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Sample records for antibodies promote initiation

  1. EXPERIENCES WITH IDEA PROMOTING INITIATIVES

    DEFF Research Database (Denmark)

    Gish, Liv

    2011-01-01

    In new product development a central activity is to provide new ideas. Over the last decades experiences with stimulating employee creativity and establishing idea promoting initiatives have been made in industrial practice. Such initiatives are often labeled Idea Management – a research field...... with a growing interest. In this paper I examine three different idea promoting initiatives carried out in Grundfos, a leading pump manufacturer. In the analysis I address what understandings of idea work are inscribed in the initiatives and what role these initiatives play in the organization with respect...... understandings of idea work are inscribed in the idea promoting initiatives as they to some degree have to fit with the understandings embedded in practice in order to work....

  2. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection.

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    Rami Sommerstein

    2015-11-01

    Full Text Available Arenaviruses such as Lassa virus (LASV can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein's globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy.

  3. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection.

    Science.gov (United States)

    Sommerstein, Rami; Flatz, Lukas; Remy, Melissa M; Malinge, Pauline; Magistrelli, Giovanni; Fischer, Nicolas; Sahin, Mehmet; Bergthaler, Andreas; Igonet, Sebastien; Ter Meulen, Jan; Rigo, Dorothée; Meda, Paolo; Rabah, Nadia; Coutard, Bruno; Bowden, Thomas A; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D

    2015-11-01

    Arenaviruses such as Lassa virus (LASV) can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein's globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy.

  4. Policy initiatives to promote healthy aging.

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    Infeld, Donna Lind; Whitelaw, Nancy

    2002-08-01

    An overwhelming array of policies and programs can be used to help older people (and future older people) maintain healthy lifestyles. How can clinicians help ensure that their patients take advantage of these opportunities? How can these broad-scope policies, educational and information initiatives, and direct service programs be turned into tools to help older people maximize health and independence? First, physicians do not need to do it all themselves. They need to know where to send their patients. For example, case managers in local aging service organizations and social workers, nurses, and discharge planners in hospitals can help connect elderly patients to appropriate benefits and services. Physicians play a critical role in creating a bridge between patients and the array of programs and information that can help them change their individual patterns of behavior. A serious lack of integration exists between what is known about healthy behaviors and lifestyles and what is really happening and available to older people today. From the earlier articles in this issue we know that much can be done to prevent many types of age-related disease and disability. This article provides examples of mechanisms that can be used to broadly disseminate knowledge about effective behavior and treatment changes and create mechanisms to turn this knowledge into real and widespread client-level, practice-level, health system, and community-wide interventions. Second, physicians need to understand that they are not merely subject to these policies and initiatives. They can help formulate and shape them. This political involvement includes active participation in policy initiatives of professional associations, involvement in research and demonstration activities, keeping informed about policy proposals at the federal and state levels, and helping advance ideas for improving health behaviors by speaking up and working toward change. These changes go beyond health initiatives to

  5. Interventions for promoting the initiation of breastfeeding

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    Lisa Dyson

    Full Text Available BACKGROUND: Despite the widely documented health advantages of breastfeeding over formula feeding, initiation rates remain relatively low in many high-income countries, particularly among women in lower income groups. OBJECTIVE : To evaluate the effectiveness of interventions which aim to encourage women to breastfeed in terms of changes in the number of women who start to breastfeed. METHODS : Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2007, handsearched the Journal of Human Lactation, Health Promotion International and Health Education Quarterly from inception to 15 August 2007, and scanned reference lists of all articles obtained. Selection criteria: Randomized controlled trials, with or without blinding, of any breastfeeding promotion intervention in any population group except women and infants with a specific health problem. Data collection and analysis: One review author independently extracted data and assessed trial quality, checked by a second author. We contacted investigators to obtain missing information. MAIN RESULTS: Main results: Eleven trials were included. Statistical analyses were conducted on data from eight trials (1553 women. Five studies (582 women on low incomes in the USA with typically low breastfeeding rates showed breastfeeding education had a significant effect on increasing initiation rates compared to standard care (risk ratio (RR 1.57, 95% confidence interval (CI 1.15 to 2.15, P = 0.005. Subgroup analyses showed that one-to-one, needs-based, informal repeat education sessions and generic, formal antenatal education sessions are effective in terms of an increase in breastfeeding rates among women on low incomes regardless of ethnicity and feeding intention. Needs-based, informal peer support in the antenatal and postnatal periods was also shown to be effective in one study conducted among Latina women who were considering breastfeeding in the USA (RR 4.02, 95% CI

  6. Initiating a watch list for Ebola virus antibody escape mutations

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    Craig R. Miller

    2016-02-01

    Full Text Available The 2014 Ebola virus (EBOV outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

  7. Health Promoting Schools: Initiatives in Africa

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    Macnab, Andrew J.; Stewart, Donald; Gagnon, Faith A.

    2014-01-01

    Purpose: The purpose of this paper is to describe the rationale for and potential of World Health Organization (WHO) health promoting schools (HPS) in Africa. Design/Methodology/Approach: Overview of the related literature and presentations at the 2011 Stellenbosch international colloquium on HPS relating to sub-Saharan Africa. Findings: Schools…

  8. Construction of chimeric antibodies: cloning of immunoglobulin genes including their promoter regions by PCR.

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    Mocikat, R; Kütemeier, G; Harloff, C

    1992-03-01

    In the production of recombinant antibodies, it is necessary to have an immunoglobulin gene promoter for driving the expression of the antibody genes. Here we describe a simple PCR method that allows cloning of the immunoglobulin genes together with their own promoters despite the fact that the sequence of the upstream part of the gene is unknown.

  9. The invisibilization of health promotion in Australian public health initiatives.

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    O'Hara, Lily; Taylor, Jane; Barnes, Margaret

    2016-07-19

    The field of health promotion has arguably shifted over the past thirty years from being socially proactive to biomedically defensive. In many countries this has been accompanied by a gradual decline, or in some cases the almost complete removal of health promotion designated positions within Government health departments. The language or discourse used to describe the practice and discipline of health promotion is reflective of such changes. In this study, critical discourse analysis was used to determine the representation of health promotion as a practice and a discipline within 10 Australian Government weight-related public health initiatives. The analysis revealed the invisibilization of critical health promotion in favour of an agenda described as 'preventive health'. This was achieved primarily through the textual practices of overlexicalization and lexical suppression. Excluding document titles, there were 437 uses of the terms health promotion, illness prevention, disease prevention, preventive health, preventative health in the documents analysed. The term 'health promotion' was used sparingly (16% of total terms), and in many instances was coupled with the term 'illness prevention'. Conversely, the terms 'preventive health' and 'preventative health' were used extensively, and primarily used alone. The progressive invisibilization of critical health promotion has implications for the perceptions and practice of those identifying as health promotion professionals and for people with whom we work to address the social and structural determinants of health and wellbeing. Language matters, and the language and intent of critical health promotion will struggle to survive if its speakers are professionally unidentifiable or invisible.

  10. Exploring Australian health promotion and environmental sustainability initiatives.

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    Patrick, Rebecca; Kingsley, Jonathan

    2016-04-01

    Issue addressed Health promotion practitioners have important roles in applying ecosystem approaches to health and actively promoting environmental sustainability within community-level practice. The present study identified the nature and scope of health promotion activities across Australia that tackle environmental sustainability. Methods A mixed-method approach was used, with 82 participants undertaking a quantitative survey and 11 undertaking a qualitative interview. Purposeful sampling strategies were used to recruit practitioners who were delivering community-level health promotion and sustainability programs in Australia. The data were analysed thematically and interpretation was guided by the principles of triangulation. Results Study participants were at various stages of linking health promotion and environmental sustainability. Initiatives focused on healthy and sustainable food, active transport, energy efficiency, contact with nature and capacity building. Conclusion Capacity building approaches were perceived as essential to strengthening this field of practice. Healthy and sustainable food and active transport were suitable platforms for simultaneously promoting community health and sustainability. There was potential for expansion of programs that emphasise contact with nature and energy issues, as well as interventions that emphasise systems thinking and interdisciplinary approaches. So what? It was promising that Australian health promotion programs have started to address complexity rather than single issues, as evidenced by explicit engagement with environmental sustainability. However, more effort is required to enable a shift towards ecosystem approaches to health.

  11. Astronomy Olympiad: An Initiative To Promote Astronomy Education In Nepal

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    Bhattarai, Suresh

    2015-08-01

    This paper presents National Astronomy Olympiad Program as a new initiative towards the development of astronomy education in Nepal by Nepal Astronomical Society (NASO).Innovoative components of the olympiad programs designed by NASO to engage both scince and non-science backgound people will be discussed in detail. It will discuss the first National Astronomy Olympiad 2014 and Second National Astronomy Olympiad 2015 in details. It will also present crowd funding, its effectiveness to outreach as well as collecting funds from around the world will be presented in brief. Proposed module of astronomy olympiad to promote astronnomy in the countries without formal astronomy education in high school like Nepal,will be presented in dedail. Possible strategry to strengthen such programs in developing nations and role of IAU to promote such educational program will be explored in detail.

  12. Tumor scintigraphy by the method for subtracting the initial image with technetium-99m labeled antibody

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    Karube, Yoshiharu; Katsuno, Kentaro; Ito, Sanae; Matsunaga, Kazuhisa; Takata, Jiro [Fukuoka Univ. (Japan). Faculty of Pharmaceutical Sciences; Kuroki, Masahide; Murakami, Masaaki; Matsuoka, Yuji

    1999-12-01

    The method for subtracting the initial image from the localization image was evaluated for radioimmunoscintigraphy of tumors with technetium-99m (Tc-99m) labeled antibodies. Monoclonal antibodies were parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, both of which have been found to discriminate CEA in tumor tissues from the CEA-related antigens. After reduction of the intrinsic disulfide bonds, these antibodies were labeled with Tc-99m. In vivo studies were performed on athymic nude mice bearing the human CEA-producing gastric carcinoma xenografts. Though biodistribution results showed selective and progressive accumulation of Tc-99m labeled antibodies at the tumor site, high radioactivity in blood was inappropriate for scintigraphic visualization of the tumors within a few hours. We examined the subtraction of the initial Tc-99m image from the Tc-99m localization image after a few hours. Subtracted images of the same count reflected the in vivo behavior of the Tc-99m radioactivity. The subtracted scintigrams revealed excellent tumor images with no significant extrarenal background. Visualization of the tumor site was dependent on antigen-specific binding and nonspecific exudation. These results demonstrate that a method of subtraction of the initial image may serve as a potentially useful diagnostic method for an abnormal site for agents with a low pharmacokinetic value. (author)

  13. PROMOTION OF EMPLOYMENT AMONG YOUTH – REMARKS FOR NEXT INITIATIVES

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    VLADIMIR MODRAK

    2011-01-01

    Full Text Available In the paper authors presets experience of Czestochowa University of Technology within collaboration with Czestochowa Business Incubator (CBI. In 2010, chosen staff of Czestochowa UT have been working within brand new Phare project “Promotion of employment among youth”. Because relatively high unemployment level among young people in Czestochowa city and region, the project has been implemented in order to help graduates to find their strengths and to advise in planning individual job track, to extend their job skills adequate to present and foreseen market needs, prepare them to the job interviews, prepare and help in starting own business. Authors also describes CBI’s other initiatives undertaken to increase number of new business set up by young people, especially.

  14. Antibody to collapsin response mediator protein 1 promotes neurite outgrowth from rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Hongsheng Lin; Jing Chen; Wenbin Zhang; Xiaobing Gong; Biao Chen; Guoqing Guo

    2011-01-01

    This study examined the role of collapsin response mediator protein 1 (CRMP-1) on neurite outgrowth from rat hippocampal neurons by blocking its function using an antibody. Hippocampal neurons, cultured in vitro, were treated (blocked) using a polyclonal antibody to CRMP-1, and neurite outgrowth and cytoskeletal changes w ere captured using atomic force microscopy and laser confocal microscopy. Control cells, treated with normal rabbit IgG, established their characteristic morphology and had a large number of processes emerging from the soma, including numerous branches. Microtubules were clearly visible in the soma, formed an elaborate network, and were aligned in parallel arrays to form bundles which projected into neurites. After blocking with CRMP-1 antibody, the number of branches emerging from axons and dendrites significantly increased and were substantially longer, compared with control cells. However, the microtubule network nearly disappeared and only a few remnants were visible. When CRMP-1 antibody-blocked neurons were treated with the Rho inhibitor, Y27632, numerous neurites emerged from the soma, and branches were more abundant than in control neurons. Although the microtubules were not as clearly visible compared with neurons cultured in control medium, the microtubule network recovered in cells treated with Y27632, when compared with cells that were blocked by CRMP-1 antibody (but not treated with Y27632). These results demonstrate that neurite outgrowth from hippocampal neurons can be promoted by blocking CRMP-1 with a polyclonal antibody.

  15. Antibodies against the envelope glycoprotein promote infectivity of immature dengue virus serotype 2.

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    Júlia M da Silva Voorham

    Full Text Available Cross-reactive dengue virus (DENV antibodies directed against the envelope (E and precursor membrane (prM proteins are believed to contribute to the development of severe dengue disease by facilitating antibody-dependent enhancement of infection. We and others recently demonstrated that anti-prM antibodies render essentially non-infectious immature DENV infectious in Fcγ-receptor-expressing cells. Immature DENV particles are abundantly present in standard (st virus preparations due to inefficient processing of prM to M during virus maturation. Structural analysis has revealed that the E protein is exposed in immature particles and this prompted us to investigate whether antibodies to E render immature particles infectious. To this end, we analyzed the enhancing properties of 27 anti-E antibodies directed against distinct structural domains. Of these, 23 bound to immature particles, and 15 enhanced infectivity of immature DENV in a furin-dependent manner. The significance of these findings was subsequently tested in vivo using the well-established West Nile virus (WNV mouse model. Remarkably, mice injected with immature WNV opsonized with anti-E mAbs or immune serum produced a lethal infection in a dose-dependent manner, whereas in the absence of antibody immature WNV virions caused no morbidity or mortality. Furthermore, enhancement infection studies with standard (st DENV preparations opsonized with anti-E mAbs in the presence or absence of furin inhibitor revealed that prM-containing particles present within st virus preparations contribute to antibody-dependent enhancement of infection. Taken together, our results support the notion that antibodies against the structural proteins prM and E both can promote pathogenesis by enhancing infectivity of prM-containing immature and partially mature flavivirus particles.

  16. Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2

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    da Silva Voorham, Júlia M.; Rodenhuis-Zybert, Izabela A.; Ayala Nuñez, Nilda Vanesa; Colpitts, Tonya M.; van der Ende-Metselaar, Heidi; Fikrig, Erol; Diamond, Michael S.; Wilschut, Jan; Smit, Jolanda M.

    2012-01-01

    Cross-reactive dengue virus (DENV) antibodies directed against the envelope (E) and precursor membrane (prM) proteins are believed to contribute to the development of severe dengue disease by facilitating antibody-dependent enhancement of infection. We and others recently demonstrated that anti-prM antibodies render essentially non-infectious immature DENV infectious in Fcγ-receptor-expressing cells. Immature DENV particles are abundantly present in standard (st) virus preparations due to inefficient processing of prM to M during virus maturation. Structural analysis has revealed that the E protein is exposed in immature particles and this prompted us to investigate whether antibodies to E render immature particles infectious. To this end, we analyzed the enhancing properties of 27 anti-E antibodies directed against distinct structural domains. Of these, 23 bound to immature particles, and 15 enhanced infectivity of immature DENV in a furin-dependent manner. The significance of these findings was subsequently tested in vivo using the well-established West Nile virus (WNV) mouse model. Remarkably, mice injected with immature WNV opsonized with anti-E mAbs or immune serum produced a lethal infection in a dose-dependent manner, whereas in the absence of antibody immature WNV virions caused no morbidity or mortality. Furthermore, enhancement infection studies with standard (st) DENV preparations opsonized with anti-E mAbs in the presence or absence of furin inhibitor revealed that prM-containing particles present within st virus preparations contribute to antibody-dependent enhancement of infection. Taken together, our results support the notion that antibodies against the structural proteins prM and E both can promote pathogenesis by enhancing infectivity of prM-containing immature and partially mature flavivirus particles. PMID:22431958

  17. Evaluating Maori community initiatives to promote healthy eating, healthy action.

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    Hamerton, Heather; Mercer, Christine; Riini, Denise; McPherson, Brighid; Morrison, Laurie

    2014-03-01

    Māori, the indigenous people of Aotearoa New Zealand, experience poorer health than non-Māori across a range of health measures. Interventions focused at an individual level have proved largely ineffective; 'bottom-up' approaches where communities determine their own priorities may be more sustainable than 'top-down' approaches where goals are determined by health authorities. The purpose of this paper is to illustrate an innovative health promotion programme aimed at improving Māori health and to discuss the importance of ownership and control of health initiatives by Māori. Evaluators conducted a comprehensive evaluation of a Healthy Eating Healthy Action programme in six small Māori health agencies, gathering information from programme managers and co-ordinators, participants and wider community members about what changes were occurring at individual, family and community levels. Effective interventions built on cultural values and practices and were delivered by Māori with close connections to the community. Changes in nutrition and physical activity made by participants also benefitted their wider families and community. The changes demonstrated subtle but important shifts in thinking about healthy eating and healthy activity that in the longer term could lead to more measurable change towards improved quality of life for people within communities.

  18. Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.

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    Fredrik Kahn

    Full Text Available Streptococcal toxic shock syndrome (STSS caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP, an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein-induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein-fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response.

  19. Antibody

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    An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... microorganisms (bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

  20. Promotion of Tumor Invasion by Cooperation of Granulocytes and Macrophages Activated by Anti-tumor Antibodies

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    Emilio Barbera-Guillem

    1999-11-01

    Full Text Available We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.

  1. Autophagy-associated dengue vesicles promote viral transmission avoiding antibody neutralization

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    Wu, Yan-Wei; Mettling, Clément; Wu, Shang-Rung; Yu, Chia-Yi; Perng, Guey-Chuen; Lin, Yee-Shin; Lin, Yea-Lih

    2016-01-01

    One of the major defense mechanisms against virus spread in vivo is the blocking of viral infectibility by neutralizing antibodies. We describe here the identification of infectious autophagy-associated dengue vesicles released from infected cells. These vesicles contain viral proteins E, NS1, prM/M, and viral RNA, as well as host lipid droplets and LC3-II, an autophagy marker. The viral RNA can be protected within the autophagic organelles since anti-dengue neutralizing antibodies do not have an effect on the vesicle-mediated transmission that is able to initiate a new round of infection in target cells. Importantly, such infectious vesicles were also detected in a patient serum. Our study suggests that autophagy machinery plays a new role in dengue virus transmission. This discovery explains the inefficiency of neutralizing antibody upon dengue infection as a potential immune evasion mechanism in vivo. PMID:27558165

  2. Faithful transcription initiation from a mitochondrial promoter in transgenic plastids.

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    Bohne, Alexandra-Viola; Ruf, Stephanie; Börner, Thomas; Bock, Ralph

    2007-01-01

    The transcriptional machineries of plastids and mitochondria in higher plants exhibit striking similarities. All mitochondrial genes and part of the plastid genes are transcribed by related phage-type RNA polymerases. Furthermore, the majority of mitochondrial promoters and a subset of plastid promoters show a similar structural organization. We show here that the plant mitochondrial atpA promoter is recognized by plastid RNA polymerases in vitro and in vivo. The Arabidopsis phage-type RNA polymerase RpoTp, an enzyme localized exclusively to plastids, was found to recognize the mitochondrial atpA promoter in in vitro assays suggesting the possibility that mitochondrial promoters might function as well in plastids. We have, therefore, generated transplastomic tobacco plants harboring in their chloroplast genome the atpA promoter fused to the coding region of the bacterial nptII gene. The chimeric nptII gene was found to be efficiently transcribed in chloroplasts. Mapping of the 5' ends of the nptII transcripts revealed accurate recognition of the atpA promoter by the chloroplast transcription machinery. We show further that the 5' untranslated region (UTR) of the mitochondrial atpA transcript is capable of mediating translation in chloroplasts. The functional and evolutionary implications of these findings as well as possible applications in chloroplast genome engineering are discussed.

  3. Antibody-mediated inhibition of Nogo-A signaling promotes neurite growth in PC-12 cells

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    Iman K Yazdi

    2016-01-01

    Full Text Available The use of a monoclonal antibody to block the neurite outgrowth inhibitor Nogo-A has been of great interest for promoting axonal recovery as a treatment for spinal cord injury. While several cellular and non-cellular assays have been developed to quantify the bioactive effects of Nogo-A signaling, demand still exists for the development of a reliable approach to characterize the effectiveness of the anti-Nogo-A antibody. In this study, we developed and validated a novel cell-based approach to facilitate the biological quantification of a Nogo-A antibody using PC-12 cells as an in vitro neuronal cell model. Changes in the mRNA levels of the neuronal differentiation markers, growth-associated protein 43 and neurofilament light-polypeptide, suggest that activation of the Nogo-A pathway suppresses axonal growth and dendrite formation in the tested cell line. We found that application of anti-Nogo-A monoclonal antibody can significantly enhance the neuronal maturity of PC-12 cells by blocking the Nogo-A inhibitory effects, providing enhanced effects on neural maturity at the molecular level. No adverse effects were observed on cell viability.

  4. Lupus erythematosus panniculitis presenting with initial periorbital swelling and positive antiphospholipid antibodies: A rare association

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    Jyotsna Oak

    2013-01-01

    Full Text Available Lupus erythematosus panniculitis (LEP, an unusual form of chronic cutaneous lupus erythematosus, is characterized by chronic inflammation and fibrosis of subcutaneous tissue. Clinically, it presents as subcutaneous nodules on common locations such as forehead, cheeks, proximal limbs and buttocks. Ulceration of the nodules may occur in certain cases. Very few case studies have reported the occurrence of early solitary periorbital involvement, highlighting the need for a high index of suspicion in such cases. We report here a case having generalized extensive LEP with initial manifestation of a solitary periorbital swelling, autoimmune hemolytic anemia, and associated antiphospholipid antibodies positivity.

  5. Promoting Global Initiatives and Cross-Cultural Understanding in China

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    Brand, Susan Trostle; Snodgress, Faye

    2012-01-01

    As an "international" honor society in education, Kappa Delta Pi (KDP) recognizes the importance of encouraging and promoting education internationally in the 21st century. The challenge shared by educators in many countries is to achieve higher levels of learning for all students. Committed educators around the globe are already working…

  6. Parent-Implemented Script Fading to Promote Play-Based Verbal Initiations in Children with Autism

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    Reagon, Kara A.; Higbee, Thomas S.

    2009-01-01

    We trained 3 mothers of children with autism to create, implement, and systematically fade scripts to promote vocal initiations during play. All 3 children's scripted and unscripted initiations increased after the introduction and fading of scripts, and unscripted initiations were maintained at the 2-week follow-up. The results indicate that…

  7. Regulation of Drosophila Adh promoter switching by an initiator-targeted repression mechanism.

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    Ren, B; Maniatis, T

    1998-01-01

    The stage-specific expression of the Drosophila alcohol dehydrogenase (Adh) gene is achieved through the alternate activation of two tandem promoters. The proximal promoter is active primarily during late embryonic development and early larval stages, while the distal promoter is active in late third instar larvae and adults. Here, we provide evidence that this Adh promoter switch is regulated by a zinc finger repressor protein (AEF-1) that is expressed predominantly in adult flies and targets the initiator region of the proximal promoter. We propose that AEF-1 plays a critical role in Adh promoter switching by blocking interactions between a component of the general transcription machinery and the initiator region of the proximal promoter. PMID:9463385

  8. Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen.

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    Kinzel, Silke; Lehmann-Horn, Klaus; Torke, Sebastian; Häusler, Darius; Winkler, Anne; Stadelmann, Christine; Payne, Natalie; Feldmann, Linda; Saiz, Albert; Reindl, Markus; Lalive, Patrice H; Bernard, Claude C; Brück, Wolfgang; Weber, Martin S

    2016-07-01

    In the pathogenesis of central nervous system (CNS) demyelinating disorders, antigen-specific B cells are implicated to act as potent antigen-presenting cells (APC), eliciting waves of inflammatory CNS infiltration. Here, we provide the first evidence that CNS-reactive antibodies (Ab) are similarly capable of initiating an encephalitogenic immune response by targeting endogenous CNS antigen to otherwise inert myeloid APC. In a transgenic mouse model, constitutive production of Ab against myelin oligodendrocyte glycoprotein (MOG) was sufficient to promote spontaneous experimental autoimmune encephalomyelitis (EAE) in the absence of B cells, when mice endogenously contained MOG-recognizing T cells. Adoptive transfer studies corroborated that anti-MOG Ab triggered activation and expansion of peripheral MOG-specific T cells in an Fc-dependent manner, subsequently causing EAE. To evaluate the underlying mechanism, anti-MOG Ab were added to a co-culture of myeloid APC and MOG-specific T cells. At otherwise undetected concentrations, anti-MOG Ab enabled Fc-mediated APC recognition of intact MOG; internalized, processed and presented MOG activated naïve T cells to differentiate in an encephalitogenic manner. In a series of translational experiments, anti-MOG Ab from two patients with an acute flare of CNS inflammation likewise facilitated detection of human MOG. Jointly, these observations highlight Ab-mediated opsonization of endogenous CNS auto-antigen as a novel disease- and/or relapse-triggering mechanism in CNS demyelinating disorders.

  9. Promoting the export of environmental technologies: An analysis of governmental initiatives from eight countries

    OpenAIRE

    Kanda, Wisdom; Hjelm, Olof; Dugand, Santiago Mejiá

    2016-01-01

    Export represents a means for the diffusion of environmental technologies with potential socio-economic and environmental benefits. However, environmental technology providers experience export barriers which stifle export and thus several governments continue to formulate export promotion initiatives towards this sector. Although export promotion is identified as essential in the environmental technology policy literature, it is yet to receive attention as to which initiatives are available ...

  10. A role for the H4 subunit of vaccinia RNA polymerase in transcription initiation at a viral early promoter.

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    Deng, L; Shuman, S

    1994-05-13

    The vaccinia virus H4 gene encodes an essential subunit of the DNA-dependent RNA polymerase holoenzyme encapsidated within virus particles (Ahn, B., and Moss, B. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3536-3540; Kane, E. M., and Shuman, S. (1992) J. Virol. 66, 5752-5762). The role of this protein in transcription of viral early genes was revealed by the effects of affinity-purified anti-H4 antibody on discrete phases of the early transcription reaction in vitro. Anti-H4 specifically prevented the synthesis of a 21-nucleotide nascent RNA chain but had no impact on elongation of the 21-mer RNA by preassembled ternary complexes. Inhibition of initiation but not elongation was also observed with affinity-purified anti-D6 antibody directed against the 70-kDa subunit of the vaccinia early transcription initiation factor (ETF). Native gel mobility-shift assays showed that anti-H4 prevented the NTP-dependent recruitment of RNA polymerase to the preinitiation complex of ETF bound at the early promoter. Two species of ternary complexes could be resolved by native gel electrophoresis. Addition of anti-H4 to preformed complexes elicited a supershift of both ternary species but not of the preinitiation complex. Supeshift by anti-D6 revealed that the more rapidly migrating species of ternary complex did not contain immunoreactive ETF. Loss of ETF from the ternary complex was time-dependent. Thus, whereas the H4 protein was a stable constituent of the elongation complex, ETF was dissociable. We suggest that H4 functions as a molecular bridge to ETF and thereby allows specific recognition of early promoters by the core RNA polymerase. H4 is unlike bacterial sigma factor in that it remains bound to polymerase after the elongation complex is established.

  11. Elucidation of the potential disease-promoting influence of IgM apoptotic cell-reactive antibodies in lupus.

    Science.gov (United States)

    Malik, M; Arora, P; Sachdeva, R; Sharma, L; Ramachandran, V G; Pal, R

    2016-06-01

    The undigested remnants of apoptosis are believed to stimulate the generation of autoantibodies in lupus. The biological properties of initiator, disease-specific IgM antibodies that specifically recognize apoptotic cells, readily detected in the sera of lupus patients, remain unclear. Apoptotic cell-reactive IgM monoclonal antibodies (generated from lupus-prone mice), as opposed to control IgM, preferentially stimulated maturation of bone marrow-derived dendritic cells (BMDCs) derived from such mice, relative to BMDCs derived from healthy mice. An influence of both antibody specificity and cell genotype was also apparent in the secretion of signature inflammatory cytokines. Immunization of such antibodies in lupus-prone animals induced increases in total serum IgG levels, with the elicited antibodies also preferentially recognizing moieties on dying cells. An expanded specificity was apparent both upon Western blot on cellular lysate and from the enhanced recognition of dsDNA, Ro60, RNP68 and Sm; the antibody most efficient in mediating autoreactive diversity, while being germline encoded, also induced the highest degree of phenotypic changes on BMDCs. Apoptotic cell-reactive IgM antibodies may therefore be potentially capable of influencing the course of systemic autoimmune disease by affecting both innate and adaptive immunity.

  12. Viral promoters can initiate expression of toxin genes introduced into Escherichia coli

    Directory of Open Access Journals (Sweden)

    Jacob Daniela

    2005-06-01

    Full Text Available Abstract Background The expression of recombinant proteins in eukaryotic cells requires the fusion of the coding region to a promoter functional in the eukaryotic cell line. Viral promoters are very often used for this purpose. The preceding cloning procedures are usually performed in Escherichia coli and it is therefore of interest if the foreign promoter results in an expression of the gene in bacteria. In the case molecules toxic for humans are to be expressed, this knowledge is indispensable for the specification of safety measures. Results We selected five frequently used viral promoters and quantified their activity in E. coli with a reporter system. Only the promoter from the thymidine kinase gene from HSV1 showed no activity, while the polyhedrin promoter from baculovirus, the early immediate CMV promoter, the early SV40 promoter and the 5' LTR promoter from HIV-1 directed gene expression in E. coli. The determination of transcription start sites in the immediate early CMV promoter and the polyhedrin promoter confirmed the existence of bacterial -10 and -35 consensus sequences. The importance of this heterologous gene expression for safety considerations was further supported by analysing fusions between the aforementioned promoters and a promoter-less cytotoxin gene. Conclusion According to our results a high percentage of viral promoters have the ability of initiating gene expression in E. coli. The degree of such heterologous gene expression can be sufficient for the expression of toxin genes and must therefore be considered when defining safety measures for the handling of corresponding genetically modified organisms.

  13. Anti-nuclear antibodies positive serum from systemic lupus erythematosus patients promotes cardiovascular manifestations and the presence of human antibody in the brain

    Directory of Open Access Journals (Sweden)

    Marie Kelly-Worden

    2014-01-01

    Full Text Available Background: Systemic lupus erythematosus (SLE is characterized by the presence of anti-nuclear antibodies (ANAs in the serum of patients. These antibodies may cross over into the brain resulting in the development of neuropsychiatric symptoms and result in abnormal pathology in other organs such as the heart and kidneys. Objective: The objective of this study was to determine if SLE pathology could be detected in the hearts and brains of rats injected with positive human ANA serum. Materials and Methods: Lewis rats (n = 31 were selected for this study due to documented research already performed with this strain in the investigation of serum sickness, encephalitis and autoimmune related carditis. Rats were injected once a week with either ANA positive or negative control serum or saline. Hearts were examined for initial signs of heart disease including the presence of lipid deposits, vegetation, increased ventricular thickness and a change in heart weight. Brains were examined for the presence of human antibody and necrotic lesions. Animals were observed for outward signs of neuropathy as well. Blood samples were taken in order to determine final circulating concentrations of IgG and monitor histamine levels. Results: Animals injected with ANA were significantly higher for lipid deposits in the heart and an increased ventricular thickness was noted. One animal even displayed Libman-Sacks endocarditis. Brains were positive for the presence of human IgG and diffuse internal lesions occurred in 80% of the ANA positive serum injected animals examined. Blood histamine levels were not significantly different, but actually lower than controls by the end of the experiment. Conclusion: Since human antibodies were detected in the brain, further studies will have to identify which antibody cross reactions are occurring within the brain, examine cell infiltration as well as characterize the antibodies associated with more destructive consequences such as

  14. Environmental Technology Export Promotion : A study of governmental initiatives in selected countries

    OpenAIRE

    Kanda, Wisdom; Hjelm, Olof; Mejia-Dugand, Santiago

    2012-01-01

    Introduction-This report is based on structured literature reviews and brainstorming sections on governmental export promotion initiatives for environmental technology in selected countries. It is intended to answer two fundamental questions: why governments intervene to promote environmental technology export and how this intervention is actually executed. These questions emerged in-light of two general challenges: 1) the lack of vivid scientific insights with robust theoretical underpinning...

  15. Governmental export promotion initiatives : awareness, participation, and perceived effectiveness among Swedish environmental technology firms

    OpenAIRE

    Kanda, Wisdom; Mejiá-Dugand, Santiago; Hjelm, Olof

    2015-01-01

    Some countries rely heavily on exports as an essential component of their economic competitiveness. With the current trends in economic globalization, promoting exports has become a common strategy to boost economic growth. Exports of environmental technologies represent a new window of opportunity for economic growth and a contribution to global sustainability. With this in mind, national governments have designed initiatives that aim to promote exports within this sector. To address their o...

  16. Stabilization of serum antibody responses triggered by initial mucosal contact with the antigen independently of oral tolerance induction

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    B.A. Verdolin

    2001-02-01

    Full Text Available Initial contacts with a T-dependent antigen by mucosal routes may result in oral tolerance, defined as the inhibition of specific antibody formation after subsequent parenteral immunizations with the same antigen. We describe here an additional and permanent consequence of these initial contacts, namely, the blockade of secondary-type responsiveness to subsequent parenteral contacts with the antigen. When repeatedly boosted ip with small doses (3 µg of ovalbumin (OVA (or lysozyme, primed B6D2F1 mice showed progressively higher antibody responses. In contrast, mice primed after a single oral exposure to the antigen, although repeatedly boosted, maintained their secondary antibody titers on a level which was inversely proportional to the dose of antigen in the oral pretreatment. This phenomenon also occurred in situations in which oral tolerance was not induced. For example, senile 70-week-old B6D2F1 mice pretreated with a single gavage of 20 mg OVA did not become tolerant, i.e., they formed the same secondary levels of anti-OVA antibodies as non-pretreated mice. However, after 4 weekly challenges with 3 µg OVA ip, orally pretreated mice maintained the same anti-OVA serum levels, whereas the levels of control mice increased sequentially. This "stabilizing" effect of mucosal exposure was dose dependent, occurred with different proteins and was triggered by single or multiple oral or nasal exposures to the antigen.

  17. Initial study with Tc99m antigranulocyte antibody (MAK-47) in detection sources of infection

    Energy Technology Data Exchange (ETDEWEB)

    Cwikla, J.B.; Buscombe, J.R.; Hilson, A.J. [Dept. of Nuclear Medicine and Medical Physics, Royal Free Hospital and School of Medicine, London (United Kingdom); Janoki, G.A. [FJC National Research Inst. for Radiology and Radiohygene, Dept. of Applied Radioisotopes, Budapest (Hungary)

    1997-12-31

    Antigranulocytes antibodies (AGAB) are antibodies directed against glycoprotein on the surface of granulocytes and as such provides in vivo cell labelling. They are easily labelled with Tc99m and comes a one step labelling technique. 20 patients have been studied 1 h and 4-6 hours after administration of 200 MBq of Tc99m AGAB (MAK-47). Less then 0.5 mg of antibody was given to each patients. Sites of uptake and outside of the reticular-endothelial system were reported as showing positive accumulation. Clinical results were confirmed by microbiological, pathological examinations, clinical follow-up and autopsy. There were 8 patients who had sites of infection confirmed by additional examination. All patients were visualized by Tc99m AGAB (MAK-47). There were 4 cases of osteomyelitis and septic arthritis and 4 cases of focal intra-abdominal infection. Two patients had uptake in non-infected/inflammatory arthritis, both in the knee. The remaining patients had true negative studies. The diagnostic accuracy of this study was as follows: sensitivity 100%, specificity 83%, positive predictive value (PPV) was 80% and negative predictive value (NPV) was 100%. Antigranulocyte antibody (MAK-47) seems to by promising tool in detecting focal infection in bone and soft tissue, except physiological accumulation in some parts of the body. It should be considered that antibodies can have non-specific uptake in non-infected, inflammation sites. It is easy to use and no had allergic reaction and HAMA antibody (human antimouse antibody). (author) 18 refs, 4 figs, 2 tabs

  18. Nutrition Education Initiative: A School-Based Program to Promote Healthy Eating Practices of Preadolescents

    Science.gov (United States)

    Greenwood, Bonnie; Ralston, Penny A.; Young-Clark, Iris; Cornille, Tom; Brown, Linda Lockett; Davis, Kimberly E.; Salley, Tihesha J.; Goehrig, Marianne Henderson; Mullins, Amy Piper; Gaskins, Dykibra J.

    2009-01-01

    The implementation of the Nutrition Education Initiative (NEI), a project to promote the adoption of healthy eating practices by middle school students in North Florida, included the development of the "NEI Resource Guide" and pilot study outcomes. Eight schools in North Florida participated in the pilot project. Food recall data from 331 and 768…

  19. Assessment of Site Specific Mutational Effect on Transcription Initiation at Escherichia coli Promoter

    Directory of Open Access Journals (Sweden)

    S. Kannan

    2009-01-01

    extended promoter region also played a key role in regulation transcription initiation in JM109 strain of E. coli. Conclusion: The present study concluded that the site specific changed in the extended promoter regions, particularly the-17/-16 base pairs had greater influence in the transcription initiation in E. coli. Thus the promoter engineering study will definitely pave the way to do both, on or off the genetic switches in bacterial system according to our needs to produce high protein of interest or decrease or block the expression of a particular unwanted protein.

  20. Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2

    NARCIS (Netherlands)

    Voorham, Julia M. da Silva; Rodenhuis-Zybert, Izabela A.; Nunez, Nilda Vanesa Ayala; Colpitts, Tonya M.; van der Ende-Metselaar, Heidi; Fikrig, Erol; Diamond, Michael S.; Wilschut, Jan; Smit, Jolanda M.

    2012-01-01

    Cross-reactive dengue virus (DENV) antibodies directed against the envelope (E) and precursor membrane (prM) proteins are believed to contribute to the development of severe dengue disease by facilitating antibody-dependent enhancement of infection. We and others recently demonstrated that anti-prM

  1. Aptamers to the sigma factor mimic promoter recognition and inhibit transcription initiation by bacterial RNA polymerase.

    Science.gov (United States)

    Miropolskaya, Nataliya; Kulbachinskiy, Andrey

    2016-01-08

    Promoter recognition by bacterial RNA polymerase (RNAP) is a multi-step process involving multiple protein-DNA interactions and several structural and kinetic intermediates which remain only partially characterized. We used single-stranded DNA aptamers containing specific promoter motifs to probe the interactions of the Thermus aquaticus RNAP σ(A) subunit with the -10 promoter element in the absence of other parts of the promoter complex. The aptamer binding decreased intrinsic fluorescence of the σ subunit, likely as a result of interactions between the -10 element and conserved tryptophan residues of the σ DNA-binding region 2. By monitoring these changes, we demonstrated that DNA binding proceeds through a single rate-limiting step resulting in formation of very stable complexes. Deletion of the N-terminal domain of the σ(A) subunit increased the rate of aptamer binding while replacement of this domain with an unrelated N-terminal region 1.1 from the Escherichia coli σ(70) subunit restored the original kinetics of σ-aptamer interactions. The results demonstrate that the key step in promoter recognition can be modelled in a simple σ-aptamer system and reveal that highly divergent N-terminal domains similarly modulate the DNA-binding properties of the σ subunit. The aptamers efficiently suppressed promoter-dependent transcription initiation by the holoenzyme of RNA polymerase, suggesting that they may be used for development of novel transcription inhibitors.

  2. Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination.

    Science.gov (United States)

    Tam, Hok Hei; Melo, Mariane B; Kang, Myungsun; Pelet, Jeisa M; Ruda, Vera M; Foley, Maria H; Hu, Joyce K; Kumari, Sudha; Crampton, Jordan; Baldeon, Alexis D; Sanders, Rogier W; Moore, John P; Crotty, Shane; Langer, Robert; Anderson, Daniel G; Chakraborty, Arup K; Irvine, Darrell J

    2016-10-25

    Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency.

  3. Exploring Opportunities for Promoting Synergies between Climate Change Adaptation and Mitigation in Forest Carbon Initiatives

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    Eugene L. Chia

    2016-01-01

    Full Text Available There is growing interest in designing and implementing climate change mitigation and adaptation (M + A in synergy in the forest and land use sectors. However, there is limited knowledge on how the planning and promotion of synergies between M + A can be operationalized in the current efforts to mitigate climate change through forest carbon. This paper contributes to fill this knowledge gap by exploring ways of planning and promoting M + A synergy outcomes in forest carbon initiatives. It examines eight guidelines that are widely used in designing and implementing forest carbon initiatives. Four guiding principles with a number of criteria that are relevant for planning synergy outcomes in forest carbon activities are proposed. The guidelines for developing forest carbon initiatives need to demonstrate that (1 the health of forest ecosystems is maintained or enhanced; (2 the adaptive capacity of forest-dependent communities is ensured; (3 carbon and adaptation benefits are monitored and verified; and (4 adaptation outcomes are anticipated and planned in forest carbon initiatives. The forest carbon project development guidelines can encourage the integration of adaptation in forest carbon initiatives. However, their current efforts guiding projects and programs to deliver biodiversity and environmental benefits, ecosystem services, and socioeconomic benefits are not considered explicitly as efforts towards enhancing adaptation. An approach for incentivizing and motivating project developers, guideline setters, and offset buyers is imperative in order to enable existing guidelines to make clear contributions to adaptation goals. We highlight and discuss potential ways of incentivizing and motivating the explicit planning and promotion of adaptation outcomes in forest carbon initiatives.

  4. Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia.

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    Maria Licursi

    Full Text Available Internal ribosome entry site (IRES-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV, foot-and-mouth disease virus (FMDV, hepatitis C virus (HCV, human rhinovirus (HRV or poliovirus (PV. Under mild hypothermic conditions (30 and 35°C, we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB and upstream of N-Ras (unr, the IRES trans-acting factors (ITAFs of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent.

  5. Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia

    Science.gov (United States)

    Licursi, Maria; Carmona-Martinez, Ricardo A.; Razavi, Seyd; Hirasawa, Kensuke

    2015-01-01

    Internal ribosome entry site (IRES)-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), hepatitis C virus (HCV), human rhinovirus (HRV) or poliovirus (PV). Under mild hypothermic conditions (30 and 35°C), we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB) and upstream of N-Ras (unr), the IRES trans-acting factors (ITAFs) of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent. PMID:25951166

  6. Role of Libraries in Promoting E-Learning : A Review of Singapore Initiatives

    OpenAIRE

    Chaudhary, Abdus Sattar

    2006-01-01

    In line with the emphasis of Singapore Government in exploiting information technology for national competitiveness, public service institutions were quick to undertake initiatives to promote e-learning among their staff. This is part of the campaign for readiness for e-governance in the country. The Library and Information sector was no exception in this national campaign. National Library Board, which had earlier won awards for use of technology and introduction of network services, took fu...

