An equal number of control experiments were conducted in which cells were irradiated but did not receive Johrei treatment. Samples were assigned to treatment conditions randomly and data analysis was conducted in a blinded fashion. Radiation exposure decreased the rate of cell division (cell cycle arrest in a dose-dependent manner. Division rates were estimated for each 30 min and averaged over 8 independent experiments (4 control and 4 with Johrei treatment for each of 4 doses of X-rays (0, 2, 4 and 8 Gy. Because few cell deaths were observed, pooled data from the entire observation period were used to estimate death rates. Analysis of variance did not reveal any significant differences on division rate or death rate between treatment groups. Only radiation dose was statistically significant. We found no indication that the radiation response of cultured cells is affected by Johrei treatment.

  15. Radiation response of cultured human cells is unaffected by Johrei.

    Science.gov (United States)

    Hall, Zach; Luu, Tri; Moore, Dan; Yount, Garret

    2007-06-01

    Johrei has been credited with healing thousands from radiation wounds after the Hiroshima and Nagasaki bombs in 1945. This alternative medical therapy is becoming increasingly popular in the United States, as are other Energy Medicine modalities that purport to influence a universal healing energy. Human brain cells were cultured and exposed to increasing doses of ionizing radiation. Experienced Johrei practitioners directed healing intentionality toward the cells for 30 min from a distance of 20 cm and the fate of the cells was observed by computerized time-lapse microscopy. Cell death and cell divisions were tallied every 30 min before, during and after Johrei treatment for a total of 22.5 h. An equal number of control experiments were conducted in which cells were irradiated but did not receive Johrei treatment. Samples were assigned to treatment conditions randomly and data analysis was conducted in a blinded fashion. Radiation exposure decreased the rate of cell division (cell cycle arrest) in a dose-dependent manner. Division rates were estimated for each 30 min and averaged over 8 independent experiments (4 control and 4 with Johrei treatment) for each of 4 doses of X-rays (0, 2, 4 and 8 Gy). Because few cell deaths were observed, pooled data from the entire observation period were used to estimate death rates. Analysis of variance did not reveal any significant differences on division rate or death rate between treatment groups. Only radiation dose was statistically significant. We found no indication that the radiation response of cultured cells is affected by Johrei treatment. PMID:17549235

  16. Interleukin-21 triggers effector cell responses in the gut

    Institute of Scientific and Technical Information of China (English)

    Daniela; De; Nitto; Massimiliano; Sarra; Francesco; Pallone; Giovanni; Monteleone

    2010-01-01

    In the gut of patients with Crohn's disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-talk between immune and non-immune cells.Accumulating evidence indicates also that cytokines produced by these cells play a major role in initiating and shaping this pathologic process.One such cytokine seems to be interleukin(IL)-21,a member of the common γ-chainreceptor family.IL-21 is produced in e...

  17. Cells responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers

    International Nuclear Information System (INIS)

    Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). 154 references

  18. Activation of regulatory T cells during inflammatory response is not an exclusive property of stem cells.

    Directory of Open Access Journals (Sweden)

    Jan-Hendrik Gosemann

    Full Text Available BACKGROUND: Sepsis and systemic-inflammatory-response-syndrome (SIRS remain major causes for fatalities on intensive care units despite up-to-date therapy. It is well accepted that stem cells have immunomodulatory properties during inflammation and sepsis, including the activation of regulatory T cells and the attenuation of distant organ damage. Evidence from recent work suggests that these properties may not be exclusively attributed to stem cells. This study was designed to evaluate the immunomodulatory potency of cellular treatment during acute inflammation in a model of sublethal endotoxemia and to investigate the hypothesis that immunomodulations by cellular treatment during inflammatory response is not stem cell specific. METHODOLOGY/PRINCIPAL FINDINGS: Endotoxemia was induced via intra-peritoneal injection of lipopolysaccharide (LPS in wild type mice (C3H/HeN. Mice were treated with either vital or homogenized amniotic fluid stem cells (AFS and sacrificed for specimen collection 24 h after LPS injection. Endpoints were plasma cytokine levels (BD™ Cytometric Bead Arrays, T cell subpopulations (flow-cytometry and pulmonary neutrophil influx (immunohistochemistry. To define stem cell specific effects, treatment with either vital or homogenized human-embryonic-kidney-cells (HEK was investigated in a second subset of experiments. Mice treated with homogenized AFS cells showed significantly increased percentages of regulatory T cells and Interleukin-2 as well as decreased amounts of pulmonary neutrophils compared to saline-treated controls. These results could be reproduced in mice treated with vital HEK cells. No further differences were observed between plasma cytokine levels of endotoxemic mice. CONCLUSIONS/SIGNIFICANCE: The results revealed that both AFS and HEK cells modulate cellular immune response and distant organ damage during sublethal endotoxemia. The observed effects support the hypothesis, that immunomodulations are not

  19. Curcumin prevents human dendritic cell response to immune stimulants

    Science.gov (United States)

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

    2012-01-01

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14+ monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing naïve CD4+ T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant. PMID:18639521

  20. Oral epithelial cell responses to multispecies microbial biofilms.

    Science.gov (United States)

    Peyyala, R; Kirakodu, S S; Novak, K F; Ebersole, J L

    2013-03-01

    This report describes the use of a novel model of multispecies biofilms to stimulate profiles of cytokines/chemokines from oral epithelial cells that contribute to local inflammation in the periodontium. Streptococcus gordonii (Sg)/S. oralis (So)/S. sanguinis (Ss) and Sg/Fusobacterium nucleatum (Fn)/Porphyromonas gingivalis (Pg) biofilms elicited significantly elevated levels of IL-1α and showed synergistic stimulatory activity compared with an additive effect of the 3 individual bacteria. Only the Sg/Actinomyces naeslundii (An)/Fn multispecies biofilms elicited IL-6 levels above those of control. IL-8 was a primary response to the Sg/An/Fn biofilms, albeit the level was not enhanced compared with a predicted composite level from the monospecies challenges. These results represent some of the first data documenting alterations in profiles of oral epithelial cell responses to multispecies biofilms. PMID:23300185

  1. Curcumin prevents human dendritic cell response to immune stimulants

    International Nuclear Information System (INIS)

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14+ monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4+ T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

  2. Purinergic responses of chondrogenic stem cells to dynamic loading

    Directory of Open Access Journals (Sweden)

    Gađanski Ivana

    2013-01-01

    Full Text Available In habitually loaded tissues, dynamic loading can trigger ATP (adenosine 5’- triphosphate release to extracellular environment, and result in calcium signaling via ATP binding to purine P2 receptors1. In the current study we have compared purinergic responses (ATP release of two types of cells: bovine chondrocytes (bCHs and human mesenchymal stem cells (hMSC that were encapsulated in agarose and subjected to dynamic loading. Both cell types were cultured under chondrogenic conditions, and their responses to loading were evaluated by ATP release assay in combination with connexin (Cx-sensitive fluorescent dye (Lucifer Yellow - LY and a Cx-hemichannel blocker (Flufenamic acid - FFA. In response to dynamic loading, chondrogenic hMSCs released significantly higher amounts of ATP (5-fold in comparison to the bCHs early in culture (day 2. Triggering of LY uptake in the bCHs and hMSCs by dynamic loading implies opening of the Cx-hemichannels. However, the number of LY-positive cells in hMSC-constructs was 2.5-fold lower compared to the loaded bCH-constructs, suggesting utilization of additional mechanisms of ATP release. Cx-reactive sites were detected in both bCHs and hMSCs-constructs. FFA application led to reduced ATP release both in bCHs and hMSCs, which confirms the involvement of connexin hemichannels, with more prominent effects in bCHs than in hMSCs, further implying the existence of additional mechanism of ATP release in chondrogenic hMSCs. Taken together, these results indicate stronger purinergic response to dynamic loading of chondrogenic hMSCs than primary chondrocytes, by activation of connexin hemichannels and additional mechanisms of ATP release. [Projekat Ministrastva nauke Republike Srbije, ON174028 i br. III41007

  3. The intestinal B-cell response in celiac disease.

    OpenAIRE

    Mesin, Luka; Sollid, Ludvig M.; Niro, Roberto Di

    2012-01-01

    The function of intestinal immunity is to provide protection toward pathogens while preserving the composition of the microflora and tolerance to orally fed nutrients. This is achieved via a number of tightly regulated mechanisms including production of IgA antibodies by intestinal plasma cells. Celiac disease is a common gut disorder caused by a dysfunctional immune regulation as signified, among other features, by a massive intestinal IgA autoantibody response. Here we review the current kn...

  4. Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.

    Science.gov (United States)

    Lau, Colleen M; Nish, Simone A; Yogev, Nir; Waisman, Ari; Reiner, Steven L; Reizis, Boris

    2016-03-01

    A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3(ITD) knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3(ITD/ITD) mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8(+) cDCs and noncanonical CD8(+) cDCs were expanded and showed specific alterations in their expression profiles. Flt3(ITD) mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. PMID:26903243

  5. NK cells enhance dendritic cell response against parasite antigens via NKG2D pathway.

    Science.gov (United States)

    Guan, Hongbing; Moretto, Magali; Bzik, David J; Gigley, Jason; Khan, Imtiaz A

    2007-07-01

    Recent studies have shown that NK-dendritic cell (DC) interaction plays an important role in the induction of immune response against tumors and certain viruses. Although the effect of this interaction is bidirectional, the mechanism or molecules involved in this cross-talk have not been identified. In this study, we report that coculture with NK cells causes several fold increase in IL-12 production by Toxoplasma gondii lysate Ag-pulsed DC. This interaction also leads to stronger priming of Ag-specific CD8+ T cell response by these cells. In vitro blockade of NKG2D, a molecule present on human and murine NK cells, neutralizes the NK cell-induced up-regulation of DC response. Moreover, treatment of infected animals with Ab to NKG2D receptor compromises the development of Ag-specific CD8+ T cell immunity and reduces their ability to clear parasites. These studies emphasize the critical role played by NKG2D in the NK-DC interaction, which apparently is important for the generation of robust CD8+ T cell immunity against intracellular pathogens. To the best of our knowledge, this is the first work that describes in vivo importance of NKG2D during natural infection. PMID:17579080

  6. Radiotherapy preserves fingers in the management of subungual squamous cell carcinoma, obviating the need for amputation

    International Nuclear Information System (INIS)

    A retrospective study of the use of radiotherapy in 12 patients with subungual squamous cell carcinoma of the finger was conducted at two radiotherapy departments in the Netherlands. This malignancy has little tendency to metastasize and is usually treated by amputation. Primary radiotherapy resulted in a permanent local control of 92% with only one serious adverse effect leading to an amputation of the initially involved digit. No regional or distant failure was seen during follow-up. Radiotherapy should be considered as an alternative for amputation to treat patients with subungual squamous cell carcinoma of the finger

  7. Intestinal T cell responses to cereal proteins in celiac disease.

    Science.gov (United States)

    Kilmartin, C; Wieser, H; Abuzakouk, M; Kelly, J; Jackson, J; Feighery, C

    2006-01-01

    Celiac disease is caused by sensitivity to wheat gluten in genetically susceptible individuals. The etiological role of the other wheat-related cereals, barley, rye, and oats, is still debated. In order to investigate this issue further, in this study we examined the immune response of celiac mucosal T cell lines to fractions from all four cereals. Cell stimulation was assessed by measuring proliferation (employing (3)H-thymidine incorporation) or cytokine (IL-2, IFN-gamma) production. All five T cell lines demonstrated immunoreactivity to protein fractions from the four related cereals. In some cell lines, reactivity to wheat, barley, and rye was only evident when these cereal fractions had been pretreated with tissue transglutaminase. This study confirms the similar T cell antigenic reactivity of these four related cereals and has implications for their exclusion in the gluten-free diet. However, despite oats stimulation of T cell lines, this cereal does not activate a mucosal lesion in most celiac patients. PMID:16416236

  8. Putting Corporate Social Responsibility to Work in Mining Communities: Exploring Community Needs for Central Appalachian Wastewater Treatment

    Directory of Open Access Journals (Sweden)

    Nicholas Cook

    2015-04-01

    Full Text Available Due to the finite nature of non-renewable mineral and energy resources such as coal, resource extraction is inherently unsustainable; however, mining and related activities can contribute to sustainable development. Indeed, the principles of corporate social responsibility (CSR require that mine operators design and conduct their activities in ways that provide for net positive impacts on surrounding communities and environments. In Central Appalachia, there appears to be a particularly ripe opportunity for the coal industry to put CSR to work: participation in sustainable solutions to the long-standing problem of inadequately treated wastewater discharges—which not only represent a potential human health hazard, but also contribute to the relatively high incidence of bacterial impairments in surface waters in the region. In this paper, we outline the underlying factors of this problem and the advantages of industry-aided solutions in a region where limited economic and technical resources are not always aligned with social and environmental needs. We also suggest a framework for problem-solving, which necessarily involves all interested stakeholders, and identify the primary challenges that must be overcome in pursuit of sustainable solutions.

  9. Gene expression in epithelial cells in response to pneumovirus infection

    Directory of Open Access Journals (Sweden)

    Rosenberg Helene F

    2001-05-01

    Full Text Available Abstract Respiratory syncytial virus (RSV and pneumonia virus of mice (PVM are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood. Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner.

  10. Cell mediated immune response in human antirabies revaccination

    Directory of Open Access Journals (Sweden)

    Débora Regina Veiga

    1987-04-01

    Full Text Available The occurrence of secondary cell mediated immune response (CMI in human antirabies immunization was studied. The Puenzalida & Palácios vaccine was used because it is routinely used in Brazil. CMI was evaluated by lymphoblastic transformation indices obtained in whole blood culture in the presence of rabies and control (nervous tissue antigens. Eleven volunteers submitted to revaccination constituted the group under study, while three other volunteers submitted primo vaccination were utilized as control group. A clear secondary CMI to rabies antigen was detected in all the revaccinated volunteers who showed earlier and more intense response than the control group. Response to the control antigen, however, present in all the components of the first group was not detectable in two out of the three primovaccinated and very low in the third one.

  11. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro

    OpenAIRE

    1989-01-01

    We used well-gassed hanging drop (20 microliters) cultures with high concentrations of purified T cells from normal BALB/c mice to examine whether dendritic cells (DC) can induce primary antiviral proliferative T cell responses and generate virus-specific CTL. We found that DC exposed to infectious influenza virus in vitro or in vivo in small numbers (0.1-1%) resulted in strong proliferation of responder T cells within 3 d, and this was strongly inhibited by antibodies to class II MHC molecul...

  12. Transcriptional profiling of foam cells in response to hypercholesterolemia.

    Science.gov (United States)

    Goo, Young-Hwa; Yechoor, Vijay K; Paul, Antoni

    2016-09-01

    Hypercholesterolemia is a main risk factor for atherosclerosis development. Arterial macrophages, or foam cells, take-up and process lipoprotein particles deposited in arteries, and store much of the cholesterol carried by these particles in their cytoplasm. However, the effects of exposure to different cholesterol levels on foam cells remain poorly understood. Given the remarkable plasticity of macrophages in response to environmental variables, studies on macrophage biology should ideally be performed in the environment where they exert their physiological functions, namely atherosclerotic lesions in the case of foam cells. We used a mouse model of atherosclerosis, the apolipoprotein E-deficient mouse, to study in vivo the transcriptional response of foam cells to short- and long-term elevations in plasma cholesterol, induced by feeding mice a western type diet. The microarray data sets from this study have been deposited in NCBI's Gene Expression Omnibus under the accession number GSE70619. Here we provide detailed information on the experimental set-up, on the isolation of RNA by laser capture microdissection, and on the methodology used for RNA amplification and analysis by microarray and quantitative real-time PCR. PMID:27408807

  13. Modification of radiation response in V79 cells with solcoseryl

    International Nuclear Information System (INIS)

    Solcoseryl is a deproteinized extract of calf serum which has been used for various purposes. It has been shown to simulate wound healing, to protect against carbon monoxide poisoning and to prevent teratogenic effects of cyclosphosphamide in mice. In addition, it has been reported to be a radiation protector and to modify radiation response in patients undergoing radiation treatment. The present study attempted to assess the effect of Solcoseryl on V79 cell survival and DNA damage after gamma irradiation. WR-1065 (4mM) was tested for comparative purpose. DNA damage was assayed using the alkaline elution technique while cell survival was determined in vitro using a standard clongenic assay. The results indicate that Solcoseryl doses protect against single-strand DNA breaks (SSB) but has little if any protective effect on cell survival. WR-1065- however, protects against both SSB and survival after gamma irradiation

  14. A new method to address unmet needs for extracting individual cell migration features from a large number of cells embedded in 3D volumes.

    Directory of Open Access Journals (Sweden)

    Ivan Adanja

    Full Text Available BACKGROUND: In vitro cell observation has been widely used by biologists and pharmacologists for screening molecule-induced effects on cancer cells. Computer-assisted time-lapse microscopy enables automated live cell imaging in vitro, enabling cell behavior characterization through image analysis, in particular regarding cell migration. In this context, 3D cell assays in transparent matrix gels have been developed to provide more realistic in vitro 3D environments for monitoring cell migration (fundamentally different from cell motility behavior observed in 2D, which is related to the spread of cancer and metastases. METHODOLOGY/PRINCIPAL FINDINGS: In this paper we propose an improved automated tracking method that is designed to robustly and individually follow a large number of unlabeled cells observed under phase-contrast microscopy in 3D gels. The method automatically detects and tracks individual cells across a sequence of acquired volumes, using a template matching filtering method that in turn allows for robust detection and mean-shift tracking. The robustness of the method results from detecting and managing the cases where two cell (mean-shift trackers converge to the same point. The resulting trajectories quantify cell migration through statistical analysis of 3D trajectory descriptors. We manually validated the method and observed efficient cell detection and a low tracking error rate (6%. We also applied the method in a real biological experiment where the pro-migratory effects of hyaluronic acid (HA were analyzed on brain cancer cells. Using collagen gels with increased HA proportions, we were able to evidence a dose-response effect on cell migration abilities. CONCLUSIONS/SIGNIFICANCE: The developed method enables biomedical researchers to automatically and robustly quantify the pro- or anti-migratory effects of different experimental conditions on unlabeled cell cultures in a 3D environment.

  15. Monosaccharide-responsive phenylboronate-polyol cell scaffolds for cell sheet and tissue engineering applications.

    Directory of Open Access Journals (Sweden)

    Rachamalla Maheedhar Reddy

    Full Text Available Analyte-responsive smart polymeric materials are of great interest and have been actively investigated in the field of regenerative medicine. Phenylboronate containing copolymers form gels with polyols under alkaline conditions. Monosaccharides, by virtue of their higher affinity towards boronate, can displace polyols and solubilize such gels. In the present study, we investigate the possibility of utilizing phenylboronate-polyol interactions at physiological pH in order to develop monosaccharide-responsive degradable scaffold materials for systems dealing with cells and tissues. Amine assisted phenylboronate-polyol interactions were employed to develop novel hydrogel and cryogel scaffolds at neutral pH. The scaffolds displayed monosaccharide inducible gel-sol phase transformability. In vitro cell culture studies demonstrated the ability of scaffolds to support cell adhesion, viability and proliferation. Fructose induced gel degradation is used to recover cells cultured on the hydrogels. The cryogels displayed open macroporous structure and superior mechanical properties. These novel phase transformable phenylboronate-polyol based scaffolds displayed a great potential for various cell sheet and tissue engineering applications. Their monosaccharide responsiveness at physiological pH is very useful and can be utilized in the fields of cell immobilization, spheroid culture, saccharide recognition and analyte-responsive drug delivery.

  16. Parallel analysis of mucosally derived B- and T-cell responses to an oral typhoid vaccine using simplified methods.

    Science.gov (United States)

    Lundgren, Anna; Kaim, Joanna; Jertborn, Marianne

    2009-07-16

    There is a great need for simple methods for analysis of immune responses to mucosal vaccines that can be used on small blood volumes in field trials in both children and adults. We have investigated if mucosally derived B- and T-cell responses can be monitored in parallel by analysis of antibodies and T-cell effector molecules in culture supernatants from circulating blood lymphocytes obtained from orally vaccinated Swedes. Immunization with a live oral model vaccine, i.e. Salmonellaenterica serovar Typhi Ty21a, gave rise to secretion of typhoid specific IgA and IgM antibodies from peripheral blood mononuclear cells (PBMCs) and this response could be equally well detected by ELISA and ELISPOT 7 days after vaccination. The ELISA based assay could be further simplified by using buffy coat cells, but not by using whole blood or frozen PBMCs. Vaccine induced T-cell responses appeared later than the B-cell responses, but could be detected by ELISA assessment of IFN-gamma and granzymes in supernatants from antigen stimulated PBMCs 21 days after vaccination. Thus, both B- and T-cell responses could be detected using simple ELISA based assays that would be practical to use in large-scale vaccine trials. PMID:19446596

  17. Highly sensitive quantitative imaging for monitoring single cancer cell growth kinetics and drug response.

    Directory of Open Access Journals (Sweden)

    Mustafa Mir

    Full Text Available The detection and treatment of cancer has advanced significantly in the past several decades, with important improvements in our understanding of the fundamental molecular and genetic basis of the disease. Despite these advancements, drug-screening methodologies have remained essentially unchanged since the introduction of the in vitro human cell line screen in 1990. Although the existing methods provide information on the overall effects of compounds on cell viability, they are restricted by bulk measurements, large sample sizes, and lack capability to measure proliferation kinetics at the individual cell level. To truly understand the nature of cancer cell proliferation and to develop personalized adjuvant therapies, there is a need for new methodologies that provide quantitative information to monitor the effect of drugs on cell growth as well as morphological and phenotypic changes at the single cell level. Here we show that a quantitative phase imaging modality known as spatial light interference microscopy (SLIM addresses these needs and provides additional advantages over existing proliferation assays. We demonstrate these capabilities through measurements on the effects of the hormone estradiol and the antiestrogen ICI182,780 (Faslodex on the growth of MCF-7 breast cancer cells. Along with providing information on changes in the overall growth, SLIM provides additional biologically relevant information. For example, we find that exposure to estradiol results in rapidly growing cells with lower dry mass than the control population. Subsequently blocking the estrogen receptor with ICI results in slower growing cells, with lower dry masses than the control. This ability to measure changes in growth kinetics in response to environmental conditions provides new insight on growth regulation mechanisms. Our results establish the capabilities of SLIM as an advanced drug screening technology that provides information on changes in proliferation

  18. TGF-β-Induced Regulatory T Cells Directly Suppress B Cell Responses through a Noncytotoxic Mechanism.

    Science.gov (United States)

    Xu, Anping; Liu, Ya; Chen, Weiqian; Wang, Julie; Xue, Youqiu; Huang, Feng; Rong, Liming; Lin, Jin; Liu, Dahai; Yan, Mei; Li, Quan-Zhen; Li, Bin; Song, Jianxun; Olsen, Nancy; Zheng, Song Guo

    2016-05-01

    Foxp3(+) regulatory T cells (Treg) playing a crucial role in the maintenance of immune tolerance and prevention of autoimmune diseases consist of thymus-derived naturally occurring CD4(+)Foxp3(+) Treg cells (nTreg) and those that can be induced ex vivo with TGF-β (iTreg). Although both Treg subsets share similar phenotypes and functional characteristics, they also have potential biologic differences on their biology. The role of iTreg in regulating B cells remains unclear so far. The suppression assays of Treg subsets on activation, proliferation, and Abs production of B cells were measured using a Treg and B cell coculture system in vitro. Transwell and Ab blockade experiments were performed to assess the roles of cell contact and soluble cytokines. Treg were adoptively transferred to lupus mice to assess in vivo effects on B cells. Like nTreg, iTreg subset also directly suppressed activation and proliferation of B cells. nTreg subset suppressed B cell responses through cytotoxic manner related to expression of granzyme A, granzyme B, and perforin, whereas the role of iTreg subset on B cells did not involve in cytotoxic action but depending on TGF-β signaling. Furthermore, iTreg subset can significantly suppress Ab produced by lupus B cells in vitro. Comparison experiments using autoantibodies microarrays demonstrated that adoptive transfer of iTreg had a superior effect than nTreg subset on suppressing lupus B cell responses in vivo. Our data implicate a role and advantage of iTreg subset in treating B cell-mediated autoimmune diseases, boosting the translational potential of these findings. PMID:27001954

  19. PKC activation induces inflammatory response and cell death in human bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hyunhee Kim

    Full Text Available A variety of airborne pathogens can induce inflammatory responses in airway epithelial cells, which is a crucial component of host defence. However, excessive inflammatory responses and chronic inflammation also contribute to different diseases of the respiratory system. We hypothesized that the activation of protein kinase C (PKC is one of the essential mechanisms of inflammatory response in airway epithelial cells. In the present study, we stimulated human bronchial lung epithelial (BEAS-2B cells with the phorbol ester Phorbol 12, 13-dibutyrate (PDBu, and examined gene expression profile using microarrays. Microarray analysis suggests that PKC activation induced dramatic changes in gene expression related to multiple cellular functions. The top two interaction networks generated from these changes were centered on NFκB and TNF-α, which are two commonly known pathways for cell death and inflammation. Subsequent tests confirmed the decrease in cell viability and an increase in the production of various cytokines. Interestingly, each of the increased cytokines was differentially regulated at mRNA and/or protein levels by different sub-classes of PKC isozymes. We conclude that pathological cell death and cytokine production in airway epithelial cells in various situations may be mediated through PKC related signaling pathways. These findings suggest that PKCs can be new targets for treatment of lung diseases.

  20. Common and cell type-specific responses of human cells to mitochondrial dysfunction

    International Nuclear Information System (INIS)

    In yeast, mitochondrial dysfunction activates a specific pathway, termed retrograde regulation, which alters the expression of specific nuclear genes and results in increased replicative life span. In mammalian cells, the specific nuclear genes induced in response to loss of mitochondrial function are less well defined. This study characterizes responses in nuclear gene expression to loss of mitochondrial DNA sequences in three different human cell types: T143B, an osteosarcoma-derived cell line; ARPE19, a retinal pigment epithelium cell line; and GMO6225, a fibroblast cell population from an individual with Kearns-Sayre syndrome (KSS). Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure gene expression of a selection of glycolysis, TCA cycle, mitochondrial, peroxisomal, extracellular matrix, stress response, and regulatory genes. Gene expression changes that were common to all three cell types included up-regulation of GCK (glucokinase), CS (citrate synthase), HOX1 (heme oxygenase 1), CKMT2 (mitochondrial creatine kinase 2), MYC (v-myc myelocytomatosis viral oncogene homolog), and WRN (Werner syndrome helicase), and down-regulation of FBP1 (fructose-1, 6-bisphosphatase 1) and COL4A1 (collagen, type IV, alpha 1). RNA interference experiments show that induction of MYC is important in ρ0 cells for the up-regulation of glycolysis. In addition, a variety of cell type-specific gene changes was detected and most likely depended upon the differentiated functions of the individual cell types. These expression changes may help explain the response of different tissues to the loss of mitochondrial function due to aging or disease

  1. Analysis of H2 storage needs for early market non-motive fuel cell applications.

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Terry Alan; Moreno, Marcina; Arienti, Marco; Pratt, Joseph William; Shaw, Leo; Klebanoff, Leonard E.

    2012-03-01

    Hydrogen fuel cells can potentially reduce greenhouse gas emissions and the United States dependence on foreign oil, but issues with hydrogen storage are impeding their widespread use. To help overcome these challenges, this study analyzes opportunities for their near-term deployment in five categories of non-motive equipment: portable power, construction equipment, airport ground support equipment, telecom backup power, and man-portable power and personal electronics. To this end, researchers engaged end users, equipment manufacturers, and technical experts via workshops, interviews, and electronic means, and then compiled these data into meaningful and realistic requirements for hydrogen storage in specific target applications. In addition to developing these requirements, end-user benefits (e.g., low noise and emissions, high efficiency, potentially lower maintenance costs) and concerns (e.g., capital cost, hydrogen availability) of hydrogen fuel cells in these applications were identified. Market data show potential deployments vary with application from hundreds to hundreds of thousands of units.

  2. Who needs RDD? Combining directory listings with cell phone exchanges for an alternative telephone sampling frame

    OpenAIRE

    Guterbock, Thomas; Diop, Abdoulaye; Ellis, James; Trung Le, Kien

    2011-01-01

    Abstract The traditional Random Digit Dialing method (list-assisted RDD using a frame of landline phone numbers) is clearly under threat. The difficulty and costs of completing telephone surveys have increased due to rising rates of refusal and non-contact. The completeness of coverage of list-assisted RDD samples has diminished due to the proliferation of cell-phone only households. The ability of list-assisted RDD to capture young, mobile, unmarried, and minority households is thus dimin...

  3. SINGLE-CELL LEVEL INVESTIGATION OF CYTOSKELETAL/CELLULAR RESPONSE TO EXTERNAL STIMULI

    Energy Technology Data Exchange (ETDEWEB)

    Hiddessen, A L

    2007-02-26

    A detailed understanding of the molecular mechanisms by which chemical signals control cell behavior is needed if the complex biological processes of embryogenesis, development, health and disease are to be completely understood. Yet, if we are to fully understand the molecular mechanisms controlling cell behavior, measurements at the single cell level are needed to supplement information gained from population level studies. One of the major challenges to accomplishing studies at the single cell level has been a lack of physical tools to complement the powerful molecular biological assays which have provided much of what we currently know about cell behavior. The goal of this exploratory project is the development of an experimental platform that facilitates integrated observation, tracking and analysis of the responses of many individual cells to controlled environmental factors (e.g. extracellular signals). Toward this goal, we developed chemically-patterned microarrays of both adherent and suspension mammalian cell types. A novel chemical patterning methodology, based on photocatalytic lithography, was developed to construct biomolecule and cell arrays that facilitate analysis of biological function. Our patterning techniques rely on inexpensive stamp materials and visible light, and do not necessitate mass transport or specified substrates. Patterned silicon and glass substrates are modified such that there is a non-biofouling polymer matrix surrounding the adhesive regions that target biomolecules and cells. Fluorescence and reflectance microscopy reveal successful patterning of proteins and single to small clusters of mammalian cells. In vitro assays conducted upon cells on the patterned arrays demonstrate the viability of cells interfacing with this synthetic system. Hence, we have successfully established a versatile cell measurement platform which can be used to characterize the molecular regulators of cellular behavior in a variety of important

  4. Tracking erythroid progenitor cells in times of need and times of plenty.

    Science.gov (United States)

    Koury, Mark J

    2016-08-01

    Red blood cell production rates increase rapidly following blood loss or hemolysis, but the expansion of erythropoiesis in these anemic states is tightly regulated such that rebound polycythemia does not occur. The erythroid cells that respond to erythropoietic stimulation or suppression are the progenitor stages of burst-forming units-erythroid (BFU-Es) and colony-forming units-erythroid (CFU-Es). Results from an early study of the changes in the size, location, and cell cycling status of BFU-E and CFU-E populations in mice under normal conditions, erythropoietic stimulation, and erythropoietic suppression are used as reference points to review subsequent developments related to erythroid progenitor populations and regulation of their size. The review concerns development of erythroid progenitor populations mainly in mice and humans, with a focus on the mechanisms related to the rapid but highly regulated expansion of erythropoiesis in spleens of erythropoietically stimulated mice. Current knowledge is used as a model of erythroid progenitor populations in mice under normal, erythropoietically suppressed, and erythropoietically stimulated conditions. Clinical applications of information learned from studies of erythropoietic expansion, in terms of current therapies for anemia, are reviewed. PMID:26646992

  5. An atypical unfolded protein response in heat shocked cells.

    Directory of Open Access Journals (Sweden)

    Lonneke Heldens

    Full Text Available BACKGROUND: The heat shock response (HSR and the unfolded protein response (UPR are both activated by proteotoxic stress, although in different compartments, and share cellular resources. How these resources are allocated when both responses are active is not known. Insight in possible crosstalk will help understanding the consequences of failure of these systems in (age-related disease. RESULTS: In heat stressed HEK293 cells synthesis of the canonical UPR transcription factors XBP1s and ATF4 was detected as well as HSF1 independent activation of the promoters of the ER resident chaperones HSPA5 (BiP and DNAJB9 (ERdj4. However, the heat stress activation of the DNAJB9 promoter, a XBP1s target, was not blocked in cells expressing a dominant negative IRE1α mutant, and thus did not require XBP1s. Furthermore, the DNA element required for heat stress activation of the DNAJB9 promoter is distinct from the ATF4 and ATF6 target elements; even though inhibition of eIF2α phosphorylation resulted in a decreased activation of the DNAJB9 promoter upon heat stress, suggesting a role for an eIF2α phosphorylation dependent product. CONCLUSIONS: The initial step in the UPR, synthesis of transcription factors, is activated by heat stress but the second step, transcriptional transactivation by these factors, is blocked and these pathways of the UPR are thus not productive. Expression of canonical ER chaperones is part of the response of heat stressed cells but another set of transcription factors has been recruited to regulate expression of these ER chaperones.

  6. Hemopoietic cell precursor responses to erythropoietin in plasma clot cultures

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, W.L.