  7. A survey of local health promotion initiatives for older people in Wales

    Directory of Open Access Journals (Sweden)

    Williams Nefyn H

    2008-06-01

    Full Text Available Abstract Background As the demographic profile of the UK changes, policy makers and practitioners have to respond to health challenges presented by a progressively ageing population. The health promotion plan for older people, aged over 50 years, in Wales included eight key areas: physical activity, healthy eating, home safety and warmth, emotional health, health protection, smoking, alcohol and sexual health. The aim of this study was to describe the extent, content and regional variation of existing health promotion initiatives for older people in Wales, provided by statutory, voluntary and private sector agencies. Method A questionnaire was sent to senior health promotion specialists employed in the 22 local authority areas in Wales to ascertain details of all projects promoting health and wellbeing in the eight key areas where the priority population was aged over 50, or the majority of users were older people. Additional information was sought from project leads and websites. Results Eighteen questionnaires were returned; not all were fully completed. Four areas did not return a questionnaire. Additional information was obtained from internet searches but this mainly concerned national initiatives rather than local projects. In all, 120 projects were included, 11 were throughout Wales. Best provision was for physical activity, with 3 national and 42 local initiatives, but local provision was patchy. Healthy eating, and home safety and warmth had far fewer initiatives, as did health protection, which comprised two national immunisation campaigns. Smoking and alcohol misuse were poorly provided for, and there was no provision for older people's sexual health. Evaluation arrangements were poorly described. Half of those who responded identified unmet training needs. Conclusion The reasons for patchy provision of services were not clear. Increased efforts to improve the coverage of interventions known to be effective should be made. Rigorous

  8. Immune antibodies and helminth products drive CXCR2-dependent macrophage-myofibroblast crosstalk to promote intestinal repair.

    Science.gov (United States)

    Esser-von Bieren, Julia; Volpe, Beatrice; Sutherland, Duncan B; Bürgi, Jérôme; Verbeek, J Sjef; Marsland, Benjamin J; Urban, Joseph F; Harris, Nicola L

    2015-03-01

    Helminth parasites can cause considerable damage when migrating through host tissues, thus making rapid tissue repair imperative to prevent bleeding and bacterial dissemination particularly during enteric infection. However, how protective type 2 responses targeted against these tissue-disruptive multicellular parasites might contribute to homeostatic wound healing in the intestine has remained unclear. Here, we observed that mice lacking antibodies (Aid-/-) or activating Fc receptors (Fcrg-/-) displayed impaired intestinal repair following infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb), whilst transfer of immune serum could partially restore chemokine production and rescue wound healing in Aid-/- mice. Impaired healing was associated with a reduced expression of CXCR2 ligands (CXCL2/3) by macrophages (MΦ) and myofibroblasts (MF) within intestinal lesions. Whilst antibodies and helminths together triggered CXCL2 production by MΦ in vitro via surface FcR engagement, chemokine secretion by intestinal MF was elicited by helminths directly via Fcrg-chain/dectin2 signaling. Blockade of CXCR2 during Hpb challenge infection reproduced the delayed wound repair observed in helminth infected Aid-/- and Fcrg-/- mice. Finally, conditioned media from human MΦ stimulated with infective larvae of the helminth Ascaris suum together with immune serum, promoted CXCR2-dependent scratch wound closure by human MF in vitro. Collectively our findings suggest that helminths and antibodies instruct a chemokine driven MΦ-MF crosstalk to promote intestinal repair, a capacity that may be harnessed in clinical settings of impaired wound healing.

  9. Immune antibodies and helminth products drive CXCR2-dependent macrophage-myofibroblast crosstalk to promote intestinal repair.

    Directory of Open Access Journals (Sweden)

    Julia Esser-von Bieren

    2015-03-01

    Full Text Available Helminth parasites can cause considerable damage when migrating through host tissues, thus making rapid tissue repair imperative to prevent bleeding and bacterial dissemination particularly during enteric infection. However, how protective type 2 responses targeted against these tissue-disruptive multicellular parasites might contribute to homeostatic wound healing in the intestine has remained unclear. Here, we observed that mice lacking antibodies (Aid-/- or activating Fc receptors (Fcrg-/- displayed impaired intestinal repair following infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb, whilst transfer of immune serum could partially restore chemokine production and rescue wound healing in Aid-/- mice. Impaired healing was associated with a reduced expression of CXCR2 ligands (CXCL2/3 by macrophages (MΦ and myofibroblasts (MF within intestinal lesions. Whilst antibodies and helminths together triggered CXCL2 production by MΦ in vitro via surface FcR engagement, chemokine secretion by intestinal MF was elicited by helminths directly via Fcrg-chain/dectin2 signaling. Blockade of CXCR2 during Hpb challenge infection reproduced the delayed wound repair observed in helminth infected Aid-/- and Fcrg-/- mice. Finally, conditioned media from human MΦ stimulated with infective larvae of the helminth Ascaris suum together with immune serum, promoted CXCR2-dependent scratch wound closure by human MF in vitro. Collectively our findings suggest that helminths and antibodies instruct a chemokine driven MΦ-MF crosstalk to promote intestinal repair, a capacity that may be harnessed in clinical settings of impaired wound healing.

  10. Initiation-promotion model of tumor prevalence in mice from space radiation exposures.

    Science.gov (United States)

    Cucinotta, F A; Wilson, J W

    1995-08-01

    Exposures in space consist of low-level background components from galactic cosmic rays (GCR), occasional intense-energetic solar-particle events, periodic passes through geomagnetic-trapped radiation, and exposure from possible onboard nuclear-propulsion engines. Risk models for astronaut exposure from such diverse components and modalities must be developed to assure adequate protection in future NASA missions. The low-level background exposures (GCR), including relativistic heavy ions (HZE), will be the ultimate limiting factor for astronaut career exposure. We consider herein a two-mutation, initiation-promotion, radiation-carcinogenesis model in mice in which the initiation stage is represented by a linear kinetics model of cellular repair/misrepair, including the track-structure model for heavy ion action cross-sections. The model is validated by comparison with the harderian gland tumor experiments of Alpen et al. for various ion beams. We apply the initiation-promotion model to exposures from galactic cosmic rays, using models of the cosmic-ray environment and heavy ion transport, and consider the effects of the age of the mice prior to and after the exposure and of the length of time in space on predictions of relative risk. Our results indicate that biophysical models of age-dependent radiation hazard will provide a better understanding of GCR risk than models that rely strictly on estimates of the initial slopes of these radiations.

  11. Tumor initiating and promoting activities of various benzo(a)pyrene metabolites in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T J; Bracken, W M; Viaje, A; Berry, D L; Fischer, S M; Miller, D R; Levin, W; Conney, A H; Yagi, H; Jerina, D M

    1977-01-01

    The skin tumor-initiating activities of the twelve isomeric phenols of BP revealed that 2-OHBP was as potent as BP while 11-OHBP was moderately active and the others were weak or inactive. However, 2-OHBP has not been shown to be formed from BP in the skin or any other tissue. The (-)-trans-7,8-diol of BP skin was found to be more active as a skin tumor initiator than BP suggesting that it is a proximal carcinogen. The data on carcinogenicity, mutagenicity and metabolism suggest that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is the ultimate carcinogenic form of BP. The skin tumor-initiating activities of the various BP metabolites correlate very well with their complete carcinogenic in mouse skin except for BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide. It was found to have skin tumor initiating activity but not complete carcinogenic activity. However, BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide was found to be a very potent complete carcinogen in newborn mice. It is possible that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is only a tumor initiator in which a promoting stimulus must be supplied for carcinogenic activity. A natural tumor promoting stimulus may be present in the newborn mouse. There is also a good correlation between the skin tumor initiating activities of the various BP metabolites and their mutagenic activity in the V79 mammalian cell mediated mutagenesis system.

  12. Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression

    OpenAIRE

    Rogier, Eric W.; Frantz, Aubrey L.; Bruno, Maria E. C.; Wedlund, Leia; Cohen, Donald A.; Stromberg, Arnold J; Kaetzel, Charlotte S.

    2014-01-01

    An experimental system was developed in mice to study the long-term benefits of early exposure to secretory antibodies of the IgA class (SIgA) in breast milk. We found that breast milk-derived SIgA promoted intestinal epithelial barrier function in suckling neonates, preventing systemic infection by potential pathogens. Long-term benefits of early exposure to SIgA included maintenance of a healthy gut microbiota and regulation of gene expression in intestinal epithelial cells. These findings ...

  13. BRCA1-IRIS overexpression promotes and maintains the tumor initiating phenotype: implications for triple negative breast cancer early lesions.

    Science.gov (United States)

    Sinha, Abhilasha; Paul, Bibbin T; Sullivan, Lisa M; Sims, Hillary; El Bastawisy, Ahmed; Yousef, Hend F; Zekri, Abdel-Rahman N; Bahnassy, Abeer A; ElShamy, Wael M

    2017-02-07

    Tumor-initiating cells (TICs) are cancer cells endowed with self-renewal, multi-lineage differentiation, increased chemo-resistance, and in breast cancers the CD44+/CD24-/ALDH1+ phenotype. Triple negative breast cancers show lack of BRCA1 expression in addition to enhanced basal, epithelial-to-mesenchymal transition (EMT), and TIC phenotypes. BRCA1-IRIS (hereafter IRIS) is an oncogene produced by the alternative usage of the BRCA1 locus. IRIS is involved in induction of replication, transcription of selected oncogenes, and promoting breast cancer cells aggressiveness. Here, we demonstrate that IRIS overexpression (IRISOE) promotes TNBCs through suppressing BRCA1 expression, enhancing basal-biomarkers, EMT-inducers, and stemness-enforcers expression. IRISOE also activates the TIC phenotype in TNBC cells through elevating CD44 and ALDH1 expression/activity and preventing CD24 surface presentation by activating the internalization pathway EGFR→c-Src→cortactin. We show that the intrinsic sensitivity to an anti-CD24 cross-linking antibody-induced cell death in membranous CD24 expressing/luminal A cells could be acquired in cytoplasmic CD24 expressing IRISOE TNBC/TIC cells through IRIS silencing or inactivation. We show that fewer IRISOE TNBC/TICs cells form large tumors composed of TICs, resembling TNBCs early lesions in patients that contain metastatic precursors capable of disseminating and metastasizing at an early stage of the disease. IRIS-inhibitory peptide killed these IRISOE TNBC/TICs, in vivo and prevented their dissemination and metastasis. We propose IRIS inactivation could be pursued to prevent dissemination and metastasis from early TNBC tumor lesions in patients.

  14. Core Promoter Plasticity Between Maize Tissues and Genotypes Contrasts with Predominance of Sharp Transcription Initiation Sites.

    Science.gov (United States)

    Mejía-Guerra, María Katherine; Li, Wei; Galeano, Narmer F; Vidal, Mabel; Gray, John; Doseff, Andrea I; Grotewold, Erich

    2015-12-01

    Core promoters are crucial for gene regulation, providing blueprints for the assembly of transcriptional machinery at transcription start sites (TSSs). Empirically, TSSs define the coordinates of core promoters and other regulatory sequences. Thus, experimental TSS identification provides an essential step in the characterization of promoters and their features. Here, we describe the application of CAGE (cap analysis of gene expression) to identify genome-wide TSSs used in root and shoot tissues of two maize (Zea mays) inbred lines (B73 and Mo17). Our studies indicate that most TSS clusters are sharp in maize, similar to mice, but distinct from Arabidopsis thaliana, Drosophila melanogaster, or zebra fish, in which a majority of genes have broad-shaped TSS clusters. We established that ∼38% of maize promoters are characterized by a broader TATA-motif consensus, and this motif is significantly enriched in genes with sharp TSSs. A noteworthy plasticity in TSS usage between tissues and inbreds was uncovered, with ∼1500 genes showing significantly different dominant TSSs, sometimes affecting protein sequence by providing alternate translation initiation codons. We experimentally characterized instances in which this differential TSS utilization results in protein isoforms with additional domains or targeted to distinct subcellular compartments. These results provide important insights into TSS selection and gene expression in an agronomically important crop.

  15. Reassembly of nucleosomes at the MLH1 promoter initiates resilencing following decitabine exposure.

    Directory of Open Access Journals (Sweden)

    Luke B Hesson

    Full Text Available Hypomethylating agents reactivate tumor suppressor genes that are epigenetically silenced in cancer. Inevitably these genes are resilenced, leading to drug resistance. Using the MLH1 tumor suppressor gene as a model, we showed that decitabine-induced re-expression was dependent upon demethylation and eviction of promoter nucleosomes. Following decitabine withdrawal, MLH1 was rapidly resilenced despite persistent promoter demethylation. Single molecule analysis at multiple time points showed that gene resilencing was initiated by nucleosome reassembly on demethylated DNA and only then was followed by remethylation and stable silencing. Taken together, these data establish the importance of nucleosome positioning in mediating resilencing of drug-induced gene reactivation and suggest a role for therapeutic targeting of nucleosome assembly as a mechanism to overcome drug resistance.

  16. Releasing stimuli and aggression in crickets: octopamine promotes escalation and maintenance but not initiation

    Directory of Open Access Journals (Sweden)

    Jan eRillich

    2015-04-01

    Full Text Available Biogenic amines have widespread effects on numerous behaviors, but their natural functions are often unclear. We investigated the role of octopamine (OA, the invertebrate analogue of noradrenaline, on initiation and maintenance of aggression in male crickets of different social status. The key-releasing stimulus for aggression is antennal fencing between males, a behavior occurring naturally on initial contact. We show that mechanical antennal stimulation (AS alone is sufficient to initiate an aggressive response (mandible threat display. The efficacy of AS was augmented in winners of a previous fight, but unaffected in losers. The efficacy of AS was not, however, influenced by OA receptor (OAR agonists or antagonists, regardless of social status. Additional experiments indicate that the efficacy of AS is also not influenced by dopamine (DA or serotonin (5HT. In addition to initiating an aggressive response, prior AS enhanced aggression exhibited in subsequent fights, whereby AS with a male antenna was now necessary, indicating a role for male contact pheromones. This priming effect of male-AS on subsequent aggression was dependent on OA since it was blocked by OAR-antagonists, and enhanced by OAR-agonists. Together our data reveal that neither OA, DA nor 5HT are required for initiating aggression in crickets, nor do these amines influence the efficacy of the natural releasing stimulus to initiate aggression. OA’s natural function is restricted to promoting escalation and maintenance of aggression once initiated, and this can be invoked by numerous experiences, including prior contact with a male antenna as shown here.

  17. Parents' Perspectives of School Mental Health Promotion Initiatives Are Related to Parents' Self-Assessed Parenting Capabilities

    Science.gov (United States)

    Askell-Williams, Helen

    2016-01-01

    Achieving broad-scale parent engagement with school initiatives has proven elusive. This article reports survey data from 287 Maltese parents about their perceptions of the quality of their child's school's initiatives for promoting students' wellbeing and mental health. Findings indicate that, on average, parents rated school initiatives highly.…

  18. Differential phosphorylation of perilipin 1A at the initiation of lipolysis revealed by novel monoclonal antibodies and high content analysis.

    Science.gov (United States)

    McDonough, Patrick M; Maciejewski-Lenoir, Dominique; Hartig, Sean M; Hanna, Rita A; Whittaker, Ross; Heisel, Andrew; Nicoll, James B; Buehrer, Benjamin M; Christensen, Kurt; Mancini, Maureen G; Mancini, Michael A; Edwards, Dean P; Price, Jeffrey H

    2013-01-01

    Lipolysis in adipocytes is regulated by phosphorylation of lipid droplet-associated proteins, including perilipin 1A and hormone-sensitive lipase (HSL). Perilipin 1A is potentially phosphorylated by cAMP(adenosine 3',5'-cyclic monophosphate)-dependent protein kinase (PKA) on several sites, including conserved C-terminal residues, serine 497 (PKA-site 5) and serine 522 (PKA-site 6). To characterize perilipin 1A phosphorylation, novel monoclonal antibodies were developed, which selectively recognize perilipin 1A phosphorylation at PKA-site 5 and PKA-site 6. Utilizing these novel antibodies, as well as antibodies selectively recognizing HSL phosphorylation at serine 563 or serine 660, we used high content analysis to examine the phosphorylation of perilipin 1A and HSL in adipocytes exposed to lipolytic agents. We found that perilipin PKA-site 5 and HSL-serine 660 were phosphorylated to a similar extent in response to forskolin (FSK) and L-γ-melanocyte stimulating hormone (L-γ-MSH). In contrast, perilipin PKA-site 6 and HSL-serine 563 were phosphorylated more slowly and L-γ-MSH was a stronger agonist for these sites compared to FSK. When a panel of lipolytic agents was tested, including multiple concentrations of isoproterenol, FSK, and L-γ-MSH, the pattern of results was virtually identical for perilipin PKA-site 5 and HSL-serine 660, whereas a distinct pattern was observed for perilipin PKA-site 6 and HSL-serine 563. Notably, perilipin PKA-site 5 and HSL-serine 660 feature two arginine residues upstream from the phospho-acceptor site, which confers high affinity for PKA, whereas perilipin PKA-site 6 and HSL-serine 563 feature only a single arginine. Thus, we suggest perilipin 1A and HSL are differentially phosphorylated in a similar manner at the initiation of lipolysis and arginine residues near the target serines may influence this process.

  19. Differential phosphorylation of perilipin 1A at the initiation of lipolysis revealed by novel monoclonal antibodies and high content analysis.

    Directory of Open Access Journals (Sweden)

    Patrick M McDonough

    Full Text Available Lipolysis in adipocytes is regulated by phosphorylation of lipid droplet-associated proteins, including perilipin 1A and hormone-sensitive lipase (HSL. Perilipin 1A is potentially phosphorylated by cAMP(adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA on several sites, including conserved C-terminal residues, serine 497 (PKA-site 5 and serine 522 (PKA-site 6. To characterize perilipin 1A phosphorylation, novel monoclonal antibodies were developed, which selectively recognize perilipin 1A phosphorylation at PKA-site 5 and PKA-site 6. Utilizing these novel antibodies, as well as antibodies selectively recognizing HSL phosphorylation at serine 563 or serine 660, we used high content analysis to examine the phosphorylation of perilipin 1A and HSL in adipocytes exposed to lipolytic agents. We found that perilipin PKA-site 5 and HSL-serine 660 were phosphorylated to a similar extent in response to forskolin (FSK and L-γ-melanocyte stimulating hormone (L-γ-MSH. In contrast, perilipin PKA-site 6 and HSL-serine 563 were phosphorylated more slowly and L-γ-MSH was a stronger agonist for these sites compared to FSK. When a panel of lipolytic agents was tested, including multiple concentrations of isoproterenol, FSK, and L-γ-MSH, the pattern of results was virtually identical for perilipin PKA-site 5 and HSL-serine 660, whereas a distinct pattern was observed for perilipin PKA-site 6 and HSL-serine 563. Notably, perilipin PKA-site 5 and HSL-serine 660 feature two arginine residues upstream from the phospho-acceptor site, which confers high affinity for PKA, whereas perilipin PKA-site 6 and HSL-serine 563 feature only a single arginine. Thus, we suggest perilipin 1A and HSL are differentially phosphorylated in a similar manner at the initiation of lipolysis and arginine residues near the target serines may influence this process.

  20. European Commission Initiatives to Promote Social Concern on the Market: a Counterbalance to Fiscal Discipline?

    Directory of Open Access Journals (Sweden)

    Laura Gómez Urquijo

    2014-03-01

    Full Text Available The aim of this article is to analyse the significance of recent European Commission initiatives in the face of evidence of non-compliance with the social objectives targeted in the EU 2020 Strategy. In the midst of the ongoing debate regarding austerity and growth, we stress the need to further the EU trend toward differentiated growth-friendly fiscal consolidation. Given that “conditionality” is a new keystone of economic governance and cohesion policy, the difficulties that the Member States encounter and the diversity of their social protections give a new meaning to the European coordination policies that are intended to promote social cohesion. By analysing EU proposals and official documents, we will show how the Commission’s initiatives have introduced diverse elements that are intended to address the social consequences of the economic crisis and reveal how new ideas of growth and new ways to deepen the internal market have been promoted. We will also determine whether we can consider these ideas to be a valid response to current social challenges.

  1. Exposure to Brefeldin A promotes initiation of meiosis in murine female germ cells.

    Science.gov (United States)

    Zhang, Lian-Jun; Chen, Bo; Feng, Xin-Lei; Ma, Hua-Gang; Sun, Li-Lan; Feng, Yan-Min; Liang, Gui-Jin; Cheng, Shun-Feng; Li, Lan; Shen, Wei

    2015-01-01

    In mammals, ontogenesis starts from a fusion of spermatozoon and oocyte, which are produced by reductive nuclear division of a diploid germ cell in a specialised but complex biological process known as meiosis. However, little is known about the mechanism of meiotic initiation in germ cells, although many factors may be responsible for meiosis both in male and female gonads. In this study, 11.5 days post coitum (dpc) female fetal mouse genital ridges were cultured in vitro with exposure to Brefeldin A (BFA) for 6h, and the changes in meiosis were detected. Synaptonemal-complex analysis implied that BFA played a positive role in meiosis initiation and this hypothesis was confirmed by quantitative PCR of meiosis-specific genes: stimulated by retinoic acid gene 8 (Stra8) and deleted in a zoospermia-like (DAZL). At the same time, mRNA expression of retinoic acid synthetase (Raldh2) and retinoic acid (RA) receptors increased in female gonads with in vitro exposure to BFA. Transplanting genital ridges treated with BFA into the kidney capsule of immunodeficient mice demonstrated that the development capacity of female germ cells was normal, while formation of primordial follicles was seen to be a result of accelerated meiosis after exposure to BFA. In conclusion, the study indicated that BFA stimulated meiosis initiation partly by RA signalling and then promoted the development of follicles.

  2. Antithyroglobulin antibody

    Science.gov (United States)

    Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

  3. PROMOTING RURAL DESTINATION BUCOVINA VIA FACEBOOK. AN EMPIRICAL IDENTIFICATION OF SUPPORTING ONLINE MARKETING INITIATIVES

    Directory of Open Access Journals (Sweden)

    Pavel STANCIU

    2016-09-01

    Full Text Available The villages of Bucovina possess a particular charm, mainly through the orthodox churches with heritage value, the deep spiritual character sent both to local communities and tourists, the architecture based on wood handicraft, the manner in which traditions, local customs and crafts are still preserved, the multicultural character, and, not least, the outstanding hospitality of the hosts.Continuous improvement of performance in rural tourism refers to an integrated approach of specific elements in the destination Bucovina, online marketing becoming more present in everyday practice of small entrepreneurs in local tourism. From an empirical point of view, promotion of rural tourism on Facebook and YouTube represents an easy initiative accessible to the general public, which has the ability to create the foundation of a competitive tourism.

  4. Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells.

    Directory of Open Access Journals (Sweden)

    Ines Herrmann

    Full Text Available With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof.

  5. Recent federal initiatives to promote unconventional gas: High octane delivery of just hot air?

    Energy Technology Data Exchange (ETDEWEB)

    Griff, M.T.

    1995-10-01

    This paper provides an overview of recent initiatives of the United States which promote greater use of natural gas and unconventional gas as one part of this nations`s larger response to the global warming threat. Measurable increases in greenhouse gas concentrations since the beginning of the industrial revolution have led to the belief in the existence of a global warming problem. The international community has responded to the global warming threat with the United Nations Framework Convention on Climate Change which is directed toward the stabilization of greenhouse gases in the atmosphere. The Climate Change Action Plan is the Clinton Administration`s detailed response to the global warming threat. It is designed to return United States emissions of greenhouse gases to their 1990 levels by the year 2000. The Action Plan targets all greenhouse gases and emphasizes energy efficiency. Significant regulatory reformation designed to increase the efficiency of the natural gas industry has already occurred and will be continued. Recovery of methane emissions from landfills will be encouraged through indentification of suitable sites and use of existing technology and development of new technology. Recovery of methane from coal mining operations will be promoted by targeting 50 of the gassiest mines in the United States. Even if the Action Plan is fully implemented. legitimate questions arise as to whether its goals will be achieved as a result of funding shortfalls.

  6. A Social Partnership Model to Promote Educators' Development in Mauritius through Formal and Informal Capacity-Building Initiatives

    Science.gov (United States)

    Santally, Mohammad Issack; Cooshna-Naik, Dorothy; Conruyt, Noel; Wing, Caroline Koa

    2015-01-01

    This paper describes a social partnership model based on the living lab concept to promote the professional development of educators through formal and informal capacity-building initiatives. The aim is to have a broader impact on society through community outreach educational initiatives. A Living Lab is an environment for user-centered…

  7. Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis.

    Science.gov (United States)

    Misra, Uma Kant; Mowery, Yvonne; Kaczowka, Steven; Pizzo, Salvatore Vincent

    2009-05-01

    Binding of activated α(2)-macroglobulin to GRP78 on the surface of human prostate cancer cells promotes proliferation by activating signaling cascades. Autoantibodies directed against the activated α(2)-macroglobulin binding site in the NH(2)-terminal domain of GRP78 are receptor agonists, and their presence in the sera of cancer patients is a poor prognostic indicator. We now show that antibodies directed against the GRP78 COOH-terminal domain inhibit [(3)H]thymidine uptake and cellular proliferation while promoting apoptosis as measured by DNA fragmentation, Annexin V assay, and clonogenic assay. These antibodies are receptor antagonists blocking autophosphorylation and activation of GRP78. Using 1-LN and DU145 prostate cancer cell lines and A375 melanoma cells, which express GRP78 on their cell surface, we show that antibodies directed against the COOH-terminal domain of GRP78 up-regulate the tumor suppressor protein p53. By contrast, antibody directed against the NH(2)-terminal domain of GRP78 shows negligible effects on p53 expression. PC-3 prostate cancer cells, which do not express GRP78 on their cell surface, are refractory to the effects of anti-GRP78 antibodies directed against either the COOH- or NH(2)-terminal domains. However, overexpression of GRP78 in PC-3 cells causes translocation of GRP78 to the cell surface and promotes apoptosis when these cells are treated with antibody directed against its COOH-terminal domain. Silencing GRP78 or p53 expression by RNA interference significantly blocked the increase in p53 induced by antibodies. Antibodies directed against the COOH-terminal domain may play a therapeutic role in cancer patients whose tumors trigger the production of autoantibodies directed against the NH(2)-terminal domain of GRP78.

  8. A STUDY ON LIMITATION OF GOVERNMENT INITIATIVE MODEL FOR ALTERNATIVE FUEL VEHICLE (AFV PROMOTION IN CHINA

    Directory of Open Access Journals (Sweden)

    Byunghun Choi

    2016-04-01

    Full Text Available Chinese responsibility for reducing Greenhouse Gas or carbon dioxide emission increases continuously. Chinese government suggested two targets; Alternative Fuel Vehicle output volume 500 thousand and AFV market share 5% by the end of 2011. However any of two targets did not come true. Therefore this study accessed the question, ‘why Chinese government initiative model for AFV promotion has been so poor?’ This study reviewed the transition process for AFV policies in China and made a structural analysis for three key policies since 2009. As a result the number of articles for related industries or factor endowments was relatively more than firm strategy or demand conditions. Also this study accessed the AFV strategy of Six SOEs from the perspective of social responsibility. Six SOEs have more concentrated on electric vehicle rather than hybrid vehicle with following the government leadership. However major EV or HEV models of them mostly were made by Joint Ventures being under control of foreign makers and the JVs have actually controlled over AFV business. So the limitation of Chinese government initiative model resulted from supplier-centric approach with targeting for public transportation and institution consumer, and it caused a failure to create the demand conditions of general customers.

  9. FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells.

    Directory of Open Access Journals (Sweden)

    Sungeun Kim

    Full Text Available Emerging evidence suggests that some cancers contain a population of stem-like TICs (tumor-initiating cells and eliminating TICs may offer a new strategy to develop successful anti-cancer therapies. As molecular mechanisms underlying the maintenance of the TIC pool are poorly understood, the development of TIC-specific therapeutics remains a major challenge. We first identified and characterized TICs and non-TICs isolated from a mouse breast cancer model. TICs displayed increased tumorigenic potential, self-renewal, heterogeneous differentiation, and bipotency. Gene expression analysis and immunostaining of TICs and non-TICs revealed that FGFR2 was preferentially expressed in TICs. Loss of FGFR2 impaired self-renewal of TICs, thus resulting in marked decreases in the TIC population and tumorigenic potential. Restoration of FGFR2 rescued the defects in TIC pool maintenance, bipotency, and breast tumor growth driven by FGFR2 knockdown. In addition, pharmacological inhibition of FGFR2 kinase activity led to a decrease in the TIC population which resulted in suppression of breast tumor growth. Moreover, human breast TICs isolated from patient tumor samples were found enriched in a FGFR2+ population that was sufficient to initiate tumor growth. Our data suggest that FGFR2 is essential in sustaining the breast TIC pool through promotion of self-renewal and maintenance of bipotent TICs, and raise the possibility of FGFR2 inhibition as a strategy for anti-cancer therapy by eradicating breast TICs.

  10. Asphalt fume dermal carcinogenicity potential: II. Initiation-promotion assay of Type III built-up roofing asphalt.

    Science.gov (United States)

    Freeman, James J; Schreiner, Ceinwen A; Beazley, S; Burnett, Donald M; Clark, Charles R; Mahagaokar, Suneeta; Parker, Craig M; Stewart, Christopher W; Swanson, Mark S; Arp, Earl W

    2011-10-01

    Clark et al. (accepted for publication) reported that a sample of field-matched fume condensate from a Type III built-up roofing asphalt (BURA) resulted in a carcinogenic response in a mouse skin bioassay, with relatively few tumor-bearing animals, long tumor latency and chronic skin irritation. This mouse skin initiation/promotion study was conducted to assess possible mechanisms, i.e., genotoxic initiation vs. tumor promotion subsequent to repeated skin injury and repair. The same Type III BURA fume condensate sample was evaluated in groups of 30 male Crl:CD1® mice by skin application twice per week (total dose of 50 mg/week) for 2 weeks during the initiation phase and for 26 weeks during the promotion phase. Positive control substances were 7,12-dimethylbenz(a)anthracene (DMBA, 50 μg applied once) as an initiator and 12-O-tetradecanoyl-13-acetate (TPA, 5 μg, applied twice weekly) during the promotion phase. During the 6 months of study with the asphalt fume condensate, eight skin masses were observed when tested for initiation, five of which were confirmed microscopically to be benign squamous cell papillomas. Only two papillomas were observed when tested for promotion. There was no apparent relationship between skin irritation and tumor development in this study. These results are more indicative of genotoxicity rather than a non-genotoxic mode of action.

  11. Comparison between indirect enzyme-linked immunosorbent assays for Anaplasma marginale antibodies with recombinant major surface protein 5 and initial body antigens

    Directory of Open Access Journals (Sweden)

    Virgínia MG Silva

    2006-08-01

    Full Text Available Indirect enzyme-linked immunosorbent assays (ELISAs based on recombinant major surface protein 5 (rMSP5 and initial body (IB antigens from a Brazilian isolate of Anaplasma marginale were developed to detect antibodies against this rickettsia in cattle. Both tests showed the same sensitivity (98.2% and specificities (100% for rMSP5 and 93.8% for IB ELISA which did not differ statistically. No cross-reactions were detected with Babesia bigemina antibodies, but 5 (rMSP5 ELISA to 15% (IB ELISA of cross-reactions were detected with B. bovis antibodies. However, such difference was not statistically significant. Prevalences of seropositive crossbred beef cattle raised extensively in Miranda county, state of Mato Grosso do Sul, Brazil, were 78.1% by rMSP5 ELISA and 79.7% by IB ELISA. In the analysis of sera from dairy calves naturally-infected with A. marginale, the dynamics of antibody production was very similar between both tests, with maternal antibodies reaching the lowest levels at 15-30 days, followed by an increase in the mean optical densities in both ELISAs, suggesting the development of active immunity against A. marginale. Results showed that all calves were seropositive by one-year old, characterizing a situation of enzootic stability. The similar performances of the ELISAs suggest that both tests can be used in epidemiological surveys for detection of antibodies to A. marginale in cattle.

  12. Ultraviolet irradiation initiates ectopic foot formation in regenerating hydra and promotes budding

    Indian Academy of Sciences (India)

    Saroj S Ghaskadbi; Leena Shetye; Shashi Chiplonkar; Surendra Ghaskadbi

    2005-03-01

    We have studied the effects of ultraviolet-C (UVC) and Ultraviolet-B (UVB) on growth and pattern formation in Pelmatohydra oligactis. UVC brings about a significant increase in budding in intact hydra while UVB does not exhibit such an effect. Excessive budding could be a response for survival at wavelengths that damage biological tissues. If the head or base piece of a bisected hydra is irradiated and recombined with the unirradiated missing part, regeneration proceeds normally indicating that exposure of a body part with either an intact head or foot to UVC does not influence pattern formation. Most significantly, in the middle piece, but not in the head or the base piece of a trisected hydra, UVC leads to initiation of ectopic feet formation in almost one third of the cases. Thus, UV irradiation interferes with pattern formation in regenerating hydra, possibly by changing positional values, and promotes budding in intact hydra. This is the first report on induction of ectopic feet formation by UV in regenerating hydra and opens up the possibility of using UV irradiation as a tool to understand pattern formation in the enigmatic hydra.

  13. Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch.

    Science.gov (United States)

    Muto, Akihiko; Ochiai, Kyoko; Kimura, Yoshitaka; Itoh-Nakadai, Ari; Calame, Kathryn L; Ikebe, Dai; Tashiro, Satoshi; Igarashi, Kazuhiko

    2010-12-01

    Two transcription factors, Pax5 and Blimp-1, form a gene regulatory network (GRN) with a double-negative loop, which defines either B-cell (Pax5 high) or plasma cell (Blimp-1 high) status as a binary switch. However, it is unclear how this B-cell GRN registers class switch DNA recombination (CSR), an event that takes place before the terminal differentiation to plasma cells. In the absence of Bach2 encoding a transcription factor required for CSR, mouse splenic B cells more frequently and rapidly expressed Blimp-1 and differentiated to IgM plasma cells as compared with wild-type cells. Genetic loss of Blimp-1 in Bach2(-/-) B cells was sufficient to restore CSR. These data with mathematical modelling of the GRN indicate that Bach2 achieves a time delay in Blimp-1 induction, which inhibits plasma cell differentiation and promotes CSR (Delay-Driven Diversity model for CSR). Reduction in mature B-cell numbers in Bach2(-/-) mice was not rescued by Blimp-1 ablation, indicating that Bach2 regulates B-cell differentiation and function through Blimp-1-dependent and -independent GRNs.

  14. Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters

    DEFF Research Database (Denmark)

    Chen, Yun; Pai, Athma A.; Herudek, Jan;

    2016-01-01

    sites, promoters often cluster so that the divergent activity of one might impact another. Here we found that the distance between promoters strongly correlates with the expression, stability and length of their associated PROMPTs. Adjacent promoters driving divergent mRNA transcription support PROMPT...... suggest that basic building blocks of divergently transcribed core promoter pairs, in combination with the wealth of TSSs in mammalian genomes, provide a framework with which evolution shapes transcriptomes....

  15. Promoting Space Education and Awareness in Pakistan- Initiatives, Achievements, Challenges and Issues

    Science.gov (United States)

    Jagirani, Aisha

    With about 180 million inhabitants, Pakistan is the sixth most populous and the 34th largest country in the world in terms of area. Pakistan's economy, which is pre-dominantly based on agriculture, is the 26th largest in the world in terms of purchasing power parity and 45th largest in terms of nominal GDP. Pakistan is counted among the Next Eleven (N11) countries that have the potential to become the world's largest economies in the 21st century. Despite considerable potential to develop into a stable, moderate and democratic state, major challenges of internal security, poor agricultural productivity, inadequate infrastructure, food insecurity, insufficient health and educational facilities, depletion of natural resources, rapid environmental degradation and recurring natural disasters have burdened the country and have hampered sustainable development of Pakistan. Space technology applications offer a cost-effective means of addressing many of the above mentioned issues and have made impressive advances in the last few years in different countries in the region. Unfortunately, for various reasons, Pakistan has not been able to fully exploit the benefits of space technology and its applications to meet the challenges she faces. One of the reasons is lack of awareness and understanding by planners, decision-makers and users about the potential benefits of space technology in planning and implementation of developmental plans as well as good governance. Similarly, Pakistan's space program enjoys little public support due, primarily, to lack of awareness of the benefits space offers and the ubiquitousness of space applications in modern life. There is thus an acute need to create awareness and educate all segments of the society and stakeholders in Pakistan about the potential benefits of space technology and its applications. In the past ten years, many initiatives have been taken to promote space education and awareness for students as well as decision-makers in

  16. Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse.

    Science.gov (United States)

    Sødring, Marianne; Gunnes, Gjermund; Paulsen, Jan Erik

    2016-04-15

    The C57BL/6J multiple intestinal neoplasia (Min/+) mouse is a widely used murine model for familial adenomatous polyposis, a hereditary form of human colorectal cancer. However, it is a questionable model partly because the vast majority of tumors arise in the small intestine, and partly because the fraction of tumors that progress to invasive carcinomas is minuscule. A/J mice are typically more susceptible to carcinogen-induced colorectal cancer than C57BL/6J mice. To investigate whether the novel Min/+ mouse on the A/J genetic background could be a better model for colorectal cancer, we examined the spontaneous intestinal tumorigenesis in 81 A/J Min/+ mice ranging in age from 4 to 60 weeks. The A/J Min/+ mouse exhibited a dramatic increase in number of colonic lesions when compared to what has been reported for the conventional Min/+ mouse; however, an increase in small intestinal lesions did not occur. In addition, this novel mouse model displayed a continual development of colonic lesions highlighted by the transition from early lesions (flat ACF) to tumors over time. In mice older than 40 weeks, 13 colonic (95% CI: 8.7-16.3) and 21 small intestinal (95% CI: 18.6-24.3) tumors were recorded. Notably, a considerable proportion of those lesions progressed to carcinomas in both the colon (21%) and small intestine (51%). These findings more closely reflect aspects of human colorectal carcinogenesis. In conclusion, the novel A/J Min/+ mouse may be a relevant model for initiation, promotion and progression of colorectal cancer.

  17. Mental health promotion initiatives for children and youth in contexts of poverty: the case of South Africa.

    Science.gov (United States)

    Petersen, Inge; Swartz, Leslie; Bhana, Arvin; Flisher, Alan J

    2010-09-01

    In order to achieve sustainable development and a consequent reduction in levels of poverty, a multisectoral response to development incorporating pro-poor economic policies in low- to middle-income countries (LMICs) is required. An important aspect is strengthening the human capital asset base of vulnerable populations. This should include the promotion of mental health, which can play an important role in breaking the intergenerational cycle of poverty and mental ill-health through promoting positive mental health outcomes within the context of risk. For each developmental phase of early childhood, middle childhood and adolescence, this article provides: (i) an overview of the critical risk influences and evidence of the role of mental health promotion initiatives in mediating these influences; (ii) a background to these risk influences in South Africa; and (iii) a review of mental health promotion initiatives addressing distal upstream influences at a macro-policy level in South Africa, as well as evidence-based micro- and community-level interventions that have the potential to be scaled up. From this review, strengths and gaps in existing micro- and community-level evidence-based mental health promotion interventions as well as macro-policy-level initiatives are identified, and recommendations made for South Africa that may also have applicability for other LMICs.

  18. Sustainable Professional Learning for Early Childhood Educators: Lessons from an Australia-Wide Mental Health Promotion Initiative

    Science.gov (United States)

    Askell-Williams, Helen; Murray-Harvey, Rosalind

    2016-01-01

    New policy initiatives, such as those concerned with promoting young children's positive mental health, highlight the need for good quality professional education in the early childhood education and care sector. However, although a wealth of literature exists from the school sector, little is known about professional education in early childhood…

  19. Protection against Chlamydia trachomatis infection and upper genital tract pathological changes by vaccine-promoted neutralizing antibodies directed to the VD4 of the major outer membrane protein

    DEFF Research Database (Denmark)

    Olsen, Anja W.; Follmann, Frank; Erneholm, Karin Susanne

    2015-01-01

    The VD4 region from the Chlamydia trachomatis major outer membrane protein contains important neutralizing B-cell epitopes of relevance for antibody-mediated protection against genital tract infection. We developed a multivalent vaccine construct based on VD4s and their surrounding constant segme...... of the major outer membrane protein resulted in a protective and broadly neutralizing vaccine. Our findings emphasize the important role of antibodies in protection against Chlamydia trachomatis.......The VD4 region from the Chlamydia trachomatis major outer membrane protein contains important neutralizing B-cell epitopes of relevance for antibody-mediated protection against genital tract infection. We developed a multivalent vaccine construct based on VD4s and their surrounding constant...... segments from serovars D, E, and F. Adjuvanted with cationic liposomes, this construct promoted strong immune responses to serovar-specific epitopes, the conserved LNPTIAG epitope and neutralized serovars D, E, and F. Vaccinated mice were protected against challenge, with protection defined as reduced...

  20. Mental health promotion in the health care setting: collaboration and engagement in the development of a mental health promotion capacity-building initiative.

    Science.gov (United States)

    Horn, Michelle A; Rauscher, Alana B; Ardiles, Paola A; Griffin, Shannon L

    2014-01-01

    Health Compass is an innovative, multiphased project that aims to transform health care practice and shift organizational culture by building the capacity of Provincial Health Services Authority (PHSA) health care providers to further promote the mental health and well-being of patients and families accessing PHSA's health care services. Health Compass was developed within a health promotion framework, which involved collaboration and engagement with stakeholders across all partnering PHSA agencies. This approach led to the development of an educational and training resource that contributes to increased capacity for mental health promotion within the health care setting. Based on interviews with Health Compass' internal Project Team and findings from a Stakeholder Engagement Evaluation Report, this article outlines the participatory approach taken to develop the Health Compass Mental Health Promotion Resource and E-Learning Tool. A number of key facilitators for collaboration and engagement are discussed, which may be particularly applicable to the implementation of a mental health promotion program or initiative within a complex health care setting.

  1. Designing a HER2/neu promoter to drive alpha1,3galactosyltransferase expression for targeted anti-alphaGal antibody-mediated tumor cell killing.

    OpenAIRE

    Lanteri, Marion; Ollier, Laurence; Giordanengo, Valérie; Lefebvre, Jean-Claude

    2005-01-01

    INTRODUCTION: Our goal was to specifically render tumor cells susceptible to natural cytolytic anti-alphaGal antibodies by using a murine alpha1,3galactosyltransferase (malphaGalT) transgene driven by a designed form of HER2/neu promoter (pNeu), the transcription of which is frequently observed to be above basal in breast tumors. Indeed, the alphaGalT activity that promotes Galalpha1,3Galbeta1,4GlcNAc-R (alphaGal) epitope expression has been mutationally disrupted during the course of evoluti...

  2. Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.

    OpenAIRE

    Maronpot, R R; Foley, J F; Takahashi, K; Goldsworthy, T; Clark, G; Tritscher, A; Portier, C; Lucier, G

    1993-01-01

    The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses ...

  3. Using the tax system to promote physical activity: critical analysis of Canadian initiatives.

    Science.gov (United States)

    von Tigerstrom, Barbara; Larre, Tamara; Sauder, Joanne

    2011-08-01

    In Canada, tax incentives have been recently introduced to promote physical activity and reduce rates of obesity. The most prominent of these is the federal government's Children's Fitness Tax Credit, which came into effect in 2007. We critically assess the potential benefits and limitations of using tax measures to promote physical activity. Careful design could make these measures more effective, but any tax-based measures have inherent limitations, and the costs of such programs are substantial. Therefore, it is important to consider whether public funds are better spent on other strategies that could instead provide direct public funding to address environmental and systemic factors.

  4. Effects of dietary β-carotene and selenium on initiation and promotion of pancreatic carcinogenesis in azaserine-treated rats

    NARCIS (Netherlands)

    Appel, M.J.; Woutersen, R.A.

    1996-01-01

    In the present study the effects of 0.1 or 1.0 g β-carotene/kg diet (LβC or HβC) and 1.0 mg or 2.5 mg selenium/kg diet (LSel or HSel), as well as combinations of the respective low and high concentrations of p-carotene and selenium (LMix or HMix) on the initiation/early promotion phase or on the lat

  5. Promotion of initial cell adhesion on trisuccinimidyl citrate-modified nickel-free high-nitrogen stainless steel.

    Science.gov (United States)

    Sasaki, Makoto; Inoue, Motoki; Katada, Yasuyuki; Taguchi, Tetsushi

    2013-04-01

    The surface of nickel-free high-nitrogen stainless steel (HNS) was modified with a citric acid-based cross-linker, trisuccinimidyl citrate (TSC), to promote initial cell adhesion in external skeletal fixation pins. The remaining active ester groups on TSC-immobilized HNS reacted with the amino groups of serum proteins. The immobilized serum proteins formed cell recognition sites to promote the initial cell adhesion immediately after cell seeding. The amount of fibronectin, which is a typical cell adhesion protein, immobilized on the TSC-immobilized HNS surface was threefold greater than on the original HNS after only 15 min. The fibroblastic cell culture experiments showed that the initial cell adhesion was significantly enhanced on the TSC-immobilized HNS compared with the original HNS at 3 h. Furthermore, the cell adhesion activity of the TSC-immobilized HNS continued to promote cell proliferation even at 7 days. Therefore, TSC-immobilized HNS may enable the rapid integration of soft tissues through its reaction with the patient's serum proteins and extracellular proteins around the surgical site.

  6. The 'Practice Entrepreneur' - An Australian case study of a systems thinking inspired health promotion initiative.

    Science.gov (United States)

    Joyce, A; Green, C; Carey, G; Malbon, E

    2017-01-23

    The potential of systems science concepts to inform approaches for addressing complex public health problems, such as obesity prevention, has been attracting significant attention over the last decade. Despite its recent popularity, there are very few studies examining the application of systems science concepts, termed systems thinking, in practice and whether (if at all) it influences the implementation of health promotion in real world settings and in what ways. Healthy Together Victoria (HTV) was based on a systems thinking approach to address obesity prevention alongside other chronic health problems and was implemented across 14 local government areas. This paper examines the experience of practitioners from one of those intervention sites. In-depth interviews with eight practitioners revealed that there was a rigidity with which they had experienced previous health promotion jobs relative to the flexibility and fluidity of HTV. While the health promotion literature does not indicate that health promotion should be overly prescriptive, the experience of these practitioners suggests it is being applied as such in real world settings. Within HTV, asking people to work with 'systems thinking', without giving a prescription about what systems thinking is, enabled practitioners to be 'practice entrepreneurs' by choosing from a variety of systems thinking methods (mapping, reflection) to engage actively in their positions. This highlights the importance of understanding how key concepts, both traditional planning approaches and systems science concepts, are interpreted and then implemented in real world settings.

  7. From DDR to Security Promotion: Connecting national programs to community initiatives

    NARCIS (Netherlands)

    Verkoren, W.; Willems, R.C.; Kleingeld, J.; Rouw, H.

    2010-01-01

    Disarmament, demobilization and reintegration (DDR) is a set of activities that forms part of strategies for peacebuilding after civil war. DDR has become the standard way of addressing security threats in immediate post-conflict situations. However, DDR is designed to promote national security, rat

  8. Nonalcoholic steatohepatitis induced by a high-fat diet promotes diethylnitrosamine initiated early hepatocarcinogenesis in rats

    Science.gov (United States)

    It has been suggested that patients with nonalcoholic steatohepatitis (NASH) are at a high risk for liver cancer. However, it is unknown whether high-fat diet induced NASH promotes hepatocarcinogenesis. In the present study, Sprague-Dawley rats were injected with a low dose of hepatic carcinogen die...

  9. Mechanism of initiation site selection promoted by the human rhinovirus 2 internal ribosome entry site.

    Science.gov (United States)

    Kaminski, Ann; Pöyry, Tuija A A; Skene, Peter J; Jackson, Richard J

    2010-07-01

    Translation initiation site usage on the human rhinovirus 2 internal ribosome entry site (IRES) has been examined in a mixed reticulocyte lysate/HeLa cell extract system. There are two relevant AUG triplets, both in a base-paired hairpin structure (domain VI), with one on the 5' side at nucleotide (nt) 576, base paired with the other at nt 611, which is the initiation site for polyprotein synthesis. A single residue was inserted in the apical loop to put AUG-576 in frame with AUG-611, and in addition another in-frame AUG was introduced at nt 593. When most of the IRES was deleted to generate a monocistronic mRNA, the use of these AUGs conformed to the scanning ribosome model: improving the AUG-576 context increased initiation at this site and decreased initiation at downstream sites, whereas the converse was seen when AUG-576 was mutated to GUA; and AUG-593, when present, took complete precedence over AUG-611. Under IRES-dependent conditions, by contrast, much less initiation occurred at AUG-576 than in a monocistronic mRNA with the same AUG-576 context, mutation of AUG-576 decreased initiation at downstream sites by approximately 70%, and introduction of AUG-593 did not completely abrogate initiation at AUG-611, unless the apical base pairing in domain VI was destroyed by point mutations. These results indicate that ribosomes first bind at the AUG-576 site, but instead of initiating there, most of them are transferred to AUG-611, the majority by strictly linear scanning and a substantial minority by direct transfer, which is possibly facilitated by the occasional persistence of base pairing in the apical part of the domain VI stem.

  10. Inhibition of adenovirus replication by the E1A antisense transcript initiated from hsp70 and VA-1 promoters.

    Science.gov (United States)

    Miroshnichenko, O I; Borisenko, A S; Ponomareva, T I; Tikhonenko, T I

    1990-03-01

    The E1A region of the adenoviral genome, important for initiation of virus infection and activation of other viral genes, was chosen as a target for engineering antisense RNA (asRNA) to inhibit adenovirus 5 (Ad5) replication in COS-1 cell culture in vitro. The hsp70 promoter, taken from the appropriate heat-shock-protein gene of Drosophila melanogaster, and the VA-1 RNA promoter, derived from the Ad5 gene coding for low-molecular-mass VA-1 RNA and recognized by RNA polymerase III were used as regulatory elements of transcription. The two types of recombinant constructs contained E1A fragments of 710 bp (hsp70 constructs) or 380 or 740 bp (VA-1 RNA constructs) in reverse orientation relative to the promoter position, as well as a transcription termination signal, the SV40 ori, and the gene controlling Geneticin (antibiotic G418) resistance (G418R). After selection of transfected COS-1 cells in the presence of G418, a number of stable G418R cell lines were raised which expressed engineered asRNAs. Plating of Ad5 suspensions of known titre on monolayers of transfected COS-1 cells clearly showed strong inhibition of adenovirus replication by asRNAs: 75% with the hsp70 promoter and 90% with the VA-1 RNA promoter.

  11. The effects of tobacco sales promotion on initiation of smoking--experiences from Finland and Norway.

    Science.gov (United States)

    Rimpelä, M K; Aarø, L E; Rimpelä, A H

    1993-01-01

    Norway and Finland were among the first countries to adopt a total ban on tobacco sales promotion. Such legislation came into force in Norway and Finland in 1975 and 1978 respectively. These two countries are sometimes referred to as illustrations that such legislation has been successfully used as a means to reduce tobacco consumption. Tobacco industry spokesmen seem to interpret available evidence in the opposite way and maintain that the prohibition has not contributed to reducing the use of tobacco. Among the publications referred to and misused by tobacco industry spokesmen are publications from the authors of the present report. The effects of a ban on advertising can only be properly examined after describing a reasonable conceptual model. Such a model has to take into account (i) other social and cultural predictors of smoking, (ii) tobacco sales promotion in the contexts of all other mass communication, (iii) control measures other than a ban, and (iv) the degree of success in implementing the ban on advertising. Like any other kind of mass communication tobacco advertising influences the individual in a rather complex way. Behaviour change may be regarded as the outcome of an interpersonal and intrapersonal process. Social science research on tobacco advertising and the effects of banning such advertising has a short history, most studies having been carried out in the late 1980s. After examining available evidence related to the effects of tobacco advertising on the smoking habits of adolescents we conclude as follows: the few scientifically valid reports available today give both theoretical and empirical evidence for a causal relationship. Tobacco sales promotion seems both to promote and to reinforce smoking among young people. The dynamic tobacco market represented by children and adolescents is probably the main target of tobacco sales promotion. In Finland, there have been few studies explicitly addressing the causal links between tobacco sales

  12. The legal framework and initiatives for promoting safety in the United Arab Emirates.

    Science.gov (United States)

    Grivna, Michal; Aw, Tar-Ching; El-Sadig, Mohamed; Loney, Tom; Sharif, Amer Ahmad; Thomsen, Jens; Mauzi, Mariam; Abu-Zidan, Fikri M

    2012-01-01

    Injury is a leading cause of morbidity and mortality in the United Arab Emirates (UAE). The UAE is a rapidly developing country with fast economic growth, demographical and environmental changes that are associated with new hazards emerging at a similar pace. The UAE as a federal entity has federal and local systems responsible for safety policy, regulations and enforcement. To set priorities for safety promotion and injury prevention, it is necessary to have data on the most frequent external causes of injury and the main individual, equipment and environmental risk factors that contribute to injury. However good quality data for injury prevention are scarce. The aim of this paper is to describe the scale of injury as a public health problem in the UAE, and the development of safety policies, regulations and promotion efforts with special emphasis on traffic, occupational and child safety.

  13. Limited in vivo bioassays on some benzodiazepines: lack of experimental initiating or promoting effect of the benzodiazepine tranquillizers diazepam, clorazepate, oxazepam and lorazepam.

    Science.gov (United States)

    Mazue, G; Remandet, B; Gouy, D; Berthe, J; Roncucci, R; Williams, G M

    1982-05-01

    Four benzodiazepine tranquillizers were tested for their ability to initiate or promote the development of preneoplastic and neoplastic rat liver lesions. In comparison with the liver carcinogen, N-2-fluorenylacetamide, the benzodiazepines exhibited no initiating activity during a 14-week period of daily administration by gavage. To study the promoting activity, N-2-fluorenylacetamide was used to initiate altered foci and neoplastic nodules in rat liver during 8 weeks and then the benzodiazepines were administered by daily gavage for a period of 12 weeks. The liver tumor promoter phenobarbital had a substantial enhancing effect upon the persistence of nodules but none of the benzodiazepines showed a similar effect. Thus, in the process model systems used, to detect initiating or promoting potential effect, the benzodiazepine tranquillizers failed to exhibit either an initiating or a promoting action.

  14. The Efficacy of Humanized Antibody against the Sporothrix Antigen, gp70, in Promoting Phagocytosis and Reducing Disease Burden

    Science.gov (United States)

    de Almeida, José R. F.; Santiago, Karla L.; Kaihami, Gilberto H.; Maranhão, Andrea Q.; de Macedo Brígido, Marcelo; de Almeida, Sandro R.

    2017-01-01

    Sporotrichosis is a subcutaneous mycosis distributed worldwide and is frequently reported in countries with tropical climates, as Latin America countries. We previously demonstrated that mice with sporotrichosis produce specific antibodies against a 70-kDa fungal protein, indicating that specific antibodies against this molecule may help to control the sporotrichosis. IgG1 monoclonal antibody was generated, and called mAbP6E7, in mice against a 70-kDa glycoprotein (gp70) of S. schenckii. The mAbP6E7 showed prophylactic and therapeutic activity against sporotrichosis. However, this antibody has a murine origin, and this can generate an immune response when administered to humans, precluding its use for a prolonged time. For its possible use in the treatment of human sporotrichosis, we humanized the mAbP6E7 by genetic engineering. Once expressed, the humanized antibodies had good stability and were able to bind to the 70-kDa cell wall antigens of Sporothrix schenckii and S. brasiliensis. The humanized P6E7 were able to opsonize S. schenckii yeasts, thus increasing the phagocytic index in human monocyte-derived macrophages. The treatment with humanized P6E7 decreased fungal burden in vivo. These data suggest that humanized P6E7 may have a therapeutic role in sporotrichosis.

  15. Protection against Chlamydia trachomatis infection and upper genital tract pathological changes by vaccine-promoted neutralizing antibodies directed to the VD4 of the major outer membrane protein

    DEFF Research Database (Denmark)

    Olsen, Anja W.; Follmann, Frank; Erneholm, Karin Susanne;

    2015-01-01

    The VD4 region from the Chlamydia trachomatis major outer membrane protein contains important neutralizing B-cell epitopes of relevance for antibody-mediated protection against genital tract infection. We developed a multivalent vaccine construct based on VD4s and their surrounding constant...... segments from serovars D, E, and F. Adjuvanted with cationic liposomes, this construct promoted strong immune responses to serovar-specific epitopes, the conserved LNPTIAG epitope and neutralized serovars D, E, and F. Vaccinated mice were protected against challenge, with protection defined as reduced...... bacterial numbers in vagina and prevention of pathological changes in the upper genital tract. Adoptive transfer of serumand T-cell depletion experiments demonstrated a dominant role for antibodies and CD4+ T cells in the protective immune response. Integrating a multivalent VD4 construct into the sequence...

  16. The initial antibody response to HIV-1: induction of ineffective early B cell responses against GP41 by the transmitted/founder virus

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Leslie L [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    A window of opportunity for immune responses to extinguish HIV -1 exists from the moment of transmission through establishment of the latent pool of HIV -I-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus) but, to date, this period has been logistically difficult to analyze. Studies in non-human primates challenged with chimeric simianhuman immunodeficiency virus have shown that neutralizing antibodies, when present at the time of infection, can prevent virus infection.

  17. Toward the assessment of psychological empowerment in health promotion: initial tests of validity and reliability.

    Science.gov (United States)

    Rissel, C; Perry, C; Finnegan, J

    1996-08-01

    Because of the importance of empowerment in health promotion, the measurement of empowerment is a priority for health promotion research. The present study sought to develop a valid and reliable instrument to assess psychological empowerment and to resolve the theoretical question of whether psychological empowerment is a topic-specific or general construct. University of Minnesota employees (n = 160) completed two different versions of empowerment questionnaires. One of the questionnaires measured general empowerment; the other was specific to alcohol use prevention. Reasonable reliability was demonstrated in a previously developed general empowerment instrument (Cronbach's alpha coefficient of 0.84) and for an alcohol-specific instrument (Cronbach's alpha coefficient of 0.78). Construct validity for the alcohol-specific instrument was demonstrated by appropriate significant correlations between subscales and overall scores for both instruments. Predictive validity tests partially supported the concept that psychological empowerment is topic-specific, although further testing with a more representative population may be needed to resolve this question. The results suggest that the alcohol-specific psychological empowerment instrument could be used in the evaluation of community alcohol abuse prevention programmes.

  18. Regional initiatives to promote economic development in North-east Asia.

    OpenAIRE

    Nijkamp, P.; Wiegmans, B.W.

    1996-01-01

    This paper addresses the economic development potential of the Asian Pacific Rim, with a particular view on north East Asia. It is argued that growth triangles are likely to be a proper way of organizing regional development forces. Next, the attention is focused on the Tumen River Area Development Programme as a potentially interesting region for joint transnational development initiatives. The opportunities and threats of this area are explored by means of scenario analysis. It is conc1uded...

  19. Promoting the export of environmental technologies : governmental initiatives in selected countries

    OpenAIRE

    Kanda, Wisdom; Hjelm, Olof; Mejiá-Dugand, Santiago

    2013-01-01

    Rapid international and widespread diffusion of environmental technologies remains an essential requirement within the framework of sustainable development. Export offers a desired means for technology diffusion due to its strategic flexibility compared to other means such as foreign direct investment and aid. However, the export of environmental technologies is stifled by market failures. Among other reasons and as a response to such market failures, several governments are formulating initi...

  20. Radiation Promotes Colorectal Cancer Initiation and Progression by Inducing Senescence-Associated Inflammatory Responses

    Science.gov (United States)

    Kim, Sang Bum; Bozeman, Ronald; Kaisani, Aadil; Kim, Wanil; Zhang, Lu; Richardson, James A.; Wright, Woodring E.; Shay, Jerry W.

    2015-01-01

    Proton radiotherapy is becoming more common since protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared to conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIR) which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence associated gene (P19Arf) are markedly increased. Following these changes loss of Casein kinase Iα (CKIα) and induction of chronic DNA damage and TP53 mutations are increased compared to x-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, CDDO-EA, reduces proton irradiation associated SIR and tumorigenesis. Thus, exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA. PMID:26477319

  1. Relevance of the mouse skin initiation-promotion model for the classification of carcinogenic substances encountered at the workplace.

    Science.gov (United States)

    Schwarz, Michael; Thielmann, Heinz W; Meischner, Veronika; Fartasch, Manigé

    2015-06-01

    The Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission of the Deutsche Forschungsgemeinschaft) evaluates chemical substances using scientific criteria to prevent adverse effects on health at the work place. As part of this task there is a need to evaluate tumor promoting activity of chemicals (enhancement of formation of squamous cell carcinomas via premalignant papillomas) obtained from two-stage initiation/promotion experiments using the mouse skin model. In the present communication we address this issue by comparing responses seen in mouse skin with those in humans. We conclude that tumor promotional effects seen in such animal models be carefully analyzed on a case by case basis. Substances that elicit a rather non-specific effect that is restricted to the high dose range are considered to be irrelevant to humans and thus do not require classification as carcinogens. In contrast, substances that might have both a mode of action and a potency similar to the specific effects seen with TPA (12-O-tetradecanoylphorbol-13-acetate), the prototype tumor promoter in mouse skin, which triggers receptor-mediated signal cascades in the very low dose range, have to be classified in a category for carcinogens.

  2. Sexual experience promotes adult neurogenesis in the hippocampus despite an initial elevation in stress hormones.

    Directory of Open Access Journals (Sweden)

    Benedetta Leuner

    Full Text Available Aversive stressful experiences are typically associated with increased anxiety and a predisposition to develop mood disorders. Negative stress also suppresses adult neurogenesis and restricts dendritic architecture in the hippocampus, a brain region associated with anxiety regulation. The effects of aversive stress on hippocampal structure and function have been linked to stress-induced elevations in glucocorticoids. Normalizing corticosterone levels prevents some of the deleterious consequences of stress, including increased anxiety and suppressed structural plasticity in the hippocampus. Here we examined whether a rewarding stressor, namely sexual experience, also adversely affects hippocampal structure and function in adult rats. Adult male rats were exposed to a sexually-receptive female once (acute or once daily for 14 consecutive days (chronic and levels of circulating glucocorticoids were measured. Separate cohorts of sexually experienced rats were injected with the thymidine analog bromodeoxyuridine in order to measure cell proliferation and neurogenesis in the hippocampus. In addition, brains were processed using Golgi impregnation to assess the effects of sexual experience on dendritic spines and dendritic complexity in the hippocampus. Finally, to evaluate whether sexual experience alters hippocampal function, rats were tested on two tests of anxiety-like behavior: novelty suppressed feeding and the elevated plus maze. We found that acute sexual experience increased circulating corticosterone levels and the number of new neurons in the hippocampus. Chronic sexual experience no longer produced an increase in corticosterone levels but continued to promote adult neurogenesis and stimulate the growth of dendritic spines and dendritic architecture. Chronic sexual experience also reduced anxiety-like behavior. These findings suggest that a rewarding experience not only buffers against the deleterious actions of early elevated

  3. Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy

    DEFF Research Database (Denmark)

    Litvinov, Ivan V.; Shtreis, Anna; Kobayashi, Kenneth

    2016-01-01

    -Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV). In this report, we review recent evidence evaluating the involvement of these agents in cancer initiation/progression. Most importantly, recent molecular experimental evidence documented for the first time that S...... are then able to activate STAT3 and STAT5 oncogenic signaling and promote cancer progression and IL-17 secretion. In light of these findings, it might be important for patients with exacerbation of their CTCL symptoms to maintain high index of suspicion and treat these individuals for S. aureus colonization and...

  4. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer.

    Science.gov (United States)

    Koliaraki, Vasiliki; Pasparakis, Manolis; Kollias, George

    2015-12-14

    The importance of mesenchymal cells in inflammation and/or neoplastic transformation is well recognized, but their role in the initiation of these processes, particularly in the intestine, remains elusive. Using mouse models of colorectal cancer, we show that IKKβ in intestinal mesenchymal cells (IMCs) is critically involved in colitis-associated, but not spontaneous tumorigenesis. We further demonstrate that IMC-specific IKKβ is involved in the initiation of colitis-associated cancer (CAC), as in its absence mice develop reduced immune cell infiltration, epithelial cell proliferation, and dysplasia at the early stages of the disease. At the molecular level, these effects are associated with decreased early production of proinflammatory and protumorigenic mediators, including IL-6, and reduced STAT3 activation. Ex vivo IKKβ-deficient IMCs show defective responses to innate immune stimuli such as LPS, as shown by decreased NF-κB signaling and reduced expression of important NF-κB target genes. Collectively, our results reveal a hitherto unknown role of mesenchymal IKKβ in driving inflammation and enabling carcinogenesis in the intestine.

  5. Phosphazene-promoted metal-free ring-opening polymerization of ethylene oxide initiated by carboxylic acid

    KAUST Repository

    Zhao, Junpeng

    2014-03-11

    The effectiveness of carboxylic acid as initiator for the anionic ring-opening polymerization of ethylene oxide was investigated with a strong phosphazene base (t-BuP4) used as promoter. Kinetic study showed an induction period, i.e., transformation of carboxylic acid to hydroxyl ester, followed by slow chain growth together with simultaneous and fast end-group transesterification, which led to poly(ethylene oxide) (PEO) consisting of monoester (monohydroxyl), diester, and dihydroxyl species. An appropriate t-BuP4/acid ratio was proven to be essential to achieve better control over the polymerization and low dispersity of PEO. This work provides important information and enriches the toolbox for macromolecular and biomolecular engineering with protic initiating sites. © 2014 American Chemical Society.

  6. Promotional tone in reviews of menopausal hormone therapy after the Women's Health Initiative: an analysis of published articles.

    Directory of Open Access Journals (Sweden)

    Adriane Fugh-Berman

    2011-03-01

    Full Text Available BACKGROUND: Even after the Women's Health Initiative (WHI found that the risks of menopausal hormone therapy (hormone therapy outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy. METHODS AND FINDINGS: We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1 Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2 acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement

  7. Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance.

    Directory of Open Access Journals (Sweden)

    Yang Lu

    2011-07-01

    Full Text Available Phenotypic plasticity is common in development. For Candida albicans, the most common cause of invasive fungal infections in humans, morphological plasticity is its defining feature and is critical for its pathogenesis. Unlike other fungal pathogens that exist primarily in either yeast or hyphal forms, C. albicans is able to switch reversibly between yeast and hyphal growth forms in response to environmental cues. Although many regulators have been found involved in hyphal development, the mechanisms of regulating hyphal development and plasticity of dimorphism remain unclear. Here we show that hyphal development involves two sequential regulations of the promoter chromatin of hypha-specific genes. Initiation requires a rapid but temporary disappearance of the Nrg1 transcriptional repressor of hyphal morphogenesis via activation of the cAMP-PKA pathway. Maintenance requires promoter recruitment of Hda1 histone deacetylase under reduced Tor1 (target of rapamycin signaling. Hda1 deacetylates a subunit of the NuA4 histone acetyltransferase module, leading to eviction of the NuA4 acetyltransferase module and blockage of Nrg1 access to promoters of hypha-specific genes. Promoter recruitment of Hda1 for hyphal maintenance happens only during the period when Nrg1 is gone. The sequential regulation of hyphal development by the activation of the cAMP-PKA pathway and reduced Tor1 signaling provides a molecular mechanism for plasticity of dimorphism and how C. albicans adapts to the varied host environments in pathogenesis. Such temporally linked regulation of promoter chromatin by different signaling pathways provides a unique mechanism for integrating multiple signals during development and cell fate specification.

  8. Sea-ice dynamics strongly promote Snowball Earth initiation and destabilize tropical sea-ice margins

    Directory of Open Access Journals (Sweden)

    A. Voigt

    2012-12-01

    Full Text Available The Snowball Earth bifurcation, or runaway ice-albedo feedback, is defined for particular boundary conditions by a critical CO2 and a critical sea-ice cover (SI, both of which are essential for evaluating hypotheses related to Neoproterozoic glaciations. Previous work has shown that the Snowball Earth bifurcation, denoted as (CO2, SI*, differs greatly among climate models. Here, we study the effect of bare sea-ice albedo, sea-ice dynamics and ocean heat transport on (CO2, SI* in the atmosphere–ocean general circulation model ECHAM5/MPI-OM with Marinoan (~ 635 Ma continents and solar insolation (94% of modern. In its standard setup, ECHAM5/MPI-OM initiates a~Snowball Earth much more easily than other climate models at (CO2, SI* ≈ (500 ppm, 55%. Replacing the model's standard bare sea-ice albedo of 0.75 by a much lower value of 0.45, we find (CO2, SI* ≈ (204 ppm, 70%. This is consistent with previous work and results from net evaporation and local melting near the sea-ice margin. When we additionally disable sea-ice dynamics, we find that the Snowball Earth bifurcation can be pushed even closer to the equator and occurs at a hundred times lower CO2: (CO2, SI* ≈ (2 ppm, 85%. Therefore, the simulation of sea-ice dynamics in ECHAM5/MPI-OM is a dominant determinant of its high critical CO2 for Snowball initiation relative to other models. Ocean heat transport has no effect on the critical sea-ice cover and only slightly decreases the critical CO2. For disabled sea-ice dynamics, the state with 85% sea-ice cover is stabilized by the Jormungand mechanism and shares characteristics with the Jormungand climate states. However, there is no indication of the Jormungand bifurcation and hysteresis in ECHAM5/MPI-OM. The state with 85% sea-ice cover therefore is a soft Snowball state rather than a true

  9. Promoting policy and environmental change using photovoice in the Kaiser Permanente Community Health Initiative.

    Science.gov (United States)

    Kramer, Leila; Schwartz, Pamela; Cheadle, Allen; Borton, J Elaine; Wright, Merrick; Chase, Charlie; Lindley, Corina

    2010-05-01

    Creative ways must be found to engage both community residents and political leaders around policy and environmental solutions to public health issues. Photovoice is a community-based, participatory approach to documentary photography that provides people with training on photography, ethics, critical discussion, and policy advocacy. Photovoice projects have been implemented across the nation as part of Kaiser Permanente's Community Health Initiative-a community-based obesity prevention effort. This article focuses on the first Photovoice project implemented in three communities in Colorado. Photovoice themes related to healthy eating and active living include a lack of access to healthy food choices in stores and schools, unsafe street crossings and sidewalks, and the need to redevelop certain areas to encourage safe recreation. The involvement of policy leaders in the project combined with several dissemination activities has contributed to healthier food offerings in schools and neighborhoods and city planning efforts that emphasize walkability and access to healthy food, and park revitalization.

  10. MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer.

    Science.gov (United States)

    Edmonds, Mick D; Boyd, Kelli L; Moyo, Tamara; Mitra, Ramkrishna; Duszynski, Robert; Arrate, Maria Pia; Chen, Xi; Zhao, Zhongming; Blackwell, Timothy S; Andl, Thomas; Eischen, Christine M

    2016-01-01

    MicroRNA (miR) are important regulators of gene expression, and aberrant miR expression has been linked to oncogenesis; however, little is understood about their contribution to lung tumorigenesis. Here, we determined that miR-31 is overexpressed in human lung adenocarcinoma and this overexpression independently correlates with decreased patient survival. We developed a transgenic mouse model that allows for lung-specific expression of miR-31 to test the oncogenic potential of miR-31 in the lung. Using this model, we observed that miR-31 induction results in lung hyperplasia, followed by adenoma formation and later adenocarcinoma development. Moreover, induced expression of miR-31 in mice cooperated with mutant KRAS to accelerate lung tumorigenesis. We determined that miR-31 regulates lung epithelial cell growth and identified 6 negative regulators of RAS/MAPK signaling as direct targets of miR-31. Our study distinguishes miR-31 as a driver of lung tumorigenesis that promotes mutant KRAS-mediated oncogenesis and reveals that miR-31 directly targets and reduces expression of negative regulators of RAS/MAPK signaling.

  11. Promoting Robust Design of Diode Lasers for Space: A National Initiative

    Science.gov (United States)

    Tratt, David M.; Amzajerdian, Farzin; Kashem, Nasir B.; Shapiro, Andrew A.; Mense, Allan T.

    2007-01-01

    The Diode-laser Array Working Group (DAWG) is a national-level consumer/provider forum for discussion of engineering and manufacturing issues which influence the reliability and survivability of high-power broad-area laser diode devices in space, with an emphasis on laser diode arrays (LDAs) for optical pumping of solid-state laser media. The goals of the group are to formulate and validate standardized test and qualification protocols, operational control recommendations, and consensus manufacturing and certification standards. The group is using reliability and lifetime data collected by laser diode manufacturers and the user community to develop a set of standardized guidelines for specifying and qualifying laser diodes for long-duration operation in space, the ultimate goal being to promote an informed U.S. Government investment and procurement strategy for assuring the availability and durability of space-qualified LDAs. The group is also working to establish effective implementation of statistical design techniques at the supplier design, development, and manufacturing levels to help reduce product performance variability and improve product reliability for diodes employed in space applications

  12. Combination of chondroitinase ABC, glial cell line-derived neurotrophic factor and Nogo A antibody delayed-release microspheres promotes the functional recovery of spinal cord injury.

    Science.gov (United States)

    Zhang, Yu; Gu, Zuchao; Qiu, Guixing; Song, Yueming

    2013-11-01

    Spinal cord injury (SCI) is one of the most devastating injuries for patients. Glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophic factor for the regeneration of the spinal neuraxial bundle, but GDNF would degrade rapidly if the protein was injected into the site of injury; thus, it cannot exert its fullest effects. Therefore, we introduced a delivery system of GDNF, poly(lactide-co-glycolic acid) (PLGA) delayed-release microspheres, in the current study and observed the effect of PLGA-GDNF and the combination of PLGA-GDNF and another 2 agents PLGA-chondroitinase ABC (ChABC) and PLGA-Nogo A antibody in the treatment of SCI rats. Our results showed that PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres could elevate the locomotor scores of SCI rats. The effect of PLGA-GDNF was much better than that of GDNF. The cortical somatosensory evoked potential was also improved by PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres. Our results suggest that PLGA delayed-release microsphere may be a useful and effective tool in delivering protein agents into the injury sites of patients with SCI. This novel combination therapy may provide a new idea in promoting the functional recovery of the damaged spinal cord.

  13. Adjuvant and carrier protein-dependent T-cell priming promotes a robust antibody response against the Plasmodium falciparum Pfs25 vaccine candidate

    Science.gov (United States)

    Radtke, Andrea J.; Anderson, Charles F.; Riteau, Nicolas; Rausch, Kelly; Scaria, Puthupparampil; Kelnhofer, Emily R.; Howard, Randall F.; Sher, Alan; Germain, Ronald N.; Duffy, Patrick

    2017-01-01

    Humoral immune responses have the potential to maintain protective antibody levels for years due to the immunoglobulin-secreting activity of long-lived plasma cells (LLPCs). However, many subunit vaccines under development fail to generate robust LLPC responses, and therefore a variety of strategies are being employed to overcome this limitation, including conjugation to carrier proteins and/or formulation with potent adjuvants. Pfs25, an antigen expressed on malaria zygotes and ookinetes, is a leading transmission blocking vaccine (TBV) candidate for Plasmodium falciparum. Currently, the conjugate vaccine Pfs25-EPA/Alhydrogel is in Phase 1 clinical trials in the USA and Africa. Thus far, it has proven to be safe and immunogenic, but it is expected that a more potent formulation will be required to establish antibody titers that persist for several malaria transmission seasons. We sought to determine the contribution of carrier determinants and adjuvants in promoting high-titer, long-lived antibody responses against Pfs25. We found that both adjuvants and carrier proteins influence the magnitude and capacity of Pfs25-specific humoral responses to remain above a protective level. Furthermore, a liposomal adjuvant with QS21 and a TLR4 agonist (GLA-LSQ) was especially effective at inducing T follicular helper (Tfh) and LLPC responses to Pfs25 when coupled to immunogenic carrier proteins. PMID:28091576

  14. Initial experience at a university teaching hospital from using telemedicine to promote education through video conferencing

    Directory of Open Access Journals (Sweden)

    Bruno Monteiro Tavares Pereira

    Full Text Available CONTEXT AND OBJECTIVE: Telehealth and telemedicine services are advancing rapidly, with an increasing spectrum of information and communication technologies that can be applied broadly to the population's health, and to medical education. The aim here was to report our institution's experience from 100 videoconferencing meetings between five different countries in the Americas over a one-year period. DESIGN AND SETTING: Retrospective study at Universidade Estadual de Campinas. METHODS: Through a Microsoft Excel database, all conferences in all specialties held at our institution from September 2009 to August 2010 were analyzed retrospectively. RESULTS: A total of 647 students, physicians and professors participated in telemedicine meetings. A monthly mean of 8.3 (± 4.3 teleconferences were held over the analysis period. Excluding holidays and the month of inaugurating the telemedicine theatre, our teleconference rate reached a mean of 10.3 (± 2.7, or two teleconferences a week, on average. Trauma surgery and meetings on patient safety were by far the most common subjects discussed in our teleconference meetings, accounting for 22% and 21% of the total calls. CONCLUSION: Our experience with telemedicine meetings has increased students' interest; helped our institution to follow and discuss protocols that are already accepted worldwide; and stimulated professors to promote telemedicine-related research in their own specialties and keep up-to-date. These high-technology meetings have shortened distances in our vast country, and to other reference centers abroad. This virtual proximity has enabled discussion of international training with students and residents, to increase their overall knowledge and improve their education within this institution.

  15. The putative RNA helicase HELZ promotes cell proliferation, translation initiation and ribosomal protein S6 phosphorylation.

    Directory of Open Access Journals (Sweden)

    Philippe A Hasgall

    Full Text Available The hypoxia-inducible transcription factor (HIF is a key component of the cellular adaptation mechanisms to hypoxic conditions. HIFα subunits are degraded by prolyl-4-hydroxylase domain (PHD enzyme-dependent prolyl-4-hydroxylation of LxxLAP motifs that confer oxygen-dependent proteolytic degradation. Interestingly, only three non-HIFα proteins contain two conserved LxxLAP motifs, including the putative RNA helicase with a zinc finger domain HELZ. However, HELZ proteolytic regulation was found to be oxygen-independent, supporting the notion that a LxxLAP sequence motif alone is not sufficient for oxygen-dependent protein destruction. Since biochemical pathways involving RNA often require RNA helicases to modulate RNA structure and activity, we used luciferase reporter gene constructs and metabolic labeling to demonstrate that HELZ overexpression activates global protein translation whereas RNA-interference mediated HELZ suppression had the opposite effect. Although HELZ interacted with the poly(A-binding protein (PABP via its PAM2 motif, PABP was dispensable for HELZ function in protein translation. Importantly, downregulation of HELZ reduced translational initiation, resulting in the disassembly of polysomes, in a reduction of cell proliferation and hypophosphorylation of ribosomal protein S6.

  16. Where and how breastfeeding promotion initiatives should focus its attention? A study from rural Wardha

    Directory of Open Access Journals (Sweden)

    Dongre A

    2010-01-01

    Full Text Available Background: In India, the practice of breastfeeding is almost universal, but initiation of breastfeeding is generally quite late and colostrum is discarded. Integrated Management of Neonatal and Childhood Illness (IMNCI strategy recommended systematic assessment of breastfeeding and emphasized counseling of the mother on proper positioning and attachment of infant to the breast. Objective: To assess breastfeeding among mothers of below six months children in rural Wardha. Materials and Methods: The present cross-sectional study was undertaken in surrounding 23 villages of Kasturba Rural Health Training Center (KRHTC, Anji. Two Auxiliary Nurse Midwives (ANMs trained in IMNCI paid house visits to 99 mothers during the study period and undertook the assessment of breastfeeding using IMNCI assessment form for young infants. Auxiliary Nurse Midwives observed and recorded the positioning and attachment of infant to the breast as per IMNCI guidelines. The data were entered and analyzed using Epi_Info (version 6.04d software package. Results: Most of the deliveries 94 (94.9% took place in the healthcare facilities. Majority 61 (61.6% newborn babies had received breastfeeding within half an hour. About half of the mothers had any of the feeding problems like feeding less than eight times in 24 h, giving any other food or drinks or is low weight for age. Significantly more mothers with feeding problems had problems in positioning and attachment of infant to the breast as compared with those mothers who did not have any feeding problems. Conclusions: In the settings, where practice of institutional delivery is high, the staff of healthcare facility should ensure education of the mothers regarding position and attachment of infant to the breast before discharge from the healthcare facility. At the village level, Village Health Nutrition Day (VHND can be utilized for health education of future mothers and support for the breastfeeding mothers. The IMNCI

  17. Investigating ultra high-enthalpy geothermal systems: a collaborative initiative to promote scientific opportunities

    Science.gov (United States)

    Elders, W. A.; Nielson, D.; Schiffman, P.; Schriener, A., Jr.

    2014-12-01

    Scientists, engineers, and policy makers gathered at a workshop in the San Bernardino Mountains of southern California in October 2013 to discuss the science and technology involved in developing high-enthalpy geothermal fields. A typical high-enthalpy geothermal well between 2000 and 3000 m deep produces a mixture of hot water and steam at 200-300 °C that can be used to generate about 5-10 MWe of electric power. The theme of the workshop was to explore the feasibility and economic potential of increasing the power output of geothermal wells by an order of magnitude by drilling deeper to reach much higher pressures and temperatures. Development of higher enthalpy geothermal systems for power production has obvious advantages; specifically higher temperatures yield higher power outputs per well so that fewer wells are needed, leading to smaller environmental footprints for a given size of power plant. Plans for resource assessment and drilling in such higher enthalpy areas are already underway in Iceland, New Zealand, and Japan. There is considerable potential for similar developments in other countries that already have a large production of electricity from geothermal steam, such as Mexico, the Philippines, Indonesia, Italy, and the USA. However drilling deeper involves technical and economic challenges. One approach to mitigating the cost issue is to form a consortium of industry, government and academia to share the costs and broaden the scope of investigation. An excellent example of such collaboration is the Iceland Deep Drilling Project (IDDP), which is investigating the economic feasibility of producing electricity from supercritical geothermal reservoirs, and this approach could serve as model for future developments elsewhere. A planning committee was formed to explore creating a similar initiative in the USA.

  18. Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.

    Science.gov (United States)

    Maronpot, R R; Foley, J F; Takahashi, K; Goldsworthy, T; Clark, G; Tritscher, A; Portier, C; Lucier, G

    1993-12-01

    The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses were 3.5, 10.7, 35.7, and 125 ng TCDD/kg body weight/day. A significant body weight reduction was present in the noninitiated group that received 125 ng TCDD. Relative liver weight was statistically increased in initiated rats treated with > or = 10.7 ng TCDD and in noninitiated rats treated with > or = 35.7 ng TCDD. Histopathologic evidence of cytotoxicity was dose-related in all TCDD-treated groups. There was a statistically significant dose response in the bromodeoxyuridine (BrdU) S-phase labeling index (LI) in the DEN-initiated rats (p < 0.01) and a marginally significant trend in the saline-treated rats (p = 0.10), but proliferating cell nuclear antigen S-phase LI and growth fraction within altered hepatic foci showed no increase. Among the DEN-initiated groups there was a significant increase in glutathione S-transferase altered hepatic foci stereological parameters in the 125 ng TCDD group. This study demonstrates that dose-response relationships for TCDD's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on P450 gene expression, indicating that different biological or biochemical responses may exhibit different dose-response relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Designing a HER2/neu promoter to drive α1,3galactosyltransferase expression for targeted anti-αGal antibody-mediated tumor cell killing

    Science.gov (United States)

    Lanteri, Marion; Ollier, Laurence; Giordanengo, Valérie; Lefebvre, Jean-Claude

    2005-01-01

    Introduction Our goal was to specifically render tumor cells susceptible to natural cytolytic anti-αGal antibodies by using a murine α1,3galactosyltransferase (mαGalT) transgene driven by a designed form of HER2/neu promoter (pNeu), the transcription of which is frequently observed to be above basal in breast tumors. Indeed, the αGalT activity that promotes Galα1,3Galβ1,4GlcNAc-R (αGal) epitope expression has been mutationally disrupted during the course of evolution, starting from Old World primates, and this has led to the counter-production of large amounts of cytotoxic anti-αGal antibodies in recent primates, including man. Method Expression of the endogenous c-erbB-2 gene was investigated in various cell lines by northern blotting. A mαGalT cDNA was constructed into pcDNA3 vector downstream of the original CMV promoter (pCMV/mαGalT) and various forms of pNeu were prepared by PCR amplification and inserted in the pCMV/mαGalT construct upstream of the mαGalT cDNA, in the place of the CMV promoter. These constructs were transferred into HEK-293 control and breast tumor cell lines. Stably transfected cells were analyzed by northern blotting for their expression of αGalT and c-erbB-2, and by flow cytometry for their binding with fluorescein isothiocyanate-conjugated Griffonia simplicifolia/isolectin B4. Results We show that expression of the mαGalT was up- or down-modulated according to the level of endogenous pNeu activity and the particular form of constructed pNeu. Among several constructs, two particular forms of the promoter, pNeu250 containing the CCAAT box and the PEA3 motif adjacent to the TATAA box, and pNeu664, which has three additional PEA3 motifs upstream of the CCAAT box, were found to promote differential αGalT expression. Conclusion Our results strengthen current concepts about the crucial role played by the proximal PEA3 motif of pNeu, and may represent a novel therapeutic approach for the development of targeted transgene expression

  20. Anti-Pseudomonas aeruginosa IgY antibodies promote bacterial opsonization and augment the phagocytic activity of polymorphonuclear neutrophils

    DEFF Research Database (Denmark)

    Thomsen, Kim; Christophersen, Lars; Jensen, Peter Østrup

    2016-01-01

    Moderation of polymorphonuclear neutrophils (PMNs) as part of a critical defense against invading pathogens may offer a promising therapeutic approach to supplement the antibiotic eradication of Pseudomonas aeruginosa infection in non-chronically infected cystic fibrosis (CF) patients. We have...... observed that egg yolk antibodies (IgY) harvested from White leghorn chickens that target P. aeruginosa opsonize the pathogen and enhance the PMN-mediated respiratory burst and subsequent bacterial killing in vitro. The effects on PMN phagocytic activity were observed in different Pseudomonas aeruginosa...

  1. Improved micro-distribution of antibody-photon absorber conjugates after initial near infrared photoimmunotherapy (NIR-PIT).

    Science.gov (United States)

    Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Harada, Toshiko; Choyke, Peter L; Kobayashi, Hisataka

    2016-06-28

    Near infrared photoimmunotherapy (NIR-PIT), a targeted cancer therapy which uses an antibody-photo absorber conjugate (APC) and near infrared light exposure, dramatically improves nano-drug delivery into treated tumor beds due to enhanced vascular permeability. We investigated the micro-distribution of APCs in a variety of NIR-PIT treated tumors. Either cetuximab (cet) or trastuzumab (tra) conjugated with IR700 (cet-tra-IR700) was administered, as appropriate, to each mouse model of tumor. Tumor-bearing mice implanted with A431-GFP, MDAMB468-GFP, 3T3Her2-GFP or N87-GFP were separated into 5 groups: group 1=no treatment; group 2=cet-tra-IR700 i.v., no light exposure; group 3=cet-tra-IR700 i.v., NIR light exposure; group 4=cet-tra-IR700 i.v. and additional cet-tra-IR700 i.v. at 24h but no light exposure; group 5=cet-tra-IR700 i.v., NIR light exposure and additional cet-tra-IR700 i.v. immediately after NIR but no additional NIR light exposure. In vivo, ex vivo and microscopic fluorescence imaging was performed. Fluorescence from the surface of the tumor (s-tumor) was compared to fluorescence from deeper areas of the tumor (d-tumor). In general, there was no significant difference in the fluorescence intensity of GFP in the tumors among all groups, however the highest IR700 fluorescence intensity was consistently shown in group 5 tumors due to added APC after NIR-PIT. Fluorescence microscopy in all tumor types demonstrated that GFP relative fluorescence intensity (RFI) in s-tumor was significantly lower in group 3 and 5 (NIR-PIT groups) than in group 1, 2, and 4 (no NIR-PIT) yet there was no significant difference in d-tumor RFI among all groups. IR700 fluorescent RFI in the d-tumor was highest in group 5 (NIR-PIT+additional APC) compared to the other groups. Cell killing after NIR-PIT was primarily on the surface, however, APCs administered immediately after NIR-PIT penetrated deeper into tissue resulting in improved cell killing after a 2nd NIR-PIT session. This

  2. Evaluation of the Mental Healthiness Aging Initiative: community program to promote awareness about mental health and aging issues.