    1979-01-01

    The time dependence of the response of mouse bone marrow cells to erythropoietin (Ep) in vitro was studied. Experiments include studies on the Ep response of marrow cells from normal, plethoric, or bled mice. Results with normal marrow reveal: (1) Not all erythroid precursors (CFU-E) are alike in their response to Ep. A significant number of the precursors develop to a mature erythroid colony after very short Ep exposures, but they account for only approx. 13% of the total colonies generated when Ep is active for 48 hrs. If Ep is active more than 6 hrs, a second population of erythroid colonies emerges at a nearly constant rate until the end of the culture. Full erythroid colony production requires prolonged exposure to erythropoietin. (2) The longer erythropoietin is actively present, the larger the number of erythroid colonies that reach 17 cells or more. Two distinct populations of immediate erythroid precursors are also present in marrow from plethoric mice. In these mice, total colony numbers are equal to or below those obtained from normal mice. However, the population of fast-responding CFU-E is consistently decreased to 10 to 20% of that found in normal marrow. The remaining colonies are formed from plethoric marrow at a rate equal to normal marrow. With increasing Ep exposures, the number of large colonies produced increases. From the marrow of bled mice, total erythroid colony production is equal to or above that of normal marrow. Two populations of colony-forming cells are again evident, with the fast-responding CFU-E being below normal levels. The lack of colonies from this group was compensated in bled mice by rapid colony production in the second population. A real increase in numbers of precursors present in this pool increased the rate of colony production in culture to twice that of normal marrow. The number of large colonies obtained from bled mice was again increased as the Ep exposure was lengthened. (ERB)

  7. Alert cell strategy: mechanisms of inflammatory response and organ protection.

    Science.gov (United States)

    Hatakeyama, Noboru; Matsuda, Naoyuki

    2014-01-01

    Systemic inflammatory response syndrome (SIRS) is triggered by various factors such as surgical operation, trauma, burn injury, ischemia, pancreatitis and bacterial translocation. Sepsis is a SIRS associated with bacterial infection. SIRS and sepsis tend to trigger excessive production of inflammatory cytokines and other inflammatory molecules and induce multiple organ failure, such as acute lung injury, acute kidney injury and inflammatory cardiac injury. Epithelial and endothelial cells in some major organs express inflammatory receptors on the plasma membrane and work as alert cells for inflammation, and regulation of these alert cells could have a relieving effect on the inflammatory response. In inflammatory conditions, initial cardiac dysfunction is mediated by decreased preload and adequate infusion therapy is required. Tachyarrhythmia is a complication of inflammatory conditions and early control of the inflammatory reaction would prevent the structural remodeling that is resistant to therapies. Furthermore, there seems to be crosstalk between major organs with a central focus on the kidneys in inflammatory conditions. As an alert cell strategy, volatile anesthetics, sevoflurane and isoflurane, seem to have anti-inflammatory effects, and both experimental and clinical studies have shown the beneficial effects of these drugs in various settings of inflammatory conditions. On the other hand, in terms of intravenous anesthetics, propofol and ketamine, their current status is still controversial as there is a lack of confirmatory evidence on whether they have an organ-protective effect in inflammatory conditions. The local anesthetic lidocaine suppressed inflammatory responses upon both systemic and local administration. For the control of inflammatory conditions, anesthetic agents may be a target of drug development in accordance with other treatments and drugs. PMID:25229471

  8. Adaptive Response of T and B Cells in Atherosclerosis.

    Science.gov (United States)

    Ketelhuth, Daniel F J; Hansson, Göran K

    2016-02-19

    Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of cholesterol-containing lipoproteins, particularly low-density lipoprotein, in the artery wall. In the arterial intima, lipoprotein components that are generated through oxidative, lipolytic, and proteolytic activities lead to the formation of several danger-associated molecular patterns, which can activate innate immune cells as well as vascular cells. Moreover, self- and non-self-antigens, such as apolipoprotein B-100 and heat shock proteins, can contribute to vascular inflammation by triggering the response of T and B cells locally. This process can influence the initiation, progression, and stability of plaques. Substantial clinical and experimental data support that the modulation of adaptive immune system may be used for treating and preventing atherosclerosis. This may lead to the development of more selective and less harmful interventions, while keeping host defense mechanisms against infections and tumors intact. Approaches such as vaccination might become a realistic option for cardiovascular disease, especially if they can elicit regulatory T and B cells and the secretion of atheroprotective antibodies. Nevertheless, difficulties in translating certain experimental data into new clinical therapies remain a challenge. In this review, we discuss important studies on the function of T- and B-cell immunity in atherosclerosis and their manipulation to develop novel therapeutic strategies against cardiovascular disease. PMID:26892965

  9. AIRWAY EPITHELIAL CELL RESPONSE TO HUMAN METAPNEUMOVIRUS INFECTION

    Science.gov (United States)

    X, Bao; T, Liu; L, Spetch; D, Kolli; R.P, Garofalo; A, Casola

    2007-01-01

    Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar type II-like epithelial cell line (A549) was similar, suggesting that A549 cells can be used as a model to study lower airway epithelial cell responses to hMPV infection. A549 secreted a variety of CXC and CC chemokines, cytokines and type I interferons, following hMPV infection. hMPV was also a strong inducer of transcription factors belonging to nuclear factor (NF)-κB, interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) families, which are known to orchestrate the expression of inflammatory and immuno-modulatory mediators. PMID:17655903

  10. Beta-cell mitochondrial carriers and the diabetogenic stress response.

    Science.gov (United States)

    Brun, Thierry; Maechler, Pierre

    2016-10-01

    Mitochondria play a central role in pancreatic beta-cells by coupling metabolism of the secretagogue glucose to distal events of regulated insulin exocytosis. This process requires transports of both metabolites and nucleotides in and out of the mitochondria. The molecular identification of mitochondrial carriers and their respective contribution to beta-cell function have been uncovered only recently. In type 2 diabetes, mitochondrial dysfunction is an early event and may precipitate beta-cell loss. Under diabetogenic conditions, characterized by glucotoxicity and lipotoxicity, the expression profile of mitochondrial carriers is selectively modified. This review describes the role of mitochondrial carriers in beta-cells and the selective changes in response to glucolipotoxicity. In particular, we discuss the importance of the transfer of metabolites (pyruvate, citrate, malate, and glutamate) and nucleotides (ATP, NADH, NADPH) for beta-cell function and dysfunction. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID:26979549

  11. The acquisition of cytokine responsiveness by murine B cells

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1994-01-01

    The mechanism whereby small resting (high buoyant density) murine B cells are induced to express interleukin-2 receptors (IL-2R) and to respond to IL-2 was addressed by staining with anti-IL-2R alpha and -IL-2R beta monoclonal antibodies (mAb), and using receptor-specific cDNA probes. Resting B...... staining and mRNA were induced by the combination of LPS plus IL-5. LPS+IL-5-treated B cells responded to IL-2 by Ig secretion. This indicates that B cells regulate their responsiveness to IL-2 similarly to T cells, via the combined level of expression of IL-2R beta and IL-2R alpha. The synergy between IL...... cells expressed undetectable levels of both IL-2R alpha and beta chains on their surface and did not respond to IL-2, even at supra-physiological concentrations. Sepharose-coupled, but not streptavidin-cross-linked, plastic-adsorbed or soluble, anti-mu up-regulated the expression of IL-2R alpha and beta...

  12. Responsiveness of fetal rat brain cells to glia maturation factor during neoplastic transformation in cell culture

    DEFF Research Database (Denmark)

    Haugen, A; Laerum, O D; Bock, E

    1981-01-01

    The effect of partially purified extracts from adult pig brains containing a glia maturation protein factor (BE) has been investigated on neural cells during carcinogenesis. Pregnant BD IX-rats were given a single transplacental dose of the carcinogen ethylnitrosourea (EtNU) on the 18th day of...... gestation. The brains of the treated fetuses were transferred to cell culture and underwent neoplastic transformation with a characteristic sequence of phenotypic alterations which could be divided into five different stages. During the first 40 days after explantation (stage I & II) BE induced...... appreciable effect on GFA-content was seen any longer, although some few weakly GFA positive cells could be observed in all permanent cell lines. Fetal rat brain cells therefore seem to become less responsive to this differentiation inducer during neoplastic transformation in cell culture....

  13. Innate immune response to pulmonary contusion: Identification of cell-type specific inflammatory responses

    OpenAIRE

    Hoth, J. Jason; Wells, Jonathan D.; Yoza, Barbara K.; McCall, Charles E.

    2012-01-01

    Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll like receptors 2 and 4 (TLR2 and TLR4) mediate the ...

  14. Groundwater Flow Systems and Their Response to Climate Change: A Need for a Water-System View Approach

    Directory of Open Access Journals (Sweden)

    Joel J. Carrillo-Rivera

    2012-01-01

    Full Text Available Problem statement: The interest in early hydrogeological studies was the aquifer unit, as it is the physical media that stores and permits groundwater transfers from the recharge zone to the discharge zone, making groundwater available to boreholes for water extraction. Approach: Recently, the aquifer concept has been complemented by the groundwater flow system theory, where groundwater may be defined by local, intermediate and regional flow systems. This implies that groundwater may travel from one aquifer unit to another aquifer unit (or more located above or below the former. Water in a local flow system takes months or several years to travel from the recharge to the discharge zone. These flows usually transfer the best natural quality water, so a reduction in precipitation would lessen recharge and diminish stored water, making them more vulnerable to contamination and variability in climatic conditions. Thus, there is a need to define local flows and to enhance actions to protect them from contamination and inefficient extraction. Results: In contrast to local flows, intermediate and regional flows travel from a region, or country, into another, with their recharge processes usually taking place in a zone located far away from the discharge zone (natural or by boreholes. There is a need of groundwater flow systems evaluation by means of an integrated wide system-view analysis of partial evidence represented by surface (soil and vegetation covers as well as hydraulic, isotopic and chemical groundwater characterization in the related geological media where the depth of actual basement rock is paramount as well as discharge areas. The flow system definition may assist in extraction management strategies to control related issues as subsidence, obtained the water quality change, desiccation of springs and water bodies, soil erosion, flooding response, contamination processes in recharge areas, among others; many of which could be efficiently

  15. Response of cultured human airway epithelial cells to X-rays and energetic α-particles

    International Nuclear Information System (INIS)

    Radon and its progeny, which emit α-particles during decay, may play an important role in inducing human lung cancer. To gain a better understanding of the biological effects of α-particles in human lung we studied the response of cultured human airway epithelial cells to X-rays and monoenergetic helium ions. Experimental results indicated that the radiation response of primary cultures was similar to that for airway epithelial cells that were transformed with a plasmid containing an origin-defective SV40 virus. The RBE for cell inactivation determined by the ratio of D0 for X-rays to that for 8 MeV helium ions was 1.8-2.2. The cross-section for helium ions, calculated from the D0 value, was about 24 μm2 for cells of the primary culture. This cross-section is significantly smaller than the average geometric nuclear area (∼ 180 μm2), suggesting that an average of 7.5 α-particles (8 MeV helium ions) per cell nucleus are needed to induce a lethal lesion. (author)

  16. From microgravity to osmotic conditions: mechanical integration of plant cells in response to stress

    Science.gov (United States)

    Wojtaszek, Przemyslaw; Kasprowicz, Anna; Michalak, Michal; Janczara, Renata; Volkmann, Dieter; Baluska, Frantisek

    Chemical reactions and interactions between molecules are commonly thought of as being at the basis of Life. Research of recent years, however, is more and more evidently indicating that physical forces are profoundly affecting the functioning of life at all levels of its organiza-tion. To detect and to respond to such forces, plant cells need to be integrated mechanically. Cell walls are the outermost functional zone of plant cells. They surround the individual cells, and also form a part of the apoplast. In cell suspensions, cell walls are embedded in the cul-ture medium which can be considered as a superapoplast. Through physical and chemical interactions they provide a basis for the structural and functional cell wall-plasma membrane-cytoskeleton (WMC) continuum spanning the whole cell. Here, the working of WMC contin-uum, and the participation of signalling molecules, like NO, would be presented in the context of plant responses to stress. In addition, the effects of the changing composition of WMC continuum will be considered, with particular attention paid to the modifications of the WMC components. Plant cells are normally adapted to changing osmotic conditions, resulting from variable wa-ter availability. The appearance of the osmotic stress activates adaptory mechanisms. If the strength of osmotic stress grows relatively slowly over longer period of time, the cells are able to adapt to conditions that are lethal to non-adapted cells. During stepwise adaptation of tobacco BY-2 suspension cells to the presence of various osmotically active agents, cells diverged into independent, osmoticum type-specific lines. In response to ionic agents (NaCl, KCl), the adhe-sive properties were increased and randomly dividing cells formed clumps, while cells adapted to nonionic osmotica (mannitol, sorbitol, PEG) revealed ordered pattern of precisely positioned cell divisions, resulting in the formation of long cell files. Changes in the growth patterns were accompanied by

  17. Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responses.

    Science.gov (United States)

    Balandya, Emmanuel; Reynolds, Teri; Obaro, Stephen; Makani, Julie

    2016-09-01

    Individuals with sickle cell anemia (SCA) have increased susceptibility to infections, secondary to impairment of immune function. Besides the described dysfunction in innate immunity, including impaired opsonization and phagocytosis of bacteria, evidence of dysfunction of T and B lymphocytes in SCA has also been reported. This includes reduction in the proportion of circulating CD4+ and CD8+ T cells, reduction of CD4+ helper: CD8+ suppressor T cell ratio, aberrant activation and dysfunction of regulatory T cells (Treg ), skewing of CD4+ T cells towards Th2 response and loss of IgM-secreting CD27 + IgM(high) IgD(low) memory B cells. These changes occur on the background of immune activation characterized by predominance of memory CD4+ T cell phenotypes, increased Th17 signaling and elevated levels of C-reactive protein and pro-inflammatory cytokines IL-6 and TNF-α, which may affect the immunogenicity and protective efficacy of vaccines available to prevent infections in SCA. Thus, in order to optimize the use of vaccines in SCA, a thorough understanding of T and B lymphocyte functions and vaccine reactivity among individuals with SCA is needed. Studies should be encouraged of different SCA populations, including sub-Saharan Africa where the burden of SCA is highest. This article summarizes our current understanding of lymphocyte biology in SCA, and highlights areas that warrant future research. Am. J. Hematol. 91:938-946, 2016. © 2016 Wiley Periodicals, Inc. PMID:27237467

  18. Cell signalling in the immune response of mussel hemocytes

    Directory of Open Access Journals (Sweden)

    L Canesi

    2006-05-01

    Full Text Available In this work data on immune cell signallling in the circulating hemocytes of the edible bivalve, themussel Mytilus spp, are summarized. Studies with different bacterial species and strains, heterologouscytokines and natural hormones, as well as with organic environmental chemicals, led to theidentification of the role of conserved components of kinase-mediated transduction pathways,including cytosolic kinases (such as MAPKs and PKC and kinase-activated transcription factors (suchas STATs, CREB, NF-kB, in the immune response. From these data a general scenario emergedindicating that close similarities exist in the signalling pathways involved in cell mediated immunity inbivalve and mammalian immunocytes. In particular, the results indicate that both the extent andduration of activation of components of kinase-mediated cascades are crucial in determining thehemocyte response to extracellular stimuli. The identification of the basic mechanisms of immunityand its modulation in mussels can give important information for the possible utilization of thesespecies as an invertebrate model for studies on innate immunity. Moreover, the application of thisknowledge to the understanding of the actual adaptive responses of bivalves when exposed to microorganismsin their natural environment can represent significant ecological, economical and publichealth-related interest.

  19. Transient Treg-cell depletion in adult mice results in persistent self-reactive CD4(+) T-cell responses.

    Science.gov (United States)

    Nyström, Sofia N; Bourges, Dorothée; Garry, Sarah; Ross, Ellen M; van Driel, Ian R; Gleeson, Paul A

    2014-12-01

    Depletion of Foxp3(+) CD4(+) regulatory T cells (Treg) in adults results in chronic inflammation and autoimmune disease. However, the impact of transient Treg-cell depletion on self-reactive responses is poorly defined. Here, we studied the effect of transient depletion of Treg cells on CD4(+) T-cell responses to endogenous self-antigens. Short-term ablation of Treg cells in mice resulted in rapid activation of CD4(+) T cells, increased percentage of IFN-γ(+) and Th17 cells in lymphoid organs, and development of autoimmune gastritis. To track self-reactive responses, we analyzed the activation of naïve gastric-specific CD4(+) T cells. There was a dramatic increase in proliferation and acquisition of effector function of gastric-specific T cells in the stomach draining LNs of Treg-cell-depleted mice, compared with untreated mice, either during Treg-cell depletion or after Treg-cell reconstitution. Moreover, the hyperproliferation of gastric-specific T cells in the Treg-cell-ablated mice was predominantly antigen-dependent. Transient depletion of Treg cells resulted in a shift in the ratio of peripheral:thymic Treg cells in the reemerged Treg-cell population, indicating an altered composition of Treg cells. These findings indicate that transient Treg-cell depletion results in ongoing antigen-driven self-reactive T-cell responses and emphasize the continual requirement for an intact Treg-cell population. PMID:25231532

  20. High proportions of CD4⁺ T cells among residual bone marrow T cells in childhood acute lymphoblastic leukemia are associated with favorable early responses.

    Science.gov (United States)

    Lustfeld, Imke; Altvater, Bianca; Ahlmann, Martina; Ligges, Sandra; Brinkrolf, Peter; Rosemann, Annegret; Moericke, Anja; Rossig, Claudia

    2014-01-01

    Residual nonmalignant T cells in the bone marrow of patients with acute leukemias may be involved in active immune responses to leukemic cells. Here, we investigated the phenotypic signature of T cells present at diagnosis in 39 pediatric patients with acute lymphoblastic leukemia (ALL) treated within standardized ALL-BFM study protocols. Previously described age associations of lymphocyte subpopulations in the peripheral blood of healthy children were reproduced in leukemic bone marrow. Analysis of individual lymphocyte parameters and risk-associated variables using univariate linear regression models revealed a correlation of higher CD4/CD8 ratios at diagnosis with a favorable bone marrow response on day 15. Separate analysis of CD4⁺ cells with the CD4⁺CD25(hi)FoxP3⁺ T(reg) cell phenotype showed that the association was caused by non-T(reg) CD4⁺ cells. The association of higher CD4/CD8 ratios with a favorable bone marrow response on day 15 of treatment persisted in a cohort extended to 69 patients. We conclude that CD4⁺ non-T(reg) cells in leukemic bone marrow at diagnosis may have a role in early response to treatment. Prospective analysis of the CD4/CD8 ratio in a large cohort of pediatric patients is now needed. Moreover, future experiments will establish the functional role of the individual T cell subsets in immune control in pediatric ALL. PMID:24021585

  1. Naturally Occurring Extracellular Matrix Scaffolds for Dermal Regeneration: Do They Really Need Cells?

    Directory of Open Access Journals (Sweden)

    A. M. Eweida

    2015-01-01

    Full Text Available The pronounced effect of extracellular matrix (ECM scaffolds in supporting tissue regeneration is related mainly to their maintained 3D structure and their bioactive components. These decellularized matrix scaffolds could be revitalized before grafting via adding stem cells, fibroblasts, or keratinocytes to promote wound healing. We reviewed the online published literature in the last five years for the studies that performed ECM revitalization and discussed the results of these studies and the related literature. Eighteen articles met the search criteria. Twelve studies included adding cells to acellular dermal matrix (ADM, 3 studies were on small intestinal mucosa (SIS, one study was on urinary bladder matrix (UBM, one study was on amniotic membrane, and one study included both SIS and ADM loaded constructs. We believe that, in chronic and difficult-to-heal wounds, revitalizing the ECM scaffolds would be beneficial to overcome the defective host tissue interaction. This belief still has to be verified by high quality randomised clinical trials, which are still lacking in literature.

  2. Cord stem-cell transplantation in Ontario: do we need a public bank?

    Science.gov (United States)

    Gassas, A

    2011-06-01

    It has been 21 years since the first successful use of umbilical cord blood as a source of donor cells for hematopoietic stem cell transplantation (HSCT). Over those years, cord blood transplantation (CBT) has shown marked success as an effective modality in the treatment of children and adults with hematologic malignancies, marrow failure, immunodeficiency, hemoglobinopathy, and inherited metabolic diseases. Furthermore, transplantation without full human leukocyte antigen (HLA) matching is possible and, despite a lower incidence of graft-versus-host disease, graft-versus-leukemia effect is preserved. More than 20,000 cbts have been performed worldwide. Ontario is the most populated province in Canada, and its cbt numbers have increased dramatically in recent years, but most of the umbilical cord blood units are purchased from unrelated international registries. There is no public cord bank in Ontario, but there is a private cord banking option, and notably, Ontario has the largest number of live births in Canada [approximately 40% of all Canadian live births per year occur in Ontario (Statistics Canada, 2007)]. In this brief review, the pros and cons of private and public cord banking and the feasibility of starting an Ontario public cord bank are discussed. PMID:21655150

  3. Hydroxyurea in Pediatric Patients With Sickle Cell Disease: What Nurses Need to Know.

    Science.gov (United States)

    Rees, Allison L

    2016-09-01

    Sickle cell disease (SCD) is an inherited disorder in which sickled red blood cells occlude the small vessels of the body, reducing oxygen delivery to tissues and ultimately negatively affecting many of the body's major organs. Hydroxyurea has proven beneficial in the treatment of SCD and prevention of disease-related complications. The 2014 guidelines put forth by the National Heart, Lung, and Blood Institute recommend hydroxyurea treatment in infants 9 months and older, children, and adolescents with SCD-SS or SCD-Sβ(0) thalassemia regardless of clinical severity. This is a change from the 2002 guidelines in which hydroxyurea was recommended for adolescents and children with SCD-SS or SCD-Sβ(0) thalassemia with frequent episodes of pain, a history of acute chest syndrome, severe and symptomatic anemia or other severe vaso-occlusive events. Nurses play a critical role in working with patients and families to provide education, guidance, and support to improve compliance to mitigate the long-term effects of SCD. PMID:26611755

  4. "Children Need Their Parents More than a Pizza in the Fridge!": Parental Responsibility in a Finnish Newspaper

    Science.gov (United States)

    Book, Marja Leena; Perala-Littunen, Satu

    2008-01-01

    The aim of this study is to find constructions of parental responsibility by analysing letters sent by readers to a newspaper on the topic of parenting and parental responsibility. The study takes a methodological approach, focusing on the meanings of responsibility and looking at different portrayals of parenthood. Three dimensions of…

  5. A call to arms: a critical need for interventions to limit pulmonary toxicity in the stem cell transplantation patient population.

    Science.gov (United States)

    Radhakrishnan, Sabarinath Venniyil; Hildebrandt, Gerhard C

    2015-03-01

    Noninfectious pulmonary toxicity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) causes significant morbidity and mortality. Main presentations are idiopathic pneumonia syndrome (IPS) in the acute setting and bronchiolitis obliterans syndrome (BOS) and cryptogenic organizing pneumonia (COP) at later time point. While COP responds well to corticosteroids, IPS and BOS often are treatment refractory. IPS, in most cases, is rapidly fatal, whereas BOS progresses over time, resulting in chronic respiratory failure, impaired quality of life, and eventually, death. Standard second-line treatments are currently lacking, and current approaches, such as augmented T cell-directed immunosuppression, B cell depletion, TNF blockade, extracorporeal photopheresis, and tyroskine kinase inhibitor therapy, are unsatisfactory with responses in only a subset of patients. Better understanding of underlying pathophysiology hopefully results in the identification of future targets for preventive and therapeutic strategies along with an emphasis on currently underutilized rehabilitative and supportive measures. PMID:25662904

  6. Which Patients With Mantle Cell Lymphoma Do Not Need Aggressive Therapy.

    Science.gov (United States)

    Ruan, Jia; Martin, Peter

    2016-06-01

    Mantle cell lymphoma (MCL) is a heterogeneous disease, and it has been well-established over the last decade that a subset of patients can have indolent presentation. It is therefore important to adopt a risk-stratified approach in order to minimize unnecessary toxicities while maximizing survival and quality of life in selected MCL patients. This review provides an up-to-date assessment of clinical and pathologic entities associated with indolent disease course and delineates available biomarkers with predictive significance. Initial treatment decisions should be guided by risk assessment to discern patients who might do well with deferred therapy, from those who would require treatment with non-aggressive first-line regimens. PMID:27068437

  7. Non-small-cell lung cancer cells combat epidermal growth factor receptor tyrosine kinase inhibition through immediate adhesion-related responses

    Directory of Open Access Journals (Sweden)

    Wang HY

    2016-05-01

    Full Text Available Hsian-Yu Wang,1,2 Min-Kung Hsu,3,4 Kai-Hsuan Wang,1 Ching-Ping Tseng,2,4 Feng-Chi Chen,3,4 John T-A Hsu1,4 1Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 2Institute of Molecular Medicine and Bioengineering, National Chiao Tung University (NCTU, Hsinchu, 3Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 4Department of Biological Science and Technology, National Chiao Tung University (NCTU, Hsinchu, Taiwan, Republic of China Background: Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs, such as gefitinib, erlotinib, and afatinib, have greatly improved treatment efficacy in non-small cell lung cancer (NSCLC patients with drug-sensitive EGFR mutations. However, in some TKI responders, the benefits of such targeted therapies are limited by the rapid development of resistance, and strategies to overcome this resistance are urgently needed. Studies of drug resistance in cancer cells typically involve long term in vitro induction to obtain stably acquired drug-resistant cells followed by elucidation of resistance mechanisms, but the immediate responses of cancer cells upon drug treatment have been ignored. The aim of this study was to investigate the immediate responses of NSCLC cells upon treatment with EGFR TKIs.Results: Both NSCLC cells, ie, PC9 and H1975, showed immediate enhanced adhesion-related responses as an apoptosis-countering mechanism upon first-time TKI treatment. By gene expression and pathway analysis, adhesion-related pathways were enriched in gefitinib-treated PC9 cells. Pathway inhibition by small-hairpin RNAs or small-molecule drugs revealed that within hours of EGFR TKI treatment, NSCLC cells used adhesion-related responses to combat the drugs. Importantly, we show here that the Src family inhibitor, dasatinib, dramatically inhibits

  8. Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    Giddings Ian

    2011-06-01

    Full Text Available Abstract Background Benzo[a]pyrene (BaP is a widespread environmental genotoxic carcinogen that damages DNA by forming adducts. This damage along with activation of the aryl hydrocarbon receptor (AHR induces complex transcriptional responses in cells. To investigate whether human cells are more susceptible to BaP in a particular phase of the cell cycle, synchronised breast carcinoma MCF-7 cells were exposed to BaP. Cell cycle progression was analysed by flow cytometry, DNA adduct formation was assessed by 32P-postlabeling analysis, microarrays of 44K human genome-wide oligos and RT-PCR were used to detect gene expression (mRNA changes and Western blotting was performed to determine the expression of some proteins, including cytochrome P450 (CYP 1A1 and CYP1B1, which are involved in BaP metabolism. Results Following BaP exposure, cells evaded G1 arrest and accumulated in S-phase. Higher levels of DNA damage occurred in S- and G2/M- compared with G0/G1-enriched cultures. Genes that were found to have altered expression included those involved in xenobiotic metabolism, apoptosis, cell cycle regulation and DNA repair. Gene ontology and pathway analysis showed the involvement of various signalling pathways in response to BaP exposure, such as the Catenin/Wnt pathway in G1, the ERK pathway in G1 and S, the Nrf2 pathway in S and G2/M and the Akt pathway in G2/M. An important finding was that higher levels of DNA damage in S- and G2/M-enriched cultures correlated with higher levels of CYP1A1 and CYP1B1 mRNA and proteins. Moreover, exposure of synchronised MCF-7 cells to BaP-7,8-diol-9,10-epoxide (BPDE, the ultimate carcinogenic metabolite of BaP, did not result in significant changes in DNA adduct levels at different phases of the cell cycle. Conclusions This study characterised the complex gene response to BaP in MCF-7 cells and revealed a strong correlation between the varying efficiency of BaP metabolism and DNA damage in different phases of the cell

  9. Antigen-specific regulatory T-cell subsets in transplantation tolerance regulatory T-cell subset quality reduces the need for quantity.

    NARCIS (Netherlands)

    Koenen, H.J.P.M.; Joosten, I.

    2006-01-01

    Regulatory T cells (Treg) are critical controllers of the immune response. Disturbed Treg function results in autoimmunity, whereas in transplantation Treg are crucial in graft survival and transplant tolerance. Hence therapeutic modalities that influence Treg numbers or function hold great clinical

  10. Monitoring Antigen-Specific T Cell Responses Using Real-Time PCR

    Science.gov (United States)

    Lowe, Devin B.; Taylor, Jennifer L.; Storkus, Walter J.

    2016-01-01

    Flow cytometry-, ELISA-, and ELISpot-based in vitro assays have played important roles in assessing the frequencies and functional competence of antigen-specific T cells in the setting of infectious disease and cancer. Such methods have helped in the development of antigen-specific vaccines for human disease prevention/treatment and have also served as a foundation for the monitoring of patients’ immune responsiveness based on antigen-induced T cell expression of effector molecules (such as cytokines, chemokines, or proteins associated with cytolysis) as a consequence of therapeutic intervention. The following method outlines a protocol employing quantitative real-time PCR (qRT-PCR) with SYBR® green technology to examine antigen-specific CD8+ T cell responses based on their rapid up-regulation of IFN-γ mRNA transcription following in vitro stimulation with peptide (antigen)-loaded, autologous peripheral blood mononuclear cells (PBMCs). The advantages of the current qRT-PCR approach over protein-based detection methods include the sensitivity to distinguish resident CD8+ T cell responses against multiple antigens without the need to artificially pre-expand T cell numbers ex vivo, as is commonly required for the latter in vitro assay systems. Following qRT-PCR setup and run, the level of human IFN-γ transcript is normalized to CD8 transcript expression level, with data reported as the relative fold change in this index versus a patient-matched PBMC sample stimulated with a negative control peptide (e.g., HIV NEF). PMID:25149303

  11. ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells.

    Science.gov (United States)

    Yoshihara, Eiji; Wei, Zong; Lin, Chun Shi; Fang, Sungsoon; Ahmadian, Maryam; Kida, Yasuyuki; Tseng, Tiffany; Dai, Yang; Yu, Ruth T; Liddle, Christopher; Atkins, Annette R; Downes, Michael; Evans, Ronald M

    2016-04-12

    Pancreatic β cells undergo postnatal maturation to achieve maximal glucose-responsive insulin secretion, an energy intensive process. We identify estrogen-related receptor γ (ERRγ) expression as a hallmark of adult, but not neonatal β cells. Postnatal induction of ERRγ drives a transcriptional network activating mitochondrial oxidative phosphorylation, the electron transport chain, and ATP production needed to drive glucose-responsive insulin secretion. Mice deficient in β cell-specific ERRγ expression are glucose intolerant and fail to secrete insulin in response to a glucose challenge. Notably, forced expression of ERRγ in iPSC-derived β-like cells enables glucose-responsive secretion of human insulin in vitro, obviating in vivo maturation to achieve functionality. Moreover, these cells rapidly rescue diabetes when transplanted into β cell-deficient mice. These results identify a key role for ERRγ in β cell metabolic maturation, and offer a reproducible, quantifiable, and scalable approach for in vitro generation of functional human β cell therapeutics. PMID:27076077

  12. Autophagy in response to photodynamic therapy: cell survival vs. cell death

    Science.gov (United States)

    Oleinick, Nancy L.; Xue, Liang-yan; Chiu, Song-mao; Joseph, Sheeba

    2009-02-01

    Autophagy (or more properly, macroautophagy) is a pathway whereby damaged organelles or other cell components are encased in a double membrane, the autophagosome, which fuses with lysosomes for digestion by lysosomal hydrolases. This process can promote cell survival by removing damaged organelles, but when damage is extensive, it can also be a mechanism of cell death. Similar to the Kessel and Agostinis laboratories, we have reported the vigorous induction of autophagy by PDT; this was found in human breast cancer MCF-7 cells whether or not they were able to efficiently induce apoptosis. One way to evaluate the role of autophagy in PDT-treated cells is to silence one of the essential genes in the pathway. Kessel and Reiners silenced the Atg7 gene of murine leukemia L1210 cells using inhibitory RNA and found sensitization to PDT-induced cell death at a low dose of PDT, implying that autophagy is protective when PDT damage is modest. We have examined the role of autophagy in an epithelium-derived cancer cell by comparing parental and Atg7-silenced MCF-7 cells to varying doses of PDT with the phthalocyanine photosensitizer Pc 4. In contrast to L1210 cells, autophagy-deficient MCF-7 cells were more resistant to the lethal effects of PDT, as judged by clonogenic assays. A possible explanation for the difference in outcome for L1210 vs. MCF-7 cells is the greatly reduced ability of the latter to undergo apoptosis, a deficiency that may convert autophagy into a cell-death process even at low PDT doses. Experiments to investigate the mechanism(s) responsible are in process.

  13. Induction of mucosal HIV-specific B and T cell responses after oral immunization with live coxsackievirus B4 recombinants

    OpenAIRE

    Gu, Rui; Stagnar, Cristy; Zaichenko, Lesya; Ramsingh, Arlene I.

    2012-01-01

    Given the limited success of clinical HIV vaccine trials, new vaccine strategies are needed for the HIV pipeline. The present study explored the novel concept that a live enteric virus, with limited disease potential, is a suitable vaccine vector to elicit HIV-specific immune responses in the gut mucosa of immunized mice. Two coxsackievirus B4 (CVB4) vaccine vectors were designed to induce HIV-specific B or T cell responses. A B cell immunogen, CVB4/gp41(2F5), was constructed by expressing an...

  14. The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses

    Directory of Open Access Journals (Sweden)

    María Guadalupe Reyes García

    2013-01-01

    Full Text Available T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial “nurse cells” and retained in vacuoles, where most of them (95% are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called “regulatory cells,” which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.

  15. Radiofrequency ablation in primary non-small cell lung cancer: What a radiologist needs to know

    Directory of Open Access Journals (Sweden)

    Shivank Bhatia

    2016-01-01

    Full Text Available Lung cancer continues to be one of the leading causes of death worldwide. In advanced cases of lung cancer, a multimodality approach is often applied, however with poor local control rates. In early non-small cell lung cancer (NSCLC, surgery is the standard of care. Only 15-30% of patients are eligible for surgical resection. Improvements in imaging and treatment delivery systems have provided new tools to better target these tumors. Stereotactic body radiation therapy (SBRT has evolved as the next best option. The role of radiofrequency ablation (RFA is also growing. Currently, it is a third-line option in stage 1 NSCLC, when SBRT cannot be performed. More recent studies have demonstrated usefulness in recurrent tumors and some authors have also suggested combination of RFA with other modalities in larger tumors. Following the National Lung Screening Trial (NLST, screening by low-dose computed tomography (CT has demonstrated high rates of early-stage lung cancer detection in high-risk populations. Hence, even considering the current role of RFA as a third-line option, in view of increasing numbers of occurrences detected, the number of potential RFA candidates may see a steep uptrend. In view of all this, it is imperative that interventional radiologists be familiar with the techniques of lung ablation. The aim of this article is to discuss the procedural technique of RFA in the lung and review the current evidence regarding RFA for NSCLC.

  16. Detection of and Response to the Needs in Nuclear Security: the Roles of a Nuclear Research Institute

    International Nuclear Information System (INIS)

    Nuclear security has been receiving increased attention. This is on the one hand due to the phenomenon of illicit trafficking of nuclear and other radioactive materials and on the other hand due to the threat of nuclear terrorism. Should nuclear materials, in spite of measures of physical protection and safeguards, be stolen or diverted, significant efforts need to be undertaken to regain regulatory control over these materials. These efforts require the development, validation and implementation of appropriate technologies and methodologies. Moreover, the deployment for field application has to be accompanied by the respective training and exchange of expertise. Nuclear security is based on a multi-disciplinary approach and requires inter-agency collaboration. This paper will describe the different roles the Institute for Transuranium Elements (ITU) has been playing in the nuclear security area during its more than two decades of close involvement. These roles include the development of nuclear material measurement methodologies, both destructive and non-destructive, which serves as solid scientific-technical basis for developing and testing technologies applicable in nuclear security. Research and development work currently focuses on the development of nuclear forensics methods for providing hints on the history of nuclear material. Age dating and provenancing of uranium using trace element patterns and isotopic patterns are examples thereof. Portal monitors and other detection instrumentation is in the spotlight of thorough testing under field conditions. Knowledge transfer, sharing of expertise and inter-disciplinary exercises are key elements of the nuclear security training efforts being offered through the European Nuclear Security Training Centre (EUSECTRA). Training activities range from detection training for frontline officers, to training on radiological crime scene management; from the concept of developing a national response plan, to core

  17. DNA damage response signaling in lung adenocarcinoma A549 cells following gamma and carbon beam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Somnath [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Narang, Himanshi, E-mail: himinarang@gmail.com [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Sarma, Asitikantha [Radiation Biology Laboratory, Inter University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110 067 (India); Krishna, Malini [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2011-11-01

    Carbon beams (5.16 MeV/u, LET = 290 keV/{mu}m) are high linear energy transfer (LET) radiation characterized by higher relative biological effectiveness than low LET radiation. The aim of the current study was to determine the signaling differences between {gamma}-rays and carbon ion-irradiation. A549 cells were irradiated with 1 Gy carbon or {gamma}-rays. Carbon beam was found to be three times more cytotoxic than {gamma}-rays despite the fact that the numbers of {gamma}-H2AX foci were same. Percentage of cells showing ATM/ATR foci were more with {gamma}-rays however number of foci per cell were more in case of carbon irradiation. Large BRCA1 foci were found in all carbon irradiated cells unlike {gamma}-rays irradiated cells and prosurvival ERK pathway was activated after {gamma}-rays irradiation but not carbon. The noteworthy finding of this study is the early phase apoptosis induction by carbon ions. In the present study in A549 lung adenocarcinoma, authors conclude that despite activation of same repair molecules such as ATM and BRCA1, differences in low and high LET damage responses might be due to their distinct macromolecular complexes rather than their individual activation and the activation of cytoplasmic pathways such as ERK, whether it applies to all the cell lines need to be further explored.

  18. Response of hematopoietic stem cells to ionizing radiation

    International Nuclear Information System (INIS)

    single TPO administration rescued the IR-impaired reconstitution capacity of HSCs early after exposure. In addition, the use of marrow cells from transgenic ubiquitous luciferase-expressing donors combined with bioluminescence imaging technology provided a valuable strategy that allowed visualizing HSC homing of TPO-treated compared to untreated irradiated donors, and enabled the identification of a preferential cellular expansion sites which were inaccessible to investigation in most studies. Finally, we observed that TPO injection right after irradiation considerably attenuates IR-induced long-term injury to the stem/progenitor compartment. Altogether, these data provide novel insights in the cellular response of HSC to IR and the beneficial effects of TPO administration to these cells. (author)

  19. Cell wide responses to low oxygen exposure in Desulfovibriovulgaris Hildenborough

    Energy Technology Data Exchange (ETDEWEB)

    Mukhopadhyay, A.; Redding, A.; Joachimiak, M.; Arkin, A.; Borglin, S.; Dehal, P.; Chakraborty, R.; Geller, J.; Hazen, T.; He, Q.; Joyner, D.; Martin, V.; Wall, J.; Yang, Z.; Zhou, J.; Keasling, J.

    2007-03-11

    The responses of the anaerobic, sulfate-reducing Desulfovibrio vulgaris Hildenborough to low oxygen exposure (0.1% O{sub 2}) were monitored via transcriptomics and proteomics. Exposure to 0.1% O{sub 2} caused a decrease in growth rate without affecting viability. A concerted up regulation in the predicted peroxide stress response regulon (PerR) genes was observed in response to the 0.1% O{sub 2} exposure. Several of these candidates also showed increases in protein abundance. Among the remaining small number of transcript changes was the up regulation of the predicted transmembrane tetraheme cytochrome c3 complex. Other known oxidative stress response candidates remained unchanged during this low O{sub 2} exposure. To fully understand the results of the 0.1% O{sub 2} exposure, transcriptomics and proteomics data were collected for exposure to air using a similar experimental protocol. In contrast to the 0.1% O{sub 2} exposure, air exposure was detrimental to both the growth rate and viability and caused dramatic changes at both the transcriptome and proteome levels. Interestingly, the transcripts of the predicted PerR regulon genes were down regulated during air exposure. Our results highlight the differences in the cell wide response to low and high O{sub 2} levels of in D. vulgaris and suggest that while exposure to air is highly detrimental to D. vulgaris, this bacterium can successfully cope with periodic exposure to low O{sub 2} levels in its environment.

  20. WOX4 imparts auxin responsiveness to cambium cells in Arabidopsis.

    Science.gov (United States)

    Suer, Stefanie; Agusti, Javier; Sanchez, Pablo; Schwarz, Martina; Greb, Thomas

    2011-09-01

    Multipotent stem cell populations, the meristems, are fundamental for the indeterminate growth of plant bodies. One of these meristems, the cambium, is responsible for extended root and stem thickening. Strikingly, although the pivotal role of the plant hormone auxin in promoting cambium activity has been known for decades, the molecular basis of auxin responsiveness on the level of cambium cells has so far been elusive. Here, we reveal that auxin-dependent cambium stimulation requires the homeobox transcription factor WOX4. In Arabidopsis thaliana inflorescence stems, 1-N-naphthylphthalamic acid-induced auxin accumulation stimulates cambium activity in the wild type but not in wox4 mutants, although basal cambium activity is not abolished. This conclusion is confirmed by the analysis of cellular markers and genome-wide transcriptional profiling, which revealed only a small overlap between WOX4-dependent and cambium-specific genes. Furthermore, the receptor-like kinase PXY is required for a stable auxin-dependent increase in WOX4 mRNA abundance and the stimulation of cambium activity, suggesting a concerted role of PXY and WOX4 in auxin-dependent cambium stimulation. Thus, in spite of large anatomical differences, our findings uncover parallels between the regulation of lateral and apical plant meristems by demonstrating the requirement for a WOX family member for auxin-dependent regulation of lateral plant growth. PMID:21926336

  1. Human Bronchial Epithelial Cell Response to Heavy Particle Exposure

    Science.gov (United States)

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

    2012-07-01

    A battery of non-oncogenically immortalized human bronchial epithelial cells (HBECs) are being used to examine the molecular changes that lead to lung carcinogenesis after exposure to heavy particles found in the free space environment. The goal is to ultimately identify biomarkers of radioresponse that can be used for prediction of carcinogenic risk for fatal lung cancer. Our initial studies have focused on the cell line HBEC3 KT and the isogenic variant HBEC3 KTR53, which overexpresses the RASv12 mutant and where p53 has been knocked down by shRNA, and is considered to be a more oncogenically progressed variant. We have previously described the response of HBEC3 KT at the cellular and molecular level, however, the focus here is on the rate of cellular transformation after HZE radiation exposure and the molecular changes in transformed cells. When comparing the two cell lines we find that there is a maximum rate of cellular transformation at 0.25 Gy when cells are exposed to 1 GeV Fe particles, and, for the HBEC3 KTR53 there are multiple pathways upregulated that promote anchorage independent growth including the mTOR pathway, the TGF-1 pathway, RhoA signaling and the ERK/MAPK pathway as early as 2 weeks after radiation. This does not occur in the HBEC3 KT cell line. Transformed HBEC3 KT cells do not show any morphologic or phenotypic changes when grown as cell cultures. HBEC3 KTR53 cells on the other hand show substantial changes in morphology from a cobblestone epithelial appearance to a mesenchymal appearance with a lack of contact inhibition. This epithelial to mesenchymal change in morphology is accompanied by the expression of vimentin and a reduction in the expression of E-cadherin, which are hallmarks of epithelial to mesenchymal transition. Interestingly, for HBEC3 KT transformed cells there are no mutations in the p53 gene, 2 of 15 clones were found to be heterozygous for the RASV12 mutation, and 3 of 15 clones expressed high levels of BigH3, a TGFB-responsive

  2. Enhancement of Spectral Response of Dye-Sensitized Solar Cells

    Science.gov (United States)

    Chang, Shuai

    Dye-Sensitized solar cell (DSSC) is a class of third-generation solar devices. A notable feature of DSSC is that it can be manufactured by solution-based approach; this non-vacuum processing renders significant reduction in manufacturing costs. Different from conventional solar cells, in a DSSC, mesoporous semiconductor film with large surface areas is utilized for anchoring dye molecules, serving as light absorbing layer. Dye sensitizers play an important role in determining the final performance in DSSCs. Since the first highly-efficient DSSC was reported in 1991 sensitized by a ruthenium-based dye, numerous researchers have been focused on the development and characterization of various kinds of dyes for the applications in DSSCs. These include mainly metal complexes dyes, organic dyes, porphyrins and phthalocyanines dyes. The first part of my thesis work is to develop and test new dyes for DSSCs and a series of phenothiazine-based organic dyes and new porphyrin dyes are reported during the process. It has been realized that extending the response of dye sensitizers to a wider range of the solar spectrum is a key step in further improving the device efficiency. Typically, there are two ways for expanding the strong spectral response of DSSCs from visible to far red/NIR region. One approach is called co-sensitization. Herein, we demonstrate a new co-sensitization concept where small molecules is used to insert the interstitial site of between the pre-adsorbed large molecules. In this case, the co-adsorbed small ones is found to improve the light response and impede the back recombination, finally leading to the power conversion efficiency over 10% in conventional DSSC devices and a record-equaling efficiency of 9.2% in quasi-solid-state devices. I also implemented graphene sheets in the anode films for better charge transfer efficiency and break the energy conversion limit of co-sensitization in DSSCs. The optimal configuration between porphyrin dyes and

  3. Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza

    Science.gov (United States)

    Zarnitsyna, Veronika I.; Handel, Andreas; McMaster, Sean R.; Hayward, Sarah L.; Kohlmeier, Jacob E.; Antia, Rustom

    2016-01-01

    The current influenza vaccine provides narrow protection against the strains included in the vaccine, and needs to be reformulated every few years in response to the constantly evolving new strains. Novel approaches are directed toward developing vaccines that provide broader protection by targeting B and T cell epitopes that are conserved between different strains of the virus. In this paper, we focus on developing mathematical models to explore the CD8 T cell responses to influenza, how they can be boosted, and the conditions under which they contribute to protection. Our models suggest that the interplay between spatial heterogeneity (with the virus infecting the respiratory tract and the immune response being generated in the secondary lymphoid organs) and T cell differentiation (with proliferation occurring in the lymphoid organs giving rise to a subpopulation of resident T cells in the respiratory tract) is the key to understand the dynamics of protection afforded by the CD8 T cell response to influenza. Our results suggest that the time lag for the generation of resident T cells in the respiratory tract and their rate of decay following infection are the key factors that limit the efficacy of CD8 T cell responses. The models predict that an increase in the level of central memory T cells leads to a gradual decrease in the viral load, and, in contrast, there is a sharper protection threshold for the relationship between the size of the population of resident T cells and protection. The models also suggest that repeated natural influenza infections cause the number of central memory CD8 T cells and the peak number of resident memory CD8 T cells to reach their plateaus, and while the former is maintained, the latter decays with time since the most recent infection.

  4. Approach to a case of multiple irregular red cell antibodies in a liver transplant recipient: Need for developing competence

    Directory of Open Access Journals (Sweden)

    Ravi C Dara

    2015-01-01

    Full Text Available Liver transplant procedure acts as a challenge for transfusion services in terms of specialized blood components, serologic problems, and immunologic effects of transfusion. Red cell alloimmunization in patients awaiting a liver transplant complicate the process by undue delay or unavailability of compatible red blood cell units. Compatible blood units can be provided by well-equipped immunohematology laboratory, which has expertise in resolving these serological problems. This report illustrates resolution of a case with multiple alloantibodies using standard techniques, particularly rare antisera. Our case re-emphasizes the need for universal antibody screening in all patients as part of pretransfusion testing, which helps to identify atypical antibodies and plan for appropriate transfusion support well in time. We recommend that the centers, especially the ones that perform complex procedures like solid organ transplants and hematological transplants should have the necessary immunohematological reagents including rare antisera to resolve complex cases of multiple antibodies as illustrated in this case.

  5. Activated Human T Cells Secrete Exosomes That Participate in IL-2 Mediated Immune Response Signaling

    OpenAIRE

    Wahlgren, Jessica; Tanya De L Karlson; Glader, Pernilla; Telemo, Esbjörn; Valadi, Hadi

    2012-01-01

    It has previously been shown that nano-meter sized vesicles (30–100 nm), exosomes, secreted by antigen presenting cells can induce T cell responses thus showing the potential of exosomes to be used as immunological tools. Additionally, activated CD3+ T cells can secrete exosomes that have the ability to modulate different immunological responses. Here, we investigated what effects exosomes originating from activated CD3+ T cells have on resting CD3+ T cells by studying T cell proliferation, c...

  6. CD4 T cells mediate both positive and negative regulation of the immune response to HIV infection: complex role of T follicular helper cells and Regulatory T cells in pathogenesis

    Directory of Open Access Journals (Sweden)

    Chansavath ePhetsouphanh

    2015-01-01

    Full Text Available HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B cells and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely regulatory T cells (Tregs and T follicular helper cells (Tfh. These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B cell hyperplasia and increased germinal centre activity. Antiretroviral therapy (ART may reduce the lymphocyte activation, but not completely, and therefore there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B cell or Treg dysfunction.

  7. Transition from Bioinert to Bioactive Material by Tailoring the Biological Cell Response to Carboxylated Nanocellulose.

    Science.gov (United States)

    Hua, Kai; Rocha, Igor; Zhang, Peng; Gustafsson, Simon; Ning, Yi; Strømme, Maria; Mihranyan, Albert; Ferraz, Natalia

    2016-03-14

    This work presents an insight into the relationship between cell response and physicochemical properties of Cladophora cellulose (CC) by investigating the effect of CC functional group density on the response of model cell lines. CC was carboxylated by electrochemical TEMPO-mediated oxidation. By varying the amount of charge passed through the electrolysis setup, CC materials with different degrees of oxidation were obtained. The effect of carboxyl group density on the material's physicochemical properties was investigated together with the response of human dermal fibroblasts (hDF) and human osteoblastic cells (Saos-2) to the carboxylated CC films. The introduction of carboxyl groups resulted in CC films with decreased specific surface area and smaller total pore volume compared with the unmodified CC (u-CC). While u-CC films presented a porous network of randomly oriented fibers, a compact and aligned fiber pattern was depicted for the carboxylated-CC films. The decrease in surface area and total pore volume, and the orientation and aggregation of the fibers tended to augment parallel to the increase in the carboxyl group density. hDF and Saos-2 cells presented poor cell adhesion and spreading on u-CC, which gradually increased for the carboxylated CC as the degree of oxidation increased. It was found that a threshold value in carboxyl group density needs be reached to obtain a carboxylated-CC film with cytocompatibility comparable to commercial tissue culture material. Hence, this study demonstrates that a normally bioinert nanomaterial can be rendered bioactive by carefully tuning the density of charged groups on the material surface, a finding that not only may contribute to the fundamental understanding of biointerface phenomena, but also to the development of bioinert/bioactive materials. PMID:26886265

  8. Cellular cooperation during in vivo anti-hapten antibody responses. I. The effect of cell number on the response

    International Nuclear Information System (INIS)

    Cellular interactions in adoptive secondary anti-hapten antibody responses to the hapten 2,4-dinitrophenyl (DNP) have been studied. It was shown that DNP-specific B cells must interact with carrier specific helper T cells to give optimal responses. Independent titration of B cell and helper cell activity in adoptive anti-DNP antibody responses gave the following results: Doubling the number of transferred B cells approximately doubled the subsequent antibody response. Doubling the number of helper cells leads to nearly 4 times as much anti-DNP antibody, measured 7 days after boosting (''premium effect''). This marked effect of helper cell number on the antibody response is thought to be due primarily to the interaction of two populations of carrier-specific cells in the helper effect, or to the interaction of two activities of a single population of helper cells, namely clone activation and clone expansion. Only a very small proportion of the premium effect given by helper cells could be attributed to increases in antibody affinity. (U.S.)

  9. Proliferative cell response to loosening of total hip replacements: a cytofluorographic cell cycle analysis.

    Science.gov (United States)

    Santavirta, S; Pajamäki, J; Eskola, A; Konttinen, Y T; Lindholm, T

    1991-01-01

    Monocyte/macrophages and fibroblasts are the major reactive cells in the periprosthetic connective tissue in a loose totally replaced hip. Monocyte/macrophages are bone-marrow-derived, hematogenous cells, whereas mesenchymal fibroblasts replenish by local proliferation. The cell-cycle-phase frequency distribution therefore reflects the local mitotic fibroblast response to the loose total hip replacement (THR) implant. In 13 patients who underwent revision of a loose THR implant, most of the local cells were in the resting G0/G1 phase (88.1 +/- 6.3%, mean +/- SD), whereas 8.6 +/- 3.7% were in the S phase of the cycle, and 3.4 +/- 2.9% had already reached the G2/M phase. The highest DNA values were recorded in an osteoarthritic patient undergoing revision 4 years after the primary uncemented THR, while the lowest values were observed in a rheumatoid arthritis patient with a loose cemented prosthesis 15 years after the primary operation. The results suggest that the local proliferative fibroblast response in general is uniform and does not seem to depend on the type of prosthesis or the use of cement. The responses in aggressive granulomatous-type loosening and the common type of loosening were similar. PMID:1772725

  10. CD13 Regulates Dendritic Cell Cross-presentation and T Cell Responses by Inhibiting Receptor-Mediated Antigen Uptake

    OpenAIRE

    Ghosh, Mallika; McAuliffe, Beata; Subramani, Jaganathan; Basu, Sreyashi; Shapiro, Linda H.

    2012-01-01

    Dendritic cell (DC) antigen cross-presentation is generally associated with immune responses to tumors and viral antigens and enhancing this process is a focus of tumor vaccine design. In this study, we found that the myeloid cell surface peptidase CD13 is highly and specifically expressed on the subset of DCs responsible for cross-presentation, the CD8+ murine splenic DCs. In vivo studies indicated that lack of CD13 significantly enhanced T cell responses to soluble OVA antigen, although dev...

  11. Necdin modulates proliferative cell survival of human cells in response to radiation-induced genotoxic stress

    International Nuclear Information System (INIS)

    The finite replicative lifespan of cells, termed cellular senescence, has been proposed as a protective mechanism against the proliferation of oncogenically damaged cells, that fuel cancer. This concept is further supported by the induction of premature senescence, a process which is activated when an oncogene is expressed in normal primary cells as well as following intense genotoxic stresses. Thus, deregulation of genes that control this process, like the tumor suppressor p53, may contribute to promoting cancer by allowing cells to bypass senescence. A better understanding of the genes that contribute to the establishment of senescence is therefore warranted. Necdin interacts with p53 and is also a p53 target gene, although the importance of Necdin in the p53 response is not clearly understood. In this study, we first investigated Necdin protein expression during replicative senescence and premature senescence induced by gamma irradiation and by the overexpression of oncogenic RasV12. Gain and loss of function experiments were used to evaluate the contribution of Necdin during the senescence process. Necdin expression declined during replicative aging of IMR90 primary human fibroblasts or following induction of premature senescence. Decrease in Necdin expression seemed to be a consequence of the establishment of senescence since the depletion of Necdin in human cells did not induce a senescence-like growth arrest nor a flat morphology or SA-β-galactosidase activity normally associated with senescence. Similarly, overexpression of Necdin did not affect the life span of IMR90 cells. However, we demonstrate that in normal human cells, Necdin expression mimicked the effect of p53 inactivation by increasing radioresistance. This result suggests that Necdin potentially attenuate p53 signaling in response to genotoxic stress in human cells and supports similar results describing an inhibitory function of Necdin over p53-dependent growth arrest in mice

  12. Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

    Science.gov (United States)

    Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

    2016-01-01

    This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

  13. Mycoplasma Suppression of THP-1 Cell TLR Responses Is Corrected with Antibiotics

    OpenAIRE

    Ekaterina Zakharova; Jaykumar Grandhi; Wewers, Mark D.; Gavrilin, Mikhail A.

    2010-01-01

    Mycoplasma contamination of cultured cell lines is a serious problem in research, altering cellular response to different stimuli thus compromising experimental results. We found that chronic mycoplasma contamination of THP-1 cells suppresses responses of THP-1 cells to TLR stimuli. For example, E. coli LPS induced IL-1 beta was suppressed by 6 fold and IL-8 by 10 fold in mycoplasma positive THP-1 cells. Responses to live F. novicida challenge were suppressed by 50-fold and 40-fold respective...

  14. Computer simulations of the mechanical response of brushes on the surface of cancerous epithelial cells

    Science.gov (United States)

    Goicochea, A. Gama; Guardado, S. J. Alas

    2015-08-01

    We report a model for atomic force microscopy by means of computer simulations of molecular brushes on surfaces of biological interest such as normal and cancerous cervical epithelial cells. Our model predicts that the force needed to produce a given indentation on brushes that can move on the surface of the cell (called “liquid” brushes) is the same as that required for brushes whose ends are fixed on the cell’s surface (called “solid” brushes), as long as the tip of the microscope covers the entire area of the brush. Additionally, we find that cancerous cells are softer than normal ones, in agreement with various experiments. Moreover, soft brushes are found to display larger resistance to compression than stiff ones. This phenomenon is the consequence of the larger equilibrium length of the soft brushes and the cooperative association of solvent molecules trapped within the brushes, which leads to an increase in the osmotic pressure. Our results show that a careful characterization of the brushes on epithelial cells is indispensable when determining the mechanical response of cancerous cells.

  15. Stress responses in flavivirus-infected cells: activation of unfolded protein response and autophagy

    Directory of Open Access Journals (Sweden)

    Ana-Belén eBlázquez

    2014-06-01

    Full Text Available The Flavivirus is a genus of RNA viruses that includes multiple long known human, animal and zoonotic pathogens such as Dengue virus, yellow fever virus, West Nile virus or Japanese encephalitis virus, as well as other less known viruses that represent potential threats for human and animal health such as Usutu or Zika viruses. Flavivirus replication is based on endoplasmic reticulum-derived structures. Membrane remodeling and accumulation of viral factors induce endoplasmic reticulum stress that results in activation of a cellular signaling response termed unfolded protein response (UPR, which can be modulated by the viruses for their own benefit. Concomitant with the activation of the UPR, an upregulation of the autophagic pathway in cells infected with different flaviviruses has also been described. This review addresses the current knowledge of the relationship between endoplasmic reticulum stress, UPR and autophagy in flavivirus-infected cells and the growing evidences for an involvement of these cellular pathways in the replication and pathogenesis of these viruses.

  16. Nanoscale Properties of Neural Cell Prosthetic and Astrocyte Response

    Science.gov (United States)

    Flowers, D. A.; Ayres, V. M.; Delgado-Rivera, R.; Ahmed, I.; Meiners, S. A.

    2009-03-01

    Preliminary data from in-vivo investigations (rat model) suggest that a nanofiber prosthetic device of fibroblast growth factor-2 (FGF-2)-modified nanofibers can correctly guide regenerating axons across an injury gap with aligned functional recovery. Scanning Probe Recognition Microscopy (SPRM) with auto-tracking of individual nanofibers is used for investigation of the key nanoscale properties of the nanofiber prosthetic device for central nervous system tissue engineering and repair. The key properties under SPRM investigation include nanofiber stiffness and surface roughness, nanofiber curvature, nanofiber mesh density and porosity, and growth factor presentation and distribution. Each of these factors has been demonstrated to have global effects on cell morphology, function, proliferation, morphogenesis, migration, and differentiation. The effect of FGF-2 modification on the key nanoscale properties is investigated. Results from the nanofiber prosthetic properties investigations are correlated with astrocyte response to unmodified and FGF-2 modified scaffolds, using 2D planar substrates as a control.

  17. Unmet Medical Needs in Non-Small-Cell Lung Cancer Treatment: How to Design Pre-Emptive Combination Therapies

    Directory of Open Access Journals (Sweden)

    Niki Karachaliou

    2014-11-01

    Full Text Available The rapidly expanding catalogue of human oncogenic mutations, coupled with difficulties in identifying the cellular targets of active compounds in phenotypic screens, has refocused drug discovery efforts on inhibitors of specific cellular proteins. This new ‘target-based’ approach has enjoyed some spectacular successes in several types of tumours, including non-small-cell lung cancer (NSCLC. Epidermal growth factor receptor (EGFR mutations occur in 17% of NSCLC patients, with notable response to single agent therapy. Unfortunately, all patients eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs, while complete remission rate to EGFR TKIs monotherapy is low. Priming BIM, a proapoptotic signalling BH3-only protein, induces sensitivity to erlotinib [Tarceva®] in EGFR-mutant cell lines. Synthetic lethal approaches and pre-emptive therapies based on the initial expression of BIM may significantly improve treatment outcomes. EGFR mutations result in transient pro-death imbalance of survival and apoptotic signalling in response to EGFR inhibition. Src homology 2 domain-containing phosphatase 2 is essential to the balance between extracellular signal-regulated kinase, phosphoinositide- 3-kinase/protein kinase B and signal transducer and activator of transcription 3 activity. Furthermore, stromal hepatocyte growth factor confers EGFR TKI resistance and induces inter-receptor crosstalk with Ephrin Type-A receptor 2, CDCP1, AXL, and JAK1. A better understanding of the complex cancer molecular biology of EGFR mutant lung cancer is crucial for development of effective treatment and design of successful future clinical studies.

  18. Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses

    Directory of Open Access Journals (Sweden)

    Andoh Y

    2013-01-01

    Full Text Available Yoshiaki Andoh,1,2 Naohiko Makino,2 Mitsunori Yamakawa11Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanBackground: It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL and CD4+CD25high regulatory T-cells (Tregs among dendritic cells (DCs fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines.Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs, were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated.Results: The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1 was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines.Conclusion: The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs

  19. Treatment of allergic asthma: Modulation of Th2 cells and their responses

    Directory of Open Access Journals (Sweden)

    Erb Klaus J

    2011-08-01

    Full Text Available Abstract Atopic asthma is a chronic inflammatory pulmonary disease characterised by recurrent episodes of wheezy, laboured breathing with an underlying Th2 cell-mediated inflammatory response in the airways. It is currently treated and, more or less, controlled depending on severity, with bronchodilators e.g. long-acting beta agonists and long-acting muscarinic antagonists or anti-inflammatory drugs such as corticosteroids (inhaled or oral, leukotriene modifiers, theophyline and anti-IgE therapy. Unfortunately, none of these treatments are curative and some asthmatic patients do not respond to intense anti-inflammatory therapies. Additionally, the use of long-term oral steroids has many undesired side effects. For this reason, novel and more effective drugs are needed. In this review, we focus on the CD4+ Th2 cells and their products as targets for the development of new drugs to add to the current armamentarium as adjuncts or as potential stand-alone treatments for allergic asthma. We argue that in early disease, the reduction or elimination of allergen-specific Th2 cells will reduce the consequences of repeated allergic inflammatory responses such as lung remodelling without causing generalised immunosuppression.

  20. Inhibitors of glycoprotein processing alter T-cell proliferative responses to antigen and to interleukin 2.

    OpenAIRE

    Wall, K A; Pierce, J D; Elbein, A D

    1988-01-01

    Most of the cell-surface molecules involved in T-cell immune responses are N-linked glycoproteins. We have investigated the effects of inhibitors of glycoprotein processing on specific T-cell functions, with the dual aims of examining the functional role of carbohydrate and of testing the usefulness of such compounds as immunomodulators. Treatment of a cloned murine helper T-cell line with these inhibitors differentially affects the proliferative response of the cell, depending upon the natur...

  1. The role of constitutive and inducible processes in the response of human squamous cell carcinoma cell lines to ionizing radiation

    International Nuclear Information System (INIS)

    The inherent radiation sensitivity of the cells within a tumor is thought to contribute to the success or failure of radiation therapy. In vitro studies have shown that differences in the radiation sensitivity of squamous cell carcinoma cell lines reflect alterations in DNA repair. These alterations result from constitutive changes in chromosome organization, not radiation-inducible processes. While inducible responses may play some role in the radiation response of tumor cells, there is no evidence for their involvement in inherent differences in tumor cell radiosensitivity or in the success or failure of radiotherapy of squamous cell carcinomas. 21 refs., 1 fig., 1 tab

  2. State of the art: Multi-fuel reformers for automotive fuel cell applications. Problem identification and research needs

    Energy Technology Data Exchange (ETDEWEB)

    Westerholm, R. [Stockholm Univ. (Sweden). Dept. of Analytical Chemistry; Pettersson, L.J. [Royal Inst. of Tech., Stockholm (Sweden). Dept. of Chemical Engineering and Technology

    1999-12-01

    On an assignment from the Transport and Communications Research Board (KFB) a literature study and a study trip to the USA and Great Britain have been performed. The literature study and the study trip was made during late spring and autumn 1999.The purpose of the project was to collect available information about the chemical composition of the product gas from a multi-fuel reformer for a fuel cell vehicle. It was furthermore to identify problems and research needs. The report recommends directions for future major research efforts. The results of the literature study and the study trip led to the following general conclusions: With the technology available today it does not seem feasible to develop a highly efficient and reliable multi-fuel reformer for automotive applications, i. e. for applications where all types of fuels ranging from natural gas to heavy diesel fuels can be used. The potential for developing a durable and reliable system is considerably higher if dedicated fuel reformers are used.The authors propose that petroleum-derived fuels should be designed for potential use in mobile fuel cell applications. In the present literature survey and the site visit discussions we found that there are relatively low emissions from fuel cell engines compared to internal combustion engines. However, the major research work on reformers/fuel cells have been performed during steady-state operation. Emissions during start-up, shutdown and transient operation are basically unknown and must be investigated in more detail. The conclusions and findings in this report are based on open/available information, such as discussions at site visits, reports, scientific publications and symposium proceedings.

  3. Regulation of the immune response to bacterial lipopolysaccharide by adherent cells.

    OpenAIRE

    Citron, M O; Michael, J G

    1981-01-01

    Immune response to bacterial lipopolysaccharide is usually short lived, but it often reappears without additional stimulus in a cyclic fashion. Activated adherent cells, presumably macrophages, were found to have a role in the reduction of the immune response to Escherichia coli O127 lipopolysaccharide. The suppressive activity of the adherent cells was abrogated before renewal of the responsiveness.

  4. Effects of meal size and composition on incretin, alpha-cell, and beta-cell responses.

    Science.gov (United States)

    Rijkelijkhuizen, Josina M; McQuarrie, Kelly; Girman, Cynthia J; Stein, Peter P; Mari, Andrea; Holst, Jens J; Nijpels, Giel; Dekker, Jacqueline M

    2010-04-01

    The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate postprandial insulin release from the beta-cells. We investigated the effects of 3 standardized meals with different caloric and nutritional content in terms of postprandial glucose, insulin, glucagon, and incretin responses. In a randomized crossover study, 18 subjects with type 2 diabetes mellitus and 6 healthy volunteers underwent three 4-hour meal tolerance tests (small carbohydrate [CH]-rich meal, large CH-rich meal, and fat-rich meal). Non-model-based and model-based estimates of beta-cell function and incremental areas under the curve of glucose, insulin, C-peptide, glucagon, GLP-1, and GIP were calculated. Mixed models and Friedman tests were used to test for differences in meal responses. The large CH-rich meal and fat-rich meal resulted in a slightly larger insulin response as compared with the small CH-rich meal and led to a slightly shorter period of hyperglycemia, but only in healthy subjects. Model-based insulin secretion estimates did not show pronounced differences between meals. Both in healthy individuals and in those with diabetes, more CH resulted in higher GLP-1 release. In contrast with the other meals, GIP release was still rising 2 hours after the fat-rich meal. The initial glucagon response was stimulated by the large CH-rich meal, whereas the fat-rich meal induced a late glucagon response. Fat preferentially stimulates GIP secretion, whereas CH stimulates GLP-1 secretion. Differences in meal size and composition led to differences in insulin and incretin responses but not to differences in postprandial glucose levels of the well-controlled patients with diabetes. PMID:19846181

  5. To investigate the necessity of STRA6 upregulation in T cells during T cell immune responses.

    Directory of Open Access Journals (Sweden)

    Rafik Terra

    Full Text Available Our earlier study revealed that STRA6 (stimulated by retinoic acid gene 6 was up-regulated within 3 h of TCR stimulation. STRA6 is the high-affinity receptor for plasma retinol-binding protein (RBP and mediates cellular vitamin A uptake. We generated STRA6 knockout (KO mice to assess whether such up-regulation was critical for T-cell activation, differentiation and function. STRA6 KO mice under vitamin A sufficient conditions were fertile without apparent anomalies upon visual inspection. The size, cellularity and lymphocyte subpopulations of STRA6 KO thymus and spleen were comparable to those of their wild type (WT controls. KO and WT T cells were similar in terms of TCR-stimulated proliferation in vitro and homeostatic expansion in vivo. Naive KO CD4 cells differentiated in vitro into Th1, Th2, Th17 as well as regulatory T cells in an analogous manner as their WT counterparts. In vivo experiments revealed that anti-viral immune responses to lymphocytic choriomeningitis virus in KO mice were comparable to those of WT controls. We also demonstrated that STRA6 KO and WT mice had similar glucose tolerance. Total vitamin A levels are dramatically lower in the eyes of KO mice as compared to those of WT mice, but the levels in other organs were not significantly affected after STRA6 deletion under vitamin A sufficient conditions, indicating that the eye is the mouse organ most sensitive to the loss of STRA6. Our results demonstrate that 1 in vitamin A sufficiency, the deletion of STRA6 in T cells does no affect the T-cell immune responses so-far tested, including those depend on STAT5 signaling; 2 STRA6-independent vitamin A uptake compensated the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; 3 STRA6 is critical for vitamin A uptake in the eyes even in vitamin A sufficiency.

  6. A qualitative exploration of the perceptions and information needs of public health inspectors responsible for food safety

    OpenAIRE

    Sargeant Jan M; Jones Andria Q; Pham Mai T; Marshall Barbara J; Dewey Catherine E

    2010-01-01

    Abstract Background In Ontario, local public health inspectors play an important frontline role in protecting the public from foodborne illness. This study was an in-depth exploration of public health inspectors' perceptions of the key food safety issues in public health, and their opinions and needs with regards to food safety information resources. Methods Four focus group discussions were conducted with public health inspectors from the Central West region of Ontario, Canada during June an...

  7. Cytotoxic and inflammatory responses of TiO2 nanoparticles on human peripheral blood mononuclear cells.

    Science.gov (United States)

    Kongseng, Supunsa; Yoovathaworn, Krongtong; Wongprasert, Kanokpan; Chunhabundit, Rodjana; Sukwong, Patinya; Pissuwan, Dakrong

    2016-10-01

    Titanium dioxide nanoparticles (TiO2 -NPs) have been widely used in many applications. Owing to their nanoscale size, interactions between cells and NPs have been expansively investigated. With the health concerns raised regarding the adverse effects of these interactions, closer examination of whether TiO2 -NPs can induce toxicity towards human cells is greatly needed. Therefore, in this study, we investigated the cytotoxicity of TiO2 -NPs towards human blood cells (peripheral blood mononuclear cells [PBMCs]) in serum-free medium, for which there is little information regarding the cytotoxic effects of TiO2 -NPs. Our results provide evidence that PBMCs treated with TiO2 -NPs (at concentrations ≥25 μg ml(-1) ) for 24 h significantly reduced cell viability and significantly increased production of toxic mediators such as reactive oxygen species and inflammatory response cytokines such as interleukin-6 and tumor necrosis factor-α (P < 0.05). Cell apoptosis induction also occurred at these concentrations. Significant expressions of cyclooxygenase-2 and interleukin-1β were also observed in PBMCs treated with TiO2 -NPs at concentrations ≥125 μg ml(-1) . Our data presented here clearly indicate that the concentration of TiO2 -NPs (at size ~26.4 ± 1.2 nm) applied to human blood cells has a strong impact on cytotoxic induction. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27225715

  8. Microwell-Based Live Cell Imaging of NK Cell Dynamics to Assess Heterogeneity in Motility and Cytotoxic Response.

    Science.gov (United States)

    Vanherberghen, Bruno; Frisk, Thomas; Forslund, Elin; Olofsson, Per E; Guldevall, Karolin; Önfelt, Björn

    2016-01-01

    NK cell heterogeneity has primarily been studied either on the population level, measuring average responses, or on the single cell level by flow cytometry, providing static snapshots. These approaches have certain drawbacks, not enabling dynamic observations of single cells over extended periods of time. One of the primary limitations of single cell imaging has been throughput; it has been challenging to collect data for many cells due to their dynamic nature and migrating out of the field of view. Spatially confining cells combined with automated fluorescence microscopy enables the simultaneous monitoring of many NK cells in parallel for extended periods of time (>12 h). Such an approach allows us to dissect how the sum of individual NK cell responses translates to the global average response typically observed. PMID:27177659

  9. A qualitative exploration of the perceptions and information needs of public health inspectors responsible for food safety

    Directory of Open Access Journals (Sweden)

    Sargeant Jan M

    2010-06-01

    Full Text Available Abstract Background In Ontario, local public health inspectors play an important frontline role in protecting the public from foodborne illness. This study was an in-depth exploration of public health inspectors' perceptions of the key food safety issues in public health, and their opinions and needs with regards to food safety information resources. Methods Four focus group discussions were conducted with public health inspectors from the Central West region of Ontario, Canada during June and July, 2008. A questioning route was used to standardize qualitative data collection. Audio recordings of sessions were transcribed verbatim and data-driven content analysis was performed. Results A total of 23 public health inspectors participated in four focus group discussions. Five themes emerged as key food safety issues: time-temperature abuse, inadequate handwashing, cross-contamination, the lack of food safety knowledge by food handlers and food premise operators, and the lack of food safety information and knowledge about specialty foods (i.e., foods from different cultures. In general, participants reported confidence with their current knowledge of food safety issues and foodborne pathogens. Participants highlighted the need for a central source for food safety information, access to up-to-date food safety information, resources in different languages, and additional food safety information on specialty foods. Conclusions The information gathered from these focus groups can provide a basis for the development of resources that will meet the specific needs of public health inspectors involved in protecting and promoting food safety.