    Science.gov (United States)

    Zanjani, Faika; Kruger, Tina; Murray, Deborah

    2012-04-01

    The objective of this study is to evaluate the Mental Healthiness Aging Initiative, designed to promote community awareness and knowledge about mental health and aging issues. This study occurred during 2007-2009 in 67 of 120 counties in Kentucky. A rural region (11 counties) received the intervention, consisting of focus groups, Extension Agent training, and television-based social marketing campaign. Partial-intervention counties (29 counties) received only the television-based social marketing campaign. The control counties (27 counties) received no intervention activities. Results indicated that the intervention counties agreed more with being able to assist elder adults with a potential mental illness. Also, the intervention counties understood the risk of consuming alcohol and medications better, but had a poorer recognition of drinking problems in elder adults. These findings need to be considered within study limitations, such as measurement error, degree of intervention exposure, and regional differences across intervention groups. The study demonstrates that community interventions on mental health awareness and knowledge are feasible within majority rural regions, with Extension Agents being gatekeepers, for promoting positive messages about mental health and aging issues.

  3. The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.

    Directory of Open Access Journals (Sweden)

    Mauricio Menacho-Márquez

    2013-07-01

    Full Text Available The catalytic activity of GDP/GTP exchange factors (GEFs is considered critical to maintain the typically high activity of Rho GTPases found in cancer cells. However, the large number of them has made it difficult to pinpoint those playing proactive, nonredundant roles in tumors. In this work, we have investigated whether GEFs of the Vav subfamily exert such specific roles in skin cancer. Using genetically engineered mice, we show here that Vav2 and Vav3 favor cooperatively the initiation and promotion phases of skin tumors. Transcriptomal profiling and signaling experiments indicate such function is linked to the engagement of, and subsequent participation in, keratinocyte-based autocrine/paracrine programs that promote epidermal proliferation and recruitment of pro-inflammatory cells. This is a pathology-restricted mechanism because the loss of Vav proteins does not cause alterations in epidermal homeostasis. These results reveal a previously unknown Rho GEF-dependent pro-tumorigenic mechanism that influences the biology of cancer cells and their microenvironment. They also suggest that anti-Vav therapies may be of potential interest in skin tumor prevention and/or treatment.

  4. Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); Dai, Jianxin [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); Wang, Huaqing [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); Wei, Huafeng [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); Zhao, Jian [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); Guo, Yajun, E-mail: yguo_smmu@163.com [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); and others

    2014-09-26

    Highlight: • We first report that anti-osteopontin mAb could protect osteoporosis in mice. • Anti-osteopontin mAb could promote the osteoclast apoptosis. • Targeting osteopontin might have therapeutic potentials for osteoporosis. - Abstract: Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorption through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases.

  5. The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA.

    Science.gov (United States)

    Weingarten-Gabbay, S; Khan, D; Liberman, N; Yoffe, Y; Bialik, S; Das, S; Oren, M; Kimchi, A

    2014-01-30

    Translational regulation of the p53 mRNA can determine the ratio between p53 and its N-terminal truncated isoforms and therefore has a significant role in determining p53-regulated signaling pathways. Although its importance in cell fate decisions has been demonstrated repeatedly, little is known about the regulatory mechanisms that determine this ratio. Two internal ribosome entry sites (IRESs) residing within the 5'UTR and the coding sequence of p53 mRNA drive the translation of full-length p53 and Δ40p53 isoform, respectively. Here, we report that DAP5, a translation initiation factor shown to positively regulate the translation of various IRES containing mRNAs, promotes IRES-driven translation of p53 mRNA. Upon DAP5 depletion, p53 and Δ40p53 protein levels were decreased, with a greater effect on the N-terminal truncated isoform. Functional analysis using bicistronic vectors driving the expression of a reporter gene from each of these two IRESs indicated that DAP5 preferentially promotes translation from the second IRES residing in the coding sequence. Furthermore, p53 mRNA expressed from a plasmid carrying this second IRES was selectively shifted to lighter polysomes upon DAP5 knockdown. Consequently, Δ40p53 protein levels and the subsequent transcriptional activation of the 14-3-3σ gene, a known target of Δ40p53, were strongly reduced. In addition, we show here that DAP5 interacts with p53 IRES elements in in vitro and in vivo binding studies, proving for the first time that DAP5 directly binds a target mRNA. Thus, through its ability to regulate IRES-dependent translation of the p53 mRNA, DAP5 may control the ratio between different p53 isoforms encoded by a single mRNA.

  6. Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters.

    Science.gov (United States)

    Yang, Chuhu; Bolotin, Eugene; Jiang, Tao; Sladek, Frances M; Martinez, Ernest

    2007-03-01

    The core promoter of eukaryotic genes is the minimal DNA region that recruits the basal transcription machinery to direct efficient and accurate transcription initiation. The fraction of human and yeast genes that contain specific core promoter elements such as the TATA box and the initiator (INR) remains unclear and core promoter motifs specific for TATA-less genes remain to be identified. Here, we present genome-scale computational analyses indicating that approximately 76% of human core promoters lack TATA-like elements, have a high GC content, and are enriched in Sp1-binding sites. We further identify two motifs - M3 (SCGGAAGY) and M22 (TGCGCANK) - that occur preferentially in human TATA-less core promoters. About 24% of human genes have a TATA-like element and their promoters are generally AT-rich; however, only approximately 10% of these TATA-containing promoters have the canonical TATA box (TATAWAWR). In contrast, approximately 46% of human core promoters contain the consensus INR (YYANWYY) and approximately 30% are INR-containing TATA-less genes. Significantly, approximately 46% of human promoters lack both TATA-like and consensus INR elements. Surprisingly, mammalian-type INR sequences are present - and tend to cluster - in the transcription start site (TSS) region of approximately 40% of yeast core promoters and the frequency of specific core promoter types appears to be conserved in yeast and human genomes. Gene Ontology analyses reveal that TATA-less genes in humans, as in yeast, are frequently involved in basic "housekeeping" processes, while TATA-containing genes are more often highly regulated, such as by biotic or stress stimuli. These results reveal unexpected similarities in the occurrence of specific core promoter types and in their associated biological processes in yeast and humans and point to novel vertebrate-specific DNA motifs that might play a selective role in TATA-independent transcription.

  7. Corynebacterium pyruviciproducens, as an immune modulator, can promote the activity of macrophages and up-regulate antibody response to particulate antigen.

    Science.gov (United States)

    Tong, Jia; Han, Qingzhen; Wang, Shengjun; Su, Zhaoliang; Zheng, Dong; Shen, Pei; Xia, Sheng; Huang, Xinxiang; Shao, Qixiang; Xu, Huaxi

    2012-11-01

    Corynebacterium pyruviciproducens is a newly discovered Corynebacterium species with no known pathogenic components such as diphtheria toxin and tuberculostearic acid, and it has similar biological properties to Propionibacterium acnes, but its role of immunoregulation is drawing people's attention. In this work, based on the role of macrophages in removal of pathogenic bacteria as a primary scavenger and particulate antigen-presenting cell, the stimulation of macrophages by C. pyruviciproducens was analyzed through detecting the levels of cytokine secretion and expression of membrane molecules, and the effect of C. pyruviciproducens in promoting antibody response to sheep red blood cells (SRBC) in vivo was detected. In vitro, C. pyruviciproducens led to a sharp release of interleukin-6 and tumour necrosis factor-α and encouraged the activation of macrophages including enhanced expressions of MHC-II, CD40, CD80 and CD86. In vivo, it enhanced the humoral immune response against SRBC, a particulate antigen. These observations suggest that C. pyruviciproducens, as an immunoregulator, can promote the host humoral immune response to pathogenic microorganisms by regulating macrophage function.

  8. Initial Teacher Education for School Health Promotion in Austria: Does It Support the Implementation of the Health-Promoting School Approach?

    Science.gov (United States)

    Flaschberger, Edith

    2013-01-01

    Purpose: School health promotion is said to be most effective when implemented through a comprehensive, settings-based, whole-school approach. The purpose of this paper is to address the current lack of knowledge about the current state of teacher education for health promotion and its potential to further the development of settings-based…

  9. The novel adjuvant dmLT promotes dose sparing, mucosal immunity and longevity of antibody responses to the inactivated polio vaccine in a murine model.

    Science.gov (United States)

    Norton, Elizabeth B; Bauer, David L; Weldon, William C; Oberste, M Steven; Lawson, Louise B; Clements, John D

    2015-04-15

    One option for achieving global polio eradication is to replace the oral poliovirus vaccine (OPV), which has the risk of reversion to wild-type virulence, with the inactivated poliovirus vaccine (IPV) vaccine. Adjuvants and alternate routes of immunization are promising options that may reduce antigen dose in IPV vaccinations, potentially allowing dose sparing and cost savings. Use of adjuvants and alternate routes of immunization could also help promote mucosal immunity, potentially mimicking the protection against intestinal virus shedding seen with OPV. In the current study, we examined the impact of combining the novel adjuvant dmLT with trivalent IPV for dose sparing, induction of mucosal immunity and increasing longevity of anti-poliovirus (PV) responses in a mouse model following either intradermal (ID) or intramuscular (IM) delivery. We found that non-adjuvanted ID delivery was not superior to IM delivery for fractional dose sparing, but was associated with development of mucosal immunity. Vaccination with IPV+dmLT promoted serum anti-PV neutralizing antibodies with fractional IPV doses by either IM or ID delivery, achieving at least five-fold dose sparing above non-adjuvanted fractional doses. These responses were most noticeable with the PV1 component of the trivalent vaccine. dmLT also promoted germinal center formation and longevity of serum anti-PV neutralizing titers. Lastly, dmLT enhanced mucosal immunity, as defined by fecal and intestinal anti-PV IgA secretion, when included in IPV immunization by ID or IM delivery. These studies demonstrate that dmLT is an effective adjuvant for either IM or ID delivery of IPV. Inclusion of dmLT in IPV immunizations allows antigen dose sparing and enhances mucosal immunity and longevity of anti-PV responses.

  10. Initial experience with locoregional radioimmunotherapy using {sup 131}I-labelled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)

    Energy Technology Data Exchange (ETDEWEB)

    Poepperl, G.; Gildehaus, F.J.; Hahn, K.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum Grosshadern, Muenchen (Germany); Goetz, C.; Reulen, H.J. [Klinik und Poliklinik fuer Neurochirurgie, Klinikum Grosshadern, Muenchen (Germany); Yousry, T.A. [Inst. fuer Neuroradiologie der LMU Muenchen, Klinikum Grosshadern, Muenchen (Germany)

    2002-06-01

    Aim: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radioimmunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. Methods: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq {sup 131}labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. Results: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse anti-bodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remain stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n=89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. Conclusions: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration

  11. Events during eucaryotic rRNA transcription initiation and elongation: Conversion from the closed to the open promoter complex requires nucleotide substrates

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, E.; Paule, M.R.

    1988-05-01

    Chemical footprinting and topological analysis were carried out on the Acanthamoeba castellanii rRNA transcription initiation factor (TIF) and RNA polymerase I complexes with DNA during transcription initiation and elongation. The results show that the binding of TIF and polymerase to the promoter does not alter the supercoiling of the DNA template and the template does not become sensitive to modification by diethylpyro-carbonate, which can identify melted DNA regions. Thus, in contrast to bacterial RNA polymerase, the eucaryotic RNA polymerase I-promoter complex is in a closed configuration preceding addition of nucleotides in vitro. Initiation and 3'-O-methyl CTP-limited translocation by RNA polymerase I results in separation of the polymerase-TIF footprints, leaving the TIF footprint unaltered. In contrast, initiation and translocation result in a significant change in the conformation of the polymerase-DNA complex, culminating in an unwound DNA region of at least 10 base pairs.

  12. Anti-Aquaporin-4 Antibody-Positive Neuromyelitis Optica Presenting with Syndrome of Inappropriate Antidiuretic Hormone Secretion as an Initial Manifestation

    Directory of Open Access Journals (Sweden)

    H. Nakajima

    2011-10-01

    Full Text Available The distribution of neuromyelitis optica (NMO-characteristic brain lesions corresponds to sites of high aquaporin-4 (AQP4 expression, and the brainstem and hypothalamus lesions that express high levels of AQP4 protein are relatively characteristic of NMO. The syndrome of inappropriate antidiuretic hormone secretion (SIADH is one of the important causes of hyponatremia and results from an abnormal production or sustained secretion of antidiuretic hormone (ADH. SIADH has been associated with many clinical states or syndromes, and the hypothalamic-neurohypophyseal system regulates the feedback control system for ADH secretion. We report the case of a 63-year-old man with NMO, whose initial manifestation was hyponatremia caused by SIADH. Retrospective analysis revealed that the serum anti-AQP4 antibody was positive, and an MRI scan showed a unilateral lesion in the hypothalamus. SIADH recovered completely with regression of the hypothalamic lesion. As such, NMO should even be considered in patients who develop SIADH and have no optic nerve or spinal cord lesions but have MRI-documented hypothalamic lesions.

  13. Anti-aquaporin-4 antibody-positive neuromyelitis optica presenting with syndrome of inappropriate antidiuretic hormone secretion as an initial manifestation.

    Science.gov (United States)

    Nakajima, H; Fujiki, Y; Ito, T; Kitaoka, H; Takahashi, T

    2011-09-01

    The distribution of neuromyelitis optica (NMO)-characteristic brain lesions corresponds to sites of high aquaporin-4 (AQP4) expression, and the brainstem and hypothalamus lesions that express high levels of AQP4 protein are relatively characteristic of NMO. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the important causes of hyponatremia and results from an abnormal production or sustained secretion of antidiuretic hormone (ADH). SIADH has been associated with many clinical states or syndromes, and the hypothalamic-neurohypophyseal system regulates the feedback control system for ADH secretion. We report the case of a 63-year-old man with NMO, whose initial manifestation was hyponatremia caused by SIADH. Retrospective analysis revealed that the serum anti-AQP4 antibody was positive, and an MRI scan showed a unilateral lesion in the hypothalamus. SIADH recovered completely with regression of the hypothalamic lesion. As such, NMO should even be considered in patients who develop SIADH and have no optic nerve or spinal cord lesions but have MRI-documented hypothalamic lesions.

  14. The changed balance of regulatory and naive T cells promotes tolerance after TLI and anti-T-cell antibody conditioning.

    Science.gov (United States)

    Nador, R G; Hongo, D; Baker, J; Yao, Z; Strober, S

    2010-02-01

    The goal of the study was to determine how the changed balance of host naïve and regulatory T cells observed after conditioning with total lymphoid irradiation (TLI) and antithymocyte serum (ATS) promotes tolerance to combined organ and bone marrow transplants. Although previous studies showed that tolerance was dependent on host natural killer T (NKT) cells, this study shows that there is an additional dependence on host CD4(+)CD25(+) Treg cells. Depletion of the latter cells before conditioning resulted in rapid rejection of bone marrow and organ allografts. The balance of T-cell subsets changed after TLI and ATS with TLI favoring mainly NKT cells and ATS favoring mainly Treg cells. Combined modalities reduced the conventional naïve CD4(+) T cells 2800-fold. The host type Treg cells that persisted in the stable chimeras had the capacity to suppress alloreactivity to both donor and third party cells in the mixed leukocyte reaction. In conclusion, tolerance induction after conditioning in this model depends upon the ability of naturally occurring regulatory NKT and Treg cells to suppress the residual alloreactive T cells that are capable of rejecting grafts.

  15. Eaf1p Is Required for Recruitment of NuA4 in Targeting TFIID to the Promoters of the Ribosomal Protein Genes for Transcriptional Initiation In Vivo.

    Science.gov (United States)

    Uprety, Bhawana; Sen, Rwik; Bhaumik, Sukesh R

    2015-09-01

    NuA4 (nucleosome acetyltransferase of H4) promotes transcriptional initiation of TFIID (a complex of TBP and TBP-associated factors [TAFs])-dependent ribosomal protein genes involved in ribosome biogenesis. However, it is not clearly understood how NuA4 regulates the transcription of ribosomal protein genes. Here, we show that NuA4 is recruited to the promoters of ribosomal protein genes, such as RPS5, RPL2B, and RPS11B, for TFIID recruitment to initiate transcription, and the recruitment of NuA4 to these promoters is impaired in the absence of its Eaf1p component. Intriguingly, impaired NuA4 recruitment in a Δeaf1 strain depletes recruitment of TFIID (a TAF-dependent form of TBP) but not the TAF-independent form of TBP to the promoters of ribosomal protein genes. However, in the absence of NuA4, SAGA (Spt-Ada-Gcn5-acetyltransferase) is involved in targeting the TAF-independent form of TBP to the promoters of ribosomal protein genes for transcriptional initiation. Thus, NuA4 plays an important role in targeting TFIID to the promoters of ribosomal protein genes for transcriptional initiation in vivo. Such a function is mediated via its targeted histone acetyltransferase activity. In the absence of NuA4, ribosomal protein genes lose TFIID dependency and become SAGA dependent for transcriptional initiation. Collectively, these results provide significant insights into the regulation of ribosomal protein gene expression and, hence, ribosome biogenesis and functions.

  16. A Novel Antihepatitis Drug, Bicyclol, Prevents Liver Carcinogenesis in Diethylnitrosamine-Initiated and Phenobarbital-Promoted Mice Tumor Model

    Directory of Open Access Journals (Sweden)

    Hua Sun

    2012-01-01

    Full Text Available Bicyclol, an antihepatitis drug developed by Chinese scientists, has been shown to prevent the malignant transformation induced by 3-methylcholanthrene and 12-O-tetradecanoylphorbol-13-acetate in WB-F344 rat liver epithelial cells. This study provides further evidence on its role as a chemopreventive agent in experimental mice with diethylnitrosamine- (DEN- initiated and phenobarbital- (PB- promoted liver carcinoma. Liver tissue and serum were collected. In the two-stage model of hepatocarcinogenesis in mice, oral administration of bicyclol (100, 200 mg/kg before DEN injection showed significant reduction in the incidence of hepatocellular foci, nodules, or carcinoma. Histopathological examination revealed that there was no hepatocellular carcinoma (HCC and hepatoma formation in the mice pretreated with bicyclol (200 mg/kg at week 20, while the mice treated with DEN/PB developed 33.3% HCC and 55.6% hepatoma. Furthermore, the serum levels of alanine aminotransferase (ALT, alkaline phosphatase (ALP, and α-fetal protein (AFP in serum significantly increased in the DEN/PB model group in comparison with the control group. Pretreatment with bicyclol showed a marked reduction in the above condition. Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight. In this study, we also found that 10 weeks after stopping the administration of PB and drugs, the control and bicyclol-treated (200 mg/kg animals showed no HCC and hepatoma formation at the time of termination whereas DEN/PB-induced mice developed 100% hepatoma and 50% HCC. These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.

  17. Core promoter-specific gene regulation: TATA box selectivity and Initiator-dependent bi-directionality of serum response factor-activated transcription.

    Science.gov (United States)

    Xu, Muyu; Gonzalez-Hurtado, Elsie; Martinez, Ernest

    2016-04-01

    Gene-specific activation by enhancers involves their communication with the basal RNA polymerase II transcription machinery at the core promoter. Core promoters are diverse and may contain a variety of sequence elements such as the TATA box, the Initiator (INR), and the downstream promoter element (DPE) recognized, respectively, by the TATA-binding protein (TBP) and TBP-associated factors of the TFIID complex. Core promoter elements contribute to the gene selectivity of enhancers, and INR/DPE-specific enhancers and activators have been identified. Here, we identify a TATA box-selective activating sequence upstream of the human β-actin (ACTB) gene that mediates serum response factor (SRF)-induced transcription from TATA-dependent but not INR-dependent promoters and requires the TATA-binding/bending activity of TBP, which is otherwise dispensable for transcription from a TATA-less promoter. The SRF-dependent ACTB sequence is stereospecific on TATA promoters but activates in an orientation-independent manner a composite TATA/INR-containing promoter. More generally, we show that SRF-regulated genes of the actin/cytoskeleton/contractile family tend to have a TATA box. These results suggest distinct TATA-dependent and INR-dependent mechanisms of TFIID-mediated transcription in mammalian cells that are compatible with only certain stereospecific combinations of activators, and that a TBP-TATA binding mechanism is important for SRF activation of the actin/cytoskeleton-related gene family.

  18. Initial Teacher Training to Promote Health and Well-Being in Schools--A Systematic Review of Effectiveness, Barriers and Facilitators

    Science.gov (United States)

    Shepherd, Jonathan; Pickett, Karen; Dewhirst, Sue; Byrne, Jenny; Speller, Viv; Grace, Marcus; Almond, Palo; Roderick, Paul

    2016-01-01

    Objectives: To conduct a systematic review of effectiveness, and barriers and facilitators, of initial teacher training to promote health and well-being in schools. Design: Systematic review of the literature. Method: A total of 20 bibliographic databases were searched, including MEDLINE, EMBASE and the Social Science Citation Index. Studies were…

  19. Toll-like receptor 4 agonistic antibody promotes innate immunity against severe pneumonia induced by coinfection with influenza virus and Streptococcus pneumoniae.

    Science.gov (United States)

    Tanaka, Akitaka; Nakamura, Shigeki; Seki, Masafumi; Fukudome, Kenji; Iwanaga, Naoki; Imamura, Yoshifumi; Miyazaki, Taiga; Izumikawa, Koichi; Kakeya, Hiroshi; Yanagihara, Katsunori; Kohno, Shigeru

    2013-07-01

    Coinfection with bacteria is a major cause of mortality during influenza epidemics. Recently, Toll-like receptor (TLR) agonists were shown to have immunomodulatory functions. In the present study, we investigated the effectiveness and mechanisms of the new TLR4 agonistic monoclonal antibody UT12 against secondary pneumococcal pneumonia induced by coinfection with influenza virus in a mouse model. Mice were intranasally inoculated with Streptococcus pneumoniae 2 days after influenza virus inoculation. UT12 was intraperitoneally administered 2 h before each inoculation. Survival rates were significantly increased and body weight loss was significantly decreased by UT12 administration. Additionally, the production of inflammatory mediators was significantly suppressed by the administration of UT12. In a histopathological study, pneumonia in UT12-treated mice was very mild compared to that in control mice. UT12 increased antimicrobial defense through the acceleration of macrophage recruitment into the lower respiratory tract induced by c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-κB) pathway-dependent monocyte chemoattractant protein 1 (MCP-1) production. Collectively, these findings indicate that UT12 promoted pulmonary innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus and S. pneumoniae. This immunomodulatory effect of UT12 improves the prognosis of secondary pneumococcal pneumonia and makes UT12 an attractive candidate for treating severe infectious diseases.

  20. Antimitochondrial antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003529.htm Antimitochondrial antibody To use the sharing features on this page, please enable JavaScript. Antimitochondrial antibodies (AMA) are substances ( antibodies ) that form against mitochondria. ...

  1. Effects of single-base substitutions within the acanthamoeba castellanii rRNA promoter on transcription and on binding of transcription initiation factor and RNA polymerase I

    Energy Technology Data Exchange (ETDEWEB)

    Kownin, P.; Bateman, E.; Paule, M.R.

    1988-02-01

    Single-point mutations were introduced into the promoter region of the Acanthamoeba castellanii rRNA gene by chemical mutagen treatment of a single-stranded clone in vitro, followed by reverse transcription and cloning of the altered fragment. The promoter mutants were tested for transcription initiation factor (TIF) binding by a template commitment assay plus DNase I footprinting and for transcription by an in vitro runoff assay. Point mutations within the previously identified TIF interaction region (between -20 and -47, motifs A and B) indicated that TIF interacts most strongly with a sequence centered at -29 and less tightly with sequences upstream and downstream. Some alterations of the base sequence closer to the transcription start site (and outside the TIF-protected site) also significantly decrease specific RNA synthesis in vitro. These were within the region which is protected from DNAse I digestion by polymerase I, but these mutations did not detectably affect the binding of polymerase to the promoter.

  2. Choline deficient diet enhances the initiating and promoting effects of methapyrilene hydrochloride in rat liver as assayed by the induction of gamma-glutamyltranspeptidase-positive hepatocyte foci.

    Science.gov (United States)

    Perera, M. I.; Katyal, S. L.; Shinozuka, H.

    1987-01-01

    Earlier we demonstrated that short-term feeding of methapyrilene hydrochloride (MPH) and of a choline deficient (CD) diet to rats induced peroxidative damage of microsomal membrane lipids of liver cells. In the present study, we investigated whether a CD diet modifies the extent of MPH-induced lipid peroxidation and whether the modifications lead to changes in the initiating and promoting action of these agents using assays of the induction of gamma-glutamyltranspeptidase (GGT)-positive hepatocyte foci. Addition of 0.1% MPH to a CD diet enhanced the extent of microsomal lipid peroxidation induced by a CD diet alone. Feeding a choline supplemented (CS) or a CD diet containing 0.1% MPH for 2 weeks followed by 7 weeks promotion by a CD diet plus phenobarbital was ineffective in inducing GGT-positive foci. Feeding MPH in a CS or a CD diet for 4 weeks, however, resulted in the development of substantial numbers of GGT-positive foci. There was a 3 fold increase in the number of foci in rats initiated with a CD + MPH diet over that in rats initiated with a CS + MPH diet. 0.1% MPH in a CS diet or a CD diet exerted significant promotional effects on the induction of GGT-positive foci in rats initiated with a single injection of diethylnitrosamine. Addition of MPH to a CD diet was additive in inducing GGT-positive foci. The results suggest that lipid peroxidation of the liver may be involved in the carcinogenic and/or promoting effects of MPH and a CD diet. PMID:2893639

  3. Phytohormonal networks promote differentiation of fiber initials on pre-anthesis cotton ovules grown in vitro and in planta.

    Directory of Open Access Journals (Sweden)

    Hee Jin Kim

    Full Text Available The number of cotton (Gossypium sp. ovule epidermal cells differentiating into fiber initials is an important factor affecting cotton yield and fiber quality. Despite extensive efforts in determining the molecular mechanisms regulating fiber initial differentiation, only a few genes responsible for fiber initial differentiation have been discovered. To identify putative genes directly involved in the fiber initiation process, we used a cotton ovule culture technique that controls the timing of fiber initial differentiation by exogenous phytohormone application in combination with comparative expression analyses between wild type and three fiberless mutants. The addition of exogenous auxin and gibberellins to pre-anthesis wild type ovules that did not have visible fiber initials increased the expression of genes affecting auxin, ethylene, ABA and jasmonic acid signaling pathways within 1 h after treatment. Most transcripts expressed differentially by the phytohormone treatment in vitro were also differentially expressed in the ovules of wild type and fiberless mutants that were grown in planta. In addition to MYB25-like, a gene that was previously shown to be associated with the differentiation of fiber initials, several other differentially expressed genes, including auxin/indole-3-acetic acid (AUX/IAA involved in auxin signaling, ACC oxidase involved in ethylene biosynthesis, and abscisic acid (ABA 8'-hydroxylase an enzyme that controls the rate of ABA catabolism, were co-regulated in the pre-anthesis ovules of both wild type and fiberless mutants. These results support the hypothesis that phytohormonal signaling networks regulate the temporal expression of genes responsible for differentiation of cotton fiber initials in vitro and in planta.

  4. Mapping of RNA initiation sites by high doses of uv iradiation: evidence for three independent promoters within the left 11% of the Ad-2 genome

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, M.C.; Fraser, N.W.; Darnell, J.E. Jr.

    1979-04-15

    Cells infected with Ad-2 virus were irradiated so that uv-induced lesions were introduced every 500 to 1000 nucleotides in the genomes, consequently leading to the premature termination of RNA transcription. Such cells when labeled with (/sup 3/H)uridine accumulate labeled promoter proximal RNA. Hybridization of this RNA after size fractionation to restriction fragments of the Ad-2 genome allowed the identification of DNA sequences containing active RNA initiation sites. Early during the infectious cycle two active RNA initiation sites were found within the left 11% of the Ad-2 genome within the 0 to 3.0 and 4.4 to 8.0 restriction fragments. During late infection (15 hr) an additional uv resistant transcript was detected indicating that a newly activated RNA initiation site, presumably for protein IX, resides within the fragment 8.0 to 11.2.

  5. Effectiveness of Video Self-Modeling to Promote Social Initiations by 3-Year-Olds with Autism Spectrum Disorders

    Science.gov (United States)

    Buggey, Tom

    2012-01-01

    Video Self-Modeling (VSM) provides individuals the opportunity to view themselves performing a task beyond their present functioning level through the careful editing of videos. In this study, a single-case multiple-baseline design was used to determine whether VSM would facilitate social initiations across three young children (M = 3 years 10…

  6. Antibody Probes to Estrogen Receptor-alpha Transcript-Specific Upstream Peptides: Alternates ER-alpha Promoter Use and Breast Cancer Etiology/Outcome

    Science.gov (United States)

    2005-05-01

    SantaCruz Biotec), against ER protein. Methodology was established on individual sections cut from paraffin blocks, and was then applied to tissue arrays...cell transfections anti-GFP-peptide antibody ( SantaCruz Biotechnology, Santa for flow cytometry. This minimized the possibility that DNA Cruz, CA) and... SantaCruz BioTech- influence results. nology) was used as secondary antibody and detection was by chemi-luminescence using the Pierce ’super-signal’ sys- 2.2

  7. HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies.

    Directory of Open Access Journals (Sweden)

    Paolo Monini

    Full Text Available Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs via an integrin-mediated pathway. These Tat effects do not require Tat-transactivation activity and are blocked by anti-integrin antibodies (Abs. Productive DC infection promoted by Tat is associated with a highly efficient virus transmission to T cells. In the Tat/Env complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat RGD sequence remains free and directs the virus to integrins present on DCs. V2 loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env complex stability. Of note, binding of Tat to Env abolishes neutralization of Env entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom present in natural infection. This is reversed, and neutralization further enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus, both anti-Tat and anti-Env Abs are required for efficient HIV neutralization. These data suggest that the Tat/Env interaction increases HIV acquisition and spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing Abs. This may explain the low effectiveness of Env-based vaccines, which are also unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env interaction. As Tat also binds Envs from different clades, new vaccine strategies should exploit the Tat/Env interaction for both preventative and therapeutic interventions.

  8. Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure.

    Science.gov (United States)

    He, Jing; Tsai, Louis M; Leong, Yew Ann; Hu, Xin; Ma, Cindy S; Chevalier, Nina; Sun, Xiaolin; Vandenberg, Kirsten; Rockman, Steve; Ding, Yan; Zhu, Lei; Wei, Wei; Wang, Changqi; Karnowski, Alexander; Belz, Gabrielle T; Ghali, Joanna R; Cook, Matthew C; Riminton, D Sean; Veillette, André; Schwartzberg, Pamela L; Mackay, Fabienne; Brink, Robert; Tangye, Stuart G; Vinuesa, Carola G; Mackay, Charles R; Li, Zhanguo; Yu, Di

    2013-10-17

    Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5⁺ CD4⁺ T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5⁺ helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5⁺ precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory.

  9. Extending stakeholder theory to promote resource management initiatives to key stakeholders: a case study of water transfers in Alberta, Canada.

    Science.gov (United States)

    Lafreniere, Katherine C; Deshpande, Sameer; Bjornlund, Henning; Hunter, M Gordon

    2013-11-15

    Many attempts to implement resource management initiatives in Canadian and international communities have been resisted by stakeholders despite inclusion of their representatives in the decision-making process. Managers' failure to understand stakeholders' perspectives when proposing initiatives is a potential cause of this resistance. Our study uses marketing thought to enhance stakeholder theory by bringing in an audience-centric perspective. We attempt to understand how stakeholders perceive their interests in an organization and consequently decide how to influence that organization. By doing so, we investigate whether a disconnect exists between the perceptions of managers and those of stakeholders. Natural resource managers can utilize this knowledge to garner stakeholder support for the organization and its activities. We support this claim with findings from a water transfer plebiscite held in the Canadian province of Alberta. Sixteen personal interviews employing narrative inquiry were conducted to document voters' (i.e., irrigators') interpretations.

  10. Promoting Nature-Based Activity for People With Mental Illness Through the US "Exercise Is Medicine" Initiative.

    Science.gov (United States)

    Maier, Julie; Jette, Shannon

    2016-05-01

    Nature-based physical activity programming (e.g., countryside walks, hiking, horseback riding) has been found to be an effective way to help improve the health of people with mental illness. Exercise referral initiatives, whereby health practitioners prescribe exercise in an attempt to prevent or treat chronic illnesses, have helped make such nature-based activities accessible to this population in the United Kingdom and Australia; however, there is a dearth of research related to the most prominent exercise referral program in the United States: Exercise is Medicine. Taking into account the barriers to physical activity faced by people with mental illness, we explore how nature-based programming for this population might be mobilized in the United States through the growing Exercise is Medicine initiative.

  11. Deepening the impact of initiatives to promote teamwork and workplace health: a perspective from the NEKTA study.

    Science.gov (United States)

    Leiter, Michael P

    2007-01-01

    Evaluations of major policy initiatives on workplace health and teamwork have found significant progress on some issues and inertia on others. This article explores the applicability of a model describing employees' psychological relationships with work as a framework for considering workplace health initiatives. The Mediation Model contributes a way of focusing on experiences that are integral to staff nurses' day-to-day work life. As such, the model provides direction for developing and evaluating strategies for enhancing the quality of work life, especially pertaining to workplace health. The commentary considers a few key findings from the Nursing Environments: Knowledge to Action (NETKA) study that reviewed the applicability of national policy documents on the healthcare systems of Atlantic Canada. The discussion considers implications of staff nurses' participation in sharing and using new knowledge about workplace health.

  12. The pancreatitis-associated protein VMP1, a key regulator of inducible autophagy, promotes KrasG12D-mediated pancreatic cancer initiation

    Science.gov (United States)

    Loncle, C; Molejon, M I; Lac, S; Tellechea, J I; Lomberk, G; Gramatica, L; Fernandez Zapico, M F; Dusetti, N; Urrutia, R; Iovanna, J L

    2016-01-01

    Both clinical and experimental evidence have firmly established that chronic pancreatitis, in particular in the context of Kras oncogenic mutations, predisposes to pancreatic ductal adenocarcinoma (PDAC). However, the repertoire of molecular mediators of pancreatitis involved in Kras-mediated initiation of pancreatic carcinogenesis remains to be fully defined. In this study we demonstrate a novel role for vacuole membrane protein 1 (VMP1), a pancreatitis-associated protein critical for inducible autophagy, in the regulation of Kras-induced PDAC initiation. Using a newly developed genetically engineered model, we demonstrate that VMP1 increases the ability of Kras to give rise to preneoplastic lesions, pancreatic intraepithelial neoplasias (PanINs). This promoting effect of VMP1 on PanIN formation is due, at least in part, by an increase in cell proliferation combined with a decrease in apoptosis. Using chloroquine, an inhibitor of autophagy, we show that this drug antagonizes the effect of VMP1 on PanIN formation. Thus, we conclude that VMP1-mediated autophagy cooperate with Kras to promote PDAC initiation. These findings are of significant medical relevance, molecules targeting autophagy are currently being tested along chemotherapeutic agents to treat PDAC and other tumors in human trials. PMID:27415425

  13. Adult stem cell theory of the multi-stage, multi-mechanism theory of carcinogenesis: role of inflammation on the promotion of initiated stem cells.

    Science.gov (United States)

    Trosko, James E; Tai, Mei-Hui

    2006-01-01

    Inflammation, induced by microbial agents, radiation, endogenous or exogenous chemicals, has been associated with chronic diseases, including cancer. Since carcinogenesis has been characterized as consisting of the 'initiation', 'promotion' and 'progression' phases, the inflammatory process could affect any or all three phases. The stem cell theory of carcinogenesis has been given a revival, in that isolated human adult stem cells have been isolated and shown to be 'targets' for neoplastic transformation. Oct4, a transcription factor, has been associated with adult stem cells, as well as their immortalized and tumorigenic derivatives, but not with the normal differentiated daughters. These data are consistent with the stem cell theory of carcinogenesis. In addition, Gap Junctional Intercellular Communication (GJIC) seems to play a major role in cell growth. Inhibition of GJIC by non-genotoxic chemicals or various oncogenes seems to be the mechanism for the tumor promotion and progression phases of carcinogenesis. Many of the toxins, synthetic non-genotoxicants, and endogenous inflammatory factors have been shown to inhibit GJIC and act as tumor promoters. The inhibition of GJIC might be the mechanism by which the inflammatory process affects cancer and that to intervene during tumor promotion with anti-inflammatory factors might be the most efficacious anti-cancer strategy.

  14. A Gammaherpesvirus Complement Regulatory Protein Promotes Initiation of Infection by Activation of Protein Kinase Akt/PKB

    Science.gov (United States)

    Steer, Beatrix; Adler, Barbara; Jonjic, Stipan; Stewart, James P.; Adler, Heiko

    2010-01-01

    Background Viruses have evolved to evade the host's complement system. The open reading frames 4 (ORF4) of gammaherpesviruses encode homologs of regulators of complement activation (RCA) proteins, which inhibit complement activation at the level of C3 and C4 deposition. Besides complement regulation, these proteins are involved in heparan sulfate and glycosaminoglycan binding, and in case of MHV-68, also in viral DNA synthesis in macrophages. Methodology/Principal Findings Here, we made use of MHV-68 to study the role of ORF4 during infection of fibroblasts. While attachment and penetration of virions lacking the RCA protein were not affected, we observed a delayed delivery of the viral genome to the nucleus of infected cells. Analysis of the phosphorylation status of a variety of kinases revealed a significant reduction in phosphorylation of the protein kinase Akt in cells infected with ORF4 mutant virus, when compared to cells infected with wt virus. Consistent with a role of Akt activation in initial stages of infection, inhibition of Akt signaling in wt virus infected cells resulted in a phenotype resembling the phenotype of the ORF4 mutant virus, and activation of Akt by addition of insulin partially reversed the phenotype of the ORF4 mutant virus. Importantly, the homologous ORF4 of KSHV was able to rescue the phenotype of the MHV-68 ORF4 mutant, indicating that ORF4 is functionally conserved and that ORF4 of KSHV might have a similar function in infection initiation. Conclusions/Significance In summary, our studies demonstrate that ORF4 contributes to efficient infection by activation of the protein kinase Akt and thus reveal a novel function of a gammaherpesvirus RCA protein. PMID:20657771

  15. LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression

    Science.gov (United States)

    Chen, Zhen-zhen; Huang, Lan; Wu, Ya-hong; Zhai, Wen-jie; Zhu, Ping-ping; Gao, Yan-feng

    2016-01-01

    Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self-renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation. LncSox4 interacts with and recruits Stat3 to the Sox4 promoter to initiate the expression of Sox4, which is highly expressed in liver TICs and required for liver TIC self-renewal. The expression level of Sox4 correlates with HCC development, clinical severity and prognosis of patients. Altogether, we find that LncSox4 is highly expressed in liver TICs and is required for their self-renewal. PMID:27553854

  16. No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine.

    Science.gov (United States)

    Hagiwara, Akihiro; Imai, Norio; Doi, Yuko; Suguro, Mayuko; Kawabe, Mayumi; Furukawa, Fumio; Nagano, Kasuke; Fukushima, Shoji

    2013-12-01

    The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100-1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100-1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses.

  17. Correlates of Initial Recall of a Multimedia Communication Campaign to Promote Physical Activity among Tweens: the WIXX Campaign.

    Science.gov (United States)

    Bélanger-Gravel, Ariane; Cutumisu, Nicoleta; Gauvin, Lise; Lagarde, François; Laferté, Marilie

    2017-01-01

    This study examined factors associated with children's and parents' recall of a communication campaign aimed at promoting children's physical activity. A cross-sectional population-based telephone survey was conducted among 1001 children and their parents. Respondents were recruited through a random digit dialing procedure. Respondents' recall of the campaign, beliefs, sociodemographics as well as levels of physical activity and sedentary behaviors were self-reported. Logistic regression analyses were conducted for tweens and their parents separately. Girls (odds ratio [OR] = 2.1; 95%confidence interval (CI): 1.3, 3.5) were more likely to have unaided recall when compared to boys. Tweens in primary school (OR = 1.9; 95%CI: 1.0, 3.4 and OR = 2.1; 95%CI: 1.4, 3.0) and those speaking French (OR = 3.3; 95%CI: 1.4, 8.1 and OR = 2.9; 95%CI: 1.8, 4.7) were more likely to have unaided and aided recall, respectively. Among parents, tweens' unaided (OR = 12.0; 95%CI: 5.2, 28.1) and aided (OR = 3.3; 95%CI: 1.5, 7.3) recall, obesity status (OR = 2.6; 95%CI: 1.3, 5.3), and low income (OR = 5.2; 95%CI: 1.9, 14.3) were positively associated with recall. Additional beliefs were associated with tweens' and parents' recall of the campaign. The association between sex, language, and recall is in line with the branding strategy adopted and no clear evidence for communication inequalities was observed.

  18. Antiphospholipid Antibody and Antiphospholipid Syndrome

    Institute of Scientific and Technical Information of China (English)

    吴竞生

    2008-01-01

    @@ Antiphospholipid antibodies (APA) APA is a big category for all kinds of negative charge phospholipid or lecithin - a protein complex autoantibodies or the same antibody, through its recognition of antigen (target protein) different, and phospholipids or lecithin - protein complex combination of various rely on the interference Phospholipid clotting and anti-coagulation factor, and promote endothelial cells, platelets, complement activation and play a role. APA including lupus anticoagulant(LA) and anticardiolipin antibody (ACA), In addition, there are anti-β2 glycoprotein-I (β2-GPI) antibody, anti-prothrombin (a- PT) antibody, anti-lysophosphatidic acid antibody and anti-phosphatidylserine antibody, and so on. APA as the main target of phospholipid-binding protein, including β2-GPI, prothrombin, annexin, protein C (PC) and protein S (PS), plasminogen, and so on.

  19. Systemic foot-and-mouth disease vaccination in cattle promotes specific antibody secreting cells at the respiratory tract and triggers local anamnestic-compatible responses upon aerosol infection

    Science.gov (United States)

    Foot and mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated whole FMD virus (FMDV) particles, are regularly used worldwide in regions recognized as free from the disease. Here, we studied the generation of antibody ...

  20. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via beta 2GPI and apoER2

    NARCIS (Netherlands)

    Ramesh, Sangeetha; Morrell, Craig N.; Tarango, Cristina; Thomas, Gail D.; Yuhanna, Ivan S.; Girardi, Guillermina; Herz, Joachim; Urbanus, Rolf T.; de Groot, Philip G.; Thorpe, Philip E.; Salmon, Jane E.; Shaul, Philip W.; Mineo, Chieko

    2011-01-01

    In antiphospholipid syndrome (APS), antiphospholipid antibodies (aPL) binding to beta 2 glycoprotein I (beta 2GPI) induce endothelial cell-leukocyte adhesion and thrombus formation via unknown mechanisms Here we show that in mice both of these processes are caused by the inhibition of eNOS In studie

  1. Race to the Top: evaluation of a novel performance-based financing initiative to promote healthcare delivery in rural Rwanda

    Directory of Open Access Journals (Sweden)

    Evrard Nahimana

    2016-11-01

    Full Text Available Background: Performance-based financing (PBF has demonstrated a range of successes and failures in improving health outcomes across low- and middle-income countries. Evidence indicates that the success of PBF depends, in large part, on the model selected, in relation to a variety of contextual factors. Objective: Partners In Health∣Inshuti Mu Buzima aimed to evaluate health outcomes associated with a novel capacity-building model of PBF at health centers throughout Kirehe district, Rwanda. Design: Thirteen health centers in Kirehe district, which provide healthcare to a population of over 300,000 people, agreed to participate in a PBF initiative scheme that integrated data feedback, quality improvement coaching, peer-to-peer learning, and district-level priority setting. Health centers’ progress toward collectively agreed upon site-specific health targets was assessed every 6 months for 18 months. Incentives were awarded only when health centers met goals on all three priorities health centers had collectively agreed upon: 90% coverage of community-based health insurance, 70% contraceptive prevalence rate, and zero acute severe malnutrition cases. Improvement across all four time points and facilities was measured using mixed-effects linear regression. Findings: At 6-month follow-up, 4 of 13 health centers had met 1 target. At 12-month follow-up, 7 centers had met 1 target, and by 18-month follow-up, 6 centers had met 2 targets and 2 centers had met all 3. Average health center performance had improved significantly across the district for all three targets: mean insurance coverage increased from 68% at baseline to 93% (p<0.001; mean number of acute malnutrition cases in the previous 6 months declined from 24 to 5 per facility (p<0.001; and contraceptive prevalence increased from 42 to 59% (p<0.001. A number of innovative improvement initiatives were identified. Conclusion: The combining of PBF, district engagement/support, and peer

  2. Feasibility, acceptability, and initial efficacy of an online sexual health promotion program for LGBT youth: the Queer Sex Ed intervention.