  10. Protective Cytotoxic T-Cell Responses Induced by Venezuelan Equine Encephalitis Virus Replicons Expressing Ebola Virus Proteins

    OpenAIRE

    Olinger, Gene G.; Bailey, Michael A.; Dye, John M.; Bakken, Russell; Kuehne, Ana; Kondig, John; Wilson, Julie; Hogan, Robert J.; Hart, Mary Kate

    2005-01-01

    Infection with Ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. Filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from Ebola virus infection. Previous studies indicated that exposure to Ebola virus proteins expressed from packaged Venezuelan equine encephalitis virus replicons elicited protective immunity in mice and th...

  11. Immune responses of dendritic cells after acquiring antigen from apoptotic hepatocholangioma cells caused by γ-ray

    International Nuclear Information System (INIS)

    Objective: To investigate the induction of cytotoxic T lymphocytes (CTLs) in antitumor responsiveness and therapeutic effects after dendritic cells (DCs) acquired antigen from apoptotic hepatocholangioma cells. Methods: DCs from blood mononuclear cells that maintain the characteristics of immaturity-anti-gen-capturing and-processing capacity were established in vitro by using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Then, apoptosis in hepatocholangioma cells was induced with γ-radiation. The experimental groups included (1) co-culture of DCs, and apoptotic cancer cells and T cells; (2) co-culture of DCs necrotic cancer cells and T cells; (3) co-culture of DCs-cultured cancer cell and T cells. These cells were co-cultured for 7 days. DCs and T cell were enriched separately. Finally, antitumor response test was carried out. Results: These cells had typical dendritic morphology, expressed high levels of CD1a, B7 and acquired antigen from apoptotic cells caused by γ-rays and induced an increased T cell-stimulatory capacity in MLR. Conclusions: DCs obtained from blood mononuclear cells using GM-CSF and IL-4 and DCs can efficiently present antigen driven from apoptotic cells caused by γ-rays and induce T cells increasing obviously. It can probably become an effective approach of DC transduction with antigen

  12. Multiple Stressors in a Changing World: The Need for an Improved Perspective on Physiological Responses to the Dynamic Marine Environment

    Science.gov (United States)

    Gunderson, Alex R.; Armstrong, Eric J.; Stillman, Jonathon H.

    2016-01-01

    Abiotic conditions (e.g., temperature and pH) fluctuate through time in most marine environments, sometimes passing intensity thresholds that induce physiological stress. Depending on habitat and season, the peak intensity of different abiotic stressors can occur in or out of phase with one another. Thus, some organisms are exposed to multiple stressors simultaneously, whereas others experience them sequentially. Understanding these physicochemical dynamics is critical because how organisms respond to multiple stressors depends on the magnitude and relative timing of each stressor. Here, we first discuss broad patterns of covariation between stressors in marine systems at various temporal scales. We then describe how these dynamics will influence physiological responses to multi-stressor exposures. Finally, we summarize how multi-stressor effects are currently assessed. We find that multi-stressor experiments have rarely incorporated naturalistic physicochemical variation into their designs, and emphasize the importance of doing so to make ecologically relevant inferences about physiological responses to global change.

  13. Putting Corporate Social Responsibility to Work in Mining Communities: Exploring Community Needs for Central Appalachian Wastewater Treatment

    OpenAIRE

    Nicholas Cook; Emily Sarver; Leigh-Anne Krometis

    2015-01-01

    Due to the finite nature of non-renewable mineral and energy resources such as coal, resource extraction is inherently unsustainable; however, mining and related activities can contribute to sustainable development. Indeed, the principles of corporate social responsibility (CSR) require that mine operators design and conduct their activities in ways that provide for net positive impacts on surrounding communities and environments. In Central Appalachia, there appears to be a particularly ripe...

  14. Cereal supplies in rural families of the Senegalese Groundnut Basin. Who is responsible for meeting family food needs ?

    OpenAIRE

    Sakho Jimbira, Maan Suwadu; Benoit-Cattin, Michel

    2007-01-01

    In the traditional operation of production-consumption groups in rural areas of Senegal, the group chief, or Borom njël, has a social duty to make sure family food needs are met. His ability to do this is supported by certain social rules governing these groups, and by a favourable environment. However, various changes have now adversely affected the environment. These changes prompted us to assess the Borom njël's current ability to go on playing his social rule as a food provider. From data...

  15. Innate recognition of cell wall β-glucans drives invariant Natural Killer T (iNKT) cell responses against fungi

    Science.gov (United States)

    Cohen, Nadia R.; Tatituri, Raju V.V.; Rivera, Amariliz; Watts, Gerald F.M.; Kim, Edy Y.; Chiba, Asako; Fuchs, Beth B.; Mylonakis, Eleftherios; Besra, Gurdyal S.; Levitz, Stuart M.; Brigl, Manfred; Brenner, Michael B.

    2016-01-01

    SUMMARY iNKT cells are innate T lymphocytes recognizing endogenous and foreign lipid antigens presented in the MHC-like molecule CD1d. The semi-invariant iNKT cell TCR can detect certain bacterial and parasitic lipids, and drive iNKT cell responses. How iNKT cells respond to fungi, however, is unknown. We found that CD1d-deficient mice, which lack iNKT cells, poorly control infection with the fungal pathogen Aspergillus fumigatus. Furthermore, A. fumigatus rapidly activates iNKT cells in vivo and in vitro in the presence of APCs. Surprisingly, despite a requirement for CD1d recognition, the anti-fungal iNKT cell response does not require fungal lipids. Instead, Dectin-1 and MyD88-mediated responses to β-1,3 glucans, major fungal cell-wall polysaccharides, trigger IL-12 production by APCs that drives self-reactive iNKT cells to secrete IFN-γ. Innate recognition of β-1,3 glucans also drives iNKT cell responses against Candida, Histoplasma and Alternaria, suggesting that this mechanism may broadly define the basis for anti-fungal iNKT cell responses. PMID:22100160

  16. Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) isolated from human pluripotent stem cells are comparable with bone marrow-derived MSCs in their function and immunophenotype. The purpose of this exploratory study was comparative evaluation of the radiation responses of mesenchymal stem cells derived from bone marrow- (BMMSCs) and from human embryonic stem cells (hESMSCs). BMMSCs and hESMSCs were irradiated at 0 Gy (control) to 16 Gy using a linear accelerator commonly used for cancer treatment. Cells were harvested immediately after irradiation, and at 1 and 5 days after irradiation. Cell cycle analysis, colony forming ability (CFU-F), differentiation ability, and expression of osteogenic-specific runt-related transcription factor 2 (RUNX2), adipogenic peroxisome proliferator-activated receptor gamma (PPARγ), oxidative stress-specific dismutase-1 (SOD1) and Glutathione peroxidase (GPX1) were analyzed. Irradiation arrested cell cycle progression in BMMSCs and hESMSCs. Colony formation ability of irradiated MSCs decreased in a dose-dependent manner. Irradiated hESMSCs showed higher adipogenic differentiation compared with BMMSCs, together with an increase in the adipogenic PPARγ expression. PPARγ expression was upregulated as early as 4 h after irradiation, along with the expression of SOD1. More than 70% downregulation was found in Wnt3A, Wnt4, Wnt7A, Wnt10A and Wnt11 in BMMSCs, but not in hESMSCs. hESMSCs are highly proliferative but radiosensitive compared with BMMSCs. Increased PPARγ expression relative to RUNX2 and downregulation of Wnt ligands in irradiated MSCs suggest Wnt mediated the fate determination of irradiated MSCs. (author)

  17. Ionizing radiation affects generation of MART-1-specific cytotoxic T cell responses by dendritic cells

    International Nuclear Information System (INIS)

    Full text: The human MART-1/Melan-A (MART-1) melanoma tumor antigen is known to be recognized by cytotoxic T lymphocytes (CTLs) and several groups are using this target for clinical immunotherapy. Most approaches use dendritic cells (DCs) that are potent antigen presentation cells for initiating CTL responses. In order for CTL recognition to occur, DCs must display 9-residue antigenic peptides on MHC class I molecules. These peptides are generated by proteasome degradation and then transported through the endoplasmic reticulum to the cell surface where they stabilize MHC class I expression. Our previous data showed that irradiation inhibits proteasome function and, therefore, we hypothesized that irradiation may inhibit antigen processing and CTL activation, as has been shown for proteasome inhibitors. To study the importance of irradiation effects on DCs, we studied the generation MART-1-specific CTL responses. Preliminary data showed that irradiation of murine bone marrow derived DCs did not affect expression of MHC class I, II, CD80, or CD86, as assessed by flow cytometric analyses 24-hour after irradiation. The effect of irradiation on MART-1 antigen processing by DCs was evaluated using DC transduced with adenovirus MART-1 (AdVMART1). C57BL/6 mice were immunized with AdVMART1 transduced DCs, with and without prior irradiation. IFN-γ production was measured by ELISPOT assays after 10-14 days of immunization. Prior radiation treatment resulted in a significant decrease in MART-1-specific T cell responses. The ability of irradiated and non-irradiated AdVMART1/DC vaccines to protect mice against growth of murine B16 tumors, which endogenously express murine MART-1, was also examined. AdVMART1/DC vaccination protected C57BL/6 mice against challenge with viable B16 melanoma cells while DCs irradiated (10 Gy) prior to AdVMART1 transduction abrogated protection. These results suggest that proteasome inhibition in DCs by irradiation may be a possible pathway in

  18. On the significance of contaminant plume-scale and dose-response models in defining hydrogeological characterization needs

    Science.gov (United States)

    de Barros, F.; Rubin, Y.; Maxwell, R.; Bai, H.

    2007-12-01

    Defining rational and effective hydrogeological data acquisition strategies is of crucial importance since financial resources available for such efforts are always limited. Usually such strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of the impacts of uncertainty. This paper presents an approach for determining site characterization needs based on human health risk factors. The main challenge is in striking a balance between improved definition of hydrogeological, behavioral and physiological parameters. Striking this balance can provide clear guidance on setting priorities for data acquisition and for better estimating adverse health effects in humans. This paper addresses this challenge through theoretical developments and numerical testing. We will report on a wide range of factors that affect the site characterization needs including contaminant plume's dimensions, travel distances and other length scales that characterize the transport problem, as well as health risk models. We introduce a new graphical tool that allows one to investigate the relative impact of hydrogeological and physiological parameters in risk. Results show that the impact of uncertainty reduction in the risk-related parameters decreases with increasing distances from the contaminant source. Also, results indicate that human health risk becomes less sensitive to hydrogeological measurements when dealing with ergodic plumes. This indicates that under ergodic conditions, uncertainty reduction in human health risk may benefit from better understanding of the physiological component as opposed to a detailed hydrogeological characterization

  19. Electric vehicles rising from the dead: Data needs for forecasting consumer response toward sustainable energy sources in personal transportation

    International Nuclear Information System (INIS)

    Since standard vehicles are powered by internal combustion mechanisms that rely on fossil fuels, electric vehicles that are propelled by one or more electric engines have been proposed as an alternative to promote sustainable personal transportation. In this paper we propose a general demand model for vehicle purchases at the individual level assuming that the necessary microdata is available. We then list the ideal microdata that would be needed for estimating this general demand model. For elaborating this list, we take into account the particularities of low emission vehicles, with emphasis in their cost-reliability-environmental benefits tradeoff, as well as the potentiality for evaluation of welfare improving policies related to adoption of energy-efficient technologies. We discuss data sources and collection strategies for the different attributes of the model, especially for those characteristics that are nonstandard such as symbolic values. For instance, we discuss the role of range anxiety as a barrier of adoption of electric vehicles, and the implied relevance of including driving range to get consumers’ willingness to pay for better performing electric batteries. - Highlights: ► Evaluation of electric vehicles as an alternative to promote sustainable transportation. ► We propose a generalized discrete choice model for vehicle purchases. ► The model includes endogenous latent attributes such as environmental preferences. ► We describe the data needs for estimating the generalized demand model. ► We propose effect and causal indicator for the latent attributes.

  20. Assessing humoral and cell-mediated immune response in Hawaiian green turtles, Chelonia mydas

    Science.gov (United States)

    Work, T.M.; Balazs, G.H.; Rameyer, R.A.; Chang, S.P.; Berestecky, J.

    2000-01-01

    Seven immature green turtles, Chelonia mydas, captured from Kaneohe Bay on the island of Oahu were used to evaluate methods for assessing their immune response. Two turtles each were immunized intramuscularly with egg white lysozyme (EWL) in Freunda??s complete adjuvant, Gerbu, or ISA-70; a seventh turtle was immunized with saline only and served as a control. Humoral immune response was measured with an indirect enzyme linked immunosorbent assay (ELISA). Cell-mediated immune response was measured using in vitro cell proliferation assays (CPA) using whole blood or peripheral blood mononuclear cells (PBM) cultured with concanavalin A (ConA), phytohaemagglutinin (PHA), or soluble egg EWL antigen. All turtles, except for one immunized with Gerbu and the control, produced a detectable humoral immune response by 6 weeks which persisted for at least 14 weeks after a single immunization. All turtles produced an anamnestic humoral immune response after secondary immunization. Antigen specific cell-mediated immune response in PBM was seen in all turtles either after primary or secondary immunization, but it was not as consistent as humoral immune response; antigen specific cell-mediated immune response in whole blood was rarely seen. Mononuclear cells had significantly higher stimulation indices than whole blood regardless of adjuvant, however, results with whole blood had lower variability. Both Gerbu and ISA-70 appeared to potentiate the cell-mediated immune response when PBM or whole blood were cultured with PHA. This is the first time cell proliferation assays have been compared between whole blood and PBM for reptiles. This is also the first demonstration of antigen specific cell-mediated response in reptiles. Cell proliferation assays allowed us to evaluate the cell-mediated immune response of green turtles. However, CPA may be less reliable than ELISA for detecting antigen specific immune response. Either of the three adjuvants appears suitable to safely elicit a

  1. Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways

    International Nuclear Information System (INIS)

    Prostate cancer (PrCa) displays resistance to radiotherapy (RT) and requires radiotherapy dose escalation which is associated with greater toxicity. This highlights a need to develop radiation sensitizers to improve the efficacy of RT in PrCa. Ionizing radiation (IR) stimulates pathways of IR-resistance and survival mediated by the protein kinase Akt but it also activates the metabolic energy sensor and tumor suppressor AMP-Activated Protein Kinase (AMPK). Here, we examined the effects of the polyphenol resveratrol (RSV) on the IR-induced inhibition of cell survival, modulation of cell cycle and molecular responses in PrCa cells. Androgen-insensitive (PC3), sensitive (22RV1) PrCa and PNT1A normal prostate epithelial cells were treated with RSV alone (2.5-10 μM) or in combination with IR (2-8 Gy). Clonogenic assays, cell cycle analysis, microscopy and immunoblotting were performed to assess survival, cell cycle progression and molecular responses. RSV (2.5-5 μM) inhibited clonogenic survival of PC3 and 22RV1 cells but not of normal prostate PNT1A cells. RSV specifically sensitized PrCa cells to IR, induced cell cycle arrest at G1-S phase and enhanced IR-induced nuclear aberrations and apoptosis. RSV enhanced IR-induced expression of DNA damage (γH2Ax) and apoptosis (cleaved-caspase 3) markers as well as of the cell cycle regulators p53, p21cip1 and p27kip1. RSV enhanced IR-activation of ATM and AMPK but inhibited basal and IR-induced phosphorylation of Akt. Our results suggest that RSV arrests cell cycle, promotes apoptosis and sensitizes PrCa cells to IR likely through a desirable dual action to activate the ATM-AMPK-p53-p21cip1/p27kip1 and inhibit the Akt signalling pathways

  2. Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues

    International Nuclear Information System (INIS)

    Purpose: High-dose synchrotron microbeam radiation therapy (MRT) can be effective at destroying tumors in animal models while causing very little damage to normal tissues. The aim of this study was to investigate the cellular processes behind this observation of potential clinical importance. Methods and Materials: MRT was performed using a lattice of 25 μm-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-μm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of γ-H2AX allowed precise localization of irradiated cells, which were also assessed for proliferation and apoptosis. Results: MRT significantly reduced tumor cell proliferation by 24 h post-irradiation (p = 0.002). An unexpected finding was that within 24 h of MRT, peak and valley irradiated zones were indistinguishable in tumors because of extensive cell migration between the zones. This was not seen in MRT-treated normal skin, which appeared to undergo a coordinated repair response. MRT elicited an increase in median survival times of EMT-6.5 and 67NR tumor-inoculated mice similar to that achieved with conventional radiotherapy, while causing markedly less normal tissue damage. Conclusions: This study provides evidence of a differential response at a cellular level between normal and tumor tissues after synchrotron MRT.

  3. Immune response to bacteria induces dissemination of Ras-activated Drosophila hindgut cells

    OpenAIRE

    Bangi, Erdem; Pitsouli, Chrysoula; Rahme, Laurence G.; Cagan, Ross; Apidianakis, Yiorgos

    2012-01-01

    Drosophila hindgut cells exposed to bacterial infection activate the innate immune response. Concomitant expression of the Ras1V12 oncogene leads to extracellular matrix degradation, basal cell invasion and dissemination in the body cavity.

  4. SEU response of an entire SRAM cell simulated as one contiguous three dimensional device domain

    International Nuclear Information System (INIS)

    The first SEU response of a complete 3-D SRAM cell is presented. This simulation method allows to verify the accuracy of the commonly used mixed-mode technique and to study coupling effects between different junctions of the cell

  5. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan Song; Jing Huang; Ling Shan; Hong-Tu Zhang

    2015-01-01

    Background:Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC),but biomarkers of activity are lacking.The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status,vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression,and their relationships with characteristics and clinical outcome of advanced ccRCC.Methods:A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute,Chinese Academy of Medical Sciences between January 2010 and November 2012.Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry.Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and ovcrall survival (OS) were calculated and then compared based on expression status.The Chi-square test,the KaplanMeier method,and the Lon-rank test were used for statistical analyses.Results:Of 59 patients,objective responses were observed in 28 patients (47.5%).The median PFS was 13.8 months and median OS was 39.9 months.There was an improved PFS in patients with the following clinical features:Male gender,number of metastatic sites 2 or less,VEGFR-2 positive or KIT positive.Eleven patients (18.6%) had evidence of VHL mutation,with an objective response rate of 45.5%,which showed no difference with patients with no VHL mutation (47.9%).VHL mutation status did not correlate with either overall response rate (P =0.938) or PFS (P =0.277).The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients,respectively,which was significantly longer than that of VEGFR-2 or KIT negative patients (P =0.026 and P =0.043).Conclusion:VHL mutation status could not predict

  6. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yan Song

    2015-01-01

    Full Text Available Background: Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC, but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL gene status, vascular endothelial growth factor receptor (VEGFR or stem cell factor receptor (KIT expression, and their relationships with characteristics and clinical outcome of advanced ccRCC. Methods: A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS and overall survival (OS were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses. Results: Of 59 patients, objective responses were observed in 28 patients (47.5%. The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6% had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%. VHL mutation status did not correlate with either overall response rate (P = 0.938 or PFS (P = 0.277. The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043. Conclusion

  7. Differences in DNA Repair Capacity, Cell Death and Transcriptional Response after Irradiation between a Radiosensitive and a Radioresistant Cell Line.

    Science.gov (United States)

    Borràs-Fresneda, Mireia; Barquinero, Joan-Francesc; Gomolka, Maria; Hornhardt, Sabine; Rössler, Ute; Armengol, Gemma; Barrios, Leonardo

    2016-01-01

    Normal tissue toxicity after radiotherapy shows variability between patients, indicating inter-individual differences in radiosensitivity. Genetic variation probably contributes to these differences. The aim of the present study was to determine if two cell lines, one radiosensitive (RS) and another radioresistant (RR), showed differences in DNA repair capacity, cell viability, cell cycle progression and, in turn, if this response could be characterised by a differential gene expression profile at different post-irradiation times. After irradiation, the RS cell line showed a slower rate of γ-H2AX foci disappearance, a higher frequency of incomplete chromosomal aberrations, a reduced cell viability and a longer disturbance of the cell cycle when compared to the RR cell line. Moreover, a greater and prolonged transcriptional response after irradiation was induced in the RS cell line. Functional analysis showed that 24 h after irradiation genes involved in "DNA damage response", "direct p53 effectors" and apoptosis were still differentially up-regulated in the RS cell line but not in the RR cell line. The two cell lines showed different response to IR and can be distinguished with cell-based assays and differential gene expression analysis. The results emphasise the importance to identify biomarkers of radiosensitivity for tailoring individualized radiotherapy protocols. PMID:27245205

  8. Reduction of IL-17A Might Suppress the Th1 Response and Promote the Th2 Response by Boosting the Function of Treg Cells during Silica-Induced Inflammatory Response In Vitro

    Directory of Open Access Journals (Sweden)

    Wen Tang

    2014-01-01

    Full Text Available Silica inhalation can induce chronic lung inflammation and fibrosis. Upon silica stimulation, activated macrophages trigger the T-lymphocyte which can differentiate into many different types of Th cells, including the recently discovered Th17 cells. IL-17A, the typical Th17 cytokine, is reported in some inflammatory diseases. However, the role of IL-17A in silica-induced inflammatory response is still not clear. The regulatory mechanism of silica-induced Th17 response also needs to be investigated. So we established a mice primary cell coculture system (macrophage and lymphocyte to investigate the role of IL-17A in silica-induced inflammatory response in vitro, by using anti-IL-17A mAb and IL-1Ra. Both anti-IL-17A mAb and IL-1Ra decreased the level of IL-17A and increased the function of Treg cells. The Th1 response was suppressed and the Th2 response was promoted by the addition of anti-IL-17A mAb or IL-1Ra. IL-1Ra treatment decreased the level of IL-6, whereas the levels of IL-23 and ROR-γt were increased. Our study demonstrated that IL-17A reduction altered the pattern of silica-induced Th responses by boosting the function of Treg cells in vitro. Blocking the function of IL-1 signal pathway could suppress the level of IL-17A, which played the major role in modulating silica-induced Th responses in vitro.

  9. Contrasting motivational orientation and evaluative coding accounts: On the need to differentiate the effectors of approach/avoidance responses

    Directory of Open Access Journals (Sweden)

    Julia eKozlik

    2015-05-01

    Full Text Available Several emotion theorists suggest that valenced stimuli automatically trigger motivational orientations and thereby facilitate corresponding behavior. Positive stimuli were thought to activate approach motivational circuits which in turn primed approach-related behavioral tendencies whereas negative stimuli were supposed to activate avoidance motivational circuits so that avoidance-related behavioral tendencies were primed (motivational orientation account. However, recent research suggests that typically observed affective stimulus–response compatibility phenomena might be entirely explained in terms of theories accounting for mechanisms of general action control instead of assuming motivational orientations to mediate the effects (evaluative coding account. In what follows, we explore to what extent this notion is applicable. We present literature suggesting that evaluative coding mechanisms indeed influence a wide variety of affective stimulus–response compatibility phenomena. However, the evaluative coding account does not seem to be sufficient to explain affective S–R compatibility effects. Instead, several studies provide clear evidence in favor of the motivational orientation account that seems to operate independently of evaluative coding mechanisms. Implications for theoretical developments and future research designs are discussed.

  10. Contrasting motivational orientation and evaluative coding accounts: on the need to differentiate the effectors of approach/avoidance responses.

    Science.gov (United States)

    Kozlik, Julia; Neumann, Roland; Lozo, Ljubica

    2015-01-01

    Several emotion theorists suggest that valenced stimuli automatically trigger motivational orientations and thereby facilitate corresponding behavior. Positive stimuli were thought to activate approach motivational circuits which in turn primed approach-related behavioral tendencies whereas negative stimuli were supposed to activate avoidance motivational circuits so that avoidance-related behavioral tendencies were primed (motivational orientation account). However, recent research suggests that typically observed affective stimulus-response compatibility phenomena might be entirely explained in terms of theories accounting for mechanisms of general action control instead of assuming motivational orientations to mediate the effects (evaluative coding account). In what follows, we explore to what extent this notion is applicable. We present literature suggesting that evaluative coding mechanisms indeed influence a wide variety of affective stimulus-response compatibility phenomena. However, the evaluative coding account does not seem to be sufficient to explain affective S-R compatibility effects. Instead, several studies provide clear evidence in favor of the motivational orientation account that seems to operate independently of evaluative coding mechanisms. Implications for theoretical developments and future research designs are discussed. PMID:25983718

  11. Phagocytic cell function in response to immunosuppressive therapy.

    Science.gov (United States)

    Drath, D B; Kahan, B D

    1984-02-01

    The increased incidence of pulmonary infection in human renal allograft recipients is presumably related to antirejection immunosuppressive therapy. To assess immunosuppressive-related disturbances of the immune responses of the lung, we evaluated the functional abilities of the pulmonary alveolar macrophage (PAM) and polymorphonuclear leukocyte (PMN) of rats in chemotaxis, phagocytosis, and superoxide-release assays following 30 days of intraperitoneal administration of cyclosporine, azathioprine, and/or prednisolone sodium succinate. None of these drugs affected superoxide release by stimulated PAMs or PMNs. Except for a transient inhibition by azathioprine, the drugs had no effect on phagocytosis of Staphylococcus aureus by either cell type. On the other hand, cyclosporine inhibited formyl-methionyl-leucyl-phenylalanine (FMLP)-directed chemotaxis by PAMs, and both FMLP and C5a stimulated chemotaxis by PMNs. Azathioprine had more dramatic effects on PAMs than on PMNs and prednisolone at 2 mg/kg inhibited PAMs. The results indicated that, with the exception of chemotaxis, the immunosuppressive agents largely spare nonspecific elements of host defense. PMID:6320765

  12. Antibody and B cell responses to Plasmodium sporozoites

    Directory of Open Access Journals (Sweden)

    Johanna N Dups

    2014-11-01

    Full Text Available Antibodies are capable of blocking infection of the liver by Plasmodium sporozoites. Accordingly the induction of anti-sporozoite antibodies is a major aim of various vaccine approaches to malaria. In recent years our knowledge of the specificity and quantities of antibodies required for protection has been greatly expanded by clinical trials of various whole sporozoite and subunit vaccines. Moreover, the development of humanized mouse models and transgenic parasites have also aided our ability to assess the specificity of antibodies and their ability to block infection. Nonetheless, considerable gaps remain in our knowledge - in particular in understanding what antigens are recognized by infection blocking antibodies and in knowing how we can induce robust, long-lived antibody responses. Maintaining high levels of circulating antibodies is likely to be of primary importance, as antibodies must block infection in the short time it takes for sporozoites to reach the liver from the skin. It is clear that a better understanding of the development of protective B cell-mediated immunity will aid the development and refinement of malaria vaccines.

  13. The influence of Listeria monocytogenes cells on the primary immunologic response in irradiated mice

    International Nuclear Information System (INIS)

    The influence of killed Listeria monocytogenes cells on the primary immunologic response in mice irradiated with 300 or 500 R was studied. The immunologic response of the mice to sheep red blood cells used as antigen was assessed at the cellular level (by counting PFC) and humoral level. Injection of killed Listeria monocytogenes cells before irradiation of the mice diminished the immunosuppressive effect of roentgen radiation. Injection of the cells after irradiation accelerated regeneration of immunologic reactivity in the irradiated mice. (author)

  14. The cell wall and endoplasmic reticulum stress responses are coordinately regulated in Saccharomyces cerevisiae

    OpenAIRE

    Krysan, Damian J.

    2009-01-01

    The unfolded protein response (UPR) is an intracellular signaling pathway that regulates the cellular response to the accumulation of misfolded proteins in eukaryotes. Our group has demonstrated that cell wall stress activates UPR in yeast through signals transmitted by the cell wall integrity (CWI) mitogen-activated protein (MAP) kinase cascade. The UPR is required to maintain cell wall integrity; mutants lacking a functional UPR have defects in cell wall biosynthesis and are hypersensitive ...

  15. Live cell microscopy of DNA damage response in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Pinela da Silva, Sonia Cristina; Gallina, Irene; Eckert-Boulet, Nadine Valerie; Lisby, Michael

    Fluorescence microscopy of the DNA damage response in living cells stands out from many other DNA repair assays by its ability to monitor the response to individual DNA lesions in single cells. This is particularly true in yeast, where the frequency of spontaneous DNA lesions is relatively low...... live cell imaging allows for multiple cellular markers to be monitored over several hours. This chapter reviews useful fluorescent markers and genotoxic agents for studying the DNA damage response in living cells and provides protocols for live cell imaging, time-lapse microscopy, and for induction of...

  16. The role of regulatory T cells in the control of B cell mediated immune responses

    OpenAIRE

    Wollenberg, Ivonne

    2011-01-01

    Tese de doutoramento, Ciências Biomédicas (Imunologia), Universidade de Lisboa, Faculdade de Medicina, 2011 This thesis reports research on the regulation of immune responses leading to a humoral immune reaction. This type of immune phenomena is based on B-T cell interactions. The first part of the thesis is devoted to study the effect of OX40-ligand blockade in preventing allergic airways disease in mice. Allergic airways disease is a Th2-dependent pathology associated with production of ...

  17. Forecasting the response of Earth's surface to future climatic and land use changes: A review of methods and research needs

    Science.gov (United States)

    Pelletier, Jon D.; Brad Murray, A.; Pierce, Jennifer L.; Bierman, Paul R.; Breshears, David D.; Crosby, Benjamin T.; Ellis, Michael; Foufoula-Georgiou, Efi; Heimsath, Arjun M.; Houser, Chris; Lancaster, Nick; Marani, Marco; Merritts, Dorothy J.; Moore, Laura J.; Pederson, Joel L.; Poulos, Michael J.; Rittenour, Tammy M.; Rowland, Joel C.; Ruggiero, Peter; Ward, Dylan J.; Wickert, Andrew D.; Yager, Elowyn M.

    2015-07-01

    In the future, Earth will be warmer, precipitation events will be more extreme, global mean sea level will rise, and many arid and semiarid regions will be drier. Human modifications of landscapes will also occur at an accelerated rate as developed areas increase in size and population density. We now have gridded global forecasts, being continually improved, of the climatic and land use changes (C&LUC) that are likely to occur in the coming decades. However, besides a few exceptions, consensus forecasts do not exist for how these C&LUC will likely impact Earth-surface processes and hazards. In some cases, we have the tools to forecast the geomorphic responses to likely future C&LUC. Fully exploiting these models and utilizing these tools will require close collaboration among Earth-surface scientists and Earth-system modelers. This paper assesses the state-of-the-art tools and data that are being used or could be used to forecast changes in the state of Earth's surface as a result of likely future C&LUC. We also propose strategies for filling key knowledge gaps, emphasizing where additional basic research and/or collaboration across disciplines are necessary. The main body of the paper addresses cross-cutting issues, including the importance of nonlinear/threshold-dominated interactions among topography, vegetation, and sediment transport, as well as the importance of alternate stable states and extreme, rare events for understanding and forecasting Earth-surface response to C&LUC. Five supplements delve into different scales or process zones (global-scale assessments and fluvial, aeolian, glacial/periglacial, and coastal process zones) in detail.

  18. Assessing the detail needed to capture rainfall-runoff dynamics with physics-based hydrologic response simulation

    Science.gov (United States)

    Mirus, B.B.; Ebel, B.A.; Heppner, C.S.; Loague, K.

    2011-01-01

    Concept development simulation with distributed, physics-based models provides a quantitative approach for investigating runoff generation processes across environmental conditions. Disparities within data sets employed to design and parameterize boundary value problems used in heuristic simulation inevitably introduce various levels of bias. The objective was to evaluate the impact of boundary value problem complexity on process representation for different runoff generation mechanisms. The comprehensive physics-based hydrologic response model InHM has been employed to generate base case simulations for four well-characterized catchments. The C3 and CB catchments are located within steep, forested environments dominated by subsurface stormflow; the TW and R5 catchments are located in gently sloping rangeland environments dominated by Dunne and Horton overland flows. Observational details are well captured within all four of the base case simulations, but the characterization of soil depth, permeability, rainfall intensity, and evapotranspiration differs for each. These differences are investigated through the conversion of each base case into a reduced case scenario, all sharing the same level of complexity. Evaluation of how individual boundary value problem characteristics impact simulated runoff generation processes is facilitated by quantitative analysis of integrated and distributed responses at high spatial and temporal resolution. Generally, the base case reduction causes moderate changes in discharge and runoff patterns, with the dominant process remaining unchanged. Moderate differences between the base and reduced cases highlight the importance of detailed field observations for parameterizing and evaluating physics-based models. Overall, similarities between the base and reduced cases indicate that the simpler boundary value problems may be useful for concept development simulation to investigate fundamental controls on the spectrum of runoff generation

  19. Chicken primordial germ cell motility in response to stem cell factor sensing.

    Science.gov (United States)

    Srihawong, Thanida; Kuwana, Takashi; Siripattarapravat, Kannika; Tirawattanawanich, Chanin

    2015-01-01

    Avian primordial germ cells (PGCs) are destined to migrate a long distance from their extra embryonic region via the vascular system to the gonadal ridges where they form the germ cells. Although PGC migration is crucial for a genetic continuation to the next generation, the factors and mechanisms that control their migration remain largely unknown. In the present study the chemotactic effect of stem cell factor (SCF) was examined on chicken blood circulating PGCs (cPGC), employing 3D chemotaxis slides and time-lapsed imaging analyses as an in vitro study model. Upon in vitro exposure to an SCF gradient, 77.1% (54 out of 70) of cPGCs showed a clear response, of which 48.1% (26 out of 54) polarized with the consecutive formation of a persistent membrane protrusion and significant directional migration towards the gradient and the others showed transient membrane protrusions. In contrast, the controls and apparently SCF unresponsive cPGCs and c-kit-negative red blood cells (RBCs) showed only cytoplasmic cycling with random formations of membrane blebbing and no directional migration. Significant (p goat anti-mouse c-kit primary antibody, suggesting that the cPGCs were capable of SCF sensing and the potential involvement of SCF/c-kit in the chemotactic migration. Therefore, SCF is suggested to function as a chemoattractant in the migration of chicken cPGC. PMID:26864485

  20. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    International Nuclear Information System (INIS)

    Highlights: ► We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. ► Zfat-deficiency leads to reduction in the number of the peripheral T cells. ► Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. ► Decreased expression of IL-7Rα, IL-2Rα and IL-2 in Zfat-deficient peripheral T cells. ► Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7Rα and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2Rα expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  1. Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system.