    Science.gov (United States)

    Mustanski, Brian; Greene, George J; Ryan, Daniel; Whitton, Sarah W

    2015-01-01

    Lesbian, gay, bisexual, and transgender (LGBT) youth experience multiple sexual health inequities driven, in part, by deficits in parental and peer support, school-based sex education programs, and community services. Research suggests that the Internet may be an important resource in the development of sexual health among LGBT youth. We examined the feasibility of recruiting youth in same-sex relationships into an online sexual health intervention, evaluated intervention acceptability, and obtained initial estimates of intervention efficacy. LGBT youth (16 to 20 years old) completed Queer Sex Ed (QSE), an online, multimedia sexual health intervention consisting of five modules. The final sample (N = 202) completed the pretest, intervention, and posttest assessments. The primary study outcomes were sexual orientation identity and self-acceptance (e.g., coming-out self-efficacy), sexual health knowledge (e.g., sexual functioning), relationship variables (e.g., communication skills), and safer sex (e.g., sexual assertiveness). Analyses indicated that 15 of the 17 outcomes were found to be significant (p LGBT youth.

  3. Androgen signaling promotes translation of TMEFF2 in prostate cancer cells via phosphorylation of the α subunit of the translation initiation factor 2.

    Directory of Open Access Journals (Sweden)

    Ryan F Overcash

    Full Text Available The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2, is expressed mainly in brain and prostate. Expression of TMEFF2 is deregulated in prostate cancer, suggesting a role in this disease, but the molecular mechanism(s involved in this effect are not clear. Although androgens promote tmeff2 transcription, androgen delivery to castrated animals carrying CWR22 xenografts increases TMEFF2 protein levels in the absence of mRNA changes, suggesting that TMEFF2 may also be post-transcriptionally regulated. Here we show that translation of TMEFF2 is regulated by androgens. Addition of physiological concentrations of dihydrotestosterone (DHT to prostate cancer cell lines increases translation of endogenous TMEFF2 or transfected TMEFF2-Luciferase fusions, and this effect requires the presence of upstream open reading frames (uORFs in the 5'-untranslated region (5'-UTR of TMEFF2. Using chemical and siRNA inhibition of the androgen receptor (AR, we show that the androgen effect on TMEFF2 translation is mediated by the AR. Importantly, DHT also promotes phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α in an AR-dependent manner, paralleling the effect on TMEFF2 translation. Moreover, endoplasmic reticulum (ER stress conditions, which promote eIF2α phosphorylation, also stimulate TMEFF2 translation. These results indicate that androgen signaling promotes eIF2α phosphorylation and subsequent translation of TMEFF2 via a mechanism that requires uORFs in the 5'-UTR of TMEFF2.

  4. Vaccination of Plasmid DNA Encoding Somatostatin Gene Fused with GP5 Gene of Porcine Reproductive and Respiratory Syndrome Virus Induces Anti-GP5 Antibodies and Promotes Growth Performance in Immunized Pigs

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Somatostatin (SS) is a hormone that inhibits the secretion of growth hormone. Immunization against SS can promote the growth of animals. This paper described the effects of DNA immunization on the growth and antibody response in mice and pigs immunized with a plasmid DNA encoding SS fused with GP5 of porcine reproductive and respiratory syndrome virus (PRRSV). A fragment of 180 bp encoding partial SS gene was amplified by PCR from the genomic DNA of peripheral blood mononuclear cells of pigs, and cloned as a fusion gene with PRRSV GP5 in plasmid pISGRTK3. Three times of immunization with the resulting plasmid pISG-SS/GP5 induced anti-GP5 antibodies in BALB/c mice and pigs, as demonstrated by GP5-specific ELISA and immunoblotting. Compared with pigs immunized with empty vector pISGRTK3, the growth performance of pigs immunized with pISG-SS/GP5 was increased by 11.1% on the 13th week after the last vaccination. The results indicated the plasmid DNA encoding SS and PRRSV GP5 fusion gene elicited anti-GP5 antibodies and improved the growth performance of immunized pigs.

  5. Effectiveness of a grant program's efforts to promote synergy within its funded initiatives: perceptions of participants of the Southern Rural Access Program

    Directory of Open Access Journals (Sweden)

    Weiner Bryan J

    2008-12-01

    Full Text Available Abstract Background Foundations and public agencies commonly fund focused initiatives for individual grantees. These discrete, stand-alone initiatives can risk failure by being carried out in isolation. Fostering synergy among grantees' initiatives is one strategy proposed for promoting the success and impact of grant programs. We evaluate an explicit strategy to build synergy within the Robert Wood Johnson Foundation's Southern Rural Access Program (SRAP, which awarded grants to collaboratives within eight southeastern U.S. states to strengthen basic health care services in targeted rural counties. Methods We interviewed 39 key participants of the SRAP, including the program director within each state and the principal subcontractors heading the program's funded initiatives that supported heath professionals' recruitment, retention and training, made loans to health care providers, and built networks among providers. Interews were recorded and transcribed. Two investigators independently coded the transcripts and a third investigator distilled the main points. Results Participants generally perceived that the SRAP yielded more synergies than other grant programs in which they had participated and that these synergies added to the program's impact. The synergies most often noted were achieved through relationship building among grantees and with outside agencies, sharing information and know-how, sharing resources, combining efforts to yield greater capacity, joining voices to advocate for common goals, and spotting gaps in services offered and then filling these gaps. The SRAP's strategies that participants felt fostered synergy included targeting funding to culturally and geographically similar states, supporting complementary types of initiatives, promoting opportunities to network through semi-annual meetings and regular conference calls, and the advocacy efforts of the program's leadership. Participants noted that synergies were sometimes

  6. A neutralizing anti-TGF-beta1 antibody promotes proliferation of CD34+Thy-1+ peripheral blood progenitors and increases the number of transduced progenitors.

    Science.gov (United States)

    Imbert, A M; Bagnis, C; Galindo, R; Chabannon, C; Mannoni, P

    1998-05-01

    The subset of blood cells that expresses both CD34 and Thy1 (CD90) cell surface molecules is enriched in hematopoietic stem cell activity and can be obtained from the peripheral blood of cancer patients after mobilization by chemotherapy and granulocyte colony-stimulating factor (G-CSF). Because transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of hematopoietic progenitor proliferation and differentiation, in this study we analyzed the impact of neutralizing TGF-beta1 activity during culture and retroviral transduction of CD34+Thy1+ cells. When purified CD34+Thy1+ cells were cultured in the presence of a neutralizing antibody against TGF-beta1, the percentage of cycling cells, proliferation, and absolute number of clonogenic progenitors were increased in comparison to the cultures performed without the addition of antibody. Antibody-mediated neutralization of TGF-beta1 during retroviral transduction performed by coculture of CD34+Thy1+ cells with a MFG-S-nlsLacZ retroviral vector-producing cell line did not affect the percentage of transduced progenitors as assessed by direct X-Gal staining of colonies in clonogenic assays. However, due to the better expansion of CD34+Thy1+ cells in the presence of anti-TGF-beta1, the absolute number of transduced progenitors recovered at the end of the culture was increased.

  7. Recruitment of the transcriptional coactivator HCF-1 to viral immediate-early promoters during initiation of reactivation from latency of herpes simplex virus type 1.

    Science.gov (United States)

    Whitlow, Zackary; Kristie, Thomas M

    2009-09-01

    The transcriptional coactivator host cell factor 1 (HCF-1) is critical for the expression of immediate-early (IE) genes of the alphaherpesviruses herpes simplex virus type 1 (HSV-1) and varicella-zoster virus. HCF-1 may also be involved in the reactivation of these viruses from latency as it is sequestered in the cytoplasm of sensory neurons but is rapidly relocalized to the nucleus upon stimulation that results in reactivation. Here, chromatin immunoprecipitation assays demonstrate that HCF-1 is recruited to IE promoters of viral genomes during the initiation of reactivation, correlating with RNA polymerase II occupancy and IE expression. The data support the model whereby HCF-1 plays a pivotal role in the reactivation of HSV-1 from latency.

  8. A NF-κB-dependent dual promoter-enhancer initiates the lipopolysaccharide-mediated transcriptional activation of the chicken lysozyme in macrophages.

    Science.gov (United States)

    Witham, James; Ouboussad, Lylia; Lefevre, Pascal F

    2013-01-01

    The transcriptional activation of the chicken lysozyme gene (cLys) by lipopolysaccharide (LPS) in macrophages is dependent on transcription of a LPS-Inducible Non-Coding RNA (LINoCR) triggering eviction of the CCCTC-binding factor (CTCF) from a negative regulatory element upstream of the lysozyme transcription start site. LINoCR is transcribed from a promoter originally characterized as a hormone response enhancer in the oviduct. Herein, we report the characterization of this cis-regulatory element (CRE). In activated macrophages, a 60 bp region bound by NF-κB, AP1 and C/EBPβ controls this CRE, which is strictly dependent on NF-κB binding for its activity in luciferase assays. Moreover, the serine/threonine kinase IKKα, known to be recruited by NF-κB to NF-κB-dependent genes is found at the CRE and within the transcribing regions of both cLys and LINoCR. Such repartition suggests a simultaneous promoter and enhancer activity of this CRE, initiating cLys transcriptional activation and driving CTCF eviction. This recruitment was transient despite persistence of both cLys transcription and NF-κB binding to the CRE. Finally, comparing cLys with other LPS-inducible genes indicates that IKKα detection within transcribing regions can be correlated with the presence of the elongating form of RNA polymerase II or concentrated in the 3' end of the gene.

  9. AITI and GELATI - Initiatives to promote education and training for the next generation of educators and scientists during the IPY 2007/08 and beyond

    Science.gov (United States)

    Vogel, S. W.; Bouchard, M.; Das, S.; Gillermann, J.; Greve, R.; Matsuoka, K.; Pasotti, J.; Tweedie, C.

    2005-05-01

    The fourth International Polar Year (IPY) in 2007/08 provides a unique opportunity to enhance international collaboration in research and education. Here we present an IPY-teaching initiative (AITI), which proposes to develop an interdisciplinary international short course series promoting and fostering education and training of the next generation(s) of scientists and educators interested in natural and social sciences related to Polar Regions; a short course series (GELATI) focusing on the impact of the cryosphere on the Earth system. The main goals of the short course series are to: a) provide education and training for the next generation of graduate students, science teachers, researchers in science related to Polar Regions; b) provide training for junior faculty c) integrate research and education; d) create awareness for Polar Regions related questions in class-rooms and beyond; e) create international partnerships in education and training; f) promote multidisciplinary thinking; g) increase gender diversity in science and teaching; h) encourage minority participation. To achieve these goals it is intended to develop a curriculum of specialized and interdisciplinary courses considering various aspects of science and scientific activities, which study, or are concerned with processes/developments in Polar Regions. Due to the vast dimensions and distribution of Polar Regions across international boundaries as well as the complexity of environmental studies in Polar Regions these courses will internationally pool students and instructors. Pooling of experts and students internationally will not only ensure highest standards but also foster international partnership. To allow the integration of research and teaching and to provide the best possible study environment the up to two to three weeklong, courses will be held at international field stations or will be incorporated into large research projects. To ensure training of the next generation of

  10. Growth Performance, Carcass Characteristics, Antibody Titer and Blood Parameters in Broiler Chickens Fed Dietary Myrtle (Myrtus communis Essential Oil as an Alternative to Antibiotic Growth Promoter

    Directory of Open Access Journals (Sweden)

    Mahmoodi Bardzardi M

    2014-03-01

    Full Text Available This experiment was conducted to determine the effects of Myrtle Essential Oil (MEO on growth performance, carcass characteristics, antibody titer and blood parameters of broiler chickens. A total of 200 Ross 308 broiler chickens were allocated to five dietary treatments with four replicates of 10 birds each. Dietary treatments were prepared by formulating a corn-soybean meal-based diet free of antibiotics (Control and supplementing the basal diet with three levels of MEO at 100, 200, 300 mg/Kg or antibiotic Flavophospholipol (FPL at 600 mg/Kg. The results showed that diets supplemented with MEO and FPL increased the feed intake, body weight gain and improved the feed conversion ratio compared to the control treatment (P. The relative carcass weight was significantly increased, whereas the weight of gastrointestinal tract and liver were decreased in broilers fed MEO (P. Supplementing the basal diet with MEO increased the antibody titers against Avian Influenza Virus (AIV and Newcastle disease Virus (NDV, although supplementing diet with 200 mg/Kg of MEO was more effective (P. Broilers fed MEO diets especially at the level of 300 mg/Kg had a lower white blood cells count and heterophil, heterophil to lymphocyte ratio, mean corpuscular volume and mean corpuscular hemoglobin, but a higher lymphocyte and red blood cells count (P. In conclusion, data showed that diet supplemented with MEO improved the growth performance and increased antibody titers against AIV and NDV, especially at the level of 200 mg/Kg, in broiler chickens and could be an adequate alternative to antibiotics.

  11. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon

    Science.gov (United States)

    Bettini, Sarah; Boutet-Robinet, Elisa; Cartier, Christel; Coméra, Christine; Gaultier, Eric; Dupuy, Jacques; Naud, Nathalie; Taché, Sylviane; Grysan, Patrick; Reguer, Solenn; Thieriet, Nathalie; Réfrégiers, Matthieu; Thiaudière, Dominique; Cravedi, Jean-Pierre; Carrière, Marie; Audinot, Jean-Nicolas; Pierre, Fabrice H.; Guzylack-Piriou, Laurence; Houdeau, Eric

    2017-01-01

    Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer’s patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO2-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources. PMID:28106049

  12. Ethanol Does Not Promote MeIQx-initiated Rat Colon Carcinogenesis Based on Evidence from Analysis of a Colon Cancer Surrogate Marker.

    Science.gov (United States)

    Kushida, Masahiko; Wanibuchi, Hideki; Wei, Min; Kakehashi, Anna; Ozaki, Keisuke; Sukata, Tokuo; Miyata, Kaori; Ogata, Keiko; Uwagawa, Satoshi; Fukushima, Shoji

    2009-03-01

    Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer. However, the data are confounded by numerous cosegregating variables. To cast further light on the relationships between alcohol intake and colon cancer development, 21-day-old male F344/DuCrj rats were fed 200 ppm 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in their diet for 8 weeks and doses of 0, 0.1, 0.3, 1, 3, 10 and 20% of ethanol in their drinking water ad libitum for 16 weeks thereafter. The rats were sacrificed after 24 weeks of experiment, and aberrant crypt foci (ACF), surrogate lesions for colon cancer, were examined under a light microscope at low magnification. Ethanol was found not to affect the ACF formation at any dose compared with the initiated-controls. Furthermore, ethanol did not alter colon epithelial cell proliferation. These data, obtained by analysis of a colon cancer surrogate marker lesion, indicate that ethanol lacks promotion activity for MeIQx-initiated rat colon carcinogenesis.

  13. Effect of enamel organic matrix on the potential of Galla chinensis to promote the remineralization of initial enamel carious lesions in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Linglin; Zou Ling; Li Jiyao; Hao Yuqing; Xiao Liying; Zhou Xuedong; Li Wei, E-mail: leewei2000@sina.co, E-mail: zhll_sc@yahoo.c [State Key Laboratory of Oral Diseases, West China College of Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu (China)

    2009-06-15

    Galla chinensis, a natural traditional Chinese medicine with main composition of tannic acid and gallic acid, is formed when the Chinese sumac aphid Baker (Melaphis chinensis bell) parasitizes the levels of Rhus chinensis Mill. Galla chinensis has shown the potential to enhance the remineralization of initial enamel carious lesion, but the mechanism is still unknown. This study was to investigate whether the enamel organic matrix plays a significant role in the potential of Galla chinensis to promote the remineralization of initial enamel caries. Bovine sound enamel blocks and non-organic enamel blocks were demineralized and exposed to a 12 day pH cycling. During the pH cycling, 30 specimens with the enamel organic matrix were randomly divided into three groups, and treated with 1 g L{sup -1} NaF (group A), 4 g L{sup -1} Galla chinensis extract (group B1) or double deionized water (group C1). Twenty specimens without the enamel organic matrix were randomly divided into two groups, and treated with 4 g L{sup -1} Galla chinensis extract (group B2) or double deionized water (group C2). The integrated mineral loss and lesion depth of all the specimens were analysed by transverse microradiography. The integrated mineral loss and lesion depth of group B1 were less than those of groups B2, C1 and C2, and there were no statistical differences among groups B2, C1 and C2. In conclusion, Galla chinensis can enhance the remineralization of initial enamel carious lesion, and the enamel organic matrix plays a significant role in this potential of Galla chinensis.

  14. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

    Science.gov (United States)

    Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.

    2016-01-01

    The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

  15. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

    Science.gov (United States)

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

    2015-08-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.

  16. Thyroid Antibodies

    Science.gov (United States)

    ... e.g., at regular intervals after thyroid cancer treatment) Thyroid stimulating hormone receptor antibody, Thyroid Stimulating Immunoglobulin TRAb, TSHR Ab, TSI Graves disease When a person has symptoms of hyperthyroidism If a pregnant woman has a known autoimmune ...

  17. miR-125b can enhance skin tumor initiation and promote malignant progression by repressing differentiation and prolonging cell survival.

    Science.gov (United States)

    Zhang, Liang; Ge, Yejing; Fuchs, Elaine

    2014-11-15

    Previously, we identified miR-125b as a key regulator of the undifferentiated state of hair follicle stem cells. Here, we show that in both mice and humans, miR-125b is abundantly expressed, particularly at early stages of malignant progression to squamous cell carcinoma (SCC), the second most prevalent cancer worldwide. Moreover, when elevated in normal murine epidermis, miR-125b promotes tumor initiation and contributes to malignant progression. We further show that miR-125b can confer "oncomiR addiction" in early stage malignant progenitors by delaying their differentiation and favoring an SCC cancer stem cell (CSC)-like transcriptional program. To understand how, we systematically identified and validated miR125b targets that are specifically associated with tumors that are dependent on miR-125b. Through molecular and genetic analysis of these targets, we uncovered new insights underlying miR-125b's oncogenic function. Specifically, we show that, on the one hand, mir-125b directly represses stress-responsive MAP kinase genes and associated signaling. On the other hand, it indirectly prolongs activated (phosphorylated) EGFR signaling by repressing Vps4b (vacuolar protein-sorting 4 homolog B), encoding a protein implicated in negatively regulating the endosomal sorting complexes that are necessary for the recycling of active EGFR. Together, these findings illuminate miR-125b as an important microRNA regulator that is shared between normal skin progenitors and their early malignant counterparts.

  18. Diindolylmethane and Lupeol Modulates Apoptosis and Cell Proliferation in N-Butyl-N-(4-Hydroxybutyl) Nitrosamine Initiated and Dimethylarsinic Acid Promoted rat Bladder Carcinogenesis.

    Science.gov (United States)

    Prabhu, Bhoopathy; Sivakumar, Annamalai; Sundaresan, Sivapatham

    2016-10-01

    Bladder cancer has been shown to resist programmed cell death with altered expression of both pro-apoptotic and anti-apoptotic proteins. To study is to investigate the apoptotic properties of Diindolylmethane (DIM) and Lupeol on N-Butyl-N-(4-hydroxybutyl) Nitrosamine (BBN) initiated and Dimethylarsinic Acid (DMA) promoted urinary bladder cancer. Sixty male Wistar rats were divided into 6 groups. Group I: Control. Group II: Rats were experimentally developed bladder carcinogenesis with BBN and DMA. Group III and IV: DIM and lupeol were administered after BBN treatment for 28 weeks. Group V and VI: DIM and lupeol alone treatment for 36 weeks. All the experimental rats were maintained and euthanized after 36 weeks protocol. Urinary bladder tissues were collected and processed for further investigations. Apoptotis and cell proliferative marker such as Bax, Bcl-2, caspase-3, caspase-9 and PCNA were quantified using immunohistochemical analysis. The Immunohistochemical expression of Bax, Bcl-2, caspase-3, caspase-9 and PCNA were aberrant in BBN + DMA treated tumor group. Administration of DIM and lupeol inhibited the progression of bladder cancer, induced the expression of apoptotic Bax, caspase-3, caspase-9 and inhibited the expression of anti-apoptotic Bcl-2, PCNA in the urinary bladder of rats. Administration of diindolylmethane and lupeol treatment induces apoptosis and cellular proliferation by its anti-carcinogenic properties. From our results DIM and lupeol would be the agent or adjunct for the treatment of bladder carcinogenesis.

  19. Single chain fragment variable antibodies developed by using as target the 3rd fibronectin type III homologous repeat fragment of human neural cell adhesion molecule L1 promote cell migration and neuritogenesis.

    Science.gov (United States)

    Tang, Dan-Yang; Yu, Yang; Zhao, Xuan-Jun; Schachner, Melitta; Zhao, Wei-Jiang

    2015-01-15

    L1CAM plays important roles during ontogeny, including promotion of neuronal cell migration and neuritogenesis, and stimulation of axonal outgrowth, fasciculation and myelination. These functions are at least partially exerted through a 16-mer amino acid sequence in the third fibronectin type III-like repeat of L1, which associates with several interaction partners, including integrins, other adhesion molecules and growth factor receptors. Here, using the Tomlinson I library for phage display, we obtained two single-chain variable fragment antibodies (scFvs) against this peptide sequence of human L1, hereafter called H3 peptide. Both scFvs recognize the H3 peptide and the extracellular domain of L1, as tested by enzyme-linked immunosorbent assay (ELISA), Western blot analysis and immunofluorescence staining of L1 expresssing cells. Furthermore, both scFvs reduce U-87 MG cell adhesion to fibronectin, while stimulating cell migration. Application of scFvs to human neuroblastoma SK-N-SH cells promote process outgrowth. Similar to triggering of endogenous L1 functions at the cell surface, both scFvs activate the signal transducers Erk and Src in these cells. Our results indicate that scFvs against a functionally pivotal domain in L1 trigger its regeneration-beneficial functions in vitro, encouraging thoughts on therapy of neurodegenerative diseases in the hope to ameliorate human nervous system diseases.

  20. Ten steps or climbing a mountain: A study of Australian health professionals' perceptions of implementing the baby friendly health initiative to protect, promote and support breastfeeding

    Directory of Open Access Journals (Sweden)

    Sheehan Athena

    2011-08-01

    Full Text Available Abstract Background The Baby Friendly Hospital (Health Initiative (BFHI is a global initiative aimed at protecting, promoting and supporting breastfeeding and is based on the ten steps to successful breastfeeding. Worldwide, over 20,000 health facilities have attained BFHI accreditation but only 77 Australian hospitals (approximately 23% have received accreditation. Few studies have investigated the factors that facilitate or hinder implementation of BFHI but it is acknowledged this is a major undertaking requiring strategic planning and change management throughout an institution. This paper examines the perceptions of BFHI held by midwives and nurses working in one Area Health Service in NSW, Australia. Methods The study used an interpretive, qualitative approach. A total of 132 health professionals, working across four maternity units, two neonatal intensive care units and related community services, participated in 10 focus groups. Data were analysed using thematic analysis. Results Three main themes were identified: 'Belief and Commitment'; 'Interpreting BFHI' and 'Climbing a Mountain'. Participants considered the BFHI implementation a high priority; an essential set of practices that would have positive benefits for babies and mothers both locally and globally as well as for health professionals. It was considered achievable but would take commitment and hard work to overcome the numerous challenges including a number of organisational constraints. There were, however, differing interpretations of what was required to attain BFHI accreditation with the potential that misinterpretation could hinder implementation. A model described by Greenhalgh and colleagues on adoption of innovation is drawn on to interpret the findings. Conclusion Despite strong support for BFHI, the principles of this global strategy are interpreted differently by health professionals and further education and accurate information is required. It may be that the

  1. Characterization of N-diethylnitrosamine-initiated and ferric nitrilotriacetate-promoted renal cell carcinoma experimental model and effect of a tamarind seed extract against acute nephrotoxicity and carcinogenesis.

    Science.gov (United States)

    Vargas-Olvera, Chabetty Y; Sánchez-González, Dolores Javier; Solano, José D; Aguilar-Alonso, Francisco A; Montalvo-Muñoz, Fernando; Martínez-Martínez, Claudia María; Medina-Campos, Omar N; Ibarra-Rubio, María Elena

    2012-10-01

    Renal cell carcinoma (RCC), the commonest malignancy in adult kidney, lacks of early signs, resulting often in metastasis at first diagnosis. N-Diethylnitrosamine (DEN)-initiated and ferric nitrilotriacetate (FeNTA)-promoted RCC may be a useful experimental model, but it is not well characterized. In this study, histological alterations and oxidative stress markers were analyzed at different times throughout RCC development, histological subtype was re-evaluated in the light of current classification, and a tamarind seed extract (TSE) effect was examined. Male Wistar rats experimental groups were control, TSE, DEN, DEN+FeNTA, and TSE+DEN+FeNTA. TSE was given 2 weeks before DEN administration (200 mg/kg) and throughout the experiment. Fourteen days after DEN treatment, two FeNTA doses (9 mg Fe/kg) for acute nephrotoxicity study, and increasing FeNTA doses (3-9 mg Fe/kg) twice a week for 16 weeks for carcinogenesis protocol, were administered. In acute study, necrosis and renal failure were observed and TSE ameliorated them. Throughout carcinogenesis protocol, preneoplastic lesions were observed since 1 month of FeNTA treatment, which were more evident at 2 months, when also renal cysts and RCC were already detected. RCC tumors were obtained without changes in renal function, and clear cell histological subtype was identified in all cases. 4-Hydroxy-2-nonenal and 3-nitro-L: -tyrosine levels increased progressively throughout protocol. TSE decreased both oxidative stress markers and, although there was no statistical difference, it delayed RCC progress and decreased its incidence (21 %). This study brings an insight of the time course events in this carcinogenesis model, identifies clear cell subtype and establishes TSE renoprotective effects.

  2. Sox17 promotes cell cycle progression and inhibits TGF-beta/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.

    Directory of Open Access Journals (Sweden)

    Alexander W Lange

    Full Text Available The Sry-related high mobility group box transcription factor Sox17 is required for diverse developmental processes including endoderm formation, vascular development, and fetal hematopoietic stem cell maintenance. Expression of Sox17 in mature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitor cell fate. In this paper, we identify mechanisms by which Sox17 influences lung epithelial progenitor cell behavior and reprograms cell fate in the mature respiratory epithelium. Conditional expression of Sox17 in epithelial cells of the adult mouse lung demonstrated that cell cluster formation and respecification of alveolar progenitor cells toward proximal airway lineages were rapidly reversible processes. Prolonged expression of Sox17 caused the ectopic formation of bronchiolar-like structures with diverse respiratory epithelial cell characteristics in alveolar regions of lung. During initiation of progenitor cell behavior, Sox17 induced proliferation and increased the expression of the progenitor cell marker Sca-1 and genes involved in cell cycle progression. Notably, Sox17 enhanced cyclin D1 expression in vivo and activated cyclin D1 promoter activity in vitro. Sox17 decreased the expression of transforming growth factor-beta (TGF-beta-responsive cell cycle inhibitors in the adult mouse lung, including p15, p21, and p57, and inhibited TGF-beta1-mediated transcriptional responses in vitro. Further, Sox17 interacted with Smad3 and blocked Smad3 DNA binding and transcriptional activity. Together, these data show that a subset of mature respiratory epithelial cells retains remarkable phenotypic plasticity and that Sox17, a gene required for early endoderm formation, activates the cell cycle and reinitiates multipotent progenitor cell behavior in mature lung cells.

  3. Absence of an inhibitory effect of a vegetables-fruit mixture on the initiation and promotion phases of azoxymethane-induced colorectal carcinogenesis in rats fed low- or high-fat diets

    NARCIS (Netherlands)

    Rijnkels, J.M.; Hollanders, V.M.H.; Woutersen, R.A.; Koeman, J.H.; Alink, G.M.

    1998-01-01

    The potential inhibitory effects of a vegetables-fruit mixture on the initiation and promotion phases of azoxymethane-induced colorectal carcinogenesis were examined in rats fed low- or high-fat diets. Rats were fed low-fat diets (20 energy percent, Diets A and B) or high-fat diets (40 energy percen

  4. Avian Diagnostic and Therapeutic Antibodies to Viral Emerging Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    David Bradley

    2011-03-31

    During the current period the following key objectives were achieved: demonstration of high titer antibody production by geese following immunization with inactived H1N1 virus; completion of the epitope mapping of West Nile Virus-specific goose antibodies and initiation of epitope mapping of H1N1 flu-specific goose antibodies; advancement in scalable purification of goose antibodies.

  5. Two tobacco AP1-like gene promoters with highly specific, tightly regulated and uniquely expressed activity during floral transition, initiation and development

    Science.gov (United States)

    Biotech engineering of agronomic traits requires an array of highly specific and tightly regulated promoters in flower or other tissues. In this study, we isolated and characterized two tobacco AP1-like promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using GUS reporter and tissue-speci...

  6. Antiparietal cell antibody test

    Science.gov (United States)

    APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; ...

  7. Two tobacco AP1-like gene promoters drive highly specific, tightly regulated and unique expression patterns during floral transition, initiation and development.

    Science.gov (United States)

    Zhang, Jinjin; Yan, Guohua; Wen, Zhifeng; An, Young-Qiang; Singer, Stacy D; Liu, Zongrang

    2014-02-01

    The genetic engineering of agronomic traits requires an array of highly specific and tightly regulated promoters that drive expression in floral tissues. In this study, we isolated and characterized two tobacco APETALA1-like (AP1-like) promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using the GUS reporter system, along with tissue-specific ablation analyses. Our results demonstrated that the two promoters are active in floral inflorescences but not in vegetative apical meristems or other vegetative tissues, as reflected by strong GUS staining and DT-A-mediated ablation of apical shoot tips during reproductive but not vegetative growth. We also showed that the NtAP1Lb1 promoter was more active than NtAP1La in inflorescences, as the former yielded higher frequencies and greater phenotypic evidence of tissue ablation compared to the latter. We further revealed that both promoters were uniformly expressed in the meristems of stage 1 and 2 floral buds, but were differentially expressed in floral organs later during development. While NtAP1La was found to be active in stage 4-5 carpels, later becoming confined to ovary tissue from stage 9 onwards, NtAP1Lb1 activity was apparent in all floral organs from stages 3 to 7, becoming completely absent in all floral organs from stage 11 onward. Therefore, it seems that the two tobacco promoters have acquired similar but distinct inflorescence-, floral meristem- and floral organ-specific and development-dependent regulatory features without any leaky activity in vegetative tissues. These features are novel and have rarely been observed in other flower-specific promoters characterized to date. The potential application of these promoters for engineering sterility, increasing biomass production and modifying flower architecture, as well as their putative use in flower-specific transgene excision, will be discussed.

  8. Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island.

    Directory of Open Access Journals (Sweden)

    Heather M O'Hagan

    2008-08-01

    Full Text Available Chronic exposure to inducers of DNA base oxidation and single and double strand breaks contribute to tumorigenesis. In addition to the genetic changes caused by this DNA damage, such tumors often contain epigenetically silenced genes with aberrant promoter region CpG island DNA hypermethylation. We herein explore the relationships between such DNA damage and epigenetic gene silencing using an experimental model in which we induce a defined double strand break in an exogenous promoter construct of the E-cadherin CpG island, which is frequently aberrantly DNA hypermethylated in epithelial cancers. Following the onset of repair of the break, we observe recruitment to the site of damage of key proteins involved in establishing and maintaining transcriptional repression, namely SIRT1, EZH2, DNMT1, and DNMT3B, and the appearance of the silencing histone modifications, hypoacetyl H4K16, H3K9me2 and me3, and H3K27me3. Although in most cells selected after the break, DNA repair occurs faithfully with preservation of activity of the promoter, a small percentage of the plated cells demonstrate induction of heritable silencing. The chromatin around the break site in such a silent clone is enriched for most of the above silent chromatin proteins and histone marks, and the region harbors the appearance of increasing DNA methylation in the CpG island of the promoter. During the acute break, SIRT1 appears to be required for the transient recruitment of DNMT3B and subsequent methylation of the promoter in the silent clones. Taken together, our data suggest that normal repair of a DNA break can occasionally cause heritable silencing of a CpG island-containing promoter by recruitment of proteins involved in silencing. Furthermore, with contribution of the stress-related protein SIRT1, the break can lead to the onset of aberrant CpG island DNA methylation, which is frequently associated with tight gene silencing in cancer.

  9. ICT-enabled Social Innovation in support of the Implementation of the Social Investment Package (IESI) - Mapping and analysis of ICT-Enabled Social Innovation initiatives promoting social investment through integrated approaches to the provision of social services

    OpenAIRE

    MISURACA GIANLUCA; COLOMBO VILARRASA CLELIA; KUCSERA CSABA; CARRETERO GOMEZ STEPHANIE; BACIGALUPO MARGHERITA; Radescu, Raluca

    2015-01-01

    This report presents the results of the mapping and analysis of ICT-enabled social innovation initiatives promoting social investment through integrated approaches to the provision of social services, which was conducted as part of the research on ICT-Enabled Social Innovation in support of the Social Investment Package (SIP). The main goal of the research carried out by the European Commission's JRC-IPTS jointly with the Directorate General Employment, Social Affairs and Inclusion, was to ex...

  10. School Health Promotion to Increase Empowerment, Gender Equality and Pupil Participation: A Focus Group Study of a Swedish Elementary School Initiative

    Science.gov (United States)

    Gadin, Katja Gillander; Weiner, Gaby; Ahlgren, Christina

    2013-01-01

    A school health promotion project was carried out in an elementary school in Sweden where active participation, gender equality, and empowerment were leading principles. The objective of the study was to understand challenges and to identify social processes of importance for such a project. Focus group interviews were conducted with 6 single-sex…

  11. The Collective Impact Model and Its Potential for Health Promotion: Overview and Case Study of a Healthy Retail Initiative in San Francisco

    Science.gov (United States)

    Flood, Johnna; Minkler, Meredith; Lavery, Susana Hennessey; Estrada, Jessica; Falbe, Jennifer

    2015-01-01

    As resources for health promotion become more constricted, it is increasingly important to collaborate across sectors, including the private sector. Although many excellent models for cross-sector collaboration have shown promise in the health field, collective impact (CI), an emerging model for creating larger scale change, has yet to receive…

  12. Examination of the Physical and Social Environments and Their Effect on Health Promotion Program Participation, Self Initiated Physical Activity and Nutrition Choices among University Employees

    Science.gov (United States)

    Leininger, Lisa Janzen

    2011-01-01

    The worksite can be an effective arena to elicit health behavior change. Worksite health promotion programs now exist in 90% of all companies with more than 50 employees. These programs have become prevalent due to the high rates of obesity and lifestyle related diseases that are present in the United States. The purpose of this study was to…

  13. Belimumab: anti-BLyS human monoclonal antibody, anti-BLyS monoclonal antibody, BmAb, human monoclonal antibody to B-lymphocyte stimulator.

    Science.gov (United States)

    2008-01-01

    granted a 50/50 co-development and co-promotion option to GSK for certain therapies that complete phase IIa trials successfully. The companies subsequently entered into a definite worldwide, co-development and commercialization agreement in August 2006, under which HGS will be responsible for conducting phase III trials of the product, with assistance from GSK. The companies will share equally phase III/IV development costs, sales and marketing expenses, and profits. In October 2007, Cambridge Antibody Technology was integrated into MedImmune. Both companies were previously independent subsidiaries of AstraZeneca. MedImmune is now the operationally independent biologics business unit of AstraZeneca. Human Genome Sciences intends to initiate a phase II trial of subcutaneous belimumab by mid-2008. Results from a phase II trial in 449 patients with SLE demonstrated that belimumab improved or stabilized SLE over 2.5 years. The phase II trial was a double-blind, placebo-controlled, multicentre study that evaluated the safety, optimal dosing, and preliminary efficacy of belimumab in patients with active SLE over 52 weeks initially, followed by a continuation phase for a total of 2.5 years. Belimumab has received fast-track designation for the treatment of SLE from the US FDA and has also been selected for inclusion in the agency's continuous Marketing Application Pilot 2 programme.

  14. The DEAD-box helicase DDX3 substitutes for the cap-binding protein eIF4E to promote compartmentalized translation initiation of the HIV-1 genomic RNA.

    Science.gov (United States)

    Soto-Rifo, Ricardo; Rubilar, Paulina S; Ohlmann, Théophile

    2013-07-01

    Here, we show a novel molecular mechanism promoted by the DEAD-box RNA helicase DDX3 for translation of the HIV-1 genomic RNA. This occurs through the adenosine triphosphate-dependent formation of a translation initiation complex that is assembled at the 5' m(7)GTP cap of the HIV-1 mRNA. This is due to the property of DDX3 to substitute for the initiation factor eIF4E in the binding of the HIV-1 m(7)GTP 5' cap structure where it nucleates the formation of a core DDX3/PABP/eIF4G trimeric complex on the HIV-1 genomic RNA. By using RNA fluorescence in situ hybridization coupled to indirect immunofluorescence, we further show that this viral ribonucleoprotein complex is addressed to compartmentalized cytoplasmic foci where the translation initiation complex is assembled.

  15. Intrinsic Properties of immunoglobulin IgG1 Isotype-Switched B Cell Receptors Promote Microclustering and the Initiation of Signaling

    Science.gov (United States)

    Liu, Wanli; Meckel, Tobias; Tolar, Pavel; Sohn, Hae Won; Pierce, Susan K.

    2010-01-01

    Summary Memory B cells express high affinity, immunoglobulin B cell receptors (IgG-BCRs) that enhance B cell responses giving rise to the rapid production of high affinity, IgG antibodies. Despite the central role of IgG-BCRs in memory responses, the mechanisms by which the IgG-BCRs function to enhance B cell responses are not fully understood. Using high-resolution live-cell imaging we showed that independent of affinity, IgG1-BCRs dramatically enhanced the earliest BCR-intrinsic events that followed within seconds of B cells’ encounter with membrane bound antigen including BCR oligomerization and BCR microcluster growth, leading to Syk kinase recruitment and calcium responses. The enhancement of these early events was dependent on a membrane proximal region of the IgG1 cytoplasmic tail not previously appreciated to play a role in IgG1-BCR signaling. Thus, intrinsic properties of the IgG1-BCR enhance early antigen-driven events that ultimately translate into heightened signaling. PMID:20620943

  16. Initial development and preliminary evaluation of a multiplex bead assay to detect antibodies to Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis outer membrane peptides in naturally infected dogs from Grenada, West Indies.

    Science.gov (United States)

    Wilkerson, Melinda J; Black, Kelley E; Lanza-Perea, Marta; Sharma, Bhumika; Gibson, Kathryn; Stone, Diana M; George, Anushka; Nair, Arathy D S; Ganta, Roman R

    2017-01-01

    Tick-borne bacteria, Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis are significant pathogens of dogs worldwide, and coinfections of E. canis and A. platys are common in dogs on the Caribbean islands. We developed and evaluated the performance of a multiplex bead-based assay to detect antibodies to E. canis, A. platys, and E. chaffeensis peptides in dogs from Grenada, West Indies, where E. canis and A. platys infections are endemic. Peptides from outer membrane proteins of P30 of E. canis, OMP-1X of A. platys, and P28-19/P28-14 of E. chaffeensis were coupled to magnetic beads. The multiplex peptide assay detected antibodies in dogs experimentally infected with E. canis and E. chaffeensis, but not in an A. platys experimentally infected dog. In contrast, the multiplex assay and an in-house enzyme-linked immunosorbent assay (ELISA) detected A. platys antibodies in naturally infected Grenadian dogs. Following testing of 104 Grenadian canine samples, multiplex assay results had good agreement with commercially available ELISA and immunofluorescent assay for E. canis antibody-positive dogs ( K values of 0.73 and 0.84), whereas A. platys multiplex results had poor agreement with these commercial assays ( K values of -0.02 and 0.01). Prevalence of seropositive E. canis and A. platys Grenadian dogs detected by the multiplex and commercial antibody assays were similar to previous reports. Although the multiplex peptide assay performed well in detecting the seropositive status of dogs to E. canis and had good agreement with commercial assays, better antigen targets are necessary for the antibody detection of A. platys.

  17. [Antinuclear antibodies].

    Science.gov (United States)

    Cabiedes, Javier; Núñez-Álvarez, Carlos A

    2010-01-01

    Anti-nuclear antibodies (ANA) are immunoglobulin directed against autologous cell nuclear and cytoplasmic components. Besides the autoimmune ANA there are other ANA that can be detected in circulation, like natural and infectious ANA. Because of its high sensibility, detection of the ANA must be done by indirect immunofluorescence (IIF) as screening test and all of those positive samples are convenient to confirm its specificity by ELISA, western blot or other techniques. Positive ANA detected by IIF must be evaluated taking in to account the pattern and titer. The following recommended step is the specificity characterization (reactivity against extractable nuclear antigens [ENA], dsDNA, etc.) which is useful for the diagnosis and follow up of patients with autoimmune diseases, and by such reasoning, its detection must be performed in an orderly and reasonable way using guides or strategies focused to the good use and interpretation of the autoantibodies. The objective of this review is to present a compilation of the literature and our experience in the detection and study of the ANA.

  18. Human haematopoietic stem cells express Oct4 pseudogenes and lack the ability to initiate Oct4 promoter-driven gene expression

    Directory of Open Access Journals (Sweden)

    Strain Alastair J

    2010-03-01

    Full Text Available Abstract The transcription factor Oct4 is well defined as a key regulator of embryonic stem (ES cell pluripotency. In recent years, the role of Oct4 has purportedly extended to the self renewal and maintenance of multipotency in adult stem cell (ASC populations. This profile has arisen mainly from reports utilising reverse transcription-polymerase chain reaction (RT-PCR based methodologies and has since come under scrutiny following the discovery that many developmental genes have multiple pseudogenes associated with them. Six known pseudogenes exist for Oct4, all of which exhibit very high sequence homology (three >97%, and for this reason the generation of artefacts may have contributed to false identification of Oct4 in somatic cell populations. While ASC lack a molecular blueprint of transcription factors proposed to be involved with 'stemness' as described for ES cells, it is not unreasonable to assume that similar gene patterns may exist. The focus of this work was to corroborate reports that Oct4 is involved in the regulation of ASC self-renewal and differentiation, using a combination of methodologies to rule out pseudogene interference. Haematopoietic stem cells (HSC derived from human umbilical cord blood (UCB and various differentiated cell lines underwent RT-PCR, product sequencing and transfection studies using an Oct4 promoter-driven reporter. In summary, only the positive control expressed Oct4, with all other cell types expressing a variety of Oct4 pseudogenes. Somatic cells were incapable of utilising an exogenous Oct4 promoter construct, leading to the conclusion that Oct4 does not appear involved in the multipotency of human HSC from UCB.

  19. Selection of antibodies from synthetic antibody libraries.

    Science.gov (United States)

    Harel Inbar, Noa; Benhar, Itai

    2012-10-15

    More than 2 dozen years had passed since the field of antibody engineering was established, with the first reports of bacterial [1-3] and mammalian cells [4] expression of recombinant antibody fragments, and in that time a lot of effort was dedicated to the development of efficient technological means, intended to assist in the creation of therapeutic monoclonal antibodies (mAbs). Research focus was given to two intertwined technological aspects: the selection platform and the recombinant antibody repertoires. In accordance with these areas of interest, it is the goal of this chapter to describe the various selection tools and antibody libraries existing, with emphasis on the later, and their applications. This chapter gives a far from exhaustive, subjective "historic account" of the field, describing the selection platforms, the different formats of antibody repertoires and the applications of both for selecting recombinant antibodies. Several excellent books provide detailed protocols for constructing antibody libraries and selecting antibodies from those libraries [5-13]. Such books may guide a newcomer to the field in the fine details of antibody engineering. We would like to offer advice to the novice: although seemingly simple, effective library construction and antibody isolation provide best benefits in the hands of professionals. It is an art as much as it is science.