    Science.gov (United States)

    Simon, Karen A; Mosadegh, Bobak; Minn, Kyaw Thu; Lockett, Matthew R; Mohammady, Marym R; Boucher, Diane M; Hall, Amy B; Hillier, Shawn M; Udagawa, Taturo; Eustace, Brenda K; Whitesides, George M

    2016-07-01

    This work demonstrates the application of a 3D culture system-Cells-in-Gels-in-Paper (CiGiP)-in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct-prepared by stacking multiple sheets of paper containing cell-embedded hydrogels-generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium. As the distance between the cells and source of oxygenated media increased, cells show increased levels of hypoxia-inducible factor 1-alpha, decreased proliferation, and reduced sensitivity to ionizing radiation. Each of these cellular responses are characteristic of cancer cells observed in solid tumors. With this setup we were able to differentiate three isogenic variants of A549 cells based on their metabolic radiosensitivity; these three variants have known differences in their metastatic behavior in vivo. This system can, therefore, capture some aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon, carry out systematic studies of radiation response in vitro that decouple effects from migration and proliferation of cells, and regulate the exposure of oxygen to subpopulations of cells in a tissue-like construct either before or after irradiation. PMID:27116031

  2. Osteoblast cell response to surface-modified carbon nanotubes

    International Nuclear Information System (INIS)

    In order to investigate the interaction of cells with modified multi-walled carbon nanotubes (MWCNTs) for their potential biomedical applications, the MWCNTs were chemically modified with carboxylic acid groups (–COOH), polyvinyl alcohol (PVA) polymer and biomimetic apatite on their surfaces. Additionally, human osteoblast MG-63 cells were cultured in the presence of the surface-modified MWCNTs. The metabolic activities of osteoblastic cells, cell proliferation properties, as well as cell morphology were studied. The surface modification of MWCNTs with biomimetic apatite exhibited a significant increase in the cell viability of osteoblasts, up to 67.23%. In the proliferation phases, there were many more cells in the biomimetic apatite-modified MWCNT samples than in the MWCNTs–COOH. There were no obvious changes in cell morphology in osteoblastic MG-63 cells cultured in the presence of these chemically-modified MWCNTs. The surface modification of MWCNTs with apatite achieves an effective enhancement of their biocompatibility.

  3. Bone marrow function. I. Peripheral T cells are responsible for the increased auto-antiidiotype response of older mice

    International Nuclear Information System (INIS)

    After immunization with trinitrophenyl (TNP)-Ficoll, mice produced both anti-TNP antibodies and auto-anti-idiotype (auto-anti-Id) antibodies specific for the anti-TNP antibody. Older animals produced more auto-anti-Id than did young animals. When mice were exposed to a normally lethal dose of irradiation while their bone marrow (BM) was partially shielded, they survived and slowly (6 wk) regained immune function, as indicated by the number of nucleated cells in their spleen and the in vitro primary plaque-forming cell (PFC) response of their spleen cells to TNP-treated aminoethylated polyacrylamide beads. Recovery is presumably the result of repopulation of the peripheral lymphoid system by cells originating in the BM. By enzyme-linked immunosorbent assay (ELISA), and by hapten-augmentable PFC assay, the authors show that, after recovery from irradiation with their BM shielded, old animals produce low auto-anti-Id responses, like those of young animals. The transfer of splenic T cells into mice irradiated with their BM shielded provided evidence that the magnitude of the auto-anti-Id response is controlled by the peripheral T cells. Thus, mice that received splenic T cells from aged donors produced high levels of auto-anti-Id while those that received splenic T cells from young donors produce low levels of auto-anti-Id

  4. Antileukemic T-cell Responses Can Be Predicted by the Composition of Specific Regulatory T-cell Subpopulations

    OpenAIRE

    Schick, Julia; Vogt, Valentin; Zerwes, Marion; Kröll, Tanja; Kraemer, Doris; Koehne, Claus-Henning; Hausmann, Andreas; Buhmann, Raymund; Tischer, Johanna; Schmetzer, Helga

    2013-01-01

    Regulatory T cells (T-reg) are important regulators of immune responses. In acute myeloid leukemia (AML) patients before/after immunotherapy (stem cell transplantation or donor lymphocyte infusion), their suppressive role can contribute to suppress severe graft-versus-host reactions, but also to impair antileukemic reactions. As leukemia-derived dendritic cells (DCleu) are known to improve the antileukemic functionality of T cells, we evaluated the composition and development of distinct T-re...

  5. Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection

    OpenAIRE

    Srivastava, Shivani; Koch, Meghan A.; Pepper, Marion; Campbell, Daniel J.

    2014-01-01

    Regulatory T (T reg) cells play an essential role in preventing autoimmunity but can also impair clearance of foreign pathogens. Paradoxically, signals known to promote T reg cell function are abundant during infection and could inappropriately enhance T reg cell activity. How T reg cell function is restrained during infection to allow the generation of effective antiviral responses remains largely unclear. We demonstrate that the potent antiviral type I interferons (IFNs) directly inhibit co...

  6. Bio-inspired Nanomaterials for Biosensing and Cell Response

    Science.gov (United States)

    Stevens, Molly

    2012-02-01

    This talk will provide an overview of our recent developments in bio-inspired nanomaterials for tissue regeneration and sensing. Bio-responsive nanomaterials are of growing importance with potential applications including drug delivery, diagnostics and tissue engineering [1]. DNA-, protein- or peptide-functionalised nanoparticle (NP) aggregates are particularly useful systems since triggered changes in their aggregation states may be readily monitored. Our recent simple conceptually novel approaches to real-time monitoring of protease, lipase and kinase enzyme action using modular peptide functionalized NPs will be presented [2,3,4]. The highly interdisciplinary field of Tissue Engineering (TE) can also benefit from advances in the design of bio-responsive nanomaterials. TE involves the development of artificial scaffold structures on which new cells are encouraged to grow. The ability to control topography and chemistry at the nanoscale offers exciting possibilities for stimulating growth of new tissue through the development of novel nanostructured scaffolds that mimic the nanostructure of the tissues in the body [1,5,6]. Recent developments in this context will be discussed as well as novel approaches to in vivo tissue regeneration of large volumes of highly vascularised and hierarchically organized tissue [7,8,9]. [4pt] [1] MM Stevens, J George. Science 310:1135-1138 (2005)[0pt] [2] A Laromaine, L Koh, M Murugesan, RV Ulijn, MM Stevens. Journal of the American Chemical Society 129:4156-4157 (2007)[0pt] [3] J Ghadiali, MM Stevens. Advanced Materials 20: 4359-4363 (2008); J Ghadiali et al, ACS Nano 4:4915-4919 (2010)[0pt] [4] D Aili, M Mager, D Roche, MM Stevens. Nano Letters 11:1401-1405 (2011) [0pt] [5] E Place, ND Evans, MM Stevens. Nature Materials 8:457-470 (2009)[0pt] [6] MD Mager, V LaPointe, MM Stevens. Nature Chemistry 3:582-589 (2011)[0pt] [7] MM Stevens et. al. Proc. Natl. Acad. Sci. USA 102:11450-11455 (2005)[0pt] [8] E Gentleman et al. Nature

  7. The tumorigenicity of mouse embryonic stem cells and in vitro differentiated neuronal cells is controlled by the recipients' immune response.

    Directory of Open Access Journals (Sweden)

    Ralf Dressel

    Full Text Available Embryonic stem (ES cells have the potential to differentiate into all cell types and are considered as a valuable source of cells for transplantation therapies. A critical issue, however, is the risk of teratoma formation after transplantation. The effect of the immune response on the tumorigenicity of transplanted cells is poorly understood. We have systematically compared the tumorigenicity of mouse ES cells and in vitro differentiated neuronal cells in various recipients. Subcutaneous injection of 1x10(6 ES or differentiated cells into syngeneic or allogeneic immunodeficient mice resulted in teratomas in about 95% of the recipients. Both cell types did not give rise to tumors in immunocompetent allogeneic mice or xenogeneic rats. However, in 61% of cyclosporine A-treated rats teratomas developed after injection of differentiated cells. Undifferentiated ES cells did not give rise to tumors in these rats. ES cells turned out to be highly susceptible to killing by rat natural killer (NK cells due to the expression of ligands of the activating NK receptor NKG2D on ES cells. These ligands were down-regulated on differentiated cells. The activity of NK cells which is not suppressed by cyclosporine A might contribute to the prevention of teratomas after injection of ES cells but not after inoculation of differentiated cells. These findings clearly point to the importance of the immune response in this process. Interestingly, the differentiated cells must contain a tumorigenic cell population that is not present among ES cells and which might be resistant to NK cell-mediated killing.

  8. Immune Responses of Dendritic Cells Loaded with Antigens from Apoptotic Cholangiocarcinoma Cells Caused by γ-Irradation

    Institute of Scientific and Technical Information of China (English)

    WUGang; HANBenli; PEIXuetao

    2002-01-01

    Objective:To investigate the induction cytotoxic T cells(CTLs) with antitumor activity and therapeutic efficacy after dendritic cells(DCs) acquired antigen from apoptotic cholangiocarcinoma cells caused by γ-irradiation. Methods:DCs from peripheral blood mononuclear cells (PBMC) that maintain the antigen capturing and processing capacity charateristic of immature cells have been established in vitro, using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). Then, in cholangiocarcinoma cells apoptosis was induced by γ-irradiation. The experimental groups were as follows:(1)coculture of DCs and apoptotic cancer cells and T cells;(2)coculture of DCs and necrotic cancer cells and T cells;(3)coculture of DCs, cultured cancer cell and T cells. They are cocultured for 7 days.DCs and T cells were riched, isolated and their antitumor response was tested. Results:The cells had typical dendritic morphology, expressed high levels of CDla and B7, acquired antigen from apoptotic cells caused by γ-irradiation and induced an increased T cell stimulatory capacity in mixed lymphocyte reactions (MLR). Conclusion:DCs obtained from PBMCs using GM-CSF and IL-4 can efficiently present antigen derived from apoptotic cells caused by γ-irradiation and efficiently induce T cells.This strategy, therefore, may present an effective approach to transduce DCs with antigen.

  9. iNKT-cell help to B cells: a cooperative job between innate and adaptive immune responses.

    Science.gov (United States)

    Dellabona, Paolo; Abrignani, Sergio; Casorati, Giulia

    2014-08-01

    T-cell help to B lymphocytes is one of the most important events in adaptive immune responses in health and disease. It is generally delivered by cognate CD4(+) T follicular helper (T(FH)) cells via both cell-to-cell contacts and soluble mediators, and it is essential for both the clonal expansion of antibody (Ab)-secreting B cells and memory B-cell formation. CD1d-restricted invariant natural killer T (iNKT) cells are a subset of innate-like T lymphocytes that rapidly respond to stimulation with specific lipid antigens (Ags) that are derived from infectious pathogens or stressed host cells. Activated iNKT cells produce a wide range of cytokines and upregulate costimulatory molecules that can promote activation of dendritic cells (DCs), natural killer (NK) cells, and T cells. A decade ago, we discovered that iNKT cells can help B cells to proliferate and to produce IgG Abs in vitro and in vivo. This adjuvant-like function of Ag-activated iNKT cells provides a flexible set of helper mechanisms that expand the current paradigm of T-cell-B-cell interaction and highlights the potential of iNKT-cell targeting vaccine formulations. PMID:24782127

  10. Estimating Contraceptive Needs and Increasing Access to Contraception in Response to the Zika Virus Disease Outbreak--Puerto Rico, 2016.

    Science.gov (United States)

    Tepper, Naomi K; Goldberg, Howard I; Bernal, Manuel I Vargas; Rivera, Brenda; Frey, Meghan T; Malave, Claritsa; Renquist, Christina M; Bracero, Nabal Jose; Dominguez, Kenneth L; Sanchez, Ramon E; Shapiro-Mendoza, Carrie K; Rodriguez, Blanca R Cuevas; Simeone, Regina M; Pesik, Nicki T; Barfield, Wanda D; Ko, Jean Y; Galang, Romeo R; Perez-Padilla, Janice; Polen, Kara N D; Honein, Margaret A; Rasmussen, Sonja A; Jamieson, Denise J

    2016-01-01

    Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes. Increasing evidence links Zika virus infection during pregnancy to adverse pregnancy and birth outcomes, including pregnancy loss, intrauterine growth restriction, eye defects, congenital brain abnormalities, and other fetal abnormalities. The virus has also been determined to be sexually transmitted. Because of the potential risks associated with Zika virus infection during pregnancy, CDC has recommended that health care providers discuss prevention of unintended pregnancy with women and couples who reside in areas of active Zika virus transmission and do not want to become pregnant. However, limitations in access to contraception in some of these areas might affect the ability to prevent an unintended pregnancy. As of March 16, 2016, the highest number of Zika virus disease cases in the United States and U.S. territories were reported from Puerto Rico. The number of cases will likely rise with increasing mosquito activity in affected areas, resulting in increased risk for transmission to pregnant women. High rates of unintended and adolescent pregnancies in Puerto Rico suggest that, in the context of this outbreak, access to contraception might need to be improved. CDC estimates that 138,000 women of reproductive age (aged 15-44 years) in Puerto Rico do not desire pregnancy and are not using one of the most effective or moderately effective contraceptive methods, and therefore might experience an unintended pregnancy. CDC and other federal and local partners are seeking to expand access to contraception for these persons. Such efforts have the potential to increase contraceptive access and use, reduce unintended pregnancies, and lead to fewer adverse pregnancy and birth outcomes associated with Zika virus infection during pregnancy. The assessment of challenges and resources related to contraceptive access in Puerto Rico might be a useful model for other areas with active transmission

  11. Practising evidence-based medicine in an era of high placebo response: number needed to treat reconsidered.

    Science.gov (United States)

    Roose, Steven P; Rutherford, Bret R; Wall, Melanie M; Thase, Michael E

    2016-05-01

    The number needed to treat (NNT) statistic was developed to facilitate the practice of evidence-based medicine. Placebo was assumed to be therapeutically inert when the NNT was originally conceived, but more recent data for conditions such as major depressive disorder (MDD) suggest that the placebo control condition can have considerable therapeutic effects. Complications arise because the NNT calculated from randomised controlled trials (RCTs) reflects a comparison between medication plus clinical management and placebo plus clinical management, whereas, in the clinical setting, physicians choose between prescribing open medication, observing a patient over time with a supportive approach, and doing nothing. Thus, NNTs derived from clinical trials are not directly relevant to clinical decision-making, because they are based on control conditions that do not exist in standard practice. Additional difficulties may arise when using NNTs to compare alternative treatments for MDD, such as medication and psychotherapy, since these comparisons require the control conditions upon which the respective NNTs are based to be similar.Whereas pill placebo conditions include intensive clinical management and elicit expectations of improvement, attention control conditions for psychotherapy research are less well developed. Often the effects of psychotherapy are gauged against a wait-list control condition, which has substantially fewer therapeutic components than a pill placebo control condition. To improve the clinical utility of NNTs for the treatment of MDD, we advocate effectiveness studies that include treatment conditions resembling actual clinical practice, rather than using placebo-controlled RCTs for this purpose. Until such studies are performed, the effect of bias in comparing NNTs across treatments can be controlled by ensuring that the RCT control conditions upon which the NNTs are based are comparable. PMID:27143006

  12. Adrenomedullin Expression by Gastric Epithelial Cells in Response to Infection

    OpenAIRE

    Robert P. Allaker; Kapas, Supriya

    2003-01-01

    Many surface epithelial cells express adrenomedullin, a multifunctional peptide found in a wide number of body and cell systems. Recently, we and others have proposed that adrenomedullin has an important novel role in host defense. This peptide has many properties in common with other cationic antimicrobial peptides, including the human β-defensins. Upon exposure of human gastric epithelial cells to viable cells of invasive or noninvasive strains of Helicobacter pylori, Escherichia coli, Salm...

  13. Marjolin ulcer: how much of safety margin needs resection along marjolin ulcer squamous cell carcinoma in recurrence cases

    International Nuclear Information System (INIS)

    The main aim of this study was to evaluate how much of the surrounding area need to be resected to reach tumor free margin in cases of recurrent Squamous Cell Carcinoma (SCC) Marjolin ulcer. The other objective was to report the demographic characteristics, the site of development of SCC Marjolin ulcers. A total of 266 patients with ulcers created on burn scars were studied. Biopsy samples were taken from all ulcers and evaluated pathologically for chronic inflammation or SCC Marjolin ulcer. For primary SCC Marjolin ulcers a 2cm safety margin was removed, while for recurrent SCC Marjolin ulcers a 2cm safety margin was removed and assessed pathologically under frozen-section and a further 0.5cm safety margin was removed in cases of SCC involvement in any of the planes of the resected sections for reaching a SCC-clear margin. One hundred eighteen of the cases were due to chronic inflammation, and the remaining 148 cases were due to SCC Marjolin ulcers. Of this 31 cases were recurrent ones. At least one site of all the recurrent SCC Marjolin ulcer samples were found to be involved and required a second resection attempt for reaching a clear and a safe margin. Although classically 2cm safety margin is still widely used for resection of primary SCC Marjolin ulcers, we recommend that a 2.5cm safety margin is better for resection in recurrent cases. (author)

  14. Glucose responsive insulin production from human embryonic germ (EG) cell derivatives

    International Nuclear Information System (INIS)

    Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and β-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation of preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes

  15. Time to Relax: Mechanical Stress Release Guides Stem Cell Responses.

    Science.gov (United States)

    Sommerfeld, Sven D; Elisseeff, Jennifer H

    2016-02-01

    Stem cells integrate spatiotemporal cues, including the mechanical properties of their microenvironment, into their fate decisions. Chaudhuri et al. (2015) show that the ability of the extracellular matrix to dissipate cell-induced forces, referred to as stress-relaxation, is a key mechanical signal influencing stem cell fate and function. PMID:26849301

  16. IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune Response

    Directory of Open Access Journals (Sweden)

    Junjie Zhang

    2016-07-01

    Full Text Available Activation of nuclear factor of activated T cells (NFAT is crucial for immune responses. IKKε is an IκB kinase (IKK-related kinase, and the function of IKKε remains obscure in T cells, despite its abundant expression. We report that IKKε inhibits NFAT activation and T cell responses by promoting NFATc1 phosphorylation. During T cell activation, IKKε was transiently activated to phosphorylate NFATc1. Loss of IKKε elevated T cell antitumor and antiviral immunity and, therefore, reduced tumor development and persistent viral infection. IKKε was activated in CD8+ T cells of mice bearing melanoma or persistently infected with a model herpesvirus. These results collectively show that IKKε promotes NFATc1 phosphorylation and inhibits T cell responses, identifying IKKε as a crucial negative regulator of T cell activation and a potential target for immunotherapy.

  17. A community needs responsive management training model: Re-envisioning management training for pastors of the International Assemblies of God Church

    Directory of Open Access Journals (Sweden)

    Malesela J. Masenya

    2016-03-01

    Full Text Available Non-profit organisations (NGO�s play an important role in helping satisfy society�s many needs. Churches, for example, are called upon to address critical challenges facing the South African society such as discrepancies in life chances, unemployment and corruption. It largely depends on the management skills of leaders of such organisations to succeed in their endeavour to meet community needs. In order to improve these skills, this study sought to redefine the initial training of student pastors, including their management training, at the colleges of the International Assemblies of God Church (IAG. A qualitative research approach was followed. Two focus group interviews and seven individual interviews were conducted. Interviews included members of the national and provincial executive committees of the IAG, serving pastors, directors of training colleges, pastor trainees in their final year of study, and a newly graduated student. The findings of the study support the importance of formal management training for pastors before being employed in the service of the IAG. This Church has moved away from accepting ministers for service based on their faith and profession of a call to ministry only. The investigation revealed shortcomings in the initial training programmes of pastors; for example, the emphasis on theological courses at the expense of courses that are responsive to community needs and management training issues. Leaders with the competency to respond to community needs are required. The implementation of a transformational management framework, which includes community responsive courses, is recommended as a way to effectively train church leaders.Intradisciplinary and/or interdisciplinary implications: Although this article is written within the framework of Educational Management, it touches on other fields like Practical Theology and Curriculum Development. It reflects on the perceived need to include management training in

  18. Liver accumulation of Plasmodium chabaudi-infected red blood cells and modulation of regulatory T cell and dendritic cell responses.

    Directory of Open Access Journals (Sweden)

    Márcia M Medeiros

    Full Text Available It is postulated that accumulation of malaria-infected Red Blood Cells (iRBCs in the liver could be a parasitic escape mechanism against full destruction by the host immune system. Therefore, we evaluated the in vivo mechanism of this accumulation and its potential immunological consequences. A massive liver accumulation of P. c. chabaudi AS-iRBCs (Pc-iRBCs was observed by intravital microscopy along with an over expression of ICAM-1 on day 7 of the infection, as measured by qRT-PCR. Phenotypic changes were also observed in regulatory T cells (Tregs and dendritic cells (DCs that were isolated from infected livers, which indicate a functional role for Tregs in the regulation of the liver inflammatory immune response. In fact, the suppressive function of liver-Tregs was in vitro tested, which demonstrated the capacity of these cells to suppress naive T cell activation to the same extent as that observed for spleen-Tregs. On the other hand, it is already known that CD4+ T cells isolated from spleens of protozoan parasite-infected mice are refractory to proliferate in vivo. In our experiments, we observed a similar lack of in vitro proliferative capacity in liver CD4+ T cells that were isolated on day 7 of infection. It is also known that nitric oxide and IL-10 are partially involved in acute phase immunosuppression; we found high expression levels of IL-10 and iNOS mRNA in day 7-infected livers, which indicates a possible role for these molecules in the observed immune suppression. Taken together, these results indicate that malaria parasite accumulation within the liver could be an escape mechanism to avoid sterile immunity sponsored by a tolerogenic environment.

  19. Modified genetic response to X-irradiation of mouse spermatogonial stem cells surviving treatment with TEM

    International Nuclear Information System (INIS)

    Earlier studies have shown that the genetic response to X-irradiation of mouse spermatogonial stem-cell populations that are recovering from a previous radiation exposure may differ from that of a normal, unirradiated stem-cell population. Similar modified responses to X-irradiation have now been observed in stem spermatogonia that are recovering from treatment with the chemical mutagen, TEM. (orig.)

  20. Restoration of proliferative response to M. leprae antigens in lepromatous T cells against candidate antileprosy vaccines.

    Science.gov (United States)

    Mustafa, A S

    1996-09-01

    Several studies conducted in the last decade suggest that Mycobacterium lepraereactive T cells exist in lepromatous patients, but their number may be too few to yield a detectable response in cell-mediated immunity (CMI) assays. Immunizations with candidate antileprosy vaccines and stimulation of T cells with M. leprae + interleukin-2 restore the M. leprae-induced CMI response in lepromatous leprosy patients. These immunizations and stimulation may enrich the pre-existing M. leprae-responsive T cells in lepromatous patients and, thereby, induce a detectable CMI response to M. leprae antigens upon repeat testing. To verify this proposition, we carried out a study in a group of 10 lepromatous leprosy patients. Peripheral blood mononuclear cells (PBMC) obtained from these patients were anergic to M. leprae antigens in proliferative assays, but they responded to the antigens of candidate antileprosy vaccines, i.e., M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w. The enrichment of M. leprae-responsive T cells was performed by establishing T-cell lines from the PBMC after in vitro stimulation with M. leprae, M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w. When tested for their proliferative responses, 1/10, 3/10, 6/10 and 2/10 T-cell lines established against M. leprae, M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w, respectively, responded to M. leprae. These results suggest that enrichment of pre-existing M. leprae-responsive T cells may contribute to the restoration of the T-cell response to M. leprae in some lepromatous patients. Four of the 10 M. leprae-induced T-cell lines proliferated in response to the 65 kDa, 36 kDa, 28 kDa, and 12 kDa recombinant antigens of M. leprae, suggesting that the nonresponsiveness of T cells in some lepromatous patients may be overcome by using recombinant antigens of M. leprae. PMID:8862259

  1. Differential gene expression in normal and transformed human mammary epithelial cells in response to oxidative stress

    OpenAIRE

    Cortes, Diego F.; Sha, Wei; Hower, Valerie; Blekherman, Greg; Laubenbacher, Reinhard; Akman, Steven; Torti, Suzy V; Shulaev, Vladimir

    2011-01-01

    Oxidative stress plays a key role in breast carcinogenesis. To investigate whether normal and malignant breast epithelial cells differ in their responses to oxidative stress, we examined the global gene expression profiles of three cell types, representing cancer progression from a normal to a malignant stage, under oxidative stress. Normal human mammary epithelial cells (HMEC), an immortalized cell line (HMLER-1), and a tumorigenic cell line (HMLER-5), were exposed to increased levels of rea...

  2. Single-Cell Analysis of Ribonucleotide Reductase Transcriptional and Translational Response to DNA Damage

    OpenAIRE

    Mazumder, Aprotim; Tummler, Katja; Bathe, Mark; Samson, Leona D.

    2013-01-01

    The ribonucleotide reductase (RNR) enzyme catalyzes an essential step in the production of deoxyribonucleotide triphosphates (dNTPs) in cells. Bulk biochemical measurements in synchronized Saccharomyces cerevisiae cells suggest that RNR mRNA production is maximal in late G1 and S phases; however, damaged DNA induces RNR transcription throughout the cell cycle. But such en masse measurements reveal neither cell-to-cell heterogeneity in responses nor direct correlations between transcript and p...

  3. Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death.

    Science.gov (United States)

    Monzack, E L; May, L A; Roy, S; Gale, J E; Cunningham, L L

    2015-12-01

    Hearing loss and balance disorders affect millions of people worldwide. Sensory transduction in the inner ear requires both mechanosensory hair cells (HCs) and surrounding glia-like supporting cells (SCs). HCs are susceptible to death from aging, noise overexposure, and treatment with therapeutic drugs that have ototoxic side effects; these ototoxic drugs include the aminoglycoside antibiotics and the antineoplastic drug cisplatin. Although both classes of drugs are known to kill HCs, their effects on SCs are less well understood. Recent data indicate that SCs sense and respond to HC stress, and that their responses can influence HC death, survival, and phagocytosis. These responses to HC stress and death are critical to the health of the inner ear. Here we have used live confocal imaging of the adult mouse utricle, to examine the SC responses to HC death caused by aminoglycosides or cisplatin. Our data indicate that when HCs are killed by aminoglycosides, SCs efficiently remove HC corpses from the sensory epithelium in a process that includes constricting the apical portion of the HC after loss of membrane integrity. SCs then form a phagosome, which can completely engulf the remaining HC body, a phenomenon not previously reported in mammals. In contrast, cisplatin treatment results in accumulation of dead HCs in the sensory epithelium, accompanied by an increase in SC death. The surviving SCs constrict fewer HCs and display impaired phagocytosis. These data are supported by in vivo experiments, in which cochlear SCs show reduced capacity for scar formation in cisplatin-treated mice compared with those treated with aminoglycosides. Together, these data point to a broader defect in the ability of the cisplatin-treated SCs, to preserve tissue health in the mature mammalian inner ear. PMID:25929858

  4. Impact of CD40 ligand, B cells, and mast cells in peanut-induced anaphylactic responses.

    Science.gov (United States)

    Sun, Jiangfeng; Arias, Katherine; Alvarez, David; Fattouh, Ramzi; Walker, Tina; Goncharova, Susanna; Kim, Bobae; Waserman, Susan; Reed, Jennifer; Coyle, Anthony J; Jordana, Manel

    2007-11-15

    The effector immune mechanisms underlying peanut-induced anaphylaxis remain to be fully elucidated. We investigated the relative contribution of Igs, mast cells (MCs), and FcepsilonRI in the elicitation of anaphylaxis in a murine model. Assessment of peanut hypersensitivity reactions was performed clinically and biologically. Our data show that wild-type (WT; C57BL/6 strain) mice consistently developed severe anaphylaxis (median clinical score: 3.5/5), an approximately 8 degrees C drop in core body temperature, and significantly increased plasma levels of histamine and leukotrienes. CD40 ligand- and B cell-deficient mice presented evidence of allergic sensitization as demonstrated by production of Th2-associated cytokines by splenocytes and a late-phase inflammatory response that were both indistinguishable to those detected in WT mice. However, CD40 ligand- and B cell-deficient mice did not exhibit any evidence of anaphylaxis. Our data also show that MC-deficient (Kit(W)/Kit(W-v)) mice did not suffer, unlike their littermate controls, anaphylactic reactions despite the fact that serum levels of peanut-specific Igs were similarly elevated. Finally, FcepsilonRI-deficient mice experienced anaphylactic responses although to a significantly lesser degree than those observed in WT mice. Thus, these data demonstrate that the presence of peanut-specific Abs along with functional MCs comprise a necessary and sufficient condition for the elicitation of peanut-induced anaphylaxis. That the absence of FcepsilonRI prevented the development of anaphylaxis only partially insinuates the contribution of an IgE-independent pathway, and suggests that strategies to impair MC degranulation may be necessary to improve the efficacy of anti-IgE therapy. PMID:17982059

  5. Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses.

    Science.gov (United States)

    Dashti, Amir; Ebrahimi, Marzieh; Hadjati, Jamshid; Memarnejadian, Arash; Moazzeni, Seyed Mohammad

    2016-04-28

    Cancer stem cells (CSCs) are demonstrated to be usually less sensitive to conventional methods of cancer therapies, resulting in tumor relapse. It is well-known that an ideal treatment would be able to selectively target and kill CSCs, so as to avoid the tumor reversion. The aim of our present study was to evaluate the effectiveness of a dendritic cell (DC) based vaccine against CSCs in a mouse model of malignant melanoma. C57BL/6 mouse bone marrow derived DCs pulsed with a murine melanoma cell line (B16F10) or CSC lysates were used as a vaccine. Immunization of mice with CSC lysate-pulsed DCs was able to induce a significant prophylactic effect by a higher increase in lifespan and obvious depression of tumor growth in tumor bearing mice. The mice vaccinated with DCs loaded with CSC-lysate were revealed to produce specific cytotoxic responses to CSCs. The proliferation assay and cytokine (IFN-γ and IL-4) secretion of mice vaccinated with CSC lysate-pulsed DCs also showed more favorable results, when compared to those receiving B16F10 lysate-pulsed DCs. These findings suggest a potential strategy to improve the efficacy of DC-based immunotherapy of cancers. PMID:26803056

  6. Radiation response characteristics of human cell in vitro

    International Nuclear Information System (INIS)

    Improvements in tissue culture techniques and growth media have made it possible to culture a range of cells of human origin, both normal and malignant. The most recent addition to the list are endothelial cells. Interesting results have been obtained, some of which may have implications in Radiation Therapy. (i) Repair of Potentially Lethal Damage (PLDR) has been observed in all cell lines investigated; cells of normal origin repair PLD at least as well as malignant cells, which makes clinical trials of PLDR inhibitors of doubtful usefulness. (ii) PLD in fibroblasts of human origin appears to have a component that is repaired rapidly, in a matter of minutes, as well as a slower component that takes hours to repair. (iii) Sublethal damage repair, manifest by a dose-rate effect, has also been observed in all human cell lines tested. Cells of normal tissue origin, including fibroblasts and endothelial cells, exhibit a dose-rate effect that is intermediate between that for cells from traditionally resistant tumors (melanoma and osteosarcoma) and cells from more sensitive tumors (neuroblastoma and breast). (iv) Fibroblasts from patients with Ataxia Telangectasia (AT) are much more sensitive to x-rays, with a D/sub o/ about half that for normal human fibroblasts. Nevertheless repair of both PLD and SLD can be demonstrated in these cells

  7. The Human NK Cell Response to Yellow Fever Virus 17D Is Primarily Governed by NK Cell Differentiation Independently of NK Cell Education.

    Science.gov (United States)

    Marquardt, Nicole; Ivarsson, Martin A; Blom, Kim; Gonzalez, Veronica D; Braun, Monika; Falconer, Karolin; Gustafsson, Rasmus; Fogdell-Hahn, Anna; Sandberg, Johan K; Michaëlsson, Jakob

    2015-10-01

    NK cells play an important role in the defense against viral infections. However, little is known about the regulation of NK cell responses during the first days of acute viral infections in humans. In this study, we used the live attenuated yellow fever virus (YFV) vaccine 17D as a human in vivo model to study the temporal dynamics and regulation of NK cell responses in an acute viral infection. YFV induced a robust NK cell response in vivo, with an early activation and peak in NK cell function at day 6, followed by a delayed peak in Ki67 expression, which was indicative of proliferation, at day 10. The in vivo NK cell response correlated positively with plasma type I/III IFN levels at day 6, as well as with the viral load. YFV induced an increased functional responsiveness to IL-12 and IL-18, as well as to K562 cells, indicating that the NK cells were primed in vivo. The NK cell responses were associated primarily with the stage of differentiation, because the magnitude of induced Ki67 and CD69 expression was distinctly higher in CD57(-) NK cells. In contrast, NK cells expressing self- and nonself-HLA class I-binding inhibitory killer cell Ig-like receptors contributed, to a similar degree, to the response. Taken together, our results indicate that NK cells are primed by type I/III IFN in vivo early after YFV infection and that their response is governed primarily by the differentiation stage, independently of killer cell Ig-like receptor/HLA class I-mediated inhibition or education. PMID:26283480

  8. Role(s) of IL-2 inducible T cell kinase and Bruton's tyrosine kinase in mast cell response to lipopolysaccharide.

    Science.gov (United States)

    Huang, Weishan; August, Avery

    2016-06-01

    Mast cells play critical roles during immune responses to the bacterial endotoxin lipopolysaccharide (LPS) that can lead to fatal septic hypothermia [1], [2], [3]. IL-2 inducible T cell kinase (ITK) and Bruton's tyrosine kinase (BTK) are non-receptor tyrosine kinases that act downstream of numerous receptors, and have been shown to modulate mast cell responses downstream of FcεRIα [4], however, their roles in regulating mast cell responses to endotoxic stimuli were unclear. We found that the absence of ITK and BTK alters the mast cell response to LPS, and leads to enhanced pro-inflammatory cytokine production by mast cells and more severe LPS-induced hypothermia in mice [5]. Here, we detail our investigation using microarray analysis to study the transcriptomic profiles of mast cell responses to LPS, and the roles of ITK and/or BTK expression in this process. Mouse whole genome array data of WT, Itk (-/-) , Btk (-/-) , and Itk (-/-)  Btk (-/-) bone marrow-derived mast cells (BMMCs) stimulated by PBS (control) or LPS for 1 h were used in our latest research article [5] and is available in the Gene Expression Omnibus under accession number GSE64287. PMID:27081634

  9. Local Microenvironment Controls the Compartmentalization of NK Cell Responses during Systemic Inflammation in Mice.

    Science.gov (United States)

    Rasid, Orhan; Ciulean, Ioana Sonya; Fitting, Catherine; Doyen, Noelle; Cavaillon, Jean-Marc

    2016-09-15

    Systemic inflammatory response syndrome is a whole-body reaction to a triggering insult that often results in life-threatening illness. Contributing to the development of this inflammatory cascade are numerous cellular partners, among which NK cells were shown to play a key role. Accumulating evidence points to organ-specific properties of systemic inflammation and NK cells. However, little is known about compartment-specific activation of NK cells during systemic inflammatory response syndrome or the relative contribution of NK cell-intrinsic properties and microenvironmental cues. In this study, we undertook a sequential characterization of NK responses in the spleen, lungs, bone marrow, peritoneum, and blood using a mouse model of endotoxemia. We report that, despite similar systemic dynamics of NK cell responses, expression of activation markers (CD69 and CD25) and effector molecules (IFN-γ, granzyme B, and IL-10) display organ-specific thresholds of maximum activation. Using adoptive transfers of spleen and lung NK cells, we found that these cells have the capacity to quickly adapt to a new environment and adjust their response levels to that of resident NK cells. This functional adaptation occurs without significant alterations in phenotype and independently of subpopulation-specific trafficking. Thus, using a dynamic in vivo-transfer system, to our knowledge our study is the first to report the compartmentalization of NK cells responses during systemic inflammation and to show that NK cell-intrinsic properties and microenvironmental cues are involved in this process, in a sequential manner. PMID:27521338

  10. Calculation of response of Chinese hamster cells to ions based on track structure theory

    Institute of Scientific and Technical Information of China (English)

    LiuXiao-Wei; ZhangChun-Xiang

    1997-01-01

    Considering biological cells as single target two-hit detectors,an analytic formula to calculate the response of cells to ions is developed based on track structure theory.In the calculation,the splitting deposition energy between ion kill mode and γ kill mode is not used.The results of calculation are in agreement with the experimental data for response of Chinese hamster cells,whose response to γ rays can be described by the response function of single target two hit detector to ions.