  20. The Evaluation and Comparison of Transcriptionally Targeted Noxa and Puma Killer Genes to Initiate Apoptosis Under Cancer-Specific Promoter CXCR1 in Hepatocarcinoma Gene Therapy

    Directory of Open Access Journals (Sweden)

    Khoshtinat Nikkhoi

    2016-09-01

    Full Text Available Background Cancerous cells proliferate as fast as possible without a proper surveillance system. This rapid cell division leads to enormous mutation rates, which help a tumor establish. Objectives This study evaluated the potential of inducing apoptosis using Noxa and Puma in a hepatocarcinoma cell line. Methods The current study generated two recombinant lentiviruses, pLEX-GCN and pLEX-GCP, bearing Noxa and Puma, respectively. Transduction of both genes to hepatocarcinoma (HepG2 was verified using fluorescent microscopic analysis, western blotting, and quantitative real-time polymerase chain reaction (PCR. To evaluate the potential of Noxa and Puma to initiate apoptosis, a caspase-9 real-time, MTT assay, and a 4’, 6-diamidino-2-phenylindole (DAPI reagent were performed to stain apoptotic cells. Results The data verified successful transduction to HepG2 and HEK293T. Higher relative expression of Noxa and Puma rather than the untransduced cell line showed these genes are expressed more in HepG2 in comparison to HEK293T. The results of the real-time PCR, MTT assay, and DAPI reagent illustrated that higher cells initiated apoptosis following Puma transduction rather than Noxa. Conclusions In this approach, the suicide gene was transferred to transformed cells and ignited apoptosis to exterminate them. Puma is a more potent killer gene and has higher capabilities to start intrinsic apoptosis pathway.

  1. Anti-DNA antibodies--quintessential biomarkers of SLE.

    Science.gov (United States)

    Pisetsky, David S

    2016-02-01

    Antibodies that recognize and bind to DNA (anti-DNA antibodies) are serological hallmarks of systemic lupus erythematosus (SLE) and key markers for diagnosis and disease activity. In addition to common use in the clinic, anti-DNA antibody testing now also determines eligibility for clinical trials, raising important questions about the nature of the antibody-antigen interaction. At present, no 'gold standard' for serological assessment exists, and anti-DNA antibody binding can be measured with a variety of assay formats, which differ in the nature of the DNA substrates and in the conditions for binding and detection of antibodies. A mechanism called monogamous bivalency--in which high avidity results from simultaneous interaction of IgG Fab sites with a single polynucleotide chain--determines anti-DNA antibody binding; this mechanism might affect antibody detection in different assay formats. Although anti-DNA antibodies can promote pathogenesis by depositing in the kidney or driving cytokine production, they are not all alike, pathologically, and anti-DNA antibody expression does not necessarily correlate with active disease. Levels of anti-DNA antibodies in patients with SLE can vary over time, distinguishing anti-DNA antibodies from other pathogenic antinuclear antibodies. Elucidation of the binding specificities and the pathogenic roles of anti-DNA antibodies in SLE should enable improvements in the design of informative assays for both clinical and research purposes.

  2. Antibody-controlled actuation of DNA-based molecular circuits

    Science.gov (United States)

    Engelen, Wouter; Meijer, Lenny H. H.; Somers, Bram; de Greef, Tom F. A.; Merkx, Maarten

    2017-02-01

    DNA-based molecular circuits allow autonomous signal processing, but their actuation has relied mostly on RNA/DNA-based inputs, limiting their application in synthetic biology, biomedicine and molecular diagnostics. Here we introduce a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing. Our approach, antibody-templated strand exchange (ATSE), uses the characteristic bivalent architecture of antibodies to promote DNA-strand exchange reactions both thermodynamically and kinetically. Detailed characterization of the ATSE reaction allowed the establishment of a comprehensive model that describes the kinetics and thermodynamics of ATSE as a function of toehold length, antibody-epitope affinity and concentration. ATSE enables the introduction of complex signal processing in antibody-based diagnostics, as demonstrated here by constructing molecular circuits for multiplex antibody detection, integration of multiple antibody inputs using logic gates and actuation of enzymes and DNAzymes for signal amplification.

  3. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Geetaram; Farley, Kalamo [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); El-Hage, Nazira [Virginia Commonwealth University, Richmond, VA (United States); Aiamkitsumrit, Benjamas; Fassnacht, Ryan [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Kashanchi, Fatah [George Mason University, Manassas, VA (United States); Ochem, Alex [ICGEB, Wernher and Beit Building, Anzio Road, Observatory, 7925 Cape Town (South Africa); Simon, Gary L. [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Karn, Jonathan [Case Western Reserve University, Cleveland, OH (United States); Hauser, Kurt F. [Virginia Commonwealth University, Richmond, VA (United States); Tyagi, Mudit, E-mail: tmudit@email.gwu.edu [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20037 (United States)

    2015-09-15

    Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR.

  4. Application of the improved BALB/c 3T3 cell transformation assay to the examination of the initiating and promoting activities of chemicals: the second interlaboratory collaborative study by the non-genotoxic carcinogen study group of Japan.

    Science.gov (United States)

    Tsuchiya, Toshiyuki; Umeda, Makoto; Tanaka, Noriho; Sakai, Ayako; Nishiyama, Hiroshi; Yoshimura, Isao; Ajimi, Syozo; Asada, Shin; Asakura, Masumi; Baba, Hiroshi; Dewa, Yasuaki; Ebe, Youji; Fushiwaki, Yuichi; Hagiwara, Yuji; Hamada, Shuichi; Hamamura, Tetsuo; Iwase, Yumiko; Kajiwara, Yoshitsugu; Kasahara, Yasushi; Kato, Yukihiko; Kawabata, Masayoshi; Kitada, Emiko; Kaneko, Kazuko; Kizaki, Yuko; Kubo, Kinya; Miura, Daisaku; Mashiko, Kaori; Mizuhashi, Fukutaro; Muramatsu, Dai; Nakajima, Madoka; Nakamura, Tetsu; Oishi, Hidetoshi; Sasaki, Toshiaki; Shimada, Sawako; Takahashi, Chitose; Takeda, Yuko; Wakuri, Sinobu; Yajima, Nobuhiro; Yajima, Satoshi; Yatsushiro, Tomoko

    2010-03-01

    The Non-genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan organised the second step of the inter-laboratory collaborative study on one-stage and two-stage cell transformation assays employing BALB/c 3T3 cells, with the objective of confirming whether the respective laboratories could independently produce results relevant to initiation or promotion. The method was modified to use a medium consisting of DMEM/F12 supplemented with 2% fetal bovine serum and a mixture of insulin, transferrin, ethanolamine and sodium selenite, at the stationary phase of cell growth. Seventeen laboratories collaborated in this study, and each chemical was tested by three to five laboratories. Comparison between the one-stage and two-stage assays revealed that the latter method would be beneficial in the screening of chemicals. In the test for initiating activity with the two-stage assay (post-treated with 0.1microg/ml 12-O-tetradecanoylphorbol-13-acetate), the relevant test laboratories all obtained positive results for benzo[a]pyrene and methylmethane sulphonate, and negative results for phenanthrene. Of those laboratories assigned phenacetin for the initiation phase, two returned positive results and two returned negative results, where the latter laboratories tested up to one dose lower than the maximum dose used by the former laboratories. In the exploration of promoting activity with the twostage assay (pretreated with 0.2microg/ml 3-methylcholanthrene), the relevant test laboratories obtained positive results for mezerein, sodium orthovanadate and TGF-beta1, and negative results for anthralin, phenacetin and phorbol. Two results returned for phorbol 12,13-didecanoate were positive, but one result was negative - again, the maximum dose to achieve the latter result was lower than that which produced the former results. These results suggest that this modified assay method is relevant, reproducible and transferable, provided that dosing issues, such as the

  5. The Ne{sup 3}LS Network, Quebec's initiative to evaluate the impact and promote a responsible and sustainable development of nanotechnology

    Energy Technology Data Exchange (ETDEWEB)

    Endo, Charles-Anica [CHU Sainte-Justine Research Center, 3175, chemin de la Cote-Sainte-Catherine, bureau 8228, Montreal, Quebec, H3T 1C5 (Canada); Emond, Claude [Universite de Montreal, Departement de sante environnementale et sante au travail. Pavillon Marguerite-d' Youville, 2375, chemin de la Cote Ste-Catherine, local 4095 Montreal, Quebec, H3T 1A8 (Canada); Battista, Renaldo [Universite de Montreal, Departement d' administration de la sante, Pavillon Mont-Royal 1420, boul. Mont-Royal, Montreal, Quebec, H2V 4P3 (Canada); Parizeau, Marie-Helene [Universite Laval, Bureau 536, Pavillon Felix-Antoine-Savard, 2325, rue des Bibliotheques, Quebec, G1V 0A6 (Canada); Beaudry, Catherine, E-mail: claude.emond@umontreal.ca [Ecole Polytechnique de Montreal, Departement de mathematiques et de genie industriel, C.P. 6079, succ. Centre-ville, Montreal, Quebec, H3C 3A7 (Canada)

    2011-07-06

    The spectacular progress made by nanosciences and nanotechnologies elicits as much hope and fear. Consequently, a great number of research and training initiatives on the ethical, environmental, economic, legal and social issues regarding nanotechnology development (Ne{sup 3}LS) are emerging worldwide. In Quebec, Canada, a Task Force was mandated by NanoQuebec to conceive a Ne{sup 3}LS research and training strategy to assess those issues. This Task Force brought together experts from universities, governments or industry working in nanosciences and nanotechnologies or in Ne{sup 3}LS. Their resulting action plan, made public in November 2006, contained several recommendations, including the creation of a knowledge network (Ne{sup 3}LS Network). In the following years, after consulting with numerous key players concerned with the possible impacts of nanosciences and nanotechnologies in Quebec, the Ne{sup 3}LS Network was launched in January 2010 in partnership with the Fonds quebecois de la recherche sur la nature et les technologies, the Fonds quebecois de la recherche sur la societe et la culture and the Fonds de la recherche en sante du Quebec, NanoQuebec, the Institut de recherche Robert-Sauve en sante et en securite du travail as well as the University of Montreal. Its objectives are to 1) Foster the development of Ne{sup 3}LS research activities (grants and fellowships); 2) Spearhead the Canadian and international Ne{sup 3}LS network; 3) Take part in the training of researchers and experts; 4) Encourage the creation of interactive tools for the general public; 5) Facilitate collaboration between decision-makers and experts; 6) Involve the scientific community through a host of activities (symposium, conferences, thematic events); 7) Build multidisciplinary research teams to evaluate the impact of nanotechnology.

  6. The Ne3LS Network, Québec's initiative to evaluate the impact and promote a responsible and sustainable development of nanotechnology

    Science.gov (United States)

    Endo, Charles-Anica; Emond, Claude; Battista, Renaldo; Parizeau, Marie-Hélène; Beaudry, Catherine

    2011-07-01

    The spectacular progress made by nanosciences and nanotechnologies elicits as much hope and fear. Consequently, a great number of research and training initiatives on the ethical, environmental, economic, legal and social issues regarding nanotechnology development (Ne3LS) are emerging worldwide. In Québec, Canada, a Task Force was mandated by NanoQuébec to conceive a Ne3LS research and training strategy to assess those issues. This Task Force brought together experts from universities, governments or industry working in nanosciences and nanotechnologies or in Ne3LS. Their resulting action plan, made public in November 2006, contained several recommendations, including the creation of a knowledge network (Ne3LS Network). In the following years, after consulting with numerous key players concerned with the possible impacts of nanosciences and nanotechnologies in Québec, the Ne3LS Network was launched in January 2010 in partnership with the Fonds québécois de la recherche sur la nature et les technologies, the Fonds québécois de la recherche sur la société et la culture and the Fonds de la recherche en santé du Québec, NanoQuébec, the Institut de recherche Robert-Sauvé en santé et en sécurité du travail as well as the University of Montreal. Its objectives are to 1) Foster the development of Ne3LS research activities (grants and fellowships); 2) Spearhead the Canadian and international Ne3LS network; 3) Take part in the training of researchers and experts; 4) Encourage the creation of interactive tools for the general public; 5) Facilitate collaboration between decision-makers and experts; 6) Involve the scientific community through a host of activities (symposium, conferences, thematic events); 7) Build multidisciplinary research teams to evaluate the impact of nanotechnology.

  7. Oral priming with replicating adenovirus serotype 4 followed by subunit H5N1 vaccine boost promotes antibody affinity maturation and expands H5N1 cross-clade neutralization.

    Directory of Open Access Journals (Sweden)

    Surender Khurana

    Full Text Available A Phase I trial conducted in 2009-2010 demonstrated that oral vaccination with a replication competent Ad4-H5 (A/Vietnam vector with dosages ranging from 107-1011 viral particles was well tolerated. HA-specific T-cell responses were efficiently induced, but very limited hemagglutination-inhibiting (HI humoral responses were measured. However, a single boost of Ad4-H5-Vtn vaccinated individuals with a unadjuvanted licensed H5N1 (A/Vietnam subunit vaccine resulted in superior HI titers compared with unprimed subjects. In the current study, the impact of Ad4-H5 priming on the quality of the polyclonal humoral immune response was evaluated using a real-time kinetics assay by surface plasmon resonance (SPR. Total binding of serum polyclonal antibodies from the Ad4-H5-Vtn primed groups against both homologous H5N1-A/Vietnam/1194/2004 (clade 1 and heterologous A/Indonesia-5/2005 (clade 2.1 HA1 head domain was significantly higher compared with sera from individuals that received subunit H5N1 vaccination alone. SPR measurements also demonstrated that the antigen-antibody complex dissociation rates (a surrogate for antibody affinity of serum antibodies against the HA1 of H5N1-A/Vietnam were significantly higher in the Ad4-H5 primed groups compared with those from the unprimed group. Furthermore, strong correlations were observed between the antibody affinities for HA1 (but not HA2 and the virus neutralization titers against the homologous strain and a panel of heterologous clade 2 H5N1 strains. These findings support the concept of oral prime-boost vaccine approaches against pandemic influenza to elicit long-term memory B cells with high affinity capable of rapid response to variant pandemic viruses likely to emerge and adapt to human transmissions.

  8. Acetylcholine receptor antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  9. Antinuclear antibody panel

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003535.htm Antinuclear antibody panel To use the sharing features on this page, please enable JavaScript. The antinuclear antibody panel is a blood test that looks at ...

  10. Lyme disease antibody

    Science.gov (United States)

    ... JavaScript. The Lyme disease blood test looks for antibodies in the blood to the bacteria that causes ... needed. A laboratory specialist looks for Lyme disease antibodies in the blood sample using the ELISA test . ...

  11. The antibody mining toolbox

    OpenAIRE

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D.; Shen, Xiaohong; Bradbury, Andrew RM; Kiss, Csaba

    2013-01-01

    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput ...

  12. Antibody Isotype Switching in Vertebrates.

    Science.gov (United States)

    Senger, Kate; Hackney, Jason; Payandeh, Jian; Zarrin, Ali A

    2015-01-01

    The humoral or antibody-mediated immune response in vertebrates has evolved to respond to diverse antigenic challenges in various anatomical locations. Diversification of the immunoglobulin heavy chain (IgH) constant region via isotype switching allows for remarkable plasticity in the immune response, including versatile tissue distribution, Fc receptor binding, and complement fixation. This enables antibody molecules to exert various biological functions while maintaining antigen-binding specificity. Different immunoglobulin (Ig) classes include IgM, IgD, IgG, IgE, and IgA, which exist as surface-bound and secreted forms. High-affinity autoantibodies are associated with various autoimmune diseases such as lupus and arthritis, while defects in components of isotype switching are associated with infections. A major route of infection used by a large number of pathogens is invasion of mucosal surfaces within the respiratory, digestive, or urinary tract. Most infections of this nature are initially limited by effector mechanisms such as secretory IgA antibodies. Mucosal surfaces have been proposed as a major site for the genesis of adaptive immune responses, not just in fighting infections but also in tolerating commensals and constant dietary antigens. We will discuss the evolution of isotype switching in various species and provide an overview of the function of various isotypes with a focus on IgA, which is universally important in gut homeostasis as well as pathogen clearance. Finally, we will discuss the utility of antibodies as therapeutic modalities.

  13. Neoglycoproteins as carbohydrate antigens: synthesis, analysis, and polyclonal antibody response.

    Science.gov (United States)

    Kerékgyártó, Márta; Fekete, Anikó; Szurmai, Zoltán; Kerékgyártó, János; Takács, László; Kurucz, István; Guttman, András

    2013-08-01

    The analysis and polyclonal antibody response for newly synthesized maltose-BSA conjugate neoglycoproteins is described. In this first proof of concept study, a simple carbohydrate antigen, maltose, was linked to BSA by reductive amination. An aglycone spacer was utilized to conserve the intact annular maltose structure and to promote the accessibility of the carbohydrate immunogen hapten during immunization. The neoglycoproteins were investigated by CGE and the number of conjugated maltose residues was determined by MALDI-TOF MS. The neoglycoproteins were then evaluated by immunization of BALB/c mice and the polyclonal antibody response was tested by ELISA as evidence for the presence of sugar-containing epitope-specific antibodies. Selective antibody binding was demonstrated to the synthesized neoglycoproteins with different (low and high) glycosylation degrees suggesting the possible use of this approach to generate antibodies. Moreover, the polyclonal antibody response was not inhibited by maltose or other simple carbohydrates to confirm presence of the neoglycoprotein-specific antibodies.

  14. Heterologous prime-boost vaccination with MF59-adjuvanted H5 vaccines promotes antibody affinity maturation towards the hemagglutinin HA1 domain and broad H5N1 cross-clade neutralization.

    Directory of Open Access Journals (Sweden)

    Surender Khurana

    Full Text Available In an open label clinical study (2007, MF59-adjuvanted hemagglutinin (HA vaccine from H5N1-A/Vietnam/1194/2004 (clade 1 was administered to subjects previously vaccinated (primed with clade 0 H5N3 (A/duck/Singapore/97 vaccine at least 6 years earlier (in 1999 or 2001. The primed individuals responded rapidly and generated high neutralizing antibody titers against the H5N1-Vietnam strain within 7 days of a single booster vaccination. Furthermore, significant cross-neutralization titers were measured against H5N1 clade 0, 1, and 2 viruses. In the current study, the impact of MF59 adjuvant during heterologous priming on the quality of humoral polyclonal immune response in different vaccine arms were further evaluated using real time kinetics assay by surface plasmon resonance (SPR. Total anti-H5N1 HA1 polyclonal sera antibody binding from the heterologous prime-boost groups after a single MF59-H5N1 boost was significantly higher compared with sera from unprimed individuals that received two MF59-H5N1 vaccinations. The antigen-antibody complex dissociation rates (surrogate for antibody affinity of the polyclonal sera against HA1 of H5N1-A/Vietnam/1194/2004 from the MF59-H5N3 primed groups were significantly higher compared to sera from unadjuvanted primed groups or unprimed individuals that received two MF59-H5N1 vaccines. Furthermore, strong inverse correlations were observed between the antibody dissociation off-rates of the immune sera against HA1 (but not HA2 and the virus neutralization titers against H5 vaccine strains and heterologous H5N1 strains. These findings supports the use of oil-in-water-adjuvanted pandemic influenza vaccines to elicit long term memory B cells with high affinity BCR capable of responding to potential variant pandemic viruses likely to emerge and adapt to human transmissions.

  15. [VGKC-complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-04-01

    Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

  16. 以人CCR5启动子为靶的药物筛选方法的初步建立%Establishment and Initial Application of a Medicine Screening Technique Based on Human Promoter of CCR5

    Institute of Scientific and Technical Information of China (English)

    卫艳萍; 冯龙; 马云云; 董子明; 韩志强; 赵国强

    2009-01-01

    构建靶向人趋化因子受体5(CC chemokine receptors 5,CCR5)启动子的药物筛选系统.将CCR5启动子序列克隆入改建后的报告载体pGL3-neo,转染pGL3-neo-CCR5入Jurkat细胞(急性T淋巴细胞性白血病细胞),G418筛选后分组;用7种中药分别作用于各组细胞16 h后,检测细胞中CCR5启动子的表达水平.结果显示,双黄连组比对照组的荧光值明显降低(P<0.05);川琥宁组、黄芩组、黄芪组比对照组的荧光值明显升高(P<0.01).双黄连可使体外培养细胞转染的CCR5启动子活性降低,川琥宁、黄芩、黄芪可使体外培养细胞转染的CCR5启动子活性增高.表明初步构建成功靶向人CCR5启动子的药物筛选系统.%This research ws carried out to construct a medicine screening system targeting at human promoter of CCR5. The gene Human promoter of CCR5 was inserted into the rebuilt vector pGL3-neo. The pGL3-neo-CCR5 plasmids were transfected into Jurkat cells(the cell line of acute T lymphocyte leukemia).The lasting transfected cells were screened by G418. After seven kinds of traditional Chinese medicine had acted separately on the lasting transfected cells for 16h,the expression levels of CCR5 promoter in the cells were detected. The results showed that the level of luciferase activity of Shuanghuanglian-injectio group was remarkably lower than that of control(P<0.05),and the levels of luciferase activity of Chuanhuning group,Baical skullcap root group,and Milkvetch root group were remarkably higher than that of control (P<0.01). Shuanghuanglian-injectio depressed the activity of the transfected CCR5 promoter in cells cultivated in vitro; Chuanhuning,Baical skullcap root and Milkvetch root boosted the activity of the transfected CCR5 promoter in cells cultivated in vitro. Thus a medicine screening system based on Human promoter of CCR5 was initially constructed.

  17. Pneumococcal conjugate vaccines overcome splenic dependency of antibody response to pneumococcal polysaccharides

    NARCIS (Netherlands)

    Breukels, MA; Zandvoort, A; van den Dobbelsteen, GPJM; van den Muijsenberg, A; Lodewijk, ME; Beurret, M; Klok, PA; Timens, W; Rijkers, GT

    2001-01-01

    Protection against infectious with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to

  18. Bovine milk antibodies for health.

    Science.gov (United States)

    Korhonen, H; Marnila, P; Gill, H S

    2000-11-01

    The immunoglobulins of bovine colostrum provide the major antimicrobial protection against microbial infections and confer a passive immunity to the newborn calf until its own immune system matures. The concentration in colostrum of specific antibodies against pathogens can be raised by immunising cows with these pathogens or their antigens. Immune milk products are preparations made of such hyperimmune colostrum or antibodies enriched from it. These preparations can be used to give effective specific protection against different enteric diseases in calves and suckling pigs. Colostral immunoglobulin supplements designed for farm animals are commercially available in many countries. Also, some immune milk products containing specific antibodies against certain pathogens have been launched on the market. A number of clinical studies are currently in progress to evaluate the efficacy of immune milks in the prevention and treatment of various human infections, including those caused by antibiotic resistant bacteria. Bovine colostrum-based immune milk products have proven effective in prophylaxis against various infectious diseases in humans. Good results have been obtained with products targeted against rotavirus, Shigella flexneri, Escherichia coli, Clostridium difficile, Streptococcus mutans, Cryptosporidium parvum and Helicobacter pylori. Some successful attempts have been made to use immune milk in balancing gastrointestinal microbial flora. Immune milk products are promising examples of health-promoting functional foods, or nutraceuticals. This review summarises the recent progress in the development of these products and evaluates their potential as dietary supplements and in clinical nutrition.

  19. Standardization of anti-DNA antibody assays.

    Science.gov (United States)

    Pisetsky, David S

    2013-07-01

    Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus and represent important biomarkers for clinical and research purposes. These antibodies are part of a family of antibodies to nucleosomes and bind to conserved sites widely present on DNA. While the value of anti-DNA as a biomarker is well established, the assay for these antibodies has involved a variety of DNA sources and systems to detect DNA-anti-DNA interactions. The influence of these variations on antibody detection has complicated assay standardization. As an antigen, DNA has unique features since it is a highly charged polymer that has structural heterogeneity. This heterogeneity can affect antigenicity which can vary on the basis of DNA origin, size, conformation and mobility. In addition, as a polymer, DNA can promote patterns of antibody binding based on monogamous or bivalent interaction which require an extended polynucleotide structure. Understanding the nature of DNA as an antigen can facilitate interpretation of serological tests and underpin efforts at better standardization.

  20. Expression of recombinant antibodies.

    Science.gov (United States)

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with "human-like" post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

  1. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  2. Recombinant renewable polyclonal antibodies.

    Science.gov (United States)

    Ferrara, Fortunato; D'Angelo, Sara; Gaiotto, Tiziano; Naranjo, Leslie; Tian, Hongzhao; Gräslund, Susanne; Dobrovetsky, Elena; Hraber, Peter; Lund-Johansen, Fridtjof; Saragozza, Silvia; Sblattero, Daniele; Kiss, Csaba; Bradbury, Andrew R M

    2015-01-01

    Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products.

  3. The Clinical Proteomic Technologies for Cancer | Antibody Portal

    Science.gov (United States)

    An objective of the Reagents and Resources component of NCI's Clinical Proteomic Technologies for Cancer Initiative is to generate highly characterized monoclonal antibodies to human proteins associated with cancer.

  4. PLCG2-associatiated antibody deficiency immune dysregulation (PLAID)

    Science.gov (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  5. Enhancement of anamnestic immunospecific antibody response in orally immunized chickens

    DEFF Research Database (Denmark)

    Mayo, Susan; Carlsson, Hans-Erik; Zagon, Andrea;

    2008-01-01

    Production of immunospecific egg yolk antibodies (IgY antibodies) in egg laying hens through oral immunization is an attractive alternative to conventional antibody production in mammals for economic reasons as well as for animal welfare reasons. Oral immunization results in a systemic humoral...... of the immunization in week 18, demonstrating the presence of memory cells following the two initial oral immunizations. Considering that oral immunization results in approximately ten times lower concentrations of immunospecific antibodies in the egg yolk, compared to traditional subcutaneous immunization schemes...

  6. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  7. Monoclonal antibody "gold rush".

    Science.gov (United States)

    Maggon, Krishan

    2007-01-01

    The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush.

  8. Antibody engineering: facing new challenges in cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Laura SANZ; (A)ngel M CUESTA; Marta COMPTE; Luis (A)LVAREZ-VALLINA

    2005-01-01

    Antibody-based therapeutics are beginning to realize the promise enclosed in their early denomination as "magic bullets". Initial disappointment has turned into clinical and commercial success, and engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials. Recent structural and functional data have allowed the design of a new generation of therapeutic antibodies, with strategies ranging from complement-mediated and antibody-dependant cellular cytotoxicity enhancement to improved cytotoxic payloads using toxins, drugs,radionucleids and viral delivery. This review considers the structure of different types of recombinant antibodies, their mechanism of action and how their efficacy has been increased using a broad array of approaches. We will also focus on the additional benefits offered by the use of gene therapy methods for the in vivo production of therapeutic antibodies.

  9. Antiphospholipid antibody syndrome.

    Science.gov (United States)

    Kutteh, William H; Hinote, Candace D

    2014-03-01

    Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss. Thus, obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiologic mechanisms of action of aPLs have been described. This article discusses the diagnostic and obstetric challenges of obstetric APS, proposed pathophysiologic mechanisms of APS during pregnancy, and the management of women during and after pregnancy.

  10. Preparation of monoclonal antibody to P53 and its clinical application

    Institute of Scientific and Technical Information of China (English)

    Wenqing Wei; Junhua Wu; Jing Liu; Yuxia Wang

    2013-01-01

    Objective:The aim of this study was to prepare monoclonal antibody against P53, a kind of tumor suppressor protein,and use the antibody initial y in clinical immunoassay. Methods:Monoclonal antibody was prepared and identified via the classic protocol of monoclonal antibody preparation. Identified monoclonal antibodies were purified by af inity chro-matography. Antibody titer was determined by enzyme linked immunosorbent assay (ELISA). The specific binding activity of antibody was detected by Western blotting and immunohistochemistry. Results:Three strains of monoclonal antibodies named 1P15, 2P37 and 3P40 were obtained and purified by af inity chromatography. The purity of antibodies was higher than 90%. The titers of antibodies were more than 1:6000. Western blot and immunohistochemistry assay showed that the specific antibody can combine with endogenous P53 protein in the tumor celllines and determine the expression of P53 in tumor tis-sue. Conclusion:Three strains of monoclonal antibodies with high af inity to P53 were successful y established, which can be used for detecting the expression of P53 in tumor cells or tissue.

  11. Using the Concept of Health Promoting School as New Initiatives for School Based Management to Promote Healthy Educational Environments: The Hong Kong Healthy Schools Award Scheme%推动学校健康教育环境形成的新政策:香港健康学校奖励计划

    Institute of Scientific and Technical Information of China (English)

    李大拔

    2006-01-01

    大量证据显示,儿童及青少年的健康是影响他们学习能力的重要因素.学校环境对学童及职员的自信、学术成就及健康有直接的影响.健康教育及促进健康中心于1998年在香港首次推行健康促进学校计划,创办训练课程及开展香港健康学校奖励计划,为健康学校的发展提供有结构的蓝本及有系统的监察过程,以认证学校的成就.根据世界卫生组织的指引,计划有六个主要范畴:健康政策、学校环境及校风、人际关系、社区关系、个人健康生活技能及健康服务.每个范畴都包含一系列的校本改革活动,家长、学校管理层及社区的参与,以及教师培训.中心为每个主要范畴制定一套指标,以评估计划是否成功推广.%There is abundant evidence to demonstrate that the health of children and adolescents constitutes a major factor affecting their capacity to learn. The school environment has a direct impact on the self-esteem, educational achievement, and health of pupils and staff. The Centre for Health Education and Health Promotion (CHEP) initiated the Health Promoting School(HPS) programme in Hong Kong in 1998 by launching a training course, and then developed the Hong Kong Healthy Schools Award Scheme (HKHSA), which provided a structured framework for the development of a system of monitoring progress and recognition of achievement. The programme and Scheme cover six key areas, including health policy,physical and social environments, community relationships, personal health skills and health services, all being adapted from the World Health Organization's (WHO) Guidelines. Each key area has a number of components covering school-based changes and initiatives, and the involvement of parents, school management committees and community, as well as teacher training. The CHEP has developed a set of indicators for each key area and an evaluation framework to measure the success.

  12. Metazoan promoters

    DEFF Research Database (Denmark)

    Lenhard, Boris; Sandelin, Albin Gustav; Carninci, Piero

    2012-01-01

    Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters...... and their features, helping researchers who are investigating functional categories of promoters and their modes of regulation. Additional features of promoters that are being characterized include types of histone modifications, nucleosome positioning, RNA polymerase pausing and novel small RNAs. In this Review, we...... discuss recent findings relating to metazoan promoters and how these findings are leading to a revised picture of what a gene promoter is and how it works....

  13. Monoclonal antibody disulfide reduction during manufacturing

    Science.gov (United States)

    Hutterer, Katariina M.; Hong, Robert W.; Lull, Jonathon; Zhao, Xiaoyang; Wang, Tian; Pei, Rex; Le, M. Eleanor; Borisov, Oleg; Piper, Rob; Liu, Yaoqing Diana; Petty, Krista; Apostol, Izydor; Flynn, Gregory C.

    2013-01-01

    Manufacturing-induced disulfide reduction has recently been reported for monoclonal human immunoglobulin gamma (IgG) antibodies, a widely used modality in the biopharmaceutical industry. This effect has been tied to components of the intracellular thioredoxin reduction system that are released upon cell breakage. Here, we describe the effect of process parameters and intrinsic molecule properties on the extent of reduction. Material taken from cell cultures at the end of production displayed large variations in the extent of antibody reduction between different products, including no reduction, when subjected to the same reduction-promoting harvest conditions. Additionally, in a reconstituted model in which process variables could be isolated from product properties, we found that antibody reduction was dependent on the cell line (clone) and cell culture process. A bench-scale model using a thioredoxin/thioredoxin reductase regeneration system revealed that reduction susceptibility depended on not only antibody class but also light chain type; the model further demonstrates that the trend in reducibility was identical to DTT reduction sensitivity following the order IgG1λ > IgG1κ > IgG2λ > IgG2κ. Thus, both product attributes and process parameters contribute to the extent of antibody reduction during production. PMID:23751615

  14. Anti-cartilage antibody.

    Science.gov (United States)

    Greenbury, C L; Skingle, J

    1979-08-01

    Antibody to cartilage has been demonstrated by indirect immunofluorescence on rat trachea in the serum of about 3% of 1126 patients with rheumatoid arthritis. Titres ranged from 1:20 to 1:640. The antibody was not found in 284 patients with primary or secondary osteoarthritis or in 1825 blood donors, nor, with the exception of two weak reactors, in 1314 paraplegic patients. In most cases the antibody appears to be specific for native type II collagen. Using this as an antigen in a haemagglutination test 94% of anti-cartilage sera were positive, whereas among 100 rheumatoid control sera there were only three weak positives. More than 80% of patients with antibody had some erosion of articular cartilage, but there was no correlation with age, sex, duration of disease, nor any recognisable clinical event or change.

  15. Antithyroid microsomal antibody

    Science.gov (United States)

    ... to confirm the cause of thyroid problems, including Hashimoto thyroiditis . The test is also used to find ... positive test may be due to: Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also ...

  16. Serum herpes simplex antibodies

    Science.gov (United States)

    ... 2. HSV-1 most often causes cold sores (oral herpes). HSV-2 causes genital herpes. How the Test ... whether a person has ever been infected with oral or genital herpes . It looks for antibodies to herpes simplex virus ...

  17. Phage Display for the Generation of Antibodies for Proteome Research, Diagnostics and Therapy

    Directory of Open Access Journals (Sweden)

    Michael Hust

    2011-01-01

    Full Text Available Twenty years after its development, antibody phage display using filamentous bacteriophage represents the most successful in vitro antibody selection technology. Initially, its development was encouraged by the unique possibility of directly generating recombinant human antibodies for therapy. Today, antibody phage display has been developed as a robust technology offering great potential for automation. Generation of monospecific binders provides a valuable tool for proteome research, leading to highly enhanced throughput and reduced costs. This review presents the phage display technology, application areas of antibodies in research, diagnostics and therapy and the use of antibody phage display for these applications.

  18. Phage display for the generation of antibodies for proteome research, diagnostics and therapy.

    Science.gov (United States)

    Schirrmann, Thomas; Meyer, Torsten; Schütte, Mark; Frenzel, André; Hust, Michael

    2011-01-10

    Twenty years after its development, antibody phage display using filamentous bacteriophage represents the most successful in vitro antibody selection technology. Initially, its development was encouraged by the unique possibility of directly generating recombinant human antibodies for therapy. Today, antibody phage display has been developed as a robust technology offering great potential for automation. Generation of monospecific binders provides a valuable tool for proteome research, leading to highly enhanced throughput and reduced costs. This review presents the phage display technology, application areas of antibodies in research, diagnostics and therapy and the use of antibody phage display for these applications.

  19. Health promotion in Brazil.

    Science.gov (United States)

    Buss, Paulo Marchiori; de Carvalho, Antonio Ivo

    2007-01-01

    The evolution of health promotion within the Brazilian health system is examined, including an assessment of the intersectoral and development policies that have influenced the process. Particular attention is paid to the legal characteristics of the Unified Health System. Human resources formation and research initiatives in health promotion are outlined, with a summary of the obstacles that need to be overcome in order to ensure the effective implementation of health promotion in the future. Up to the end of the 20th Century health promotion was not used as a term in the Brazilian public heath context. Health promoting activities were concentrated in the area of health education, although targeting the social determinants of health and the principle of intersectoral action were part of the rhetoric. The situation has changed during the last decade, with the publication of a national policy of health promotion, issued by the Ministry of Health and jointly implemented with the States and Municipals Health Secretaries. More recently there has been a re-emergence of the discourse on the social determinants of health and the formation of intersectoral public policies as the basis of a comprehensive health promotion. Health promotion infrastructure, particularly around human resources and financing, requires strengthening in order to ensure capacity and sustainability in health promotion practice.

  20. Health-promoting schools

    DEFF Research Database (Denmark)

    Kwan, Stella Y L; Petersen, Poul Erik; Pine, Cynthia M

    2005-01-01

    Schools provide an important setting for promoting health, as they reach over 1 billion children worldwide and, through them, the school staff, families and the community as a whole. Health promotion messages can be reinforced throughout the most influential stages of children's lives, enabling...... them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School...... Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated...

  1. Heparin-Induced Thrombocytopenia Antibody Test

    Science.gov (United States)

    ... Global Sites Search Help? Heparin-induced Thrombocytopenia PF4 Antibody Share this page: Was this page helpful? Also known as: Heparin-PF4 Antibody; HIT Antibody; HIT PF4 Antibody; Heparin Induced Antibody; ...

  2. [New antibodies in cancer treatment].

    Science.gov (United States)

    Pestalozzi, B C; Knuth, A

    2004-09-22

    Since the development of hybridoma technology in 1975 monoclonal antibodies with pre-defined specificity can be produced. Only twenty years later did it become possible to make therapeutic use of monoclonal antibodies in oncology. To this end it was necessary to attach the antigen-binding site of a mouse antibody onto the scaffold of a human antibody molecule. Such chimeric or "humanized" antibodies may be used in passive immunotherapy without eliciting an immune response. Rituximab and trastuzumab are such humanized antibodies. They are used today routinely in the treatment of malignant lymphoma and breast cancer, respectively. These antibodies are usually used in combination with conventional cytostatic anticancer drugs.

  3. Engineering antibodies for cancer therapy.

    Science.gov (United States)

    Boder, Eric T; Jiang, Wei

    2011-01-01

    The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

  4. What do health-promoting schools promote?

    DEFF Research Database (Denmark)

    Simovska, Venka

    2012-01-01

    Purpose – The editorial aims to provide a brief overview of the individual contributions to the special issue, and a commentary positioning the contributions within research relating to the health-promoting schools initiative in Europe. Design/methodology/approach – The members of the Schools...... for Health in Europe Research Group were invited to submit their work addressing processes and outcomes in school health promotion to this special issue of Health Education. Additionally, an open call for papers was published on the Health Education web site. Following the traditional double blind peer...... review process, nine submissions were accepted for publication. Five of these are selected to be published in this issue and the rest will be published in a future issue of the journal. Findings – The five articles in this issue take a comprehensive approach to health promotion in schools and reflect...

  5. Natural and Man-made Antibody Repertories for Antibody Discovery

    Directory of Open Access Journals (Sweden)

    Juan C eAlmagro

    2012-11-01

    Full Text Available Antibodies are the fastest-growing segment of the biologics market. The success of antibody-based drugs resides in their exquisite specificity, high potency, stability, solubility, safety and relatively inexpensive manufacturing process in comparison with other biologics. We outline here the structural studies and fundamental principles that define how antibodies interact with diverse targets. We also describe the antibody repertoires and affinity maturation mechanisms of human, mice and chickens, plus the use of novel single-domain antibodies in camelids and sharks. These species all utilize diverse evolutionary solutions to generate specific and high affinity antibodies and illustrate the plasticity of natural antibody repertoires. In addition, we discuss the multiple variations of man-made antibody repertoires designed and validated in the last two decades, which have served as tools to explore how the size, diversity and composition of a repertoire impact the antibody discovery process.

  6. Short-term booster effect of diphtheria toxoid in initially long-term protected individuals.

    Science.gov (United States)

    Danilova, Elena; Shiryayev, Alexey; Skogen, Vegard; Kristoffersen, Einar Klaeboe; Sjursen, Haakon

    2005-02-10

    The main objective of this study was to investigate the booster antibody response in individuals with initially high levels of diphtheria antitoxin. Sixty individuals eligible for the routine booster by the age of 18 years each received a single dose of 5 Lf of diphtheria toxoid in diphtheria-tetanus vaccine. A double antigen ELISA was used for the assessment of the antibody levels. Chaotropic disruption in paired ELISA was used to test antibody avidity. The ratio between initial and maximum antibody concentrations after 1 month was >10 times higher and after 6 months still four times higher in those with initial antibody levels antibody levels >/=1 IU/ml a two-fold decrease was observed after 6 months compared to the initial levels. Thus, vaccination of individuals with initial long-term protection against diphtheria (antibody levels >/=1 IU/ml) is unnecessary and should be avoided.

  7. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    surface expression of various antibody formats in the generated knockout strain. Functional scFv and scFab fragments were efficiently displayed on yeast whereas impaired chain assembly and heavy chain degradation was observed for display of full-length IgG molecules. To identify the optimal polypeptide...... linker for yeast surface display of scFv and scFab fragments, we compared a series of different Gly-Ser-based linkers in display and antigen binding proficiency. We show that these formats of the model antibody can accommodate linkers of different lengths and that introduction of alanine or glutamate...... fragments by in vivo homologous recombination large combinatorial antibody libraries can easily be generated. We have optimized ordered assembly of three CDR fragments into a gapped vector and observed increased transformation efficiency in a yeast strain carrying a deletion of the SGS1 helicase...

  8. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi;

    2014-01-01

    to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  9. Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

  10. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    Antibodies recognize their cognate antigens in a precise and effective way. In order to do so, they target regions of the antigenic molecules that have specific features such as large exposed areas, presence of charged or polar atoms, specific secondary structure elements, and lack of similarity...... to self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  11. The Role of Complement in Antibody Therapy for Infectious Diseases.

    Science.gov (United States)

    Wibroe, Peter P; Helvig, Shen Y; Moein Moghimi, S

    2014-04-01

    The complement system is part of the innate immune system, eliciting central immunoregulatory functions. Detection of foreign surfaces is either achieved through complement-specific patternrecognition molecules or mediated by antigen recognition of antibodies. Immunoglobulin A (IgA), IgG, and IgM all have the potential to initiate a complement response, with the efficiency and response development closely related to the antibody isotype, multimeric state, and degree of glycosylation. A group of serum proteins constitutes the central effector functions of complement, thus allowing direct cell lysis, opsonization, and inflammation. These effector functions can be used in antibody therapies, especially against infectious diseases, as the target membranes lack complement regulatory proteins. The relative contribution of each function and the interplay with direct antibody-mediated clearance is not fully exploited, thus suggesting an option for further rational optimization of antibody therapies.

  12. Compositions, antibodies, asthma diagnosis methods, and methods for preparing antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hongjun; Zangar, Richard C.

    2017-01-17

    Methods for preparing an antibody are provided with the method including incorporating 3-bromo-4-hydroxy-benzoic acid into a protein to form an antigen, immunizing a mammalian host with the antigen, and recovering an antibody having an affinity for the antigen from the host. Antibodies having a binding affinity for a monohalotyrosine are provided as well as composition comprising an antibody bound with monohalotyrosine. Compositions comprising a protein having a 3-bromo-4-hydroxy-benzoic acid moiety are also provided. Methods for evaluating the severity of asthma are provide with the methods including analyzing sputum of a patient using an antibody having a binding affinity for monohalotyrosine, and measuring the amount of antibody bound to protein. Methods for determining eosinophil activity in bodily fluid are also provided with the methods including exposing bodily fluid to an antibody having a binding affinity for monohalotyrosine, and measuring the amount of bound antibody to determine the eosinophil activity.

  13. Human germline antibody gene segments encode polyspecific antibodies.

    Science.gov (United States)

    Willis, Jordan R; Briney, Bryan S; DeLuca, Samuel L; Crowe, James E; Meiler, Jens

    2013-04-01

    Structural flexibility in germline gene-encoded antibodies allows promiscuous binding to diverse antigens. The binding affinity and specificity for a particular epitope typically increase as antibody genes acquire somatic mutations in antigen-stimulated B cells. In this work, we investigated whether germline gene-encoded antibodies are optimal for polyspecificity by determining the basis for recognition of diverse antigens by antibodies encoded by three VH gene segments. Panels of somatically mutated antibodies encoded by a common VH gene, but each binding to a different antigen, were computationally redesigned to predict antibodies that could engage multiple antigens at once. The Rosetta multi-state design process predicted antibody sequences for the entire heavy chain variable region, including framework, CDR1, and CDR2 mutations. The predicted sequences matched the germline gene sequences to a remarkable degree, revealing by computational design the residues that are predicted to enable polyspecificity, i.e., binding of many unrelated antigens with a common sequence. The process thereby reverses antibody maturation in silico. In contrast, when designing antibodies to bind a single antigen, a sequence similar to that of the mature antibody sequence was returned, mimicking natural antibody maturation in silico. We demonstrated that the Rosetta computational design algorithm captures important aspects of antibody/antigen recognition. While the hypervariable region CDR3 often mediates much of the specificity of mature antibodies, we identified key positions in the VH gene encoding CDR1, CDR2, and the immunoglobulin framework that are critical contributors for polyspecificity in germline antibodies. Computational design of antibodies capable of binding multiple antigens may allow the rational design of antibodies that retain polyspecificity for diverse epitope binding.

  14. Prediction of antibody persistency from antibody titres to natalizumab

    DEFF Research Database (Denmark)

    Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn Thorup;

    2012-01-01

    In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

  15. Health Promotion

    DEFF Research Database (Denmark)

    Povlsen, Lene; Borup, I.

    2015-01-01

    In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986......, the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation...... - an associate professorship was established with a focus on health promotion. Nevertheless, the concept of health promotion had been integrated with or mentioned in courses run prior to the new post. Subsequently, a wide spectrum of courses in health promotion was introduced, such as Empowerment for Child...

  16. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.;

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  17. Antibody Blood Tests

    Science.gov (United States)

    ... What do I do if I have a negative blood test (or panel) but I’m still having symptoms? While it is rare, it is possible for patients to have a negative antibody test results and still have celiac disease. ...

  18. RBC Antibody Screen

    Science.gov (United States)

    ... test also may be used to help diagnose autoimmune-related hemolytic anemia in conjunction with a DAT. This condition may be caused when a person produces antibodies against his or her own RBC antigens. This can happen with some autoimmune disorders , such as lupus , with diseases such as ...

  19. What Is Antiphospholipid Antibody Syndrome?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Antiphospholipid Antibody Syndrome? Antiphospholipid (AN-te-fos-fo-LIP-id) antibody ... weeks or months. This condition is called catastrophic antiphospholipid syndrome (CAPS). People who have APS also are at ...

  20. Red Blood Cell Antibody Identification

    Science.gov (United States)

    ... ID, RBC; RBC Ab ID Formal name: Red Blood Cell Antibody Identification Related tests: Direct Antiglobulin Test ; RBC ... I should know? How is it used? Red blood cell (RBC) antibody identification is used as a follow- ...

  1. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  2. Anti-smooth muscle antibody

    Science.gov (United States)

    ... gov/ency/article/003531.htm Anti-smooth muscle antibody To use the sharing features on this page, please enable JavaScript. Anti-smooth muscle antibody is a blood test that detects the presence ...

  3. Antibody Engineering and Therapeutics Conference

    OpenAIRE

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A.; Burton, Dennis R.; Adams, Gregory P.; Weiner, Louis M.; Scott, Jamie K.; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M.

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Bi...

  4. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  5. Initial Study

    DEFF Research Database (Denmark)

    Torp, Kristian

    2009-01-01

    Congestion is a major problem in most cities and the problem is growing (Quiroga, 2000) (Faghri & Hamad, 2002). When the congestion level is increased the drivers notice this as delays in the traffic (Taylor, Woolley, & Zito, 2000), i.e., the travel time for the individual driver is simply...... increased. In the initial study presented here, the time it takes to pass an intersection is studied in details. Two major signal-controlled four-way intersections in the center of the city Aalborg are studied in details to estimate the congestion levels in these intersections, based on the time it takes...

  6. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the uni

  7. Immunoblotting with monoclonal antibodies: importance of the blocking solution.

    Science.gov (United States)

    Hauri, H P; Bucher, K

    1986-12-01

    Four commonly used blocking agents, i.e., fetal calf serum, mammalian gelatin-Nonidet-P40, fish gelatin-Nonidet-P40, and defatted powdered milk were compared with respect to their efficiency to block the nonspecific background and to promote maximal immunoreactivity of monoclonal antibodies against human intestinal sucrase-isomaltase during immunoblotting. Two of five monoclonal antibodies were found to react with the electroblotted enzyme. However, one of the reacting antibodies gave optimal results with fish gelatin-Nonidet-P40 and the other with defatted powdered milk, while fetal calf serum lead to unacceptably high backgrounds. The results suggest that some of the difficulties encountered with monoclonal antibodies in immunoblotting may be due to inappropriate blocking conditions.

  8. Engineering antibodies by yeast display.

    Science.gov (United States)

    Boder, Eric T; Raeeszadeh-Sarmazdeh, Maryam; Price, J Vincent

    2012-10-15

    Since its first application to antibody engineering 15 years ago, yeast display technology has been developed into a highly potent tool for both affinity maturing lead molecules and isolating novel antibodies and antibody-like species. Robust approaches to the creation of diversity, construction of yeast libraries, and library screening or selection have been elaborated, improving the quality of engineered molecules and certainty of success in an antibody engineering campaign and positioning yeast display as one of the premier antibody engineering technologies currently in use. Here, we summarize the history of antibody engineering by yeast surface display, approaches used in its application, and a number of examples highlighting the utility of this method for antibody engineering.

  9. Global healthy backpack initiatives.

    Science.gov (United States)

    Jayaratne, Kapila; Jacobs, Karen; Fernando, Dulitha

    2012-01-01

    Schoolbag use by children is a global common concern.. Children carry school books and other amenities in their school bags. Global evidence indicates that daily load carried by school children may have negative health implications. Backpack as a school bag model, is the healthiest way of load carriage for school children. Several initiatives have been launched world over to minimize unhealthy consequences resulting from schoolbags. Based on a situation analysis, Sri Lanka implemented a national healthy schoolbag campaign by joint efforts of Ministries of Health and Education. Actions were contemplated on; strategies for bag weight reduction, introduction of an ergonomically modeled schoolbag and bag behaviour change. New strategies were introduced with awareness campaigns to policy makers, bag manufacturers, parents, teachers and children. Four million schoolchildren benefitted. In 2000, the backpack strategy of "Pack it Light, Wear it Right" was started as a public health initiative in the United States by the American Occupational Therapy Association (AOTA). Over the last eleven years, thousands of occupational therapy practitioners and students participated in educational programs and outreach activities. In 2004, modeled after the success AOTA initiative, the Icelandic Occupational Therapy Association launched a national backpack awareness initiative. This article shares examples of practices that could be implemented in any context to the promote health of children.

  10. Openness initiative

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, S.S. [Los Alamos National Lab., NM (United States)

    1995-12-31

    Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: {open_quotes}Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?{close_quotes} To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need to make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts.

  11. Anti-DNA antibody mediated catalysis is isotype dependent.

    Science.gov (United States)

    Xia, Yumin; Eryilmaz, Ertan; Zhang, Qiuting; Cowburn, David; Putterman, Chaim

    2016-01-01

    Anti-DNA antibodies are the serological hallmark of systemic lupus erythematosus, and participate in the pathogenesis of lupus nephritis by cross-reacting with multiple renal antigens. Previously, using a panel of murine anti-DNA IgGs that share identical variable regions but that differ in the constant regions, we demonstrated that the cross-reaction and renal pathogenicity of anti-DNA antibodies are isotype dependent. In this study, we investigated the catalytic potential of this anti-DNA antibody panel, and determined its isotype dependency. The three isotype switch variants (IgG1, IgG2a, IgG2b) and the parent IgG3 PL9-11 anti-DNA antibodies were compared in their catalysis of 500 base pair linear double stranded DNA and a 12-mer peptide (ALWPPNLHAWVP), by gel analysis, MALDI-TOF mass spectrometry, and nuclear magnetic resonance spectroscopy. The binding affinity of anti-DNA antibodies to double stranded DNA and peptide antigens were assessed by ELISA and surface plasmon resonance. We found that the PL9-11 antibody isotypes vary significantly in their potential to catalyze the cleavage of both linear and double stranded DNA and the proteolysis of peptides. The degree of the cleavage and proteolysis increases with the incubation temperature and time. While different PL9-11 isotypes have the same initial attack sites within the ALWPPNLHAWVP peptide, there was no correlation between binding affinity to the peptide and proteolysis rates. In conclusion, the catalytic properties of anti-DNA antibodies are isotype dependent. This finding provides further evidence that antibodies that share the same variable region, but which have different constant regions, are functionally distinct. The catalytic effects modulated by antibody constant regions need to be considered in the design of therapeutic antibodies (abzymes) and peptides designed to block pathogenic autoantibodies.

  12. Antibody performance in western blot applications is context-dependent.

    Science.gov (United States)

    Algenäs, Cajsa; Agaton, Charlotta; Fagerberg, Linn; Asplund, Anna; Björling, Lisa; Björling, Erik; Kampf, Caroline; Lundberg, Emma; Nilsson, Peter; Persson, Anja; Wester, Kenneth; Pontén, Fredrik; Wernérus, Henrik; Uhlén, Mathias; Ottosson Takanen, Jenny; Hober, Sophia

    2014-03-01

    An important concern for the use of antibodies in various applications, such as western blot (WB) or immunohistochemistry (IHC), is specificity. This calls for systematic validations using well-designed conditions. Here, we have analyzed 13 000 antibodies using western blot with lysates from human cell lines, tissues, and plasma. Standardized stratification showed that 45% of the antibodies yielded supportive staining, and the rest either no staining (12%) or protein bands of wrong size (43%). A comparative study of WB and IHC showed that the performance of antibodies is application-specific, although a correlation between no WB staining and weak IHC staining could be seen. To investigate the influence of protein abundance on the apparent specificity of the antibody, new WB analyses were performed for 1369 genes that gave unsupportive WBs in the initial screening using cell lysates with overexpressed full-length proteins. Then, more than 82% of the antibodies yielded a specific band corresponding to the full-length protein. Hence, the vast majority of the antibodies (90%) used in this study specifically recognize the target protein when present at sufficiently high levels. This demonstrates the context- and application-dependence of antibody validation and emphasizes that caution is needed when annotating binding reagents as specific or cross-reactive. WB is one of the most commonly used methods for validation of antibodies. Our data implicate that solely using one platform for antibody validation might give misleading information and therefore at least one additional method should be used to verify the achieved data.

  13. Promoting Models

    Science.gov (United States)

    Li, Qin; Zhao, Yongxin; Wu, Xiaofeng; Liu, Si

    There can be multitudinous models specifying aspects of the same system. Each model has a bias towards one aspect. These models often override in specific aspects though they have different expressions. A specification written in one model can be refined by introducing additional information from other models. The paper proposes a concept of promoting models which is a methodology to obtain refinements with support from cooperating models. It refines a primary model by integrating the information from a secondary model. The promotion principle is not merely an academic point, but also a reliable and robust engineering technique which can be used to develop software and hardware systems. It can also check the consistency between two specifications from different models. A case of modeling a simple online shopping system with the cooperation of the guarded design model and CSP model illustrates the practicability of the promotion principle.

  14. Promoting Entrepreneurship - Changing Attitudes or Behaviour?

    DEFF Research Database (Denmark)

    Dreisler, Poul; Blenker, Per; Nielsen, Kent T.

    2003-01-01

    The objective of the article is to analyse the Danish policies used to promote entrepreneurship during the last 30 years. The initiatives to promote entrepreneurship have been implemented as part of Danish industrial policy. The initiatives are presented and ordered according to a model of planned...

  15. Activities for Engaging Schools in Health Promotion

    Science.gov (United States)

    Bardi, Mohammad; Burbank, Andrea; Choi, Wayne; Chow, Lawrence; Jang, Wesley; Roccamatisi, Dawn; Timberley-Berg, Tonia; Sanghera, Mandeep; Zhang, Margaret; Macnab, Andrew J.

    2014-01-01

    Purpose: The purpose of this paper is to describe activities used to initiate health promotion in the school setting. Design/Methodology/Approach: Description of successful pilot Health Promoting School (HPS) initiatives in Canada and Uganda and the validated measures central to each program. Evaluation methodologies: quantitative data from the…

  16. How antibodies use complement to regulate antibody responses.

    Science.gov (United States)

    Sörman, Anna; Zhang, Lu; Ding, Zhoujie; Heyman, Birgitta

    2014-10-01

    Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune complexes containing IgG and IgM may activate complement and in such situations also complement components will be part of the immune complex. Here, we review experimental data on how antibodies via the complement system upregulate specific antibody responses. Current data suggest that murine IgG1, IgG2a, and IgG2b upregulate antibody responses primarily via Fc-receptors and not via complement. In contrast, IgM and IgG3 act via complement and require the presence of complement receptors 1 and 2 (CR1/2) expressed on both B cells and follicular dendritic cells. Complement plays a crucial role for antibody responses not only to antigen complexed to antibodies, but also to antigen administered alone. Lack of C1q, but not of Factor B or MBL, severely impairs antibody responses suggesting involvement of the classical pathway. In spite of this, normal antibody responses are found in mice lacking several activators of the classical pathway (complement activating natural IgM, serum amyloid P component (SAP), specific intracellular adhesion molecule-grabbing non-integrin R1 (SIGN-R1) or C-reactive protein. Possible explanations to these observations will be discussed.

  17. The antibody Hijikata Tatsumi

    Directory of Open Access Journals (Sweden)

    Éden Peretta

    2012-11-01

    Full Text Available Considered one of the most influential modern dance representatives in Japan, Tatsumi Hijikata’s work was a milestone in the Japanese post-war experimental artistic scene. Heretic son of his time, he staged a fertile mix of artistic and cultural influences, overlapping subversive elements of European arts and philosophy with radical references from pre-modern Japanese culture. In this way he built the foundations of its unstable antibody, its political-artistic project of dissolution of a organism, both physical and social.

  18. Vi serology in screening of typhoid carriers: improved specificity by detection of Vi antibodies by counterimmunoelectrophoresis.

    OpenAIRE

    Chau, P. Y.; Tsang, R S

    1982-01-01

    A purified soluble Vi antigen was used in counterimmunoelectrophoresis (CIE), passive haemagglutination (HA) and solid phase radio-immunoassay (SPRIA) for detection of serum Vi antibody. Serum Vi antibody was detected in 13 of 14 chronic typhoid carriers by both CIE and HA. SPRIA studies showed that Vi antibodies in sera of these carriers were mainly of the IgG class. Successful treatment with amoxycillin in one carrier, who initially showed a positive Vi test, resulted in a reversion in 6 mo...

  19. Cancer imaging with radiolabeled antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Goldenberg, D.M. (Center for Molecular Medicine and Immunology, Newark, NJ (US))

    1990-01-01

    This book presents a perspective of the use of antibodies to target diagnostic isotopes to tumors. Antibodies with reasonable specificity can be developed against almost any substance. If selective targeting to cancer cells can be achieved, the prospects for a selective therapy are equally intriguing. But the development of cancer detection, or imaging, with radiolabeled antibodies has depended upon advances in a number of different areas, including cancer immunology and immunochemistry for identifying suitable antigen targets and antibodies to these targets, tumor biology for model systems, radiochemistry for he attachment of radionuclides to antibodies, molecular biology for reengineering the antibodies for safer and more effective use in humans, and nuclear medicine for providing the best imaging protocols and instrumentation to detect minute amounts of elevated radioactivity against a background of considerable noise. Accordingly, this book has been organized to address the advances that are being made in many of these areas.

  20. VIRAL ANTIBODIES IN PRESCHOOL CHILDREN

    Directory of Open Access Journals (Sweden)

    S. Saidi

    1974-08-01

    Full Text Available One hundred sera from children 1 - 6 years of age, representative of a large serum collection, were tested for the prevalence of antibodies against different viruses. Hemagglutination-inhibition (HI antibodies were found in 68% for measles; 61 % for rubella; 75'% for influenza A2/Hong Kong/68, 16% for influenza B/Md./59, 0% for group A arboviruses, 10% for group B arboviruses, 3% for phlebotomus fever group and 4% for Congo-Crimean hemorrhagic fever (C-CHF group of arboviruses Poliomyelitis-neutralizing antibodies for type 1, 2 and 3 were 90%; 85% and 84%~ respectively. Antibody to EH virus was detected in 84% of the sera by immuno-fluorescence. None of the sera were positive for hepatitis-B antigen or antibody by immuno-precipitation test. The prevalence of some viral antibodies found in this survey are compared with results obtained from surveys in other parts of the country.

  1. Haploinsufficiency of activation-induced deaminase for antibody diversification and chromosome translocations both in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Isora V Sernández

    Full Text Available The humoral immune response critically relies on the secondary diversification of antibodies. This diversification takes places through somatic remodelling of the antibody genes by two molecular mechanisms, Class Switch Recombination (CSR and Somatic Hypermutation (SHM. The enzyme Activation Induced Cytidine Deaminase (AID initiates both SHM and CSR by deaminating cytosine residues on the DNA of immunoglobulin genes. While crucial for immunity, AID-catalysed deamination is also the triggering event for the generation of lymphomagenic chromosome translocations. To address whether restricting the levels of AID expression in vivo contributes to the regulation of its function, we analysed mice harbouring a single copy of the AID gene (AID(+/-. AID(+/- mice express roughly 50% of normal AID levels, and display a mild hyperplasia, reminiscent of AID deficient mice and humans. Moreover, we found that AID(+/- cells have an impaired competence for CSR and SHM, which indicates that AID gene dose is limiting for its physiologic function. We next evaluated the impact of AID reduction in AID(+/- mice on the generation of chromosome translocations. Our results show that the frequency of AID-promoted c-myc/IgH translocations is reduced in AID(+/- mice, both in vivo and in vitro. Therefore, AID is haploinsufficient for antibody diversification and chromosome translocations. These findings suggest that limiting the physiologic levels of AID expression can be a regulatory mechanism that ensures an optimal balance between immune proficiency and genome integrity.

  2. Antibodies against antibodies: immunogenicity of adalimumab as a model

    NARCIS (Netherlands)

    van Schouwenburg, P.A.

    2012-01-01

    Upon repeated adalimumab exposure part of the patients start to produce ADA. The antibody response is polyclonal and consists mainly of antibodies of IgG1 and IgG4 isotype. In the majority of ADA positive patients ADA are already produced within the first 28 weeks of treatment and in part of the pat

  3. Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

    Science.gov (United States)

    Seeley, Todd W; Sternlicht, Mark D; Klaus, Stephen J; Neff, Thomas B; Liu, David Y

    2017-01-01

    The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592). In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. PMID:28331872

  4. Local Employment Initiatives: Some Recent Developments.

    Science.gov (United States)

    Kuenstler, Peter

    1988-01-01

    Intergovernmental and governmental measures to promote local employment initiatives are underway in Europe. Local authorities are assuming responsibility for economic development in their areas, and the private sector is providing direct or indirect support. (SK)

  5. An Update in the Use of Antibodies to Treat Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Norma Y. Hernández-Pedro

    2013-01-01

    Full Text Available Glioblastoma is a deadly brain disease and modest improvement in survival has been made. At initial diagnosis, treatment consists of maximum safe surgical resection, followed by temozolomide and chemoirradiation or adjuvant temozolomide alone. However, these treatments do not improve the prognosis and survival of patients. New treatment strategies are being sought according to the biology of tumors. The epidermal growth factor receptor has been considered as the hallmark in glioma tumors; thereby, some antibodies have been designed to bind to this receptor and block the downstream signaling pathways. Also, it is known that vascularization plays an important role in supplying new vessels to the tumor; therefore, new therapy has been guided to inhibit angiogenic growth factors in order to limit tumor growth. An innovative strategy in the treatment of glial tumors is the use of toxins produced by bacteria, which may be coupled to specific carrier-ligands and used for tumoral targeting. These carrier-ligands provide tumor-selective properties by the recognition of a cell-surface receptor on the tumor cells and promote their binding of the toxin-carrier complex prior to entry into the cell. Here, we reviewed some strategies to improve the management and treatment of glioblastoma and focused on the use of antibodies.

  6. An update in the use of antibodies to treat glioblastoma multiforme.

    Science.gov (United States)

    Hernández-Pedro, Norma Y; Rangel-López, Edgar; Vargas Félix, Gustavo; Pineda, Benjamín; Sotelo, Julio

    2013-01-01

    Glioblastoma is a deadly brain disease and modest improvement in survival has been made. At initial diagnosis, treatment consists of maximum safe surgical resection, followed by temozolomide and chemoirradiation or adjuvant temozolomide alone. However, these treatments do not improve the prognosis and survival of patients. New treatment strategies are being sought according to the biology of tumors. The epidermal growth factor receptor has been considered as the hallmark in glioma tumors; thereby, some antibodies have been designed to bind to this receptor and block the downstream signaling pathways. Also, it is known that vascularization plays an important role in supplying new vessels to the tumor; therefore, new therapy has been guided to inhibit angiogenic growth factors in order to limit tumor growth. An innovative strategy in the treatment of glial tumors is the use of toxins produced by bacteria, which may be coupled to specific carrier-ligands and used for tumoral targeting. These carrier-ligands provide tumor-selective properties by the recognition of a cell-surface receptor on the tumor cells and promote their binding of the toxin-carrier complex prior to entry into the cell. Here, we reviewed some strategies to improve the management and treatment of glioblastoma and focused on the use of antibodies.

  7. Biosimilar Monoclonal Antibodies for Inflammatory Bowel Disease: Current Comfort and Future Prospects.

    Science.gov (United States)

    Gecse, Krisztina B; Lakatos, Péter L

    2016-10-01

    Biosimilars are biologic medicines that enter the market after a patent for an original reference product expires. The European Medicines Agency (EMA) developed a stringent legislation process for biosimilar monoclonal antibodies, whereby similarity to the reference medicinal product in terms of quality characteristics, biological activity, clinical safety and efficacy must be demonstrated. Biosimilar infliximab CT-P13 was the first biosimilar monoclonal antibody to receive EMA marketing authorization, and further biosimilar molecules are being developed. The phase I and III clinical trials were conducted in ankylosing spondylitis and rheumatoid arthritis, and the use of CT-P13 in inflammatory bowel disease (IBD) was extrapolated on the results of these trials. Medical professionals were initially concerned about the reversed engineering process, the novel legal framework and the lack of clinical data in IBD. Emerging real-world data have confirmed the similarities between CT-P13 and the reference product in terms of efficacy, safety and immunogenicity in IBD. The cost reduction represented by biosimilars promotes industry competition and improves treatment access with sustained quality of care. This article reviews the existing and emerging clinical data for CT-P13 and a future perspective on biosimilar use in IBD.

  8. Pathogenic role of antiphospholipid antibodies

    NARCIS (Netherlands)

    Salmon, J. E.; de Groot, P. G.

    2008-01-01

    The antiphospholipid antibody syndrome (APS) is characterized by recurrent arterial and venous thrombosis and/or pregnancy in association with antiphospholipid (aPL) antibodies. The pathogenic mechanisms in APS that lead to in vivo injury are incompletely understood. Recent evidence suggests that AP

  9. Educational paper: Primary antibody deficiencies

    NARCIS (Netherlands)

    G.J.A. Driessen (Gertjan); M. van der Burg (Mirjam)

    2011-01-01

    textabstractPrimary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA a

  10. Targeting of Antibodies using Aptamers

    OpenAIRE

    2003-01-01

    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  11. New engineered antibodies against prions

    Science.gov (United States)

    Škrlj, Nives; Dolinar, Marko

    2014-01-01

    A number of recently developed and approved therapeutic agents based on highly specific and potent antibodies have shown the potential of antibody therapy. As the next step, antibody-based therapeutics will be bioengineered in a way that they not only bind pathogenic targets but also address other issues, including drug targeting and delivery. For antibodies that are expected to act within brain tissue, like those that are directed against the pathogenic prion protein isoform, one of the major obstacles is the blood-brain barrier which prevents efficient transfer of the antibody, even of the engineered single-chain variants. We recently demonstrated that a specific prion-specific antibody construct which was injected into the murine tail vein can be efficiently transported into brain tissue. The novelty of the work was in that the cell penetrating peptide was used as a linker connecting both specificity-determining domains of the antibody peptide, thus eliminating the need for the standard flexible linker, composed of an arrangement of three consecutive (Gly4Ser) repeats. This paves the road toward improved bioengineered antibody variants that target brain antigens. PMID:23941991

  12. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  13. The C-Terminal Domain of Eukaryotic Initiation Factor 5 Promotes Start Codon Recognition by Its Dynamic Interplay with eIF1 and eIF2β

    Directory of Open Access Journals (Sweden)

    Rafael E. Luna

    2012-06-01

    Full Text Available Recognition of the proper start codon on mRNAs is essential for protein synthesis, which requires scanning and involves eukaryotic initiation factors (eIFs eIF1, eIF1A, eIF2, and eIF5. The carboxyl terminal domain (CTD of eIF5 stimulates 43S preinitiation complex (PIC assembly; however, its precise role in scanning and start codon selection has remained unknown. Using nuclear magnetic resonance (NMR spectroscopy, we identified the binding sites of eIF1 and eIF2β on eIF5-CTD and found that they partially overlapped. Mutating select eIF5 residues in the common interface specifically disrupts interaction with both factors. Genetic and biochemical evidence indicates that these eIF5-CTD mutations impair start codon recognition and impede eIF1 release from the PIC by abrogating eIF5-CTD binding to eIF2β. This study provides mechanistic insight into the role of eIF5-CTD's dynamic interplay with eIF1 and eIF2β in switching PICs from an open to a closed state at start codons.

  14. Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

    Directory of Open Access Journals (Sweden)

    Seeley TW

    2017-03-01

    Full Text Available Todd W Seeley, Mark D Sternlicht, Stephen J Klaus, Thomas B Neff, David Y Liu Therapeutics R&D, FibroGen, Inc., San Francisco, CA, USA Abstract: The effects of pharmacological hypoxia-inducible factor (HIF stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF, using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs, FG-4497 or roxadustat (FG-4592. In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. Keywords: cancer progression, erythropoiesis, hypoxia-inducible factor, hypoxia-inducible factor prolyl hydroxylase inhibitors, vascular endothelial growth factor, MMTV-Neu breast cancer model

  15. Novel RNA-binding protein P311 binds eukaryotic translation initiation factor 3 subunit b (eIF3b) to promote translation of transforming growth factor β1-3 (TGF-β1-3).

    Science.gov (United States)

    Yue, Michael M; Lv, Kaosheng; Meredith, Stephen C; Martindale, Jennifer L; Gorospe, Myriam; Schuger, Lucia

    2014-12-05

    P311, a conserved 8-kDa intracellular protein expressed in brain, smooth muscle, regenerating tissues, and malignant glioblastomas, represents the first documented stimulator of TGF-β1-3 translation in vitro and in vivo. Here we initiated efforts to define the mechanism underlying P311 function. PONDR® (Predictor Of Naturally Disordered Regions) analysis suggested and CD confirmed that P311 is an intrinsically disordered protein, therefore requiring an interacting partner to acquire tertiary structure and function. Immunoprecipitation coupled with mass spectroscopy identified eIF3 subunit b (eIF3b) as a novel P311 binding partner. Immunohistochemical colocalization, GST pulldown, and surface plasmon resonance studies revealed that P311-eIF3b interaction is direct and has a Kd of 1.26 μm. Binding sites were mapped to the non-canonical RNA recognition motif of eIF3b and a central 11-amino acid-long region of P311, here referred to as eIF3b binding motif. Disruption of P311-eIF3b binding inhibited translation of TGF-β1, 2, and 3, as indicated by luciferase reporter assays, polysome fractionation studies, and Western blot analysis. RNA precipitation assays after UV cross-linking and RNA-protein EMSA demonstrated that P311 binds directly to TGF-β 5'UTRs mRNAs through a previously unidentified RNA recognition motif-like motif. Our results demonstrate that P311 is a novel RNA-binding protein that, by interacting with TGF-βs 5'UTRs and eIF3b, stimulates the translation of TGF-β1, 2, and 3.

  16. Antibodies to Phospholipids and Liposomes: Binding of Antibodies to Cells

    Science.gov (United States)

    1987-01-01

    LIPOSOMES: BINDING OF ANTIBODIES TO CELLS 12. PERSONAL AUTHOR(S) W.E. FOGLER , G. M. SWARTZ, AND C.R. ALVING 13a TYPE OF REPORT 13b. TIME COVERED 14. DATE...Elsevier BBA 73693 Antibodies to phospholipids and liposomes: binding of antibodies to cells William E. Fogler *, Glenn M. Swartz, Jr. and Carl R. Alving...Immunol. 21. Research Associateship from the U.S. National 12863-86812Hall. T. and Esser, K. (1984) 3. Immunol. 132. 2059-2063 Research Council. 13 Fogler

  17. Simultaneous expression of displayed and secreted antibodies for antibody screen.

    Directory of Open Access Journals (Sweden)

    Yuanping Zhou

    Full Text Available The display of full-length antibody on the cell surface was achieved by fusing a transmembrane domain of the platelet-derived growth factor receptor (PDGFR to the C-terminus of the heavy chain constant region. We also incorporated a furin cleavage site between the constant region and PDGFR transmembrane domain to obtain secreted antibodies. As a result, antibodies can be expressed simultaneously on the cell surface in a membrane-anchored version for screening and selecting through fluorescence-activated cell sorting (FACS analysis, as well as in conditioned medium in a secreted version for function analysis.

  18. Promoting Entrepreneurship - Changing Attitudes or Behavior?

    DEFF Research Database (Denmark)

    Dreisler, Poul; Blenker, Per; Nielsen, Kent T.

    Abstract The primary objective of this paper is to analyse some initiatives used to promote entrepreneurship during the last 30 years of Danish Industrial Policy. A statistical description is given of the development that the Danish society has undergone, from an agricultural society through the ...... in recommending strategies for launching future initiatives to promote entrepreneurship.......Abstract The primary objective of this paper is to analyse some initiatives used to promote entrepreneurship during the last 30 years of Danish Industrial Policy. A statistical description is given of the development that the Danish society has undergone, from an agricultural society through...... the industrial stage to a service or knowledge society. Parallel with this historical development, several initiatives to promote entrepreneurship have been implemented as part of Danish industrial policy. These initiatives are analysed with respect to objectives and means and ordered according to Sheth...

  19. Promoting Health in Early Childhood Environments: A Health-Promotion Approach

    Science.gov (United States)

    Minniss, Fiona Rowe; Wardrope, Cheryl; Johnston, Donni; Kendall, Elizabeth

    2013-01-01

    This paper investigates the mechanisms by which a health-promotion intervention might influence the health-promoting behaviours of staff members working in early childhood centres. The intervention was an ecological health-promotion initiative that was implemented within four early childhood centres in South-East Queensland, Australia. In-depth,…

  20. Tabhu: tools for antibody humanization

    DEFF Research Database (Denmark)

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2015-01-01

    Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can...... elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity...

  1. 分离植物目的基因全长cDNA和启动子的新方法--快速定位转录起始位点(RITIS)%Isolation of Full-length cDNA and Promoter of Target Gene from Plant by Rapid Identification of Transcriptional Initiation Site (RITIS)

    Institute of Scientific and Technical Information of China (English)

    冯丽; 任茂智; 罗洪发; 何光华

    2006-01-01

    by rapid identification of transcriptional initiation site (RITIS). Transcriptional initiation site (TIS) is cut-offpoint of promoter and transcript of target gene. Accurate position of TIS is the key for full-length cDNA and promoter isolation. Exons in transcript downstream TIS can be amplified by means of RT-PCR whereaspromoter sequence cannot be obtained in the same way. Taking advantage of this principle, we develop the approach of R1TIS which can be used to define the promoter region and the 5'-untranslated region of the gene efficiently and circumvents laborious cDNA libraries construction for full-length cDNA and promoter isolation.

  2. End-Stage Renal Disease (ESRD) Quality Initiative

    Data.gov (United States)

    U.S. Department of Health & Human Services — The End Stage Renal Disease (ESRD) Quality Initiative promotes ongoing CMS strategies to improve the quality of care provided to ESRD patients. This initiative...

  3. DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv Antibody

    Science.gov (United States)

    2016-03-01

    ECBC-TR-1356 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR ANTIBODY CHARACTERIZATION...From - To) Oct 2010 – Sep 2012 4. TITLE AND SUBTITLE DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization...Arlington, VA 22203-2114 10. SPONSOR/MONITOR’S ACRONYM(S) DARPA 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT

  4. Student initiative: A conceptual analysis

    Directory of Open Access Journals (Sweden)

    Polovina Nada

    2014-01-01

    Full Text Available In the description and scientific consideration of the attitude of children and youth towards their education and development, the concept of student initiative has been gaining ground lately, and it is hence the subject of analysis in this paper. The analysis is important because of the discrepancy between the increased efforts of the key educational policy holders to promote the idea about the importance of the development of student initiative and rare acceptance of this idea among theoreticians, researchers and practitioners dealing with the education and development of children and youth. By concretising the features of initiative student behaviour, our aim was, on the one hand, to observe the structural determinants and scientific status of the very concept of an initiative student, and, on the other, to contribute to the understanding of the initiative behaviour in practice. In the first part of the paper we deal with different notions and concretisations of the features of initiative behaviour of children and youth, which includes the consideration of: basic student initiative, academic student initiative, individual student initiative, the capacity for initiative and personal development initiative. In the second part of the paper, we discuss the relations of the concept of student initiative with the similar general concepts (activity/passivity, proactivity, agency and the concepts immediately related to school environment (student involvement, student participation. The results of our analysis indicate that the concept of student initiative has: particular features that differentiate it from similar concepts; the potential to reach the status of a scientific concept, bearing in mind the initial empirical specifications and general empirical verifiability of the yet unverified determinants of the concept. In the concluding part of the paper, we discuss the implications of the conceptual analysis for further research, as well as for

  5. Evolution of antiphospholipid antibody syndrome.

    Science.gov (United States)

    Baviskar, Rutuja R; Amonkar, Gayathri P; Chaudhary, Vinod A; Balasubramanian, Meenakshi; Mohite, Shailesh C; Puranik, Gururaj V

    2012-12-01

    Antiphospholipid antibody syndrome is a very important cause of cerebral infarction, myocardial infarction, and repeated pregnancy losses in women. We present an extremely rare case of a 44-year-old man with antiphospholipid syndrome who collapsed and died suddenly. At autopsy, he was found to have both cerebral and myocardial infarction. In all young patients with cerebral infarction, myocardial infarction, pulmonary embolism, recurrent miscarriages, and unexplained low platelet count, one must consider the strong possibility of antiphospholipid antibody syndrome.

  6. Antibodies to watch in 2016

    OpenAIRE

    Reichert, Janice M

    2015-01-01

    The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, ar...

  7. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo

    2014-10-09

    SUMMARY: Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity into a suitable human template. Unfortunately, this procedure may results in a partial or complete loss of affinity of the grafted molecule that can be restored by back-mutating some of the residues of human origin to the corresponding murine ones. This trial-and-error procedure is hard and involves expensive and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http://www.biocomputing.it/tabhu CONTACT: anna.tramontano@uniroma1.it, pierpaolo.olimpieri@uniroma1.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  8. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  9. Study of antibody/antigen binding kinetics by total internal reflection ellipsometry.

    Science.gov (United States)

    Baleviciute, Ieva; Balevicius, Zigmas; Makaraviciute, Asta; Ramanaviciene, Almira; Ramanavicius, Arunas

    2013-01-15

    Total internal reflection ellipsometry (TIRE) has been applied for the investigation of (i) kinetics of biosensing layer formation, which was based on the immobilization of fragmented and intact antibodies, and (ii) kinetics of antigen interaction with the immobilized antibodies. It has been demonstrated that ellipsometric parameter Δ(t) showed much higher sensitivity at the initial phase of Au-protein and protein-protein interaction, while the parameter Ψ(t) was more sensitive when the steady-state conditions were established. A new method, which taking into consideration this feature and nonlinear change of Δ(t) and Ψ(t) parameters during various stages of biological layer formation process, was used for the calculation of antibody and antigen adsorption/interaction kinetics. The obtained results were analyzed using a model, which took into account partial reversibility during the formation of both antibody and antigen based monolayers. It was shown that the immobilization rate of antibody during the preparation of the sensing layer was similar for the formation of both intact and fragmented antibody based layers; however, the residence time was 25 times longer for intact antibody based layer formation in comparison to that of fragmented antibody based layer formation. On the contrary, residence time of antigen interaction with immobilized antibodies was about 8 times longer for the sensor based on fragmented antibodies. Moreover, it has been determined that the structural differences of immobilized antibodies (fragmented or intact) significantly influence antibody-antigen interaction rate, the major difference being in the residence time of antigen interaction with both types of immobilized antibodies.

  10. HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) - Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

    DEFF Research Database (Denmark)

    Jensen, Sanne Skov; Fomsgaard, Anders; Borggren, Marie

    2015-01-01

    Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated...... during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART....

  11. Validating Antibodies to the Cannabinoid CB2 Receptor: Antibody Sensitivity Is Not Evidence of Antibody Specificity.

    Science.gov (United States)

    Marchalant, Yannick; Brownjohn, Philip W; Bonnet, Amandine; Kleffmann, Torsten; Ashton, John C

    2014-06-01

    Antibody-based methods for the detection and quantification of membrane integral proteins, in particular, the G protein-coupled receptors (GPCRs), have been plagued with issues of primary antibody specificity. In this report, we investigate one of the most commonly utilized commercial antibodies for the cannabinoid CB2 receptor, a GPCR, using immunoblotting in combination with mass spectrometry. In this way, we were able to develop powerful negative and novel positive controls. By doing this, we are able to demonstrate that it is possible for an antibody to be sensitive for a protein of interest-in this case CB2-but still cross-react with other proteins and therefore lack specificity. Specifically, we were able to use western blotting combined with mass spectrometry to unequivocally identify CB2 protein in over-expressing cell lines. This shows that a common practice of validating antibodies with positive controls only is insufficient to ensure antibody reliability. In addition, our work is the first to develop a label-free method of protein detection using mass spectrometry that, with further refinement, could provide unequivocal identification of CB2 receptor protein in native tissues.

  12. Production and Purification of Polyclonal Antibodies.

    Science.gov (United States)

    Nakazawa, Masami; Mukumoto, Mari; Miyatake, Kazutaka

    2016-01-01

    Polyclonal antibodies consist of a mixture of antibodies produced by multiple B-cell clones that have differentiated into antibody-producing plasma cells in response to an immunogen. Polyclonal antibodies raised against an antigen recognize multiple epitopes on a target molecule, which results in a signal amplification in indirect immunoassays including immune-electron microscopy. In this chapter, we present a basic procedure to generate polyclonal antibodies in rabbits.

  13. Elimination of islet cell antibodies and glutamic acid decarboxylase antibodies II in a patient with newly diagnosed insulin-dependent diabetes mellitus.

    Science.gov (United States)

    Richter, W O; Donner, M G; Schwandt, P

    1997-01-01

    Islet cell antibodies and glutamic acid decarboxylase II (GAD II) antibodies have been discussed in the autoimmune pathogenesis of insulin-dependent diabetes mellitus (IDDM). Hence, immunosuppressants, intravenous immunoglobulins, and plasmapheresis have been used in an effort to modulate autoimmune activity and thereby prevent the destruction of pancreatic beta-cells. We describe the autoantibody (islet cell antibody and GAD II) kinetics and clinical course in a patient with newly diagnosed IDDM treated with a specific immunoglobulin apheresis technique. Five days after the initial diagnosis a 37-year-old patient with IDDM underwent a series of seven immunoglobulin aphereses. Immunoglobulin (IgG, IgA, IgM), islet cell antibody, GAD II, and C-peptide concentrations were monitored for a time course of 74 days. Daily insulin requirements were recorded. One single immunoglobulin apheresis decreased IgG by 66.2 +/- 9.1%, IgA by 66.8 +/- 8.7%, and IgM by 57.7 +/- 12.9%. GAD II antibodies were reduced by 61.9 +/- 12.4%. The islet cell antibody titer declined from 1:32 to 1:4 after the treatment series. There were no relevant changes in the safety parameters determined nor were there any clinical side effects. The efficient decrease in islet cell antibodies and glutamic acid decarboxylase II antibodies in a patient with IDDM encourages further investigations into the impact of this treatment on the clinical course of this autoimmune disorder.

  14. Initiatives en promotion de santé et traditions culinaires

    DEFF Research Database (Denmark)

    Hedegaard, Liselotte

    Questions posées : comment cette idée de transférabilité des interventions d’un contexte national à un autre ? Pourquoi cette unanimité du discours nutritionnel ? Quels sont les choix politiques qui ont mené à une dérégulation en termes de restrictions & obligations de la part de l’industrie agro...

  15. Host Immune Responses That Promote Initial HIV Spread

    Science.gov (United States)

    2011-07-01

    been observed that Treg cells from hosts infected with HIV and FIV ( feline immunodeficiency virus) suppress antiviral responses during the chronic stage...E. R. Galemore, S. VandeWoude, and G. Dean. Regulatory T cell depletion prior to acute feline immunodeficiency virus infection does not alter...T cells is associated with improved antiviral responses in cats chronically infected with feline immunodeficiency virus. Virology, 403(2):163–72, 2010

  16. [Promoting "well-treatment" in medical imaging].

    Science.gov (United States)

    Renouf, Nicole; Llop, Marc

    2012-12-01

    A project to promote "well-treatment" has been initiated in the medical imaging department of a Parisian hospital. With the aim of promoting the well-being of the patient and developing shared values of empathy and respect, the members of this medico-technical team have undertaken to build a culture of "well-treatment" which respects the patient's dignity and rights.

  17. The antibody response in Lyme disease.

    Science.gov (United States)

    Craft, J. E.; Grodzicki, R. L.; Shrestha, M.; Fischer, D. K.; García-Blanco, M.; Steere, A. C.

    1984-01-01

    We determined the antibody response against the Ixodes dammini spirochete in Lyme disease patients by indirect immunofluorescence and an enzyme-linked immunosorbent assay (ELISA). The specific IgM response became maximal three to six weeks after disease onset, and then declined, although titers sometimes remained elevated during later disease. Specific IgM levels correlated directly with total serum IgM. The specific IgG response, often delayed initially, was nearly always present during neuritis and arthritis, and frequently remained elevated after months of remission. Although results obtained by indirect immunofluorescence and the ELISA were similar, the ELISA was more sensitive and specific. Cross-reactive antibodies from patients with other spirochetal infections were blocked by absorption of sera with Borrelia hermsii, but titers of Lyme disease sera were also decreased. To further characterize the specificity of the humoral immune response against the I. dammini spirochete, 35S-methionine-labeled spirochetal antigens were identified by immunoprecipitation with sera from Lyme arthritis patients. These polypeptides had molecular weights of 62, 60, 47, 37, 22, 18, and 15 kDa, and were not recognized by control sera. We conclude that the ELISA, without absorption, is the best method to assay the humoral immune response in Lyme disease, and we have identified methionine-containing spirochetal polypeptides that may be important in Lyme arthritis. PMID:6393607

  18. Thyroid antibody-negative euthyroid Graves’ ophthalmopathy

    Directory of Open Access Journals (Sweden)

    Arshiya Tabasum

    2016-06-01

    Full Text Available TSH receptor antibodies (TRAbs are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease.