  11. Sustained CD8+ T-cell responses induced after acute parvovirus B19 infection in humans

    DEFF Research Database (Denmark)

    Norbeck, Oscar; Isa, Adiba; Pöhlmann, Christoph;

    2005-01-01

    Murine models have suggested that CD8+ T-cell responses peak early in acute viral infections and are not sustained, but no evidence for humans has been available. To address this, we longitudinally analyzed the CD8+ T-cell response to human parvovirus B19 in acutely infected individuals. We...... observed striking CD8+ T-cell responses, which were sustained or even increased over many months after the resolution of acute disease, indicating that CD8+ T cells may play a prominent role in the control of parvovirus B19 and other acute viral infections of humans, including potentially those generated...

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

    International Nuclear Information System (INIS)

    Highlights: • LPA5 inhibits the cell growth and motile activities of 3T3 cells. • LPA5 suppresses the cell motile activities stimulated by hydrogen peroxide in 3T3 cells. • Enhancement of LPA5 on the cell motile activities inhibited by LPA1 in 3T3 cells. • The expression and activation of Mmp-9 were inhibited by LPA5 in 3T3 cells. • LPA signaling via LPA5 acts as a negative regulator of cellular responses in 3T3 cells. - Abstract: Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors (LPA1–LPA6) mediates a variety of biological functions, including cell migration. Recently, we have reported that LPA1 inhibited the cell motile activities of mouse fibroblast 3T3 cells. In the present study, to evaluate a role of LPA5 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 LPA1 and LPA5 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 LPA5 may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA1

  13. 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}.

  14. Grid Cell Responses in 1D Environments Assessed as Slices through a 2D Lattice.

    Science.gov (United States)

    Yoon, KiJung; Lewallen, Sam; Kinkhabwala, Amina A; Tank, David W; Fiete, Ila R

    2016-03-01

    Grid cells, defined by their striking periodic spatial responses in open 2D arenas, appear to respond differently on 1D tracks: the multiple response fields are not periodically arranged, peak amplitudes vary across fields, and the mean spacing between fields is larger than in 2D environments. We ask whether such 1D responses are consistent with the system's 2D dynamics. Combining analytical and numerical methods, we show that the 1D responses of grid cells with stable 1D fields are consistent with a linear slice through a 2D triangular lattice. Further, the 1D responses of comodular cells are well described by parallel slices, and the offsets in the starting points of the 1D slices can predict the measured 2D relative spatial phase between the cells. From these results, we conclude that the 2D dynamics of these cells is preserved in 1D, suggesting a common computation during both types of navigation behavior. PMID:26898777

  15. Secondary specific immune response in vitro to MSV tumor cells.

    Science.gov (United States)

    Senik, A; Hebrero, F P; Levy, J P

    1975-12-15

    The interactions which occur between antigenic tumor cells and normal or immune lymphoid cells in a 3-day in vitro culture, have been studied with a murine sarcoma virus (MSV)-induced tumor. The 3H-thymidine incorporation of lymphoma cells growing in suspension, and the radioactive-chromium release of freshly sampled lymphoma cells regularly added to the culture, have been compared to determine the part played by immune lymphoid cells in cytolysis and cytostasis of the tumor-cell population. The cytolytic activity increases in the culture from day 0 to day 3. It is due, predominantly, to T-cells, and remains specific to antigens shared by MSV tumors and related lymphomas. This activity would be difficult to detect unless freshly sampled ascitic cells were used as targets, since the lymphoma cells spontaneously lose a part of their sensitivity to immune cytolysis during in vitro culture. The method used in the present experiments is a secondary chromium release test (SCRT), which measures the invitro secondary stimulation of cytotoxic T-lymphocytes (CTL) by tumor cells. In the absence of stimulatory cells, the CTL activity would have rapidly fallen in vitro. The cytostatic activity also increases during the 3 days in vitro, in parallel to the cytolytic activity: it is due to non-T-cells and remains mainly non-specific. The significance of these data for the interpretation of invitro demonstrated cell-mediated anti-tumor immune reactions is briefly discussed, as well as their relevance in the in vivo role of immune CTL. PMID:53210

  16. Inhibition of cathepsin X enzyme influences the immune response of THP-1 cells and dendritic cells infected with Helicobacter pylori

    International Nuclear Information System (INIS)

    The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of inhibition of cathepsin X is delayed

  17. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  18. B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses

    Directory of Open Access Journals (Sweden)

    Larimore Kevin

    2012-06-01

    Full Text Available Abstract Background The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.

  19. Vascular cell responses to ECM produced by smooth muscle cells on TiO2 nanotubes

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • TiO2 nanotubes with the tube diameter of 30 nm via anodic oxidation was prepared. • SMCs on TiO2 nanotubes presented enhanced extracellular matrix secreting. • ECM prepared via decellularization retained the components: Fn, Ln and collagen. • ECM-covered TiO2 nanotubes significantly improved the proliferation of ECs. - Abstract: There is an increasing interest in developing new methods to promote biocompatibility of biomedical materials. The TiO2 nanotubes with the tube diameter of 30 nm were prepared by anodization. The response behavior of the human umbilical vein endothelial cell (HUVEC) and human umbilical artery smooth muscle cell (HUASMC) to these different nanotube sizes was investigated. Compared to the flat Ti, the growth and viability of HUVEC are prohibited, but there was no significant difference of HUASMC on 30 nm TiO2 nanotubes. In this study, extracellular matrix (ECM) as a complex cellular environment which provides structural support to cells and regulates the cells functions was further used to modify the biological properties of TiO2 nanotubes. The ECM secreted from HUASMC was successfully deposited onto the 30 nm TiO2 nanotubes. Moreover, immunofluorescence staining of common ECM components, such as fibronectin, laminin and type IV collagen, also indicated the successful ECM-covering on nanotube surfaces. Interestingly, the surface of ECM-covered TiO2 nanotubes significantly improved the proliferation of HUVECs in vitro. This suggested that the ECM secreted from HUASMCs on the TiO2 nanotubular surface could further improve the HUVECs adhesion and proliferation

  20. Umami Responses in Mouse Taste Cells Indicate More than One Receptor

    OpenAIRE

    MARUYAMA, Yutaka; Pereira, Elizabeth; Margolskee, Robert F.; Chaudhari, Nirupa; Roper, Stephen D.

    2006-01-01

    A number of gustatory receptors have been proposed to underlie umami, the taste of L-glutamate, and certain other amino acids and nucleotides. However, the response profiles of these cloned receptors have not been validated against responses recorded from taste receptor cells that are the native detectors of umami taste. We investigated umami taste responses in mouse circumvallate taste buds in an intact slice preparation, using confocal calcium imaging. Approximately 5% of taste cells select...

  1. Signals regulating myelination in peripheral nerves and the Schwann cell response to injury

    OpenAIRE

    Glenn, Thomas D.; William S Talbot

    2013-01-01

    In peripheral nerves, Schwann cells form myelin, which facilitates the rapid conduction of action potentials along axons in the vertebrate nervous system. Myelinating Schwann cells are derived from neural crest progenitors in a step-wise process that is regulated by extracellular signals and transcription factors. In addition to forming the myelin sheath, Schwann cells orchestrate much of the regenerative response that occurs after injury to peripheral nerves. In response to injury, myelinati...

  2. Complete response of metastatic renal cancer with dendritic cell vaccine

    Directory of Open Access Journals (Sweden)

    Dall'Oglio Marcos

    2003-01-01

    Full Text Available INTRODUCTION: We report a case of metastatic renal cell carcinoma that presented involution following therapy with dendritic cells. CASE REPORT: Male, 51-year old patient underwent left radical nephrectomy in September 1999 due to renal cell carcinoma, evolved with recurrence of the neoplasia in January 2002, confirmed by resection of the lesion. A vaccine therapy based on dendritic cells was then performed during 5 months (4 applications. After this period, there was occurrence of new lesions, whose resection revealed areas of necrosis and inflammatory infiltrate. DISCUSSION: The outcome of renal cell carcinoma is influenced by prognostic factors that confer more aggressive tumor characteristics. However, in cases of recurrence, the systemic therapy with dendritic cells-based vaccine can be associated with a better outcome with regression of disease.

  3. Outer hair cell piezoelectricity: Frequency response enhancement and resonance behavior

    Science.gov (United States)

    Weitzel, Erik K.; Tasker, Ron; Brownell, William E.

    2003-09-01

    Stretching or compressing an outer hair cell alters its membrane potential and, conversely, changing the electrical potential alters its length. This bi-directional energy conversion takes place in the cell's lateral wall and resembles the direct and converse piezoelectric effects both qualitatively and quantitatively. A piezoelectric model of the lateral wall has been developed that is based on the electrical and material parameters of the lateral wall. An equivalent circuit for the outer hair cell that includes piezoelectricity shows a greater admittance at high frequencies than one containing only membrane resistance and capacitance. The model also predicts resonance at ultrasonic frequencies that is inversely proportional to cell length. These features suggest all mammals use outer hair cell piezoelectricity to support the high-frequency receptor potentials that drive electromotility. It is also possible that members of some mammalian orders use outer hair cell piezoelectric resonance in detecting species-specific vocalizations.

  4. Differential and coordinated expression of defensins and cytokines by gingival epithelial cells and dendritic cells in response to oral bacteria

    Directory of Open Access Journals (Sweden)

    Clark Edward A

    2010-07-01

    Full Text Available Abstract Background Epithelial cells and dendritic cells (DCs both initiate and contribute to innate immune responses to bacteria. However, much less is known about the coordinated regulation of innate immune responses between GECs and immune cells, particularly DCs in the oral cavity. The present study was conducted to investigate whether their responses are coordinated and are bacteria-specific in the oral cavity. Results The β-defensin antimicrobial peptides hBD1, hBD2 and hBD3 were expressed by immature DCs as well as gingival epithelial cells (GECs. HBD1, hBD2 and hBD3 are upregulated in DCs while hBD2 and hBD3 are upregulated in GECs in response to bacterial stimulation. Responses of both cell types were bacteria-specific, as demonstrated by distinctive profiles of hBDs mRNA expression and secreted cytokines and chemokines in response to cell wall preparations of various bacteria of different pathogenicity: Fusobacterium nucleatum, Actinomyces naeslundii and Porphyromonas gingivalis. The regulation of expression of hBD2, IL-8, CXCL2/GROβ and CCL-20/MIP3α by GECs was greatly enhanced by conditioned medium from bacterially activated DCs. This enhancement was primarily mediated via IL-1β, since induction was largely attenuated by IL-1 receptor antagonist. In addition, the defensins influence DCs by eliciting differential cytokine and chemokine secretion. HBD2 significantly induced IL-6, while hBD3 induced MCP-1 to approximately the same extent as LPS, suggesting a unique role in immune responses. Conclusions The results suggest that cytokines, chemokines and β-defensins are involved in interaction of these two cell types, and the responses are bacteria-specific. Differential and coordinated regulation between GECs and DCs may be important in regulation of innate immune homeostasis and response to pathogens in the oral cavity.

  5. Distinct metabolic responses of an ovarian cancer stem cell line

    OpenAIRE

    Kathleen A Vermeersch; Wang, Lijuan; McDonald, John F; Styczynski, Mark P.

    2014-01-01

    Background Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to b...

  6. Stem cell dynamics in response to nutrient availability

    OpenAIRE

    McLeod, Catherine J.; Wang, Lei; Wong, Chihunt; Jones, D. Leanne

    2010-01-01

    When nutrient availability becomes limited, animals must actively adjust their metabolism to allocate limited resources and maintain tissue homeostasis [1–3]. However, it is poorly understood how tissues maintained by adult stem cells respond to chronic changes in metabolism. To begin to address this question, we fed flies a diet lacking protein (protein starvation) and assayed both germline and intestinal stem cells. Our results revealed a decrease in stem cell proliferation and a reduction ...

  7. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1.

    NARCIS (Netherlands)

    Pillay, J.; Kamp, V.M.; Hoffen, E. van; Visser, T.; Tak, T.; Lammers, J.W.; Ulfman, L.H.; Leenen, L.P.H.; Pickkers, P.; Koenderman, L.

    2012-01-01

    Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models

  8. Rituximab therapy reduces organ-specific T cell responses and ameliorates experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Nancy L Monson

    Full Text Available Recent clinical trials have established B cell depletion by the anti-CD20 chimeric antibody Rituximab as a beneficial therapy for patients with relapsing-remitting multiple sclerosis (MS. The impact of Rituximab on T cell responses remains largely unexplored. In the experimental autoimmune encephalomyelitis (EAE model of MS in mice that express human CD20, Rituximab administration rapidly depleted peripheral B cells and strongly reduced EAE severity. B cell depletion was also associated with diminished Delayed Type Hypersensitivity (DTH and a reduction in T cell proliferation and IL-17 production during recall immune response experiments. While Rituximab is not considered a broad immunosuppressant, our results indicate a role for B cells as a therapeutic cellular target in regulating encephalitogenic T cell responses in specific tissues.

  9. Acetyl CoA Carboxylase 2 Is Dispensable for CD8+ T Cell Responses.

    Directory of Open Access Journals (Sweden)

    Jang Eun Lee

    Full Text Available Differentiation of T cells is closely associated with dynamic changes in nutrient and energy metabolism. However, the extent to which specific metabolic pathways and molecular components are determinative of CD8+ T cell fate remains unclear. It has been previously established in various tissues that acetyl CoA carboxylase 2 (ACC2 regulates fatty acid oxidation (FAO by inhibiting carnitine palmitoyltransferase 1 (CPT1, a rate-limiting enzyme of FAO in mitochondria. Here, we explore the cell-intrinsic role of ACC2 in T cell immunity in response to infections. We report here that ACC2 deficiency results in a marginal increase of cellular FAO in CD8+ T cells, but does not appear to influence antigen-specific effector and memory CD8+ T cell responses during infection with listeria or lymphocytic choriomeningitis virus. These results suggest that ACC2 is dispensable for CD8+ T cell responses.

  10. Interferon-γ Added During Bacillus Calmette-Guerin Induced Dendritic Cell Maturation Stimulates Potent Th1 Immune Responses

    Directory of Open Access Journals (Sweden)

    Pestano Linda A

    2003-10-01

    Full Text Available Abstract Dendritic cells (DC are increasingly prepared in vitro for use in immunotherapy trials. Mature DC express high levels of surface molecules needed for T cell activation and are superior at antigen-presentation than immature DC. Bacillus Calmette-Guerin (BCG is one of several products known to induce DC maturation, and interferon (IFN-γ has been shown to enhance the activity of DC stimulated with certain maturation factors. In this study, we investigated the use of IFN-γ in combination with the powerful maturation agent, BCG. The treatment of immature DC with IFN-γ plus BCG led to the upregulation of CD54, CD80, and CD86 in comparison with BCG treatment alone. In MLR or recall immune responses, the addition of IFN-γ at the time of BCG-treatment did not increase the number of antigen-specific T cells but enhanced the development of IFN-γ-producing Th1 cells. In primary immune responses, on the other hand, BCG and IFN-γ co-treated DC stimulated higher proportions of specific T cells as well as IFN-γ secretion by these T cells. Thus the use of IFN-γ during BCG-induced DC maturation differentially affects the nature of recall versus naïve antigen-specific T-cell responses. IFN-γ co-treatment with BCG was found to induce IL-12 and, in some instances, inhibit IL-10 secretion by DC. These findings greatly enhance the potential of BCG-matured dendritic cells for use in cancer immunotherapy.

  11. The Functional Response of B Cells to Antigenic Stimulation: A Preliminary Report of Latent Tuberculosis

    Science.gov (United States)

    du Plessis, Willem J.; Kleynhans, Léanie; du Plessis, Nelita; Stanley, Kim; Malherbe, Stephanus T.; Maasdorp, Elizna; Ronacher, Katharina; Chegou, Novel N.; Walzl, Gerhard; Loxton, Andre G.

    2016-01-01

    Mycobacterium tuberculosis (M.tb) remains a successful pathogen, causing tuberculosis disease numbers to constantly increase. Although great progress has been made in delineating the disease, the host-pathogen interaction is incompletely described. B cells have shown to function as both effectors and regulators of immunity via non-humoral methods in both innate and adaptive immune settings. Here we assessed specific B cell functional interaction following stimulation with a broad range of antigens within the LTBI milieu. Our results indicate that B cells readily produce pro- and anti-inflammatory cytokines (including IL-1β, IL-10, IL-17, IL-21 and TNF-α) in response to stimulation. TLR4 and TLR9 based stimulations achieved the greatest secreted cytokine-production response and BCG stimulation displayed a clear preference for inducing IL-1β production. We also show that the cytokines produced by B cells are implicated strongly in cell-mediated communication and that plasma (memory) B cells (CD19+CD27+CD138+) is the subset with the greatest contribution to cytokine production. Collectively our data provides insight into B cell responses, where they are implicated in and quantifies responses from specific B cell phenotypes. These findings warrant further functional B cell research with a focus on specific B cell phenotypes under conditions of active TB disease to further our knowledge about the contribution of various cell subsets which could have implications for future vaccine development or refined B cell orientated treatment in the health setting. PMID:27050308

  12. CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization

    Science.gov (United States)

    Routine methods for enumerating antigen-specific T-helper cells may not identify low-frequency phenotypes such as Th2 cells. We compared methods of evaluating such responses to identify tetanus toxoid- (TT) specific Th1, Th2, Th17 and IL10+ cells. Eight healthy subjects were given a TT booster vacci...

  13. TRAF3 regulates the effector function of regulatory T cells and humoral immune responses

    OpenAIRE

    Chang, Jae-Hoon; Hu, Hongbo; Jin, Jin; Puebla-Osorio, Nahum; Xiao, Yichuan; Gilbert, Brian E.; Brink, Robert; Ullrich, Stephen E.; Sun, Shao-Cong

    2014-01-01

    Regulatory T cells (Treg cells) control different aspects of immune responses, but how the effector functions of Treg cells are regulated is incompletely understood. Here we identified TNF receptor–associated factor 3 (TRAF3) as a regulator of Treg cell function. Treg cell–specific ablation of TRAF3 impaired CD4 T cell homeostasis, characterized by an increase in the Th1 type of effector/memory T cells. Moreover, the ablation of TRAF3 in Treg cells resulted in increased antigen-stimulated act...

  14. Cyclic-radiation response of murine fibrosarcoma cells grown as pulmonary nodules

    International Nuclear Information System (INIS)

    The radiation age response of murine fibrosarcoma (FSa) cells grown as pulmonary nudules in C3Hf/Kam mice was determined. FSa cells were irradiated in vivo either with 10 Gy as 14 day-old lung tumors (i.e., artifical micrometastases) following cell separation and synchronization by centrifugal elutriation. Flow microfluorometry (FMF) was used to determine cell-cycle parameters and the relative synchrony of the separated populations, as well as the percent contamination of normal diploid cells in each of the tumor cells populations. Tumor populations containing up to 90% G1-, 60% S-, and 75% G2+M-phase tumor cells were obtained. Cell clonogenicity, determined using a lung colony assay, ranged from 0.7 to 6% for control FSa cells from the various elutriator fractions. The radiation sensitivity of these separated cell populations varied by a factor of 6, regardless of whether the cells were irradiated as artifical micro or macro-metastases. In each experiment, tumor population most enriched in S-phase cells exhibited the greatest radiation sensitivity. To confirm that these populations were highly enriched in S-phase cells and to demonstrate that they were more radiosensitive than FSa cells in other parts of the cell cycle, the elutriated tumor population were exposed to either suicide labeling by high specific activity tritated thymidine or hydroxyurea. The resultant age response curves were qualitatively similar to those obtained following irradiation and reflected the S-phase sensitivity of FSa cells to these agents

  15. HLA-DP specific responses in allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Rutten, Caroline Elisabeth

    2013-01-01

    Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated

  16. Relative contribution of "determinant selection" and "holes in the T-cell repertoire" to T-cell responses

    DEFF Research Database (Denmark)

    Schaeffer, E B; Sette, A; Johnson, D L; Bekoff, M C; Smith, J A; Grey, H M; Buus, S

    1989-01-01

    for a large universe of antigens. On the other hand, since the Ia molecules cannot distinguish between self and non-self, not all antigen-Ia interactions would be permitted to elicit a T-cell response. It appears that both Ia binding ("determinant selection") and T-cell repertoire act in concert to...

  17. Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor lysate

    DEFF Research Database (Denmark)

    Soleimani, A; Berntsen, A; Svane, I M; Pedersen, Anders Elm

    2009-01-01

    Patients with metastatic renal cell carcinoma (mRCC) have a limited life expectancy but still a subset of these patients develop immune and clinical responses after immunotherapy including dendritic cell (DC) vaccination. In a recently published phase I/II trials, fourteen HLA-A2 negative patients...

  18. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Hoei-Hansen, Christina E; Krizova, Katerina; Hamerlik, Petra; Skakkebæk, Niels E; Rajpert-De Meyts, Ewa; Bartek, Jiri

    2014-01-01

    were no clear aberrations in the ATM-Chk2-p53 pathway components among the PIGCT cohort; iii) Subsets of PIGCTs showed unusual cytosolic localization of Chk2 and/or ATM. Collectively, these results show that PIGCTs mimic the DDR activation patterns of their gonadal germ cell tumor counterparts, rather......The DNA damage response (DDR) machinery becomes commonly activated in response to oncogenes and during early stages of development of solid malignancies, with an exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes cell death or senescence but this anti-tumor barrier...... cell tumors (PIGCTs), to address the roles of cell-intrinsic factors including cell of origin, versus local tissue environment, in the constitutive DDR activation in vivo. Immunohistochemical analysis of 7 biomarkers on a series of 21 PIGCTs (germinomas and other subtypes), 20 normal brain specimens...

  19. The response of single human cells to zero gravity

    Science.gov (United States)

    Montgomery, P. O., Jr.; Cook, J. E.; Reynolds, R. C.; Paul, J. S.; Hayflick, L.; Schulz, W. W.; Stock, D.; Kinzey, S.; Rogers, T.; Campbell, D.

    1975-01-01

    Twenty separate cultures of Wistar-38 human embryonic lung cells were exposed to a zero-gravity environment on Skylab for periods of time ranging from one to 59 days. Duplicate cultures were run concurrently as ground controls. Ten cultures were fixed on board the satellite during the first 12 days of flight. Growth curves, DNA microspectrophotometry, phase microscopy, and ultrastructural studies of the fixed cells revealed no effects of a zero-gravity environment on the ten cultures. Two cultures were photographed with phase time lapse cinematography during the first 27 days of flight. No differences were found in mitotic index, cell cycle, and migration between the flight and control cells. Eight cultures were returned to earth in an incubated state. Karyotyping and chromosome banding tests show no differences between the flight and control cells.

  20. Roles of the plasma membrane and the cell wall in the responses of plant cells to freezing.

    Science.gov (United States)

    Yamada, Tomoyoshi; Kuroda, Katsushi; Jitsuyama, Yutaka; Takezawa, Daisuke; Arakawa, Keita; Fujikawa, Seizo

    2002-09-01

    In an effort to clarify the responses of a wide range of plant cells to freezing, we examined the responses to freezing of the cells of chilling-sensitive and chilling-resistant tropical and subtropical plants. Among the cells of the plants that we examined, those of African violet ( Saintpaulia grotei Engl.) leaves were most chilling-sensitive, those of hypocotyls in mungbean [ Vigna radiata (L.) R. Wilcz.] seedlings were moderately chilling-sensitive, and those of orchid [ Paphiopedilum insigne (Wallich ex Lindl.) Pfitz.] leaves were chilling-resistant, when all were chilled at -2 degrees C. By contrast, all these plant cells were freezing-sensitive and suffered extensive damage when they were frozen at -2 degrees C. Cryo-scanning electron microscopy (Cryo-SEM) confirmed that, upon chilling at -2 degrees C, both chilling-sensitive and chilling-resistant plant cells were supercooled. Upon freezing at -2 degrees C, by contrast, intracellular freezing occurred in Saintpaulia leaf cells, frost plasmolysis followed by intracellular freezing occurred in mungbean seedling cells, and extracellular freezing (cytorrhysis) occurred in orchid leaf cells. We postulate that chilling-related destabilization of membranes might result in the loss of the ability of the plasma membrane to act as a barrier against the propagation of extracellular ice in chilling-sensitive plant cells. We also examined the role of cell walls in the response to freezing using cells in which the plasma membrane had been disrupted by repeated freezing and thawing. In chilling-sensitive Saintpaulia and mungbean cells, the cells with a disrupted plasma membrane responded to freezing at -2 degrees C by intracellular freezing. By contrast, in chilling-resistant orchid cells, as well as in other cells of chilling-resistant and freezing-resistant plant tissues, including leaves of orchard grass ( Dactylis glomerata L.), leaves of Arabidopsis thaliana (L.) Heynh. and cortical tissues of mulberry ( Morus

  1. Molecular signatures in response to Isoliquiritigenin in lymphoblastoid cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Eun; Hong, Eun-Jung; Nam, Hye-Young [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Hwang, Meeyul [Research Center for Biomedical Resource of Oriental Medicine, Daegu Haany University (Korea, Republic of); Kim, Ji-Hyun [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Han, Bok-Ghee, E-mail: bokghee@nih.go.kr [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Jeon, Jae-Pil, E-mail: jpjeon@cdc.go.kr [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer We identified the inhibitory effect of ISL on cell proliferation of LCLs. Black-Right-Pointing-Pointer We found ISL-induced genes and miRNAs through microarray approach. Black-Right-Pointing-Pointer ISL-treated LCLs represented gene expression changes in cell cycle and p53 pathway. Black-Right-Pointing-Pointer We revealed 12 putative mRNA-miRNA functional pairs associated with ISL effect. -- Abstract: Isoliquiritigenin (ISL) has been known to induce cell cycle arrest and apoptosis of various cancer cells. However, genetic factors regulating ISL effects remain unclear. The aim of this study was to identify the molecular signatures involved in ISL-induced cell death of EBV-transformed lymphoblastoid cell lines (LCLs) using microarray analyses. For gene expression and microRNA (miRNA) microarray experiments, each of 12 LCL strains was independently treated with ISL or DMSO as a vehicle control for a day prior to total RNA extraction. ISL treatment inhibited cell proliferation of LCLs in a dose-dependent manner. Microarray analysis showed that ISL-treated LCLs represented gene expression changes in cell cycle and p53 signaling pathway, having a potential as regulators in LCL survival and sensitivity to ISL-induced cytotoxicity. In addition, 36 miRNAs including five miRNAs with unknown functions were differentially expressed in ISL-treated LCLs. The integrative analysis of miRNA and gene expression profiles revealed 12 putative mRNA-miRNA functional pairs. Among them, miR-1207-5p and miR-575 were negatively correlated with p53 pathway- and cell cycle-associated genes, respectively. In conclusion, our study suggests that miRNAs play an important role in ISL-induced cytotoxicity in LCLs by targeting signaling pathways including p53 pathway and cell cycle.

  2. HDAC1 controls CD8+ T cell homeostasis and antiviral response.

    Directory of Open Access Journals (Sweden)

    Roland Tschismarov

    Full Text Available Reversible lysine acetylation plays an important role in the regulation of T cell responses. HDAC1 has been shown to control peripheral T helper cells, however the role of HDAC1 in CD8+ T cell function remains elusive. By using conditional gene targeting approaches, we show that LckCre-mediated deletion of HDAC1 led to reduced numbers of thymocytes as well as peripheral T cells, and to an increased fraction of CD8+CD4- cells within the CD3/TCRβlo population, indicating that HDAC1 is essential for the efficient progression of immature CD8+CD4- cells to the DP stage. Moreover, CD44hi effector CD8+ T cells were enhanced in mice with a T cell-specific deletion of HDAC1 under homeostatic conditions and HDAC1-deficient CD44hi CD8+ T cells produced more IFNγ upon ex vivo PMA/ionomycin stimulation in comparison to wild-type cells. Naïve (CD44l°CD62L+ HDAC1-null CD8+ T cells displayed a normal proliferative response, produced similar amounts of IL-2 and TNFα, slightly enhanced amounts of IFNγ, and their in vivo cytotoxicity was normal in the absence of HDAC1. However, T cell-specific loss of HDAC1 led to a reduced anti-viral CD8+ T cell response upon LCMV infection and impaired expansion of virus-specific CD8+ T cells. Taken together, our data indicate that HDAC1 is required for the efficient generation of thymocytes and peripheral T cells, for proper CD8+ T cell homeostasis and for an efficient in vivo expansion and activation of CD8+ T cells in response to LCMV infection.

  3. Use and Needs in Contexts : An Ethnographic Study on Cell Phone Use from a Contextual Usability Perspective

    OpenAIRE

    Friberg, Hanna

    2003-01-01

    The focus of this thesis is usability of an everyday used product; the cell phone seen from a Human – Computer Interaction perspective. The purpose with the thesis is to create an understanding of how cell phones are used by persons in natural /public settings and in everyday activities. Further the purpose is to describe users’ experiences of using cell phones. In this study, ethnography was used as method. The theoretical framework is the contextual usability perspective. The cell phone is ...

  4. Responses of human MG-63 osteosarcoma cell line and human osteoblast-like cells to pulsed electromagnetic fields.

    Science.gov (United States)

    Sollazzo, V; Traina, G C; DeMattei, M; Pellati, A; Pezzetti, F; Caruso, A

    1997-01-01

    We have studied the effects of low-energy, low-frequency pulsed electromagnetic fields (PEMF) on cell proliferation, in both human osteoblast-like cells obtained from bone specimens and in human MG-63 osteosarcoma cell line. Assessment of osteoblastic phenotype was performed both by immunolabeling with antiosteonectin antibody and by verifying the presence of parathyroid hormone receptors. The cells were placed in multiwell plates and set in a tissue culture incubator between a pair of Helmholtz coils powered by a pulse generator (1.3 ms, 75 Hz) for different periods of time. [3H]Thymidine incorporation was used to evaluate cell proliferation. Since it had previously been observed that the osteoblast proliferative response to PEMF exposure may also be conditioned by the presence of serum in the medium, experiments were carried out at different serum concentrations. [3H]Thymidine incorporation increases in osteoblast-like cells, when they are exposed to PEMF in the presence of 10% fetal calf serum (FCS). The greatest effect is observed after 24 hours of PEMF exposure. No effects on cell proliferation are observed when osteoblast-like cells are exposed to PEMF in the presence of 0.5% FCS or in a serum-free medium. On the other hand, PEMF-exposed MG-63 cells show increased cell proliferation either at 10% FCS, 0.5% FCS and in serum-free medium. Nevertheless, the maximum effect of PEMF exposure on MG-63 cell proliferation depends on the percentage of FCS in the medium. The higher the FCS concentration, the faster the proliferative response to PEMF exposure. Our results show that, although MG-63 cells display some similarity with human bone cells, their responses to PEMF's exposure are quite different from that observed in normal human bone cells. PMID:9383242

  5. Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells.

    OpenAIRE

    Wagener, Jeanette; Weindl, Günther; de Groot, Piet W. J.; de Boer, Albert D.; Kaesler, Susanne; Thavaraj, Selvam; Bader, Oliver; Mailänder-Sanchez, Daniela; Borelli, Claudia; Weig, Michael; Biedermann, Tilo; Naglik, Julian R.; Korting, Hans Christian; Schaller, Martin

    2012-01-01

    C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the ...

  6. Characteristics of the early immune response following transplantation of mouse ES cell derived insulin-producing cell clusters.

    OpenAIRE

    Boyd, Ashleigh S.; Wood, Kathryn J.

    2010-01-01

    Background The fully differentiated progeny of ES cells (ESC) may eventually be used for cell replacement therapy (CRT). However, elements of the innate immune system may contribute to damage or destruction of these tissues when transplanted. Methodology/Principal Findings Herein, we assessed the hitherto ill-defined contribution of the early innate immune response in CRT after transplantation of either ESC derived insulin producing cell clusters (IPCCs) or adult pancreatic islets....

  7. Contribution of Herpesvirus Specific CD8 T Cells to Anti-Viral T Cell Response in Humans

    OpenAIRE

    Elena Sandalova; Diletta Laccabue; Carolina Boni; Tan, Anthony T.; Katja Fink; Eng Eong Ooi; Robert Chua; Bahar Shafaeddin Schreve; Carlo Ferrari; Antonio Bertoletti

    2010-01-01

    Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 1...

  8. Diminished COX-2/PGE2-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells

    OpenAIRE

    Lin, Hsin-Ru; Wu, Yi-Hsuan; Yen, Wei-Chen; Yang, Chuen-Mao; Chiu, Daniel Tsun-Yee

    2016-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) provides the reducing agent NADPH to meet the cellular needs for reductive biosynthesis and the maintenance of redox homeostasis. G6PD-deficient cells experience a high level of oxidative stress and an increased susceptibility to viral infections. Cyclooxygenase-2 (COX-2) is a key mediator in the regulation of viral replication and inflammatory response. In the current study, the role of G6PD on the inflammatory response was determined in both scramble...

  9. Treg cells expressing the co-inhibitory molecule TIGIT selectively inhibit pro-inflammatory Th1 and Th17 cell responses

    OpenAIRE

    Joller, Nicole; Lozano, Ester; Burkett, Patrick R.; Patel, Bonny; Xiao, Sheng; Zhu, Chen; Xia, Junrong; Tan, Tze G.; Sefik, Esen; Yajnik, Vijay; Sharpe, Arlene H.; Quintana, Francisco J.; Mathis, Diane; Benoist, Christophe; Hafler, David A.

    2014-01-01

    Foxp3+ T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3+ T cells expressing the co-inhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses pro-inflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT+ Treg cells as an activated Treg subse...

  10. Peripheral CD4+ T cell cytokine responses following human challenge and re-challenge with Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Kelly A Fimlaid

    Full Text Available Campylobacter jejuni is a leading cause of human gastroenteritis worldwide; however, our understanding of the human immune response to C. jejuni infection is limited. A previous human challenge model has shown that C. jejuni elicits IFNγ production by peripheral blood mononuclear cells, a response associated with protection from clinical disease following re-infection. In this study, we investigate T lymphocyte profiles associated with campylobacteriosis using specimens from a new human challenge model in which C. jejuni-naïve subjects were challenged and re-challenged with C. jejuni CG8421. Multiparameter flow cytometry was used to investigate T lymphocytes as a source of cytokines, including IFNγ, and to identify cytokine patterns associated with either campylobacteriosis or protection from disease. Unexpectedly, all but one subject evaluated re-experienced campylobacteriosis after re-challenge. We show that CD4+ T cells make IFNγ and other pro-inflammatory cytokines in response to infection; however, multifunctional cytokine response patterns were not found. Cytokine production from peripheral CD4+ T cells was not enhanced following re-challenge, which may suggest deletion or tolerance. Evaluation of alternative paradigms or models is needed to better understand the immune components of protection from campylobacteriosis.

  11. Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses.

    Directory of Open Access Journals (Sweden)

    Kelly B McClellan

    2006-06-01

    Full Text Available B cells can use antibody-dependent mechanisms to control latent viral infections. It is unknown whether this represents the sole function of B cells during chronic viral infection. We report here that hen egg lysozyme (HEL-specific B cells can contribute to the control of murine gamma-herpesvirus 68 (gammaHV68 latency without producing anti-viral antibody. HEL-specific B cells normalized defects in T cell numbers and proliferation observed in B cell-/- mice during the early phase of gammaHV68 latency. HEL-specific B cells also reversed defects in CD8 and CD4 T cell cytokine production observed in B cell-/- mice, generating CD8 and CD4 T cells necessary for control of latency. Furthermore, HEL-specific B cells were able to present virally encoded antigen to CD8 T cells. Therefore, B cells have antibody independent functions, including antigen presentation, that are important for control of gamma-herpesvirus latency. Exploitation of this property of B cells may allow enhanced vaccine responses to chronic virus infection.

  12. CD8α− Dendritic Cells Induce Antigen-Specific T Follicular Helper Cells Generating Efficient Humoral Immune Responses

    Directory of Open Access Journals (Sweden)

    Changsik Shin

    2015-06-01

    Full Text Available Recent studies on T follicular helper (Tfh cells have significantly advanced our understanding of T cell-dependent B cell responses. However, little is known about the early stage of Tfh cell commitment by dendritic cells (DCs, particularly by the conventional CD8α+ and CD8α− DC subsets. We show that CD8α− DCs localized at the interfollicular zone play a pivotal role in the induction of antigen-specific Tfh cells by upregulating the expression of Icosl and Ox40l through the non-canonical NF-κB signaling pathway. Tfh cells induced by CD8α− DCs function as true B cell helpers, resulting in significantly increased humoral immune responses against various human pathogenic antigens, including Yersinia pestis LcrV, HIV Gag, and hepatitis B surface antigen. Our findings uncover a mechanistic role of CD8α− DCs in the initiation of Tfh cell differentiation and thereby provide a rationale for investigating CD8α− DCs in enhancing antigen-specific humoral immune responses for improving vaccines and therapeutics.

  13. T-helper cell-mediated proliferation and cytokine responses against recombinant Merkel cell polyomavirus-like particles.

    Science.gov (United States)

    Kumar, Arun; Chen, Tingting; Pakkanen, Sari; Kantele, Anu; Söderlund-Venermo, Maria; Hedman, Klaus; Franssila, Rauli

    2011-01-01

    The newly discovered Merkel Cell Polyomavirus (MCPyV) resides in approximately 80% of Merkel cell carcinomas (MCC). Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT) viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL), suggesting a pathogenic role also in CLL. About 50-80% of adults display MCPyV-specific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC) of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs), using human bocavirus (HBoV) VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-γ, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyV-seropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-γ. The MCPyV antigen tended to induce stronger IFN-γ responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-γ responses. IFN-γ being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance. PMID:21991346

  14. T-helper cell-mediated proliferation and cytokine responses against recombinant Merkel cell polyomavirus-like particles.

    Directory of Open Access Journals (Sweden)

    Arun Kumar

    Full Text Available The newly discovered Merkel Cell Polyomavirus (MCPyV resides in approximately 80% of Merkel cell carcinomas (MCC. Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL, suggesting a pathogenic role also in CLL. About 50-80% of adults display MCPyV-specific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs, using human bocavirus (HBoV VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-γ, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyV-seropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-γ. The MCPyV antigen tended to induce stronger IFN-γ responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-γ responses. IFN-γ being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance.

  15. Single-cell bioelectrical impedance platform for monitoring cellular response to drug treatment

    OpenAIRE

    Asphahani, Fareid; Wang, Kui; Thein, Myo; Veiseh, Omid; Yung, Sandy; Xu, Jian; Zhang, Miqin

    2011-01-01

    The response of cells to a chemical or biological agent in terms of their impedance changes in real-time is a useful mechanism that can be utilized for a wide variety of biomedical and environmental applications. The use of a single-cell based analytical platform could be an effective approach to acquiring more sensitive cell impedance measurements, particularly in applications where only diminutive changes in impedance are expected. Here, we report the development of an on-chip cell impedanc...

  16. The Role of Treg Cells in the Cancer Immunological Response

    OpenAIRE

    Ansell, Stephen M.; Zhi-Zhang Yang

    2009-01-01

    Problem statement: T cell-mediated immunosuppression has been observed for decades without clarification as to which factor was responsible for this observation. The identification of CD4+CD25+ regulatory T (Treg) cells represents a milestone in the filed of immunology and provides an explanation for T-cell-mediated immunosuppression. Although Treg cells were originally identified for their ability to prevent organ-specific autoimmune disease in mice, emerging &#...

  17. Radioresistance of cells responsible for delayed hypersensitivity reactions in the mouse

    International Nuclear Information System (INIS)

    The cells responsible for delayed hypersensitivity reactivity in the mouse act in a radioresistant fashion only if such irradiated cells are injected directly into the site of antigen challenge. Intravenous transfer of irradiated, primed spleen cells does not achieve a transfer of sensitivity to show delayed type hypersensitivity reactions. Transfer of sensitivity by the intravenous route can be effected by injection of non-irradiated spleen cells from primed mice. (U.S.)

  18. A primary culture of guinea pig gallbladder epithelial cells that is responsive to secretagogues

    OpenAIRE

    Gunter-Smith, Pamela J.; Abdulkadir, Oluwakemi; Hammonds-Odie, Latanya; Scanlon, Mary; Terrell, Raquel

    2000-01-01

    We have developed a cell culture of guinea pig gallbladder epithelial cells with which to study ion transport. When grown on permeable supports, the cultured epithelia developed a transepithelial resistance (Rt) of ∼500 Ω·cm2. The epithelial cell origin of the cell culture was further confirmed by immunocytochemical localization of cytokeratin. Ionomycin and forskolin increased transepithelial voltage and short-circuit current (Isc) and decreased Rt. The response to ionomycin was transient, w...

  19. Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection.

    Directory of Open Access Journals (Sweden)

    Alan C-Y Hsu

    Full Text Available Innate antiviral responses in bronchial epithelial cells (BECs provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs. However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.

  20. Development of Cell-Responsive Nanophase Hydroxyapatite for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    R. Murugan

    2007-01-01

    Full Text Available Scaffold plays a critical role in engineering bone tissues by providing necessary structural support for the cells to accommodate and guiding their growth in the three dimensional (3D space. Therefore, designing scaffold that mimic composition and structural aspects of the bone is of great importance to promote cell adhesion, cell-matrix interactions, osteointegration, tissue formation and continued function. Nanophase hydroxyapatite (HA is a class of bioceramic material that mimics the bone mineral in composition and structure and possesses unique capabilities for surface interactions with biological entities than conventional HA; therefore, it can be used as a scaffolding system in engineering bone tissues. This article reports synthesis, characterization, and evaluation of nanophase HA for use in bone tissue engineering and how the nanophase characteristics help the HA to promote cells/tissue growth with suitable experimental examples.

  1. Innate immune cell response upon Candida albicans infection.

    Science.gov (United States)

    Qin, Yulin; Zhang, Lulu; Xu, Zheng; Zhang, Jinyu; Jiang, Yuan-Ying; Cao, Yongbing; Yan, Tianhua

    2016-07-01

    Candida albicans is a polymorphic fungus which is the predominant cause of superficial and deep tissue fungal infections. This microorganism has developed efficient strategies to invade the host and evade host defense systems. However, the host immune system will be prepared for defense against the microbe by recognition of receptors, activation of signal transduction pathways and cooperation of immune cells. As a consequence, C. albicans could either be eliminated by immune cells rapidly or disseminate hematogenously, leading to life-threatening systemic infections. The interplay between Candida albicans and the host is complex, requiring recognition of the invaded pathogens, activation of intricate pathways and collaboration of various immune cells. In this review, we will focus on the effects of innate immunity that emphasize the first line protection of host defense against invaded C. albicans including the basis of receptor-mediated recognition and the mechanisms of cell-mediated immunity. PMID:27078171

  2. Natural Killer Cell Mediated Cytotoxic Responses in the Tasmanian Devil

    OpenAIRE

    Brown, Gabriella K.; Kreiss, Alexandre; Lyons, A. Bruce; Woods, Gregory M.

    2011-01-01

    The Tasmanian devil (Sarcophilus harrisii), the world's largest marsupial carnivore, is under threat of extinction following the emergence of an infectious cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils during biting. The disease is consistently fatal and devils succumb without developing a protective immune response. The aim of this study was to determine if Tasmanian devils were capable of forming cytotoxic antitumour responses and develop antibodies against D...

  3. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    Energy Technology Data Exchange (ETDEWEB)

    Doi, Keiko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute of Life Sciences for the Next Generation of Women Scientists, Fukuoka University, Fukuoka (Japan); Fujimoto, Takahiro [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Okamura, Tadashi [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ogawa, Masahiro [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tanaka, Yoko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Mototani, Yasumasa; Goto, Motohito [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ota, Takeharu; Matsuzaki, Hiroshi [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Kuroki, Masahide [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tsunoda, Toshiyuki [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Sasazuki, Takehiko [Institute for Advanced Study, Kyushu University, Fukuoka (Japan); Shirasawa, Senji, E-mail: sshirasa@fukuoka-u.ac.jp [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. Black-Right-Pointing-Pointer Zfat-deficiency leads to reduction in the number of the peripheral T cells. Black-Right-Pointing-Pointer Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Decreased expression of IL-7R{alpha}, IL-2R{alpha} and IL-2 in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7R{alpha} and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2R{alpha} expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  4. Lactobacilli regulate Staphylococcus aureus 161:2-induced pro-inflammatory T-cell responses in vitro.

    Science.gov (United States)

    Haileselassie, Yeneneh; Johansson, Maria A; Zimmer, Christine L; Björkander, Sophia; Petursdottir, Dagbjort H; Dicksved, Johan; Petersson, Mikael; Persson, Jan-Olov; Fernandez, Carmen; Roos, Stefan; Holmlund, Ulrika; Sverremark-Ekström, Eva

    2013-01-01

    There seems to be a correlation between early gut microbiota composition and postnatal immune development. Alteration in the microbial composition early in life has been associated with immune mediated diseases, such as autoimmunity and allergy. We have previously observed associations between the presence of lactobacilli and Staphylococcus (S.) aureus in the early-life gut microbiota, cytokine responses and allergy development in children. Consistent with the objective to understand how bacteria modulate the cytokine response of intestinal epithelial cell (IEC) lines and immune cells, we exposed IEC lines (HT29, SW480) to UV-killed bacteria and/or culture supernatants (-sn) from seven Lactobacillus strains and three S. aureus strains, while peripheral blood mononuclear cells (PBMC) and cord blood mononuclear cells (CBMC) from healthy donors were stimulated by bacteria-sn or with bacteria conditioned IEC-sn. Although the overall IEC response to bacterial exposure was characterized by limited sets of cytokine and chemokine production, S. aureus 161:2-sn induced an inflammatory response in the IEC, characterized by CXCL1/GROα and CXCL8/IL-8 production, partly in a MyD88-dependent manner. UV-killed bacteria did not induce a response in the IEC line, and a combination of both UV-killed bacteria and the bacteria-sn had no additive effect to that of the supernatant alone. In PBMC, most of the Lactobacillus-sn and S. aureus-sn strains were able to induce a wide array of cytokines, but only S. aureus-sn induced the T-cell associated cytokines IL-2, IL-17 and IFN-γ, independently of IEC-produced factors, and induced up regulation of CTLA-4 expression and IL-10 production by T-regulatory cells. Notably, S. aureus-sn-induced T-cell production of IFN- γ and IL-17 was down regulated by the simultaneous presence of any of the different Lactobacillus strains, while the IEC CXCL8/IL-8 response was unaltered. Thus these studies present a possible role for lactobacilli in

  5. Lactobacilli regulate Staphylococcus aureus 161:2-induced pro-inflammatory T-cell responses in vitro.

    Directory of Open Access Journals (Sweden)

    Yeneneh Haileselassie

    Full Text Available There seems to be a correlation between early gut microbiota composition and postnatal immune development. Alteration in the microbial composition early in life has been associated with immune mediated diseases, such as autoimmunity and allergy. We have previously observed associations between the presence of lactobacilli and Staphylococcus (S. aureus in the early-life gut microbiota, cytokine responses and allergy development in children. Consistent with the objective to understand how bacteria modulate the cytokine response of intestinal epithelial cell (IEC lines and immune cells, we exposed IEC lines (HT29, SW480 to UV-killed bacteria and/or culture supernatants (-sn from seven Lactobacillus strains and three S. aureus strains, while peripheral blood mononuclear cells (PBMC and cord blood mononuclear cells (CBMC from healthy donors were stimulated by bacteria-sn or with bacteria conditioned IEC-sn. Although the overall IEC response to bacterial exposure was characterized by limited sets of cytokine and chemokine production, S. aureus 161:2-sn induced an inflammatory response in the IEC, characterized by CXCL1/GROα and CXCL8/IL-8 production, partly in a MyD88-dependent manner. UV-killed bacteria did not induce a response in the IEC line, and a combination of both UV-killed bacteria and the bacteria-sn had no additive effect to that of the supernatant alone. In PBMC, most of the Lactobacillus-sn and S. aureus-sn strains were able to induce a wide array of cytokines, but only S. aureus-sn induced the T-cell associated cytokines IL-2, IL-17 and IFN-γ, independently of IEC-produced factors, and induced up regulation of CTLA-4 expression and IL-10 production by T-regulatory cells. Notably, S. aureus-sn-induced T-cell production of IFN- γ and IL-17 was down regulated by the simultaneous presence of any of the different Lactobacillus strains, while the IEC CXCL8/IL-8 response was unaltered. Thus these studies present a possible role for

  6. Epigenetic cell response to an influence of ionizing radiation

    International Nuclear Information System (INIS)

    Importance of radiation modification of epigenetic activity in the general mechanism of radiobiological reactions is proved. Inheritable epigenetic changes induced by irradiation are one of the basic reasons of formation of the remote radiation pathology. It is noted that epigenetic inheritable changes of cells have the determined character distinguishing them mutation changes, being individual and not directed. It is underlined the ability of ionizing radiation to modify level of spontaneous genetic instability inherited in a number of cell generations on epigenetic mechanism

  7. Cellular response after irradiation: Cell cycle control and apoptosis

    International Nuclear Information System (INIS)

    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)

  8. Response of maternal immune cells of irradiation of mouse embryos

    International Nuclear Information System (INIS)

    This work began as an attempt to explain the paradox of pregnancy - the survival and growth of the semi-allogenic embryo in an immunologically hostile environment. In 1982 and 1983 we reported the tracing of quinacrine labelled maternal leukocytes (WBC) in maternal, placental and embryonic mouse tissues by fluorescence microscopy. We found that cells in the placenta phagocytose labelled WBC, so that after 1-2 hours the labelled nuclear DNA is found as brightly fluorescing particles in the cytoplasm of the phagocytes with no evidence of it in the nuclei. Identical cells were observed in slide preparations of embryos which had been carefully separated from their placentas. We also found a small population of intact labelled lymphocytes, clearly maternal in origin, in the embryos. This seems to be another paradox - placental phagocytes are observed to be phagocytosing maternal WBC in the placenta and embryo, but there are also free maternal cells in the placenta and embryo. A theoretical explanation is that maternal lymphocytes alloreactive against the embryo will attempt to react with placental cells and in the process be phagocytosed, while other maternal cells will be able to enter the embryo where they could have a surveillance function, removing dead or mutant embryonic cells. To test this theory a series of experiments were carried out and are reported

  9. HIV-dependent depletion of influenza-specific memory B cells impacts B cell responsiveness to seasonal influenza immunisation.

    Science.gov (United States)

    Wheatley, Adam K; Kristensen, Anne B; Lay, William N; Kent, Stephen J

    2016-01-01

    Infection with HIV drives significant alterations in B cell phenotype and function that can markedly influence antibody responses to immunisation. Anti-retroviral therapy (ART) can partially reverse many aspects of B cell dysregulation, however complete normalisation of vaccine responsiveness is not always observed. Here we examine the effects of underlying HIV infection upon humoral immunity to seasonal influenza vaccines. Serological and memory B cell responses were assessed in 26 HIV+ subjects receiving ART and 30 healthy controls immunised with the 2015 Southern Hemisphere trivalent inactivated influenza vaccine (IIV3). Frequencies and phenotypes of influenza hemagglutinin (HA)-specific B cells were assessed by flow cytometry using recombinant HA probes. Serum antibody was measured using hemagglutination inhibition assays. Serological responses to IIV3 were comparable between HIV+ and HIV- subjects. Likewise, the activation and expansion of memory B cell populations specific for vaccine-component influenza strains was observed in both cohorts, however peak frequencies were diminished in HIV+ subjects compared to uninfected controls. Lower circulating frequencies of memory B cells recognising vaccine-component and historical influenza strains were observed in HIV+ subjects at baseline, that were generally restored to levels comparable with HIV- controls post-vaccination. HIV infection is therefore associated with depletion of selected HA-specific memory B cell pools. PMID:27220898

  10. HIV-dependent depletion of influenza-specific memory B cells impacts B cell responsiveness to seasonal influenza immunisation

    Science.gov (United States)

    Wheatley, Adam K.; Kristensen, Anne B.; Lay, William N.; Kent, Stephen J.

    2016-01-01

    Infection with HIV drives significant alterations in B cell phenotype and function that can markedly influence antibody responses to immunisation. Anti-retroviral therapy (ART) can partially reverse many aspects of B cell dysregulation, however complete normalisation of vaccine responsiveness is not always observed. Here we examine the effects of underlying HIV infection upon humoral immunity to seasonal influenza vaccines. Serological and memory B cell responses were assessed in 26 HIV+ subjects receiving ART and 30 healthy controls immunised with the 2015 Southern Hemisphere trivalent inactivated influenza vaccine (IIV3). Frequencies and phenotypes of influenza hemagglutinin (HA)-specific B cells were assessed by flow cytometry using recombinant HA probes. Serum antibody was measured using hemagglutination inhibition assays. Serological responses to IIV3 were comparable between HIV+ and HIV− subjects. Likewise, the activation and expansion of memory B cell populations specific for vaccine-component influenza strains was observed in both cohorts, however peak frequencies were diminished in HIV+ subjects compared to uninfected controls. Lower circulating frequencies of memory B cells recognising vaccine-component and historical influenza strains were observed in HIV+ subjects at baseline, that were generally restored to levels comparable with HIV− controls post-vaccination. HIV infection is therefore associated with depletion of selected HA-specific memory B cell pools. PMID:27220898

  11. Cell proliferation kinetics and radiation response in 9L tumor spheroids

    Energy Technology Data Exchange (ETDEWEB)

    Sweigert, S.E.

    1984-05-01

    Cell kinetic parameters, including population doubling-time, cell cycle time, and growth fraction, were measured in 9L gliosarcoma spheroids. These parameters were studied as the spheroids grew from 50 ..mu..m to over 900 ..mu..m in diameter. Experiments relating the cell kinetic parameters to the radiation response of 9L spheroids were also carried out. The major findings were that the average cell cycle time (T/sub c/), is considerably longer in large spheroids than in exponentially-growing monolayers, the radiosensitivity of noncycling (but still viable) cells in spheroids is not significantly different from that of cycling spheroid cells, and the radiation-induced division delay is approximately twice as long in spheroid cells as in monolayer cells given equal radiation doses. The cell loss factor for spheroids of various sizes was calculated, by using the measured kinetic parameters in the basic equations for growth of a cell population. 157 references, 6 figures, 3 tables.

  12. Cell proliferation kinetics and radiation response in 9L tumor spheroids

    International Nuclear Information System (INIS)

    Cell kinetic parameters, including population doubling-time, cell cycle time, and growth fraction, were measured in 9L gliosarcoma spheroids. These parameters were studied as the spheroids grew from 50 μm to over 900 μm in diameter. Experiments relating the cell kinetic parameters to the radiation response of 9L spheroids were also carried out. The major findings were that the average cell cycle time (T/sub c/), is considerably longer in large spheroids than in exponentially-growing monolayers, the radiosensitivity of noncycling (but still viable) cells in spheroids is not significantly different from that of cycling spheroid cells, and the radiation-induced division delay is approximately twice as long in spheroid cells as in monolayer cells given equal radiation doses. The cell loss factor for spheroids of various sizes was calculated, by using the measured kinetic parameters in the basic equations for growth of a cell population. 157 references, 6 figures, 3 tables

  13. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses

    Science.gov (United States)

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G.

    2016-01-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  14. Retinal ganglion cells: mechanisms underlying depolarization block and differential responses to high frequency electrical stimulation of ON and OFF cells

    Science.gov (United States)

    Kameneva, T.; Maturana, M. I.; Hadjinicolaou, A. E.; Cloherty, S. L.; Ibbotson, M. R.; Grayden, D. B.; Burkitt, A. N.; Meffin, H.

    2016-02-01

    Objective. ON and OFF retinal ganglion cells (RGCs) are known to have non-monotonic responses to increasing amplitudes of high frequency (2 kHz) biphasic electrical stimulation. That is, an increase in stimulation amplitude causes an increase in the cell’s spike rate up to a peak value above which further increases in stimulation amplitude cause the cell to decrease its activity. The peak response for ON and OFF cells occurs at different stimulation amplitudes, which allows differential stimulation of these functional cell types. In this study, we investigate the mechanisms underlying the non-monotonic responses of ON and OFF brisk-transient RGCs and the mechanisms underlying their differential responses. Approach. Using in vitro patch-clamp recordings from rat RGCs, together with simulations of single and multiple compartment Hodgkin-Huxley models, we show that the non-monotonic response to increasing amplitudes of stimulation is due to depolarization block, a change in the membrane potential that prevents the cell from generating action potentials. Main results. We show that the onset for depolarization block depends on the amplitude and frequency of stimulation and reveal the biophysical mechanisms that lead to depolarization block during high frequency stimulation. Our results indicate that differences in transmembrane potassium conductance lead to shifts of the stimulus currents that generate peak spike rates, suggesting that the differential responses of ON and OFF cells may be due to differences in the expression of this current type. We also show that the length of the axon’s high sodium channel band (SOCB) affects non-monotonic responses and the stimulation amplitude that leads to the peak spike rate, suggesting that the length of the SOCB is shorter in ON cells. Significance. This may have important implications for stimulation strategies in visual prostheses.

  15. Dissecting the T Cell Response: Proliferation Assays vs. Cytokine Signatures by ELISPOT

    Directory of Open Access Journals (Sweden)

    Magdalena Tary-Lehmann

    2012-05-01

    Full Text Available Chronic allograft rejection is in part mediated by host T cells that recognize allogeneic antigens on transplanted tissue. One factor that determines the outcome of a T cell response is clonal size, while another is the effector quality. Studies of alloimmune predictors of transplant graft survival have most commonly focused on only one measure of the alloimmune response. Because differing qualities and frequencies of the allospecific T cell response may provide distinctly different information we analyzed the relationship between frequency of soluble antigen and allo-antigen specific memory IFN-g secreting CD4 and CD8 T cells, their ability to secrete IL-2, and their proliferative capacity, while accounting for cognate and bystander proliferation. The results show proliferative responses primarily reflect on IL-2 production by antigen-specific T cells, and that proliferating cells in such assays entail a considerable fraction of bystander cells. On the other hand, proliferation (and IL-2 production did not reflect on the frequency of IFN-γ producing memory cells, a finding particularly accentuated in the CD8 T cell compartment. These data provide rationale for considering both frequency and effector function of pre-transplant T cell reactivity when analyzing immune predictors of graft rejection.

  16. p53-Dependent Adaptive Responses in Human Cells Exposed to Space Radiations

    International Nuclear Information System (INIS)

    Purpose: It has been reported that priming irradiation or conditioning irradiation with a low dose of X-rays in the range of 0.02-0.1 Gy induces a p53-dependent adaptive response in mammalian cells. The aim of the present study was to clarify the effect of space radiations on the adaptive response. Methods and Materials: Two human lymphoblastoid cell lines were used; one cell line bears a wild-type p53 (wtp53) gene, and another cell line bears a mutated p53 (mp53) gene. The cells were frozen during transportation on the space shuttle and while in orbit in the International Space Station freezer for 133 days between November 15, 2008 and March 29, 2009. After the frozen samples were returned to Earth, the cells were cultured for 6 h and then exposed to a challenging X-ray-irradiation (2 Gy). Cellular sensitivity, apoptosis, and chromosome aberrations were scored using dye-exclusion assays, Hoechst33342 staining assays, and chromosomal banding techniques, respectively. Results: In cells exposed to space radiations, adaptive responses such as the induction of radioresistance and the depression of radiation-induced apoptosis and chromosome aberrations were observed in wtp53 cells but not in mp53 cells. Conclusion: These results have confirmed the hypothesis that p53-dependent adaptive responses are apparently induced by space radiations within a specific range of low doses. The cells exhibited this effect owing to space radiations exposure, even though the doses in space were very low.

  17. Absence of inflammatory response from upper airway epithelial cells after X irradiation.

    Science.gov (United States)

    Reiter, R; Deutschle, T; Wiegel, T; Riechelmann, H; Bartkowiak, D

    2009-03-01

    Radiotherapy of head and neck tumors causes adverse reactions in normal tissue, especially mucositis. The dose- and time-dependent response of upper airway cells to X radiation should be analyzed in terms of the pro-inflammatory potential. Immortalized BEAS-2B lung epithelial cells were treated with 2, 5 and 8 Gy. Out of 1232 genes, those that were transcribed differentially after 2, 6 and 24 h were assigned to biological themes according to the Gene Ontology Consortium. Enrichment of differentially regulated gene clusters was determined with GOTree ( http://bioinfo.vanderbilt.edu/gotm ). Eleven cytokines were measured in culture supernatants. The cell cycle response up to 24 h and induction of apoptosis up to 4 days after exposure were determined by flow cytometry. A significant dose- and time-dependent gene activation was observed for the categories response to DNA damage, oxidative stress, cell cycle arrest and cell death/apoptosis but not for immune/inflammatory response. This correlated with functional G(2) arrest and apoptosis. Pro-inflammatory cytokines accumulated in supernatants of control cells but not of X-irradiated cells. The complex gene expression pattern of X-irradiated airway epithelial cells is accompanied by cell cycle arrest and induction of apoptosis. In vivo, this may impair the epithelial barrier. mRNA and protein expression suggest at most an indirect contribution of epithelial cells to early radiogenic mucositis. PMID:19267554

  18. Activated human T cells secrete exosomes that participate in IL-2 mediated immune response signaling.

    Directory of Open Access Journals (Sweden)

    Jessica Wahlgren

    Full Text Available It has previously been shown that nano-meter sized vesicles (30-100 nm, exosomes, secreted by antigen presenting cells can induce T cell responses thus showing the potential of exosomes to be used as immunological tools. Additionally, activated CD3⁺ T cells can secrete exosomes that have the ability to modulate different immunological responses. Here, we investigated what effects exosomes originating from activated CD3⁺ T cells have on resting CD3⁺ T cells by studying T cell proliferation, cytokine production and by performing T cell and exosome phenotype characterization. Human exosomes were generated in vitro following CD3⁺ T cell stimulation with anti-CD28, anti-CD3 and IL-2. Our results show that exosomes purified from stimulated CD3⁺ T cells together with IL-2 were able to generate proliferation in autologous resting CD3⁺ T cells. The CD3⁺ T cells stimulated with exosomes together with IL-2 had a higher proportion of CD8⁺ T cells and had a different cytokine profile compared to controls. These results indicate that activated CD3⁺ T cells communicate with resting autologous T cells via exosomes.

  19. Cell-permeable Tat-NBD peptide attenuates rat pancreatitis and acinus cell inflammation response

    Institute of Scientific and Technical Information of China (English)

    You-Ming Long; Ken Chen; Xue-Jin Liu; Wen-Rui Xie; Hui Wang

    2009-01-01

    AIM: To investigate the effects of Tat-NEMO-binding domain (NBD) peptide on taurocholate-induced pancreatitis and lipopolysaccharide (LPS)-stimulated AR42J acinus cells inflammatory response in rats. METHODS: Sodium taurocholate (5%) was used to induce the pancreatitis model. Forty-eight rats from the taurocholate group aeceuved an intravenous bolus of 13 mg/kg Tat-NBD (wild-type, WT) peptide, Tat-NBD (mutant-type, MT) peptide, NBD peptide or Tat peptide. The pancreatic histopathology was analyzed by hematoxylin staining. LPS was added to the culture medium to stimulate the AR42J cells. For pretreatment, cells were incubated with different peptides for 2 h before LPS stimulation. Expression of IL-1β and TNF-α mRNA was analyzed using a semi-quantitative reverse-transcript polymerase chain reaction (RT-PCR) method. IL-1β and TNF-α protein in culture medium were detected by enzyme linked immunosorbent assay (ELISA). NF-κB DNA-binding in pancreas was examined by electrophoretic mobility shift assays. P65 expression of AR42J was determined by Strept Actividin-Biotin Complex (SABC) method. RESULTS: Pretreatment with Tat-NBD (WT) peptide at a concentration of 13 mg/kg body wt showed beneficial effect in pancreaitis model. LPS (10 mg/L) resulted in an increase of IL-1β mRNA, IL-1β protein, TNF-α mRNA and TNF-α protein, whereas significantly inhibitory effects were observed when cells were incubated with Tat-NBD (WT). Consisting with p65 expression decrease analyzed by SABC method, NF-κB DNA-binding activity significantly decreased in Tat-NBD (WT) pretreatment group, especially at the largest dose. No significant changes were found in the control peptide group. CONCLUSION: Our result supports that active NF-κB participates in the pathogenesis of STC-induced acute pancreatitis in rats. Tat-NBD (WT) peptide has antiinflammatory effects in this model and inhibits the inflammation of acinus simulated by LPS.

  20. The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses.

    Directory of Open Access Journals (Sweden)

    Shaniya H Khan

    2015-10-01

    Full Text Available Memory CD8 T cells provide protection to immune hosts by eliminating pathogen-infected cells during re-infection. While parameters influencing the generation of primary (1° CD8 T cells are well established, the factors controlling the development of secondary (2° CD8 T cell responses remain largely unknown. Here, we address the mechanisms involved in the generation and development of 2° memory (M CD8 T cells. We observed that the time at which 1° M CD8 T cells enter into immune response impacts their fate and differentiation into 2° M CD8 T cells. Late-entry of 1° M CD8 T cells into an immune response (relative to the onset of infection not only facilitated the expression of transcription factors associated with memory formation in 2° effector CD8 T cells, but also influenced the ability of 2° M CD8 T cells to localize within the lymph nodes, produce IL-2, and undergo Ag-driven proliferation. The timing of stimulation of 1° M CD8 T cells also impacted the duration of expression of the high-affinity IL-2 receptor (CD25 on 2° effector CD8 T cells and their sensitivity to IL-2 signaling. Importantly, by blocking or enhancing IL-2 signaling in developing 2° CD8 T cells, we provide direct evidence for the role of IL-2 in controlling the differentiation of Ag-driven 2° CD8 T cell responses. Thus, our data suggest that the process of 1° M to 2° M CD8 T cell differentiation is not fixed and can be manipulated, a notion with relevance for the design of future prime-boost vaccination approaches.

  1. Differential heat shock response of primary human cell cultures and established cell lines

    DEFF Research Database (Denmark)

    Richter, W W; Issinger, O G

    1986-01-01

    degrees C treatment, whereas in immortalized cell lines usually 90% of the cells were found in suspension. Enhanced expression of the major heat shock protein (hsp 70) was found in all heat-treated cells. In contrast to the primary cell cultures, established and transformed cell lines synthesized a...

  2. Dichotomy of the human T cell response to Leishmania antigens. II. Absent or Th2-like response to gp63 and Th1-like response to lipophosphoglycan-associated protein in cells from cured visceral leishmaniasis patients

    DEFF Research Database (Denmark)

    Kurtzhals, J A; Hey, A S; Jardim, A;

    1994-01-01

    The T cell response to different Leishmania donovani antigens was investigated using peripheral blood mononuclear cells (PBMC) from Kenyans cured of visceral leishmaniasis and non-exposed Danes. Crude promastigote and amastigote antigens both induced proliferation and interferon-gamma (IFN......-gamma) production in PBMC from cured patients, while cells from non-exposed donors gave weak responses. A similar pattern was induced by lipophosphoglycan-associated protein (LPGAP). By contrast, the major surface protease of Leishmania, gp63, induced only a weak proliferative response without IFN-gamma production...

  3. Memory and effector T cells modulate subsequently primed immune responses to unrelated antigens

    OpenAIRE

    Tian, Jide D; LU, Y. X.; Hanssen, L.; Dang, H.; Kaufman, D L

    2003-01-01

    Memory and effector T cells modulate subsequently primed T cell responses to the same antigen. However, little is known about the impact of pre-existing memory and effector T cell immunity on subsequently primed immune responses to unrelated antigens. Here, we show that an antigen-primed first wave of Th1 and Th2 immunity enhanced or inhibited the subsequently primed T cell immunity to an unrelated Antigen, depending on whether the second antigen was administered in the same or opposite type ...

  4. Response of Human Prostate Cancer Cells to Mitoxantrone Treatment in Simulated Microgravity Environment

    Science.gov (United States)

    Zhang, Ye; Wu, Honglu

    2012-07-01

    RESPONSE OF HUMAN PROSTATE CANCER CELLS TO MITOXANTRONE TREATMENT IN SIMULATED MICROGRAVITY ENVIRONMENT Ye Zhang1,2, Christopher Edwards3, and Honglu Wu1 1 NASA-Johnson Space Center, Houston, TX 2 Wyle Integrated Science and Engineering Group, Houston, TX 3 Oregon State University, Corvallis, OR This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of an antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to the treatment of drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulations of cells in response to antineoplastic agents, we cultured LNCaP cells in either a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as control, and treated the cells with mitoxantrone. Cell growth, as well as expressions of oxidative stress related genes, were analyzed after the drug treatment. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not present significant differences in cell viability, growth rate, or cell cycle distribution. However, after mitoxantrone treatment, a significant proportion of bioreactor cultured cells became apoptotic or was arrested in G2. Several oxidative stress related genes also showed a higher expression level post mitoxantrone treatment. Our results indicate that simulated microgravity may alter the response of LNCaP cells to mitoxantrone treatment. Understanding the mechanisms by which cells respond to drugs differently in an altered gravity environment will be useful for the improvement of cancer treatment on

  5. Imaging immune response of skin mast cells in vivo with two-photon microscopy

    Science.gov (United States)

    Li, Chunqiang; Pastila, Riikka K.; Lin, Charles P.

    2012-02-01

    Intravital multiphoton microscopy has provided insightful information of the dynamic process of immune cells in vivo. However, the use of exogenous labeling agents limits its applications. There is no method to perform functional imaging of mast cells, a population of innate tissue-resident immune cells. Mast cells are widely recognized as the effector cells in allergy. Recently their roles as immunoregulatory cells in certain innate and adaptive immune responses are being actively investigated. Here we report in vivo mouse skin mast cells imaging with two-photon microscopy using endogenous tryptophan as the fluorophore. We studied the following processes. 1) Mast cells degranulation, the first step in the mast cell activation process in which the granules are released into peripheral tissue to trigger downstream reactions. 2) Mast cell reconstitution, a procedure commonly used to study mast cells functioning by comparing the data from wild type mice, mast cell-deficient mice, and mast-cell deficient mice reconstituted with bone marrow-derived mast cells (BMMCs). Imaging the BMMCs engraftment in tissue reveals the mast cells development and the efficiency of BMMCs reconstitution. We observed the reconstitution process for 6 weeks in the ear skin of mast cell-deficient Kit wsh/ w-sh mice by two-photon imaging. Our finding is the first instance of imaging mast cells in vivo with endogenous contrast.

  6. Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission

    DEFF Research Database (Denmark)

    Alenius, Malin; Hammarlund-Udenaes, Margareta; Honoré, Per Gustaf Hartvig;

    2009-01-01

    BACKGROUND: Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms; underestimat......BACKGROUND: Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms......; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. METHOD: A naturalistic......, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment...

  7. CD4(+ cells regulate fibrosis and lymphangiogenesis in response to lymphatic fluid stasis.

    Directory of Open Access Journals (Sweden)

    Jamie C Zampell

    Full Text Available INTRODUCTION: Lymphedema is a chronic disorder that occurs commonly after lymph node removal for cancer treatment and is characterized by swelling, fibrosis, inflammation, and adipose deposition. Although previous histological studies have investigated inflammatory changes that occur in lymphedema, the precise cellular make up of the inflammatory infiltrate remains unknown. It is also unclear if this inflammatory response plays a causal role in the pathology of lymphedema. The purpose of this study was therefore to characterize the inflammatory response to lymphatic stasis and determine if these responses are necessary for the pathological changes that occur in lymphedema. METHODS: We used mouse-tail lymphedema and axillary lymph node dissection (ANLD models in order to study tissue inflammatory changes. Single cell suspensions were created and analyzed using multi-color flow cytometry to identify individual cell types. We utilized antibody depletion techniques to analyze the causal role of CD4+, CD8+, and CD25+ cells in the regulation of inflammation, fibrosis, adipose deposition, and lymphangiogenesis. RESULTS: Lymphedema in the mouse-tail resulted in a mixed inflammatory cell response with significant increases in T-helper, T-regulatory, neutrophils, macrophages, and dendritic cell populations. Interestingly, we found that ALND resulted in significant increases in T-helper cells suggesting that these adaptive immune responses precede changes in macrophage and dendritic cell infiltration. In support of this we found that depletion of CD4+, but not CD8 or CD25+ cells, significantly decreased tail lymphedema, inflammation, fibrosis, and adipose deposition. In addition, depletion of CD4+ cells significantly increased lymphangiogenesis both in our tail model and also in an inflammatory lymphangiogenesis model. CONCLUSIONS: Lymphedema and lymphatic stasis result in CD4+ cell inflammation and infiltration of mature T-helper cells. Loss of CD4+ but

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

    International Nuclear Information System (INIS)

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

  9. Nitric Oxide Modulates the Temporal Properties of the Glutamate Response in Type 4 OFF Bipolar Cells

    Science.gov (United States)

    Vielma, Alex H.; Agurto, Adolfo; Valdés, Joaquín; Palacios, Adrián G.; Schmachtenberg, Oliver

    2014-01-01

    Nitric oxide (NO) is involved in retinal signal processing, but its cellular actions are only partly understood. An established source of retinal NO are NOACs, a group of nNOS-expressing amacrine cells which signal onto bipolar, other amacrine and ganglion cells in the inner plexiform layer. Here, we report that NO regulates glutamate responses in morphologically and electrophysiologically identified type 4 OFF cone bipolar cells through activation of the soluble guanylyl cyclase-cGMP-PKG pathway. The glutamate response of these cells consists of two components, a fast phasic current sensitive to kainate receptor agonists, and a secondary component with slow kinetics, inhibited by AMPA receptor antagonists. NO shortened the duration of the AMPA receptor-dependent component of the glutamate response, while the kainate receptor-dependent component remained unchanged. Application of 8-Br-cGMP mimicked this effect, while inhibition of soluble guanylate cyclase or protein kinase G prevented it, supporting a mechanism involving a cGMP signaling pathway. Notably, perfusion with a NOS-inhibitor prolonged the duration of the glutamate response, while the NO precursor L-arginine shortened it, in agreement with a modulation by endogenous NO. Furthermore, NO accelerated the response recovery during repeated stimulation of type 4 cone bipolar cells, suggesting that the temporal response properties of this OFF bipolar cell type are regulated by NO. These results reveal a novel cellular mechanism of NO signaling in the retina, and represent the first functional evidence of NO modulating OFF cone bipolar cells. PMID:25463389

  10. Exploring opportunities to project a "responsible man" image: gatekeepers views of young men's sexual and reproductive health needs in Uttaranchal, India.

    Science.gov (United States)

    Khan, M E; Mishra, Anurag; Morankar, Sudhakar

    Increase in extramarital sex among youths, gender-based violence, lack of contraceptive knowledge among newly married couples and lack of knowledge of protection against diseases like STIs/HIV are the information and service needs of young people that need to be addressed urgently in order to make them future knowledgeable, responsible, and non-violent partners. In addressing these needs the gatekeepers, including parents, formal and informal community leaders and teachers, play a critical role, by facilitating/hindering access to appropriate and correct information about sexual and reproductive health to young people. The study was conducted in a district of Uttaranchal, India. The specific objective was to understand the social context and gatekeepers' views on family planning and sexual and reproductive health needs of young men. Thirty-two in-depth interviews and four focus group discussions were conducted with parents, formal and informal community leaders, teachers, and selected development officials. The findings indicate that gatekeepers are worried about rapid changes in the aspiration, expectation, and behavior of young men. Most of them were seriously concerned about the increasing drinking habit, use of drugs, and changing values of sexuality leading to various risk behaviors among young men. They felt that many of these changes are consequences of wider societal changes, rising aspirations, explosion of electronic media, and globalization of a new youth culture where extramarital sex, alcohol consumption, and violence are expressions of different facets of masculinity and symbols of the affluent class. Overall, there was a feeling that TV/films and their peers now influence more the socialization of young people and parents are losing control in guidance and mentoring of their children. PMID:18644762

  11. Longitudinal Numbers-Needed-To-Treat (NNT for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Wang Hongwei

    2011-07-01

    Full Text Available Abstract Background Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI score improvement and the associated NNTs. Methods This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387 comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation. Results For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks. Conclusions For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30% improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients

  12. NADPH Oxidase-Derived Superoxide Provides a Third Signal for CD4 T Cell Effector Responses.

    Science.gov (United States)

    Padgett, Lindsey E; Tse, Hubert M

    2016-09-01

    Originally recognized for their direct induced toxicity as a component of the innate immune response, reactive oxygen species (ROS) can profoundly modulate T cell adaptive immune responses. Efficient T cell activation requires: signal 1, consisting of an antigenic peptide-MHC complex binding with the TCR; signal 2, the interaction of costimulatory molecules on T cells and APCs; and signal 3, the generation of innate immune-derived ROS and proinflammatory cytokines. This third signal, in particular, has proven essential in generating productive and long-lasting immune responses. Our laboratory previously demonstrated profound Ag-specific hyporesponsiveness in the absence of NADPH oxidase-derived superoxide. To further examine the consequences of ROS deficiency on Ag-specific T cell responses, our laboratory generated the OT-II.Ncf1(m1J) mouse, possessing superoxide-deficient T cells recognizing the nominal Ag OVA323-339 In this study, we demonstrate that OT-II.Ncf1(m1J) CD4 T cells displayed a severe reduction in Th1 T cell responses, in addition to blunted IL-12R expression and severely attenuated proinflammatory chemokine ligands. Conversely, IFN-γ synthesis and IL-12R synthesis were rescued by the addition of exogenous superoxide via the paramagnetic superoxide donor potassium dioxide or superoxide-sufficient dendritic cells. Ultimately, these data highlight the importance of NADPH oxidase-derived ROS in providing a third signal for adaptive immune maturation by modulating the IL-12/IL-12R pathway and the novelty of the OT-II.Ncf1(m1J) mouse model to determine the role of redox-dependent signaling on effector responses. Thus, targeting ROS represents a promising therapeutic strategy in dampening Ag-specific T cell responses and T cell-mediated autoimmune diseases, such as type 1 diabetes. PMID:27474077

  13. The role of immunocompetent cells in the murine pulmonary granulomatous response induced by BCG

    International Nuclear Information System (INIS)

    The role of lymphocytes and macrophages in the BCG induced pulmonary granulomatous response in mice was studied. Pulmonary granulomas could be induced in mice by the intravenous injection of BCG suspended in light mineral oil. The granuloma formation with mononuclear cell infiltration reached a maximum after 3 weeks of injection (Chronic Granulomatous Response=CGR). An Accelerated Granulomatous Response (AGR) was elicited in sensitized mice (those undergoing the CGR) by an i.v. challenge with BCG suspended in saline and a maximum AGR developed within 4 days. The proliferative response of lymphocytes which were obtained from the lung was measured by 3H-Thymidine incorporation into DNA. In the case of CGR, the proliferative response stimulated by phytohemagglutinin (PHA) scarcely changed over 1 to 4 weeks of the response. In contrast, in the case of AGR, the proliferative responses stimulated by PHA rose to 10 times higher those of CGR at the point of maximum granuloma formation. These results suggested that the sensitized lymphocytes, challenged by the antigen, released some mediators related to mitogenic factors, chemotactic factors, and migration inhibitory factors, which might accelerate and enhancement of migration of T- and B-cells toward the granulomatous lesion. The pulmonary granulomatous response which was supressed by x-irradiation, was restored by intraperitoneal transplantation of syngeneic spleen cells, and thymus cells, but was only slightly affected by peritoneal exudate cells. Consequently it was suggested that lymphocytes played an important role in BCG-induced granuloma formation in mice. (auth.)

  14. X-ray-induced bystander response reduce spontaneous mutations in V79 cells

    International Nuclear Information System (INIS)

    The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm2 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10-5 (background level), and the frequency decreased to 5.3 × 10-6 with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations. (author)

  15. CD1d expression and invariant NKT cell responses in herpesvirus infections

    Directory of Open Access Journals (Sweden)

    Rusung eTan

    2015-06-01

    Full Text Available Invariant natural killer T (iNKT cells are a highly conserved subset of unconventional T lymphocytes that express a canonical, semi-invariant T cell receptor (TCR and surface markers shared with the natural killer cell lineage. iNKT cells recognize exogenous and endogenous glycolipid antigens restricted by non-polymorphic CD1d molecules, and are highly responsive to the prototypical agonist, α-galactosylceramide. Upon activation, iNKT cells rapidly coordinate signaling between innate and adaptive immune cells through the secretion of proinflammatory cytokines, leading to the maturation of antigen-presenting cells and expansion of antigen-specific CD4+ and CD8+ T cells. Because of their potent immunoregulatory properties, iNKT cells have been extensively studied and are known to play a pivotal role in mediating immune responses against microbial pathogens including viruses. Here, we review evidence that herpesviruses manipulate CD1d expression to escape iNKT cell surveillance and establish lifelong latency in humans. Collectively, published findings suggest that iNKT cells play critical roles in anti-herpesvirus immune responses and could be harnessed therapeutically to limit viral infection and viral-associated disease.

  16. Human CD4+CD25+ regulatory T cells are sensitive to low dose cyclophosphamide: implications for the immune response.

    Directory of Open Access Journals (Sweden)

    Daniel Heylmann

    Full Text Available Regulatory T cells (Treg play a pivotal role in the immune system since they inhibit the T cell response. It is well known that cyclophosphamide applied at low dose is able to stimulate the immune response while high dose cyclophosphamide exerts inhibitory activity. Data obtained in mice indicate that cyclophosphamide provokes a reduction in the number of Treg and impairs their suppressive activity, resulting in immune stimulation. Here, we addressed the question of the sensitivity of human Treg to cyclophosphamide, comparing Treg with cytotoxic T cells (CTL and T helper cells (Th. We show that Treg are more sensitive than CTL and Th to mafosfamide, which is an active derivative of cyclophosphamide, which does not need metabolic activation. The high sensitivity of Treg was due to the induction of apoptosis. Treg compared to CTL and Th were not more sensitive to the alkylating drugs temozolomide and nimustine and also not to mitomycin C, indicating a specific Treg response to mafosfamide. The high sensitivity of Treg to mafosfamide resulted not only in enhanced cell death, but also in impaired Treg function as demonstrated by a decline in the suppressor activity of Treg in a co-culture model with Th and Helios positive Treg. Treatment of Treg with mafosfamide gave rise to a high level of DNA crosslinks, which were not repaired to the same extent as observed in Th and CTL. Also, Treg showed a low level of γH2AX foci up to 6 h and a high level 24 h after treatment, indicating alterations in the DNA damage response. Overall, this is the first demonstration that human Treg are, in comparison with Th and CTL, hypersensitive to cyclophosphamide, which is presumably due to a DNA repair defect.

  17. Radiation response of floating gate EEPROM memory cells

    International Nuclear Information System (INIS)

    The effect of radiation on a floating gate EEPROM nonvolatile memory cell is determined experimentally and modeled analytically. The new model predicts the threshold voltage change resulting from radiation. A screen based on the initial 1 state (excess electron) threshold voltage is shown to be necessary to assure data retention during irradiation. Techniques to increase radiation hardness are also described. The hardness of floating gate cells is shown to be limited to less than 100 krad(Si) for a fixed reference sense amplifier. The use of a differential sense amplifier may increase this limit. Therefore, floating gate memories should be useful for those applications requiring low total-doses

  18. HLA-DP specific responses in allogeneic stem cell transplantation

    OpenAIRE

    Rutten, Caroline Elisabeth

    2013-01-01

    Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, whereas a significant decreased risk of disease relapse was still observed. In this thesis we showed that HLA-DPB1 mismatched allo-SCT followed by donor lymp...

  19. Hepatic Stellate Cells Regulate Immune Response via Induction of Myeloid Suppressor Cells

    OpenAIRE

    Chou, Hong-Shiue; Hsieh, Ching-Chuan; Yang, Horng-Ren; Wang, Lianfu; Arakawa, Yusuke; Brown, Kathleen; Wu, Qingyu; Lin, Feng; Peters, Marion; Fung, John J.; Lu, Lina; Qian, Shiguang

    2011-01-01

    Although organ transplants have been applied for decades, outcomes of somatic cell transplants remain disappointing, presumably due to lack of appropriate supporting stromal cells. Thus, cotransplantation with liver stromal cells, hepatic stellate cells (HSC), achieves long-term survival of islet allografts in mice via induction of effector T cell apoptosis and generation of regulatory T (Treg) cells. In this study, we provide evidence both in vitro and in vivo that HSC can promote generation...

  20. Timescale of silver nanoparticle transformation in neural cell cultures impacts measured cell response

    Energy Technology Data Exchange (ETDEWEB)

    Hume, Stephanie L.; Chiaramonti, Ann N.; Rice, Katherine P.; Schwindt, Rani K. [National Institute of Standards and Technology (NIST), Applied Chemicals and Materials Division (United States); MacCuspie, Robert I. [National Institute of Standards and Technology (NIST), Materials Measurement Science Division (United States); Jeerage, Kavita M., E-mail: jeerage@boulder.nist.gov [National Institute of Standards and Technology (NIST), Applied Chemicals and Materials Division (United States)

    2015-07-15

    Both serum protein concentration and ionic strength are important factors in nanoparticle transformation within cell culture environments. However, silver nanoparticles are not routinely tracked at their working concentration in the specific medium used for in vitro toxicology studies. Here we evaluated the transformation of electrostatically stabilized citrate nanoparticles (C-AgNPs) and sterically stabilized polyvinylpyrrolidone nanoparticles (PVP-AgNPs) in a low-serum (∼ 0.2 mg/mL bovine serum albumin) culture medium, while measuring the response of rat cortex neural progenitor cells, which differentiate in this culture environment. After 24 h, silver nanoparticles at concentrations up to 10 µg/mL did not affect adenosine triphosphate levels, whereas silver ions decreased adenosine triphosphate levels at concentrations of 1.1 µg/mL or higher. After 240 h, both silver nanoparticles, as well as silver ion, unambiguously decreased adenosine triphosphate levels at concentrations of 1 and 1.1 µg/mL, respectively, suggesting particle dissolution. Particle transformation was investigated in 1:10 diluted, 1:2 diluted, or undiluted differentiation medium, all having an identical protein concentration, to separate the effect of serum protein stabilization from ionic strength destabilization. Transmission electron microscopy images indicated that particles in 1:10 medium were not surrounded by proteins, whereas particles became clustered within a non-crystalline protein matrix after 24 h in 1:2 medium and at 0 h in undiluted medium. Despite evidence for a protein corona, particles were rapidly destabilized by high ionic strength media. Polyvinylpyrrolidone increased the stability of singly dispersed particles compared to citrate ligands; however, differences were negligible after 4 h in 1:2 medium or after 1 h in undiluted medium. Thus low-serum culture environments do not provide sufficient colloidal stability for long-term toxicology studies with citrate

  1. Timescale of silver nanoparticle transformation in neural cell cultures impacts measured cell response

    International Nuclear Information System (INIS)

    Both serum protein concentration and ionic strength are important factors in nanoparticle transformation within cell culture environments. However, silver nanoparticles are not routinely tracked at their working concentration in the specific medium used for in vitro toxicology studies. Here we evaluated the transformation of electrostatically stabilized citrate nanoparticles (C-AgNPs) and sterically stabilized polyvinylpyrrolidone nanoparticles (PVP-AgNPs) in a low-serum (∼ 0.2 mg/mL bovine serum albumin) culture medium, while measuring the response of rat cortex neural progenitor cells, which differentiate in this culture environment. After 24 h, silver nanoparticles at concentrations up to 10 µg/mL did not affect adenosine triphosphate levels, whereas silver ions decreased adenosine triphosphate levels at concentrations of 1.1 µg/mL or higher. After 240 h, both silver nanoparticles, as well as silver ion, unambiguously decreased adenosine triphosphate levels at concentrations of 1 and 1.1 µg/mL, respectively, suggesting particle dissolution. Particle transformation was investigated in 1:10 diluted, 1:2 diluted, or undiluted differentiation medium, all having an identical protein concentration, to separate the effect of serum protein stabilization from ionic strength destabilization. Transmission electron microscopy images indicated that particles in 1:10 medium were not surrounded by proteins, whereas particles became clustered within a non-crystalline protein matrix after 24 h in 1:2 medium and at 0 h in undiluted medium. Despite evidence for a protein corona, particles were rapidly destabilized by high ionic strength media. Polyvinylpyrrolidone increased the stability of singly dispersed particles compared to citrate ligands; however, differences were negligible after 4 h in 1:2 medium or after 1 h in undiluted medium. Thus low-serum culture environments do not provide sufficient colloidal stability for long-term toxicology studies with citrate

  2. Plasticity of gamma delta T cells: impact on the anti-tumor response

    Directory of Open Access Journals (Sweden)

    Virginie eLafont

    2014-12-01

    Full Text Available The tumor immune microenvironment contributes to tumor initiation, progression and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of gamma and delta chains (gamma delta T cells are of particular interest. gamma delta T cells can contribute to the immune response against many tumor types (lymphoma, myeloma, melanoma, breast, colon, lung, ovary and prostate cancer directly through their cytotoxic activity and indirectly by stimulating or regulating the biological functions of other cell types required for the initiation and establishment of the anti-tumor immune response, such as dendritic cells and cytotoxic CD8+ T cells. However, the notion that tumor-infiltrating gamma delta T cells are a good prognostic marker in cancer was recently challenged by studies showing that the presence of these cells in the tumor microenvironment was associated with poor prognosis in both breast and colon cancer. These findings suggest that gamma delta T cells may also display pro-tumor activities. Indeed, breast tumor-infiltrating gamma deltaT cells could exert an immunosuppressive activity by negatively regulating DC maturation. Furthermore, recent studies demonstrated that signals from the microenvironment, particularly cytokines, can confer some plasticity to gamma delta T cells and promote their differentiation into gamma delta T cells with regulatory functions. This review focuses on the current knowledge on the functional plasticity of gamma delta T cells and its effect on their anti-tumor activities. It also discusses the putative mechanisms underlying gamma delta T cell expansion, differentiation and recruitment in the tumor microenvironment.

  3. Differential effect of conditioning regimens on cytokine responses during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Andersen, J; Heilmann, C; Jacobsen, N;

    2006-01-01

    The purpose of this study was to characterize cytokine responses during conditioning in patients undergoing allogeneic stem cell transplantation (SCT) with the aim to identify which markers that may reliably reflect inflammatory activity during conditioning. We investigated inflammatory and anti...

  4. Lipid tethering of breast tumor cells enables real-time imaging of free-floating cell dynamics and drug response.

    Science.gov (United States)

    Chakrabarti, Kristi R; Andorko, James I; Whipple, Rebecca A; Zhang, Peipei; Sooklal, Elisabeth L; Martin, Stuart S; Jewell, Christopher M

    2016-03-01

    Free-floating tumor cells located in the blood of cancer patients, known as circulating tumor cells (CTCs), have become key targets for studying metastasis. However, effective strategies to study the free-floating behavior of tumor cells in vitro have been a major barrier limiting the understanding of the functional properties of CTCs. Upon extracellular-matrix (ECM) detachment, breast tumor cells form tubulin-based protrusions known as microtentacles (McTNs) that play a role in the aggregation and re-attachment of tumor cells to increase their metastatic efficiency. In this study, we have designed a strategy to spatially immobilize ECM-detached tumor cells while maintaining their free-floating character. We use polyelectrolyte multilayers deposited on microfluidic substrates to prevent tumor cell adhesion and the addition of lipid moieties to tether tumor cells to these surfaces through interactions with the cell membranes. This coating remains optically clear, allowing capture of high-resolution images and videos of McTNs on viable free-floating cells. In addition, we show that tethering allows for the real-time analysis of McTN dynamics on individual tumor cells and in response to tubulin-targeting drugs. The ability to image detached tumor cells can vastly enhance our understanding of CTCs under conditions that better recapitulate the microenvironments they encounter during metastasis. PMID:26871289

  5. Lipid tethering of breast tumor cells enables real-time imaging of free-floating cell dynamics and drug response

    Science.gov (United States)

    Whipple, Rebecca A.; Zhang, Peipei; Sooklal, Elisabeth L.; Martin, Stuart S.; Jewell, Christopher M.

    2016-01-01

    Free-floating tumor cells located in the blood of cancer patients, known as circulating tumor cells (CTCs), have become key targets for studying metastasis. However, effective strategies to study the free-floating behavior of tumor cells in vitro have been a major barrier limiting the understanding of the functional properties of CTCs. Upon extracellular-matrix (ECM) detachment, breast tumor cells form tubulin-based protrusions known as microtentacles (McTNs) that play a role in the aggregation and re-attachment of tumor cells to increase their metastatic efficiency. In this study, we have designed a strategy to spatially immobilize ECM-detached tumor cells while maintaining their free-floating character. We use polyelectrolyte multilayers deposited on microfluidic substrates to prevent tumor cell adhesion and the addition of lipid moieties to tether tumor cells to these surfaces through interactions with the cell membranes. This coating remains optically clear, allowing capture of high-resolution images and videos of McTNs on viable free-floating cells. In addition, we show that tethering allows for the real-time analysis of McTN dynamics on individual tumor cells and in response to tubulin-targeting drugs. The ability to image detached tumor cells can vastly enhance our understanding of CTCs under conditions that better recapitulate the microenvironments they encounter during metastasis. PMID:26871289

  6. Dendritic Cell-Derived Exosomes Stimulate Stronger CD8+ CTL Responses and Antitumor Immunity than Tumor Cell-Derived Exosomes

    Institute of Scientific and Technical Information of China (English)

    Siguo Hao; Ou Bai; Jinying Yuan; Mabood Qureshi; Jim Xiang

    2006-01-01

    Exosomes (EXO) derived from dendritic cells (DC) and tumor cells have been used to stimulate antitumor immune responses in animal models and in clinical trials. However, there has been no side-by-side comparison of the stimulatory efficiency of the antitumor immune responses induced by these two commonly used EXO vaccines. In this study, we selected to study the phenotype characteristics of EXO derived from a transfected EG7 tumor cells expressing ovalbumin (OVA) and OVA-pulsed DC by flow cytometry. We compared the stimulatory effect in induction of OVA-specific immune responses between these two types of EXO. We found that OVA protein-pulsed DCovA-derived EXO (EXODC) can more efficiently stimulate naive OVA-specific CD8+ T cell proliferation and differentiation into cytotoxic T lymphocytes in vivo, and induce more efficient antitumor immunity than EG7 tumor cell-derived EXO (EXOEG7). In addition, we elucidated the important role of the host DC in EXO vaccines that the stimulatory effect of EXO is delivered to T cell responses by the host DC. Therefore, DC-derived EXO may represent a more effective EXO-based vaccine in induction of antitumor immunity.

  7. T follicular helper (Tfh ) cells in normal immune responses and in allergic disorders.

    Science.gov (United States)

    Varricchi, G; Harker, J; Borriello, F; Marone, G; Durham, S R; Shamji, M H

    2016-08-01

    Follicular helper T cells (Tfh ) are located within germinal centers of lymph nodes. Cognate interaction between Tfh , B cells, and IL-21 drives B cells to proliferate and differentiate into plasma cells thereby leading to antibody production. Tfh cells and IL-21 are involved in infectious and autoimmune diseases, immunodeficiencies, vaccination, and cancer. Human peripheral blood CXCR5(+) CD4(+) T cells comprise different subsets of Tfh -like cells. Despite the importance of the IgE response in the pathogenesis of allergic disorders, little is known about the role of follicular and blood Tfh cells and IL-21 in human and experimental allergic disease. Here, we review recent advances regarding the phenotypic and functional characteristics of both follicular and blood Tfh cells and of the IL-21/IL-21R system in the context of allergic disorders. PMID:26970097

  8. SV40 large T antigen-specific human T cell memory responses.

    Science.gov (United States)

    Coleman, Sharon; Gibbs, Allen; Butchart, Eric; Mason, Malcolm D; Jasani, Bharat; Tabi, Zsuzsanna

    2008-08-01

    The continued presence of simian virus 40 (SV40), a monkey polyomavirus, in man is confirmed by the regular detection of SV40-specific antibodies in 5-10% of children who are unlikely to have received contaminated polio-vaccines. The aim of our experiments was to find cellular immunological evidence of SV40 infection in humans by testing memory T cell responses to SV40 large T antigen (Tag). As there is some indication that the virus may be present in malignant pleural mesothelioma (MPM) cells, we analyzed T cell responses in MPM patients and in healthy donors. The frequencies of responding T cells to overlapping Tag peptides were tested by cytokine flow cytometry. CD8+ T cells from 4 of 32 MPM patients responded (above twofold of control) to SV40 Tag peptides, while no positive responses were detected in 12 healthy donors. Within SV40 Tag we identified three 15 amino acid-long immunogenic sequences and one 9 amino acid-long T cell epitope (p138) (138FPSELLSFL146), the latter including a HLA-B7-restriction motif. T cell responses to p138 were SV40-specific as T cells stimulated with p138 did not cross-react with the corresponding sequences of Tag of human polyomaviruses BKV and JCV. Similarly, the relevant BKV and JCV Tag peptides did not generate T cell responses against SV40 TAg p138. Peptide-stimulated T cells also killed SV40 Tag-transfected target cells. This article demonstrates the presence, and provides a detailed analysis, of SV40-specific T cell memory in man. PMID:18551603

  9. Direct contact between dendritic cells and bronchial epithelial cells inhibits T cell recall responses towards mite and pollen allergen extracts in vitro

    DEFF Research Database (Denmark)

    Papazian, Dick; Wagtmann, Valery R; Hansen, Soren;

    2015-01-01

    (DCs), we have investigated recall T cell responses in allergic patients sensitized to house dust mite, grass, and birch pollen. Conclusions: Using allergen extract-loaded DCs to stimulate autologous allergen-specific T cell lines, we show that AEC-imprinted DCs inhibit T cell proliferation...... cell recall responses towards Bet v 1, Phl p 5 and Der p 1 in vitro, suggesting that AECs-DC contact in vivo constitute a key element in mucosal homeostasis. This article is protected by copyright. All rights reserved....

  10. Type I Alveolar Epithelial Cells Mount Innate Immune Responses during Pneumococcal Pneumonia

    OpenAIRE

    Yamamoto, Kazuko; Ferrari, Joseph D.; Cao, Yuxia; Ramirez, Maria I.; Jones, Matthew R.; Quinton, Lee J.; Mizgerd, Joseph P.

    2012-01-01

    Pneumonia results from bacteria in the alveoli. The alveolar epithelium consists of type II cells, which secrete surfactant and associated proteins, and type I cells, which constitute 95% of the surface area and met anatomic and structural needs. Other than constitutively expressed surfactant proteins, it is unknown whether alveolar epithelial cells have distinct roles in innate immunity. Since innate immunity gene induction depends on NF-κB RelA (also known as p65) during pneumonia, we gener...

  11. Magnetically responsive yeast cells: methods of preparation and applications

    Czech Academy of Sciences Publication Activity Database

    Šafařík, Ivo; Maděrová, Zdeňka; Pospišková, K.; Horská, Kateřina; Šafaříková, Miroslava

    2015-01-01

    Roč. 32, č. 1 (2015), s. 227-237. ISSN 0749-503X R&D Projects: GA MŠk(CZ) LD13023; GA MŠk(CZ) LD13021 Institutional support: RVO:67179843 Keywords : yeast cells * Saccharomyces * Kluyveromyces * Rhodotorula * Yarrowia * magnetic modification Subject RIV: EH - Ecology, Behaviour Impact factor: 1.634, year: 2014

  12. Molecular determinants of treatment response in human germ cell tumors

    NARCIS (Netherlands)

    F. Mayer; J.A. Stoop (Hans); G.L. Scheffer (George); R. Scheper; J.W. Oosterhuis (Wolter); L.H.J. Looijenga (Leendert); C. Bokemeyer

    2003-01-01

    textabstractPURPOSE: Germ cell tumors (GCTs) are highly sensitive to cisplatin-based chemotherapy. This feature is unexplained, as is the intrinsic chemotherapy resistance of mature teratomas and the resistant phenotype of a minority of refractory GCTs. Various cellular pathways ma

  13. Radiation-responsive transcriptome analysis in human lymphoid cells

    International Nuclear Information System (INIS)

    Ionising radiation (IR) causes DNA (deoxyribonucleic acid) injury and activates intracellular signal pathways including the regulation of DNA repair and cell cycle. However, the further knowledge of molecular events involved in radiation exposure is essential to more comprehensively understand the effects of irradiation. Therefore, the gene expressions of mRNA (messenger ribonucleic acid) by X-ray irradiation in human B lymphoblasts cell line (IM-9) using a microarray were investigated. The mRNA expressions of 65 genes were shown to be up-regulated at >2.0-fold in irradiated cells (4 Gy) when compared with non-irradiated cells (0 Gy) by microarray analysis. Among 65 genes, a large number of genes were up-regulated with an X-ray dose-dependent change. These results indicate that the up-regulation of their mRNAs is the effects of irradiation and may be due to biological dosimetric markers for the evaluation of radiation exposure in the future. (authors)

  14. Accurate Battery Performance Modelling: The Key to Accessing a Truly Responsive Modular Small-Cell Concept

    OpenAIRE

    Pearson, Chris; Russel, Nick; Thwaite, Carl

    2005-01-01

    The AEA Technology (AEA) Small Cell concept allows an infinite range of battery sizes to be built up using the minimum amount of re-qualification. Furthermore, an extensive rolling stock of cells is held at AEA to ensure that future demand can be met without the need for programme delays due to cell manufacture lead-time. Batteries can be composed of modular blocks so that energy storage systems can be built up from common building bricks. This eliminates the need for qualification and minimi...

  15. Enhancement of T cell responses as a result of synergy between lower doses of radiation and T cell stimulation.

    Science.gov (United States)

    Spary, Lisa K; Al-Taei, Saly; Salimu, Josephine; Cook, Alexander D; Ager, Ann; Watson, H Angharad; Clayton, Aled; Staffurth, John; Mason, Malcolm D; Tabi, Zsuzsanna

    2014-04-01

    As a side effect of cancer radiotherapy, immune cells receive varying doses of radiation. Whereas high doses of radiation (>10 Gy) can lead to lymphopenia, lower radiation doses (2-4 Gy) represent a valid treatment option in some hematological cancers, triggering clinically relevant immunological changes. Based on our earlier observations, we hypothesized that lower radiation doses have a direct positive effect on T cells. In this study, we show that 0.6-2.4 Gy radiation enhances proliferation and IFN-γ production of PBMC or purified T cells induced by stimulation via the TCR. Radiation with 1.2 Gy also lowered T cell activation threshold and broadened the Th1 cytokine profile. Although radiation alone did not activate T cells, when followed by TCR stimulation, ERK1/2 and Akt phosphorylation increased above that induced by stimulation alone. These changes were followed by an early increase in glucose uptake. Naive (CD45RA(+)) or memory (CD45RA(-)) T cell responses to stimulation were boosted at similar rates by radiation. Whereas increased Ag-specific cytotoxic activity of a CD8(+) T cell line manifested in a 4-h assay (10-20% increase), highly significant (5- to 10-fold) differences in cytokine production were detected in 6-d Ag-stimulation assays of PBMC, probably as a net outcome of death of nonstimulated and enhanced response of Ag-stimulated T cells. T cells from patients receiving pelvic radiation (2.2-2.75 Gy) also displayed increased cytokine production when stimulated in vitro. We report in this study enhanced