  19. Antibodies with thiol-S-transferase activity

    Energy Technology Data Exchange (ETDEWEB)

    Fan, E.; Oei, Yoko; Sweet, E.; Uno, Tetsuo; Schultz, P.G. [Univ. of California, Berkeley, CA (United States)

    1996-06-12

    A major detoxification pathway used by aerobic organisms involves the conjugation of the tripeptide glutathione (GSH) to the electrophilic center of toxic substances. This reaction is catalyzed by a class of enzymes referred to as the glutathione S-transferases (GST) (EC 2.5.1.18). These enzymes activate the cysteine thiol group of GSH for nucleophilic addition to a variety of substrates, including aryl halides, {alpha}{beta}-unsaturated aldehydes and ketones, and epoxides. Despite the availability of X-ray crystal structures, the mechanism whereby glutathione transferases catalyze these addition reactions remains unclear. In order to gain a greater understanding of this important biological transformation, as well as to generate new detoxification catalysts, we have asked whether antibodies can be generated that catalyze similar nucleophilic addition reactions. Our initial efforts focused on the addition reaction of thiol nucleophiles to the nitro-substituted styrene derivative 1. The ratio of k{sub cat}/K{sub m} reported for the reaction of the isozyme 4-4` of rat liver GST with the good substance, 1-chloro-2,4-dinitrobenzene, is approximately 10{sup 4} M{sup -1} s{sup -1} compared to a calculated pseudo-first-order rate constant for the uncatalyzed reaction of approximately 3 x 10{sup -2} s{sup -1} (60 mM GSH, pH = 80). These comparisons suggest that with further improvements in hapten design, catalytic antibodies may prove a good source of detoxification catalysts. 19 refs., 1 fig.

  20. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies.

    Science.gov (United States)

    Cheeseman, Hannah M; Olejniczak, Natalia J; Rogers, Paul M; Evans, Abbey B; King, Deborah F L; Ziprin, Paul; Liao, Hua-Xin; Haynes, Barton F; Shattock, Robin J

    2017-01-01

    Definition of the key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue may prove critical to effective vaccine development and the prophylactic use of monoclonal antibodies. Although direct antibody-mediated neutralization is highly effective against cell-free virus, antibodies targeting different sites of envelope vulnerability may display differential activity against mucosal infection. Nonneutralizing antibodies (nnAbs) may also impact mucosal transmission events through Fc-gamma receptor (FcγR)-mediated inhibition. In this study, a panel of broadly neutralizing antibodies (bnAbs) and nnAbs, including those associated with protection in the RV144 vaccine trial, were screened for the ability to block HIV-1 acquisition and replication across a range of cellular and mucosal tissue models. Neutralization potency, as determined by the TZM-bl infection assay, did not fully predict activity in mucosal tissue. CD4-binding site (CD4bs)-specific bnAbs, in particular VRC01, were consistent in blocking HIV-1 infection across all cellular and tissue models. Membrane-proximal external region (MPER) (2F5) and outer domain glycan (2G12) bnAbs were also efficient in preventing infection of mucosal tissues, while the protective efficacy of bnAbs targeting V1-V2 glycans (PG9 and PG16) was more variable. In contrast, nnAbs alone and in combinations, while active in a range of cellular assays, were poorly protective against HIV-1 infection of mucosal tissues. These data suggest that tissue resident effector cell numbers and low FcγR expression may limit the potential of nnAbs to prevent establishment of the initial foci of infection. The solid protection provided by specific bnAbs clearly demonstrates their superior potential over that of nonneutralizing antibodies for preventing HIV-1 infection at the mucosal portals of infection.

  1. Antibodies to watch in 2016.

    Science.gov (United States)

    Reichert, Janice M

    2016-01-01

    The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016. Commercial late-stage antibody therapeutics development exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to 53 as of late 2015. Of the 53 candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other "antibodies to watch" include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016. As evidenced by the antibody therapeutics discussed in this perspective, the biopharmaceutical industry has a highly active late-stage clinical pipeline that may deliver numerous new products to the global market in the near future. *See Note added in proof for updates through December 31, 2015.

  2. Oral antibiotics enhance antibody responses to keyhole limpet hemocyanin in orally but not muscularly immunized chickens.

    Science.gov (United States)

    Murai, Atsushi; Kitahara, Kazuki; Okumura, Shouta; Kobayashi, Misato; Horio, Fumihiko

    2016-02-01

    Recent studies have emphasized the crucial role of gut microbiota in triggering and modulating immune response. We aimed to determine whether the modification of gut microbiota by oral co-administration of two antibiotics, ampicillin and neomycin, would lead to changes in the antibody response to antigens in chickens. Neonatal chickens were given or not given ampicillin and neomycin (0.25 and 0.5 g/L, respectively) in drinking water. At 2 weeks of age, the chicks were muscularly or orally immunized with antigenic keyhole limpet hemocyanin (KLH), and then serum anti-KLH antibody levels were examined by ELISA. In orally immunized chicks, oral antibiotics treatment enhanced antibody responses (IgM, IgA, IgY) by 2-3-fold compared with the antibiotics-free control, while the antibiotics did not enhance antibody responses in the muscularly immunized chicks. Concomitant with their enhancement of antibody responses, the oral antibiotics also lowered the Lactobacillus species in feces. Low doses of antibiotics (10-fold and 100-fold lower than the initial trial), which failed to change the fecal Lactobacillus population, did not modify any antibody responses when chicks were orally immunized with KLH. In conclusion, oral antibiotics treatment enhanced the antibody response to orally exposed antigens in chickens. This enhancement of antibody response was associated with a modification of the fecal Lactobacillus content, suggesting a possible link between gut microbiota and antibody response in chickens.

  3. Studying host cell protein interactions with monoclonal antibodies using high throughput protein A chromatography.

    Science.gov (United States)

    Sisodiya, Vikram N; Lequieu, Joshua; Rodriguez, Maricel; McDonald, Paul; Lazzareschi, Kathlyn P

    2012-10-01

    Protein A chromatography is typically used as the initial capture step in the purification of monoclonal antibodies produced in Chinese hamster ovary (CHO) cells. Although exploiting an affinity interaction for purification, the level of host cell proteins in the protein A eluent varies significantly with different feedstocks. Using a batch binding chromatography method, we performed a controlled study to assess host cell protein clearance across both MabSelect Sure and Prosep vA resins. We individually spiked 21 purified antibodies into null cell culture fluid generated with a non-producing cell line, creating mock cell culture fluids for each antibody with an identical composition of host cell proteins and antibody concentration. We demonstrated that antibody-host cell protein interactions are primarily responsible for the variable levels of host cell proteins in the protein A eluent for both resins when antibody is present. Using the additives guanidine HCl and sodium chloride, we demonstrated that antibody-host cell protein interactions may be disrupted, reducing the level of host cell proteins present after purification on both resins. The reduction in the level of host cell proteins differed between antibodies suggesting that the interaction likely varies between individual antibodies but encompasses both an electrostatic and hydrophobic component.

  4. Monoclonal antibody proteomics: use of antibody mimotope displaying phages and the relevant synthetic peptides for mAb scouting.

    Science.gov (United States)

    Hajdú, István; Flachner, Beáta; Bognár, Melinda; Végh, Barbara M; Dobi, Krisztina; Lőrincz, Zsolt; Lázár, József; Cseh, Sándor; Takács, László; Kurucz, István

    2014-08-01

    Monoclonal antibody proteomics uses nascent libraries or cloned (Plasmascan™, QuantiPlasma™) libraries of mAbs that react with individual epitopes of proteins in the human plasma. At the initial phase of library creation, cognate protein antigen and the epitope interacting with the antibodies are not known. Scouting for monoclonal antibodies (mAbs) with the best binding characteristics is of high importance for mAb based biomarker assay development. However, in the absence of the identity of the cognate antigen the task represents a challenge. We combined phage display, and surface plasmon resonance (Biacore) experiments to test whether specific phages and the respective mimotope peptides obtained from large scale studies are applicable to determine key features of antibodies for scouting. We show here that mAb captured phage-mimotope heterogeneity that is the diversity of the selected peptide sequences, is inversely correlated with an important binding descriptor; the off-rate of the antibodies and that represents clues for driving the selection of useful mAbs for biomarker assay development. Carefully chosen synthetic mimotope peptides are suitable for specificity testing in competitive assays using the target proteome, in our case the human plasma.

  5. Promoter hypomethylation regulates CD133 expression in human gliomas

    Institute of Scientific and Technical Information of China (English)

    Kouichi Tabu; Ken Sasai; Taichi Kimura; Lei Wang; Eiko Aoyanagi; Shinji Kohsaka; Mishie Tanino; Hiroshi Nishihara; Shinya Tanaka

    2008-01-01

    Brain tumor-initiating cells (BTICs) have been enriched using antibodies against the cell surface protein CD133;however,the biological relevance and the regulatory mechanism of CD133 expression in human gliomas are not yet understood.In this study,we initially demonstrated that CD133 was overexpressed in high-grade human glioblastomas where CD133-positive cells were focally observed as a micro-cluster.In addition,CD133 transcripts with exon 1A,1B,or 1C were predominantly expressed in glioblastomas.To elucidate the mechanism regulating this aberrant expression of CD133,three proximal promoters (P1,P2,and P3) containing a CpG island were isolated.In U251MG and T98Gglioblastoma cells,the P1 region flanking exon 1A exhibited the highest activity among the three promoters,and this activity was significantly inactivated by in vitro methylation.After treatment with the demethylating agent 5-azacytidine and/or the histone deacetylase inhibitor valproic acid,the expression level of CD133 mRNA was significantly restored in glioma cells.Importantly,hypomethylation of CpG sites within the P1,P2,and P3 regions was observed by bisulfite sequencing in human glioblastoma tissues with abundant CD133 mRNA.Taken together,our results indicate that DNA hypomethylation is an important determinant of CD133 expression in glioblastomas,and this epigenetic event may be associated with the development of BTICs expressing CD133.

  6. How can a multilevel promotion of breastfeeding reduce the required budget for rotavirus vaccination in Indonesia?

    NARCIS (Netherlands)

    Zakiyah, N.; Suwantika, A.A.; Postma, M.J.

    2014-01-01

    Objectives: Breast milk is considered to give protection against rotavirus infection since it contains anti-rotavirus maternal antibodies and other nonspecific inhibitors. Multilevel promotion of breastfeeding is a complex intervention that modifies behavioral determinants through multiple levels of

  7. An atypical presentation of antiphospholipid antibody syndrome.

    Science.gov (United States)

    D'souza, Deepti; Dandakeri, Sukumar; Bhat, M Ramesh; Srinath, M K

    2015-01-01

    Cutaneous manifestations in antiphospholipid antibody syndrome (APS) though common, are extremely diverse and it is important to know which dermatological finding should prompt consideration of antiphospholipid syndrome. The cutaneous manifestations of APS vary from livedo reticularis to cutaneous necrosis, and systemic involvement is invariably an accomplice in APS. Cutaneous ulcers with sharp margins can be seen in APS and they are usually seen on the legs. This case had an atypical presentation, as the initial presentation was painful necrotic ulcers over the legs, which resembled pyoderma gangrenosum and she had no systemic manifestations. There was no history of any arterial or venous thrombosis or any abortions. Antiphospholipid syndrome can be tricky to diagnose when cutaneous lesions are atypical. Nonetheless, it is very important to pin down this syndrome early due to its systemic complications.

  8. An atypical presentation of antiphospholipid antibody syndrome

    Directory of Open Access Journals (Sweden)

    Deepti D′Souza

    2015-01-01

    Full Text Available Cutaneous manifestations in antiphospholipid antibody syndrome (APS though common, are extremely diverse and it is important to know which dermatological finding should prompt consideration of antiphospholipid syndrome. The cutaneous manifestations of APS vary from livedo reticularis to cutaneous necrosis, and systemic involvement is invariably an accomplice in APS. Cutaneous ulcers with sharp margins can be seen in APS and they are usually seen on the legs. This case had an atypical presentation, as the initial presentation was painful necrotic ulcers over the legs, which resembled pyoderma gangrenosum and she had no systemic manifestations. There was no history of any arterial or venous thrombosis or any abortions. Antiphospholipid syndrome can be tricky to diagnose when cutaneous lesions are atypical. Nonetheless, it is very important to pin down this syndrome early due to its systemic complications.

  9. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Directory of Open Access Journals (Sweden)

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  10. Antibodies to watch in 2013

    Science.gov (United States)

    Reichert, Janice M

    2013-01-01

    The transitions of antibody therapeutics to late-stage clinical development, regulatory review and the market are proceeding at a rapid pace in 2013. Since late 2012, two monoclonal antibody (mAb) therapeutics (itolizumab, trastuzumab emtansine) received their first approvals, first marketing applications for three mAbs (vedolizumab, ramucirumab, obinutuzumab) were submitted to regulatory agencies, and five mAbs (brodalumab, MABp1, moxetumomab pasudotox, tildrakizumab, rilotumumab) entered their first Phase 3 studies. The current total of commercially-sponsored antibody therapeutics undergoing evaluation in late-stage studies is 30. Recently announced study results for farletuzumab, naptumomab estafenatox, and tabalumab indicate that clinical endpoints were not met in some Phase 3 studies of these product candidates. PMID:23727858

  11. Epigenetics of the antibody response.

    Science.gov (United States)

    Li, Guideng; Zan, Hong; Xu, Zhenming; Casali, Paolo

    2013-09-01

    Epigenetic marks, such as DNA methylation, histone post-translational modifications and miRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR), and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and miRNAs modulate the expression of critical elements of that machinery, such as activation-induced cytidine deaminase (AID), as well as factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1 (Blimp-1). These inducible B cell-intrinsic epigenetic marks instruct the maturation of antibody responses. Their dysregulation plays an important role in aberrant antibody responses to foreign antigens, such as those of microbial pathogens, and self-antigens, such as those targeted in autoimmunity, and B cell neoplasia.

  12. Autologous antibodies that bind neuroblastoma cells.

    Science.gov (United States)

    Sun, Yujing; Sholler, Giselle S; Shukla, Girja S; Pero, Stephanie C; Carman, Chelsea L; Zhao, Ping; Krag, David N

    2015-11-01

    Antibody therapy of neuroblastoma is promising and our goal is to derive antibodies from patients with neuroblastoma for developing new therapeutic antibodies. The feasibility of using residual bone marrow obtained for clinical indications as a source of tumor cells and a source of antibodies was assessed. From marrow samples, neuroblastoma cells were recovered, grown in cell culture and also implanted into mice to create xenografts. Mononuclear cells from the marrow were used as a source to generate phage display antibody libraries and also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro and as xenografts. Antibodies from the phage libraries and from the monoclonal hybridomas bound autologous neuroblastoma cells with some selectivity. It appears feasible to recover neuroblastoma cells from residual marrow specimens and to generate human antibodies that bind autologous neuroblastoma cells. Expansion of this approach is underway to collect more specimens, optimize methods to generate antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies.

  13. Uses of monoclonal antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2013-04-09

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

  14. Selective binding of anti-DNA antibodies to native dsDNA fragments of differing sequence.

    Science.gov (United States)

    Uccellini, Melissa B; Busto, Patricia; Debatis, Michelle; Marshak-Rothstein, Ann; Viglianti, Gregory A

    2012-03-30

    Systemic autoimmune diseases are characterized by the development of autoantibodies directed against a limited subset of nuclear antigens, including DNA. DNA-specific B cells take up mammalian DNA through their B cell receptor, and this DNA is subsequently transported to an endosomal compartment where it can potentially engage TLR9. We have previously shown that ssDNA-specific B cells preferentially bind to particular DNA sequences, and antibody specificity for short synthetic oligodeoxynucleotides (ODNs). Since CpG-rich DNA, the ligand for TLR9 is found in low abundance in mammalian DNA, we sought to determine whether antibodies derived from DNA-reactive B cells showed binding preference for CpG-rich native dsDNA, and thereby select immunostimulatory DNA for delivery to TLR9. We examined a panel of anti-DNA antibodies for binding to CpG-rich and CpG-poor DNA fragments. We show that a number of anti-DNA antibodies do show preference for binding to certain native dsDNA fragments of differing sequence, but this does not correlate directly with the presence of CpG dinucleotides. An antibody with preference for binding to a fragment containing optimal CpG motifs was able to promote B cell proliferation to this fragment at 10-fold lower antibody concentrations than an antibody that did not selectively bind to this fragment, indicating that antibody binding preference can influence autoreactive B cell responses.

  15. Roles of glycans in interactions between gp120 and HIV broadly neutralizing antibodies.

    Science.gov (United States)

    Qi, Yifei; Jo, Sunhwan; Im, Wonpil

    2016-03-01

    Many novel broadly neutralizing antibodies against human immunodeficiency virus (HIV) have been identified during the past decade, providing promising templates for the development of an effective HIV-1 vaccine. Structural studies reveal that the epitopes of some of these antibodies involve one or more crucial glycans, without which the binding is completely abolished. In this study, we have investigated the critical roles of glycans in interactions between HIV-1 gp120 and two broadly neutralizing antibodies PG9 (targeting V1/V2) and PGT128 (targeting V3) that are able to neutralize more than 70% of HIV-1 isolates. We have performed molecular dynamics simulations of a number of systems including antibody-gp120 complex with and without glycans, antibody, gp120 with and without glycans, and glycan-only systems. The simulation results show that the complex structures are stabilized by the glycans, and the multivalent interactions between the antibody and gp120 promote cooperativities to further enhance the binding. In the free gp120, the glycans increase the flexibility of the V1/V2 and V3 loops, which likely increases the entropy cost of the antibody recognition. However, the antibodies are able to bind the flexible interface by recognizing the preexisting glycan conformation, and penetrating the glycan shield with flexible complementarity determining region loops that sample the bound conformations occasionally.

  16. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  17. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A; Thompson, Vicki S

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  18. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2017-03-28

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  19. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S

    2010-04-13

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  20. Developing a promotional strategy: important questions for social marketing.

    Science.gov (United States)

    Thackeray, Rosemary; Neiger, Brad L; Hanson, Carl L

    2007-10-01

    Health practitioners often use the terms marketing and promotion interchangeably. Yet, promotion is just one element of an overall marketing strategy. To realize the greatest impact there must be a combination of all the marketing components, including product, price, place, and promotion. The purpose of this article is to clarify the role of promotion and describe key elements of developing a promotional strategy within the broader context of a social marketing initiative.

  1. Aortitis with antiphospholipid antibodies: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Seror, O.; Dordea, M.; Ghenassia, C.; Coderc, E.; Sellier, N. [Department of Radiology, Centre Hospitalo-Universitaire Paris XIII, Bondy (France); Fain, O. [Department of Medicine, Centre Hospitalo-Universitaire Paris XIII, Bondy (France)

    1998-10-01

    Two cases of aortitis associated with the presence of antiphospholipid antibodies (APAs) are reported. Only CT and MR imaging were able to show these unusual form of aortitis preferentially affecting the outer aortic tunics. We conclude that aortitis could be a new manifestation of primary antiphospholipid syndrome (APS) and the initial pathological process before the development of aortic thrombosis, reported as a classical complication of APS. (orig.) (orig.) With 2 figs., 6 refs.

  2. Optimizing selection of large animals for antibody production by screening immune response to standard vaccines.

    Science.gov (United States)

    Thompson, Mary K; Fridy, Peter C; Keegan, Sarah; Chait, Brian T; Fenyö, David; Rout, Michael P

    2016-03-01

    Antibodies made in large animals are integral to many biomedical research endeavors. Domesticated herd animals like goats, sheep, donkeys, horses and camelids all offer distinct advantages in antibody production. However, their cost of use is often prohibitive, especially where poor antigen response is commonplace; choosing a non-responsive animal can set a research program back or even prevent experiments from moving forward entirely. Over the course of production of antibodies from llamas, we found that some animals consistently produced a higher humoral antibody response than others, even to highly divergent antigens, as well as to their standard vaccines. Based on our initial data, we propose that these "high level responders" could be pre-selected by checking antibody titers against common vaccines given to domestic farm animals. Thus, time and money can be saved by reducing the chances of getting poor responding animals and minimizing the use of superfluous animals.

  3. Antiphospholipid antibody syndrome and autoimmune diseases.

    Science.gov (United States)

    Ostrowski, Rochella A; Robinson, John A

    2008-02-01

    The arbitrary division between antiphospholipid antibody syndrome and secondary antiphospholipid antibody syndrome has not proven useful. Antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome often occur as epiphenomena in many autoimmune diseases. They are very common in systemic lupus erythematosus. Antiphospholipid antibody syndrome is a significant comorbidity in lupus but is uncommon in Sjögren's syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitis. Evidence is growing that antiphospholipid antibodies may have a pathogenic role in pulmonary hypertension and accelerated atherosclerosis of autoimmune diseases.

  4. Aerogenic vaccination with a Burkholderia mallei auxotroph protects against aerosol-initiated glanders in mice.

    Science.gov (United States)

    Ulrich, Ricky L; Amemiya, Kei; Waag, David M; Roy, Chad J; DeShazer, David

    2005-03-14

    Burkholderia mallei is an obligate mammalian pathogen that causes the zoonotic disease glanders. Two live attenuated B. mallei strains, a capsule mutant and a branched-chain amino acid auxotroph, were evaluated for use as vaccines against aerosol-initiated glanders in mice. Animals were aerogenically vaccinated and serum samples were obtained before aerosol challenge with a high-dose (>300 times the LD50) of B. mallei ATCC 23344. Mice vaccinated with the capsule mutant developed a Th2-like Ig subclass antibody response and none survived beyond 5 days. In comparison, the auxotrophic mutant elicited a Th1-like Ig subclass antibody response and 25% of the animals survived for 1 month postchallenge. After a low-dose (5 times the LD50) aerosol challenge, the survival rates of auxotroph-vaccinated and unvaccinated animals were 50 and 0%, respectively. Thus, live attenuated strains that promote a Th1-like Ig response may serve as promising vaccine candidates against aerosol infection with B. mallei.

  5. Development of an EGFRvIII specific recombinant antibody

    Directory of Open Access Journals (Sweden)

    Li Gordon

    2010-10-01

    Full Text Available Abstract Background EGF receptor variant III (EGFRvIII is the most common variant of the EGF receptor observed in human tumors. It results from the in frame deletion of exons 2-7 and the generation of a novel glycine residue at the junction of exons 1 and 8. This novel juxtaposition of amino acids within the extra-cellular domain of the EGF receptor creates a tumor specific and immunogenic epitope. EGFRvIII expression has been seen in many tumor types including glioblastoma multiforme (GBM, breast adenocarcinoma, non-small cell lung carcinoma, ovarian adenocarcinoma and prostate cancer, but has been rarely observed in normal tissue. Because this variant is tumor specific and highly immunogenic, it can be used for both a diagnostic marker as well as a target for immunotherapy. Unfortunately many of the monoclonal and polyclonal antibodies directed against EGFRvIII have cross reactivity to wild type EGFR or other non-specific proteins. Furthermore, a monoclonal antibody to EGFRvIII is not readily available to the scientific community. Results In this study, we have developed a recombinant antibody that is specific for EGFRvIII, has little cross reactivity for the wild type receptor, and which can be easily produced. We initially designed a recombinant antibody with two anti-EGFRvIII single chain Fv's linked together and a human IgG1 Fc component. To enhance the specificity of this antibody for EGFRvIII, we mutated tyrosine H59 of the CDRH2 domain and tyrosine H105 of the CDRH3 domain to phenylalanine for both the anti-EGFRvIII sequence inserts. This mutated recombinant antibody, called RAbDMvIII, specifically detects EGFRvIII expression in EGFRvIII expressing cell lines as well as in EGFRvIII expressing GBM primary tissue by western blot, immunohistochemistry (IHC and immunofluorescence (IF and FACS analysis. It does not recognize wild type EGFR in any of these assays. The affinity of this antibody for EGFRvIII peptide is 1.7 × 107 M-1 as

  6. The Plus 50 Initiative Evaluation: Initiative Impact

    Science.gov (United States)

    American Association of Community Colleges (NJ1), 2012

    2012-01-01

    The American Association of Community Colleges (AACC), with funding from The Atlantic Philanthropies, created the Plus 50 Initiative (2008-2012). This initiative was designed to build the capacity of community colleges nationwide to develop programming that engages the plus 50 learner. This report contains: (1) An overview of the Plus 50…

  7. DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 Human IgG Antibody Produced by AnaptysBio, Inc.

    Science.gov (United States)

    2016-02-01

    ECBC-TR-1339 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR ANTIBODY...CHARACTERIZATION: CHARACTERIZATION OF AN MS2 HUMAN IGG ANTIBODY PRODUCED BY ANAPTYSBIO, INC. DARPA ATP Standardized Test Bed for Antibody...Characterization: Characterization of an MS2 human IgG antibody produced by AnaptysBio DARPA ATP Standardized Test Bed for Antibody

  8. Polyclonal and monoclonal antibodies in clinic.

    Science.gov (United States)

    Wootla, Bharath; Denic, Aleksandar; Rodriguez, Moses

    2014-01-01

    Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino-acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. Naturally occurring antibodies protect the organism against harmful pathogens, viruses and infections. In addition, almost any organic chemical induces antibody production of antibodies that would bind specifically to the chemical. These antibodies are often produced from multiple B cell clones and referred to as polyclonal antibodies. In recent years, scientists have exploited the highly evolved machinery of the immune system to produce structurally and functionally complex molecules such as antibodies from a single B clone, heralding the era of monoclonal antibodies. Most of the antibodies currently in the clinic, target components of the immune system, are not curative and seek to alleviate symptoms rather than cure disease. Our group used a novel strategy to identify reparative human monoclonal antibodies distinct from conventional antibodies. In this chapter, we discuss the therapeutic relevance of both polyclonal and monoclonal antibodies in clinic.

  9. Antibody Engineering for Pursuing a Healthier Future

    Science.gov (United States)

    Saeed, Abdullah F. U. H.; Wang, Rongzhi; Ling, Sumei; Wang, Shihua

    2017-01-01

    Since the development of antibody-production techniques, a number of immunoglobulins have been developed on a large scale using conventional methods. Hybridoma technology opened a new horizon in the production of antibodies against target antigens of infectious pathogens, malignant diseases including autoimmune disorders, and numerous potent toxins. However, these clinical humanized or chimeric murine antibodies have several limitations and complexities. Therefore, to overcome these difficulties, recent advances in genetic engineering techniques and phage display technique have allowed the production of highly specific recombinant antibodies. These engineered antibodies have been constructed in the hunt for novel therapeutic drugs equipped with enhanced immunoprotective abilities, such as engaging immune effector functions, effective development of fusion proteins, efficient tumor and tissue penetration, and high-affinity antibodies directed against conserved targets. Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines. However, there is limited knowledge regarding dynamic antibody development approaches. Therefore, this review extends beyond our understanding of conventional polyclonal and monoclonal antibodies. Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans.

  10. Phosphazene-promoted anionic polymerization

    KAUST Repository

    Zhao, Junpeng

    2014-01-01

    In the recent surge of metal-free polymerization techniques, phosphazene bases have shown their remarkable potential as organic promoters/catalysts for the anionic polymerization of various types of monomers. By complexation with the counterion (e.g. proton or lithium cation), phosphazene base significantly improve the nucleophilicity of the initiator/chain-end resulting in rapid and usually controlled anionic/quasi-anionic polymerization. In this review, we will introduce the general mechanism, i.e. in situ activation (of initiating sites) and polymerization, and summarize the applications of such a mechanism on macromolecular engineering toward functionalized polymers, block copolymers and complex macromolecular architectures.

  11. Pharmacokinetics interactions of monoclonal antibodies.

    Science.gov (United States)

    Ferri, Nicola; Bellosta, Stefano; Baldessin, Ludovico; Boccia, Donatella; Racagni, Giorgi; Corsini, Alberto

    2016-09-01

    The clearance of therapeutic monoclonal antibodies (mAbs) typically does not involve cytochrome P450 (CYP450)-mediated metabolism or interaction with cell membrane transporters, therefore the pharmacokinetics interactions of mAbs and small molecule drugs are limited. However, a drug may affect the clearance of mAbs through the modulation of immune response (e.g., methotrexate reduces the clearance of infliximab, adalimumab, and golimumab, possibly due to methotrexate's inhibitory effect on the formation of antibodies against the mAbs). In addition, mAbs that are cytokine modulators may modify the metabolism of drugs through their effects on P450 enzymes expression. For example, cytokine modulators such as tocilizumab (anti-IL-6 receptor antibody) may reverse the "inhibitory" effect of IL-6 on CYP substrates, resulting in a "normalization" of CYP activities. Finally, a drug may alter the clearance of mAbs by either increasing or reducing the levels of expression of targets of mAbs on the cell surface. For instance, statins and fibrates induce PCSK9 expression and therefore increase cellular uptake and clearance of alirocumab and evolocumab, anti-PCSK9 antibodies. In the present review, we will provide an overview on the pharmacokinetics properties of mAbs as related to the most relevant examples of mAbs-small molecule drug interaction.

  12. Monoclonal antibodies to Treponema Pallidum.

    NARCIS (Netherlands)

    H.J.M. van de Donk; J.D.A. van Embden; M.F. van Olderen; A.D.M.E. Osterhaus (Albert); J.C. de Jong (Jan)

    1984-01-01

    textabstractThree successive fusions of mouse myeloma cells and spleen lymphocytes of a mouse immunized with Treponema Pallidum resulted in one hybridoma producing anti T. pallidum antibodies for each fusion. The mice were immunized with live pallidum cells respectively 1, 3 and 5 months before fusi

  13. Development of Antibody Against Sulfamethazine

    Institute of Scientific and Technical Information of China (English)

    LIZi-ying; XUWen-ge; LIUYi-bing; ZHANGLi-ling; GUOWei-zheng; HANShi-quan

    2003-01-01

    Polyclonal antibodies(PcAbs) against sulfamethazine(SMT) are obtained by immunizing rabbits with SMT-conjugated bovine serum albumin(BSA). The affinity constants (Ka) of the PcAbs are higher than 1×108 and the cross-reactivities with sulfadiazine(SD), sulfaquinoxaline (SQX) are lower than 0.05% (R/A).

  14. Initialized Fractional Calculus

    Science.gov (United States)

    Lorenzo, Carl F.; Hartley, Tom T.

    2000-01-01

    This paper demonstrates the need for a nonconstant initialization for the fractional calculus and establishes a basic definition set for the initialized fractional differintegral. This definition set allows the formalization of an initialized fractional calculus. Two basis calculi are considered; the Riemann-Liouville and the Grunwald fractional calculi. Two forms of initialization, terminal and side are developed.

  15. Antibody response to Hepatozoon canis in experimentally infected dogs.

    Science.gov (United States)

    Baneth, G; Shkap, V; Samish, M; Pipano, E; Savitsky, I

    1998-01-31

    Canine hepatozoonosis is a disease caused by the tick-borne protozoan Hepatozoon canis. Five puppies were inoculated by ingestion of Rhipicephalus sanguineus ticks experimentally infected with H. canis, and all became infected with H. canis: gametocytes were detected in blood smears from four dogs and schizonts were observed in the spleen and bone marrow of the fifth. Antibodies reactive with H. canis gametocytes were detected by the indirect fluorescent antibody test (IFA), with IgM detected initially in all dogs 16 to 39 days post infection (PI) and IgG 22 to 43 days PI. The presence of gametocytes was first observed within peripheral blood neutrophils in Giemsa-stained blood smears between days 28 and 43 PI. Gametocyte-reactive antibodies were detected before the appearance of blood gametocytes in three of the four parasitemic dogs and also in a dog with no observed parasitemia. The detection of serum antibodies prior to the detection of blood gametocytes, or without apparent parasitemia, suggests that antibodies reactive with gametocytes may be formed against earlier forms of the parasite developing in the parenchymal tissues. Sera of dogs experimentally infected with Babesia canis, Babesia gibsoni and Ehrlichia canis exhibited no reactivity when tested with H. canis antigen. Additionally, sera positive for H. canis were not reactive with antigens of Toxoplasma gondii, Neospora caninum, Leishmania donovani and E. canis. In conclusion, incoculation of dogs with ticks infected with H. canis results in production of antibodies reactive with peripheral blood gametocytes. Detection of IgG titres would be beneficial for the diagnosis of progressive infections with undetectable parasitemia, for seroprevalence studies, and as an adjunct to IgM titres in early infections.

  16. Epididymis-specific lipocalin promoters

    Institute of Scientific and Technical Information of China (English)

    Kichiya Suzuki; Xiuping Yu; Pierre Chaurand; Yoshihiko Araki; Jean-Jacques Lareyre; Richard M. Caprioli; Marie-Claire Orgebin-Crist; Robert J. Matusik

    2007-01-01

    Our goal is to decipher which DNA sequences are required for tissue-specific expression of epididymal genes. At least 6 epididymis-specific lipocalin genes are known. These are differently regulated and regionalized in the epididymis.Lipocalin 5 (Lcn5 or mE-RABP) and Lipocalin 8 (Lcn8 or mEP17) are homologous genes belonging to the epididymis-specific lipocalin gene cluster. Both the 5 kb promoter fragment of the Lcn5 gene and the 5.3 kb promoter fragment of the Lcn8 gene can direct transgene expression in the epididymis (Lcn5 to the distal caput and Lcn8 to the initial segment), indicating that these promoter fragments contain important cis-regulatory element(s) for epididymisspecific gene expression. To define further the fragments regulating gene expression, the Lcn5 promoter was examined in transgenic mice and immortalized epididymal cell lines. After serial deletion, the 1.8 kb promoter fragment of the Lcn5 gene was sufficient for tissue-specific and region-specific gene expression in transgenic mice. Transient transfection analysis revealed that a transcription factor forkhead box A2 (Foxa2) interacts with androgen receptor and binds to the 100 bp fragment of the Lcn5 promoter between 1.2 kb and 1.3 kb and that Foxa2 expression inhibitsandrogen-dependent induction of the Lcn5 promoter activity. Immunohistochemistry indicated a restricted expression of Foxa2 in the epididymis where endogenous Lcn5 gene expression is suppressed and that the Foxa2 inhibition of the Lcn5 promoter is consistent with the lack of expression of Lcn5 in the corpus and cauda. Our approach provides a basic strategy for further analysis of the epididymal lipocalin gene regulation and flexible control of epididymal function.

  17. Detection of Campylobacter species using monoclonal antibodies

    Science.gov (United States)

    Young, Colin R.; Lee, Alice; Stanker, Larry H.

    1999-01-01

    A panel of species specific monoclonal antibodies were raised to Campylobacter coli, Campylobacter jejuni and Campylobacter lari. The isotypes, and cross-reactivity profiles of each monoclonal antibody against an extensive panel of micro- organisms, were determined.

  18. [Neuroimmunological diseases associated with VGKC complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-05-01

    Antibodies to voltage-gated potassium channels(VGKC) were first identified by radioimmunoassay of radioisotope labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were found only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in Morvan's syndrome and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins(for example LGI-1, Caspr-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. Caspr-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability.

  19. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2014-07-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  20. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2013-01-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  1. Chemical engineering of cell penetrating antibodies.

    Science.gov (United States)

    Zhao, Y; Lou, D; Burkett, J; Kohler, H

    2001-08-01

    Antibodies, being exquisitely specific tools in biology, are routinely used to detect and identify intra-cellular structures. However, current intra-cellular application of antibodies requires that the membrane be rendered leaky, resulting in the death of cells. Here, we present a novel method to allow antibodies to penetrate the cellular membrane of living cells without affecting cell viability. A peptide (MTS, membrane transport sequence) that facilitates transport across membranes has been site-specifically attached to antibodies. MTS-antibodies enter the living cells in culture and can be detected by immunofluorescence and ELISA after extraction. Cellular structures are visualized in living cells using a specific MTS-antibody. Antibodies with membrane penetrating properties can become an important tool for the study of intra-cellular processes in living cells. Furthermore, such membrane penetrating antibodies can be used to selectively stimulate or suppress functions of the cellular machinery.

  2. Engineered single chain antibody fragments for radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huhalov, A.; Chester, K. A. [Cancer Research UK Imaging and Targeting Group Royal Free, London (United Kingdom). Department of Oncology; University College Medical School Royal Free Campus, London (United Kingdom)

    2004-12-01

    An ideal molecule to deliver radioimmunotherapy (RIT) would be target specific and have prolonged residence time at high concentrations in the tumour with rapid clearance from normal tissues. It would also be non-immunogenic. These features can be rationally introduced into recombinant antibody-based proteins using antibody engineering techniques. This reviews focuses on the use of antibody engineering in the design and development of RIT molecules which have single chain Fv (scFv) antibody fragments as building blocks.

  3. Recombinant bispecific antibodies for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Roland E KONTERMANN

    2005-01-01

    Bispecific antibodies can serve as mediators to retarget effector mechanisms to disease-associated sites. Studies over the past two decades have revealed the potentials but also the limitations of conventional bispecific antibodies. The development of recombinant antibody formats has opened up the possibility of generating bispecific molecules with improved properties. This review summarizes recent developments in the field of recombinant bispecific antibodies and discusses further requirements for clinical development.

  4. Production and Screening of Monoclonal Peptide Antibodies.

    Science.gov (United States)

    Trier, Nicole Hartwig; Mortensen, Anne; Schiolborg, Annette; Friis, Tina

    2015-01-01

    Hybridoma technology is a remarkable and indispensable tool for generating high-quality monoclonal antibodies. Hybridoma-derived monoclonal antibodies not only serve as powerful research and diagnostic reagents, but have also emerged as the most rapidly expanding class of therapeutic biologicals. In this chapter, an overview of hybridoma technology and the laboratory procedures used routinely for hybridoma production and antibody screening are presented, including characterization of peptide antibodies.

  5. Transcription factor binding site positioning in yeast: proximal promoter motifs characterize TATA-less promoters.

    Science.gov (United States)

    Erb, Ionas; van Nimwegen, Erik

    2011-01-01

    The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of 6 'proximal promoter motifs' (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1) occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters.

  6. Transcription factor binding site positioning in yeast: proximal promoter motifs characterize TATA-less promoters.

    Directory of Open Access Journals (Sweden)

    Ionas Erb

    Full Text Available The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of 6 'proximal promoter motifs' (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1 occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters.

  7. Characterization of Peptide Antibodies by Epitope Mapping Using Resin-Bound and Soluble Peptides.

    Science.gov (United States)

    Trier, Nicole Hartwig

    2015-01-01

    Characterization of peptide antibodies through identification of their target epitopes is of utmost importance. Understanding antibody specificity at the amino acid level provides the key to understand the specific interaction between antibodies and their epitopes and their use as research and diagnostic tools as well as therapeutic agents. This chapter describes a straightforward strategy for mapping of continuous peptide antibody epitopes using resin-bound and soluble peptides. The approach combines three different types of peptide sets for full characterization of peptide antibodies: (1) overlapping peptides, used to locate antigenic regions; (2) truncated peptides, used to identify the minimal peptide length required for antibody binding; and (3) substituted peptides, used to identify the key residues important for antibody binding and to determine the specific contribution of key residues. For initial screening resin-bound peptides are used for epitope estimation, while soluble peptides subsequently are used for fine mapping. The combination of resin-bound peptides and soluble peptides for epitope mapping provides a time-sparing and straightforward approach for characterization of peptide antibodies.

  8. Anti-DNA antibodies in SLE

    Energy Technology Data Exchange (ETDEWEB)

    Voss, E.W.

    1988-01-01

    This book contains 8 chapters. Some of the titles are: Anti-DNA Antibodies in SLE: Historical Perspective; Specificity of Anti-DNA Antibodies in Systemic Lupus Erythematosus; Monoclonial Autoimmune Anti-DNA Antibodies; and Structure--Function Analyses of Anti-DNA Autoantibodies.

  9. Nanoparticles for the delivery of therapeutic antibodies

    DEFF Research Database (Denmark)

    Sousa, Flávia; Castro, Pedro; Fonte, Pedro;

    2016-01-01

    INTRODUCTION: Over the past two decades, therapeutic antibodies have demonstrated promising results in the treatment of a wide array of diseases. However, the application of antibody-based therapy implies multiple administrations and a high cost of antibody production, resulting in costly therapy...

  10. Antibodies to staphylococcal enterotoxin in laboratory personnel.

    OpenAIRE

    Jozefczyk, Z; Robbins, R N; Spitz, J M; Bergdoll, M S

    1980-01-01

    Eighty-five percent of laboratory personnel working with staphylococcal enterotoxin had antibodies to enterotoxin in their sera, whereas only 23% of the control group had antibodies specific for enterotoxin. Two persons who carried enterotoxin B-producing staphylococci in their noses, throats, or both, had antibodies to enterotoxin B in their sera.

  11. Bispecific Antibody Pretargeting for Improving Cancer Imaging and Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sharkey, Robert M.

    2005-02-04

    The main objective of this project was to evaluate pretargeting systems that use a bispecific antibody (bsMAb) to improve the detection and treatment of cancer. A bsMAb has specificity to a tumor antigen, which is used to bind the tumor, while the other specificity is to a peptide that can be radiolabeled. Pretargeting is the process by which the unlabeled bsMAb is given first, and after a sufficient time (1-2 days) is given for it to localize in the tumor and clear from the blood, a small molecular weight radiolabeled peptide is given. According to a dynamic imaging study using a 99mTc-labeled peptide, the radiolabeled peptide localizes in the tumor in less than 1 hour, with > 80% of it clearing from the blood and body within this same time. Tumor/nontumor targeting ratios that are nearly 50 times better than that with a directly radiolabeled Fab fragment have been observed (Sharkey et al., ''Signal amplification in molecular imaging by a multivalent bispecific nanobody'' submitted). The bsMAbs used in this project have been composed of 3 antibodies that will target antigens found in colorectal and pancreatic cancers (CEA, CSAp, and MUC1). For the ''peptide binding moiety'' of the bsMAb, we initially examined an antibody directed to DOTA, but subsequently focused on another antibody directed against a novel compound, HSG (histamine-succinyl-glycine).

  12. Mechanisms of resistance to HER family targeting antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Kruser, Tim J. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Wheeler, Deric L., E-mail: dlwheeler@wisc.edu [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States)

    2010-04-15

    The epidermal growth factor (EGF) family of receptor tyrosine kinases consists of four members: EGFR (HER1/ErbB1), HER2/neu (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). Receptor activation via ligand binding leads to downstream signaling that influence cell proliferation, angiogenesis, invasion and metastasis. Aberrant expression or activity of EGFR and HER2 have been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer. With this, intense efforts have been made to inhibit the activity of the EGFR and HER2 by designing antibodies against the ligand binding domains (cetuximab, panitumumab and trastuzumab) or small molecules against the tyrosine kinase domains (erlotinib, gefitinib, and lapatinib). Both approaches have shown considerable clinical promise. However, increasing evidence suggests that the majority of patients do not respond to these therapies, and those who show initial response ultimately become refractory to treatment. While mechanisms of resistance to tyrosine kinase inhibitors have been extensively studied, resistance to monoclonal antibodies is less well understood, both in the laboratory and in the clinical setting. In this review, we discuss resistance to antibody-based therapies against the EGFR and HER2, similarities between these resistance profiles, and strategies to overcome resistance to HER family targeting monoclonal antibody therapy.

  13. A single-copy galK promoter cloning vector suitable for cloning strong promoters

    DEFF Research Database (Denmark)

    Dandanell, Gert; Court, Donald L.; Hammer, Karin

    1986-01-01

    We report the construction of lambda galK promoter cloning vectors for cloning and characterization of strong promoters. This phage, which contains a unique HindIII cloning site, was applied to the cloning and analysis of transcription initiations of the regulatory region of the deo-operon of...

  14. Brazilian physical activity guidelines as a strategy for health promotion.

    Science.gov (United States)

    Sebastião, Emerson; Schwingel, Andiara; Chodzko-Zajko, Wojtek

    2014-08-01

    Public health actions endorsed by the federal government, for instance, health promotion initiatives, usually have greater impact at population level compared to other types of initiatives. This commentary aims to instigate debate on the importance and necessity of producing federally endorsed brazilian physical activity guidelines as a strategy for health promotion.

  15. ROLE OF IL-6 IN EXPERIMENTAL ARTHRITIS CAUSED BY TRANSFER OF ARTHRITOGENIC ANTIBODIES

    Directory of Open Access Journals (Sweden)

    M. S. Drutskaya

    2016-01-01

    Full Text Available Interleukin-6 (IL-6 exerts important functions on immune regulation. In case of high expression, IL-6 may promote autoimmune disorders, e.g., arthritis. Systemic IL-6 blockers based on monoclonal antibodies against IL-6, or its specific receptor subunit, are already used in clinical settings, adding to a range of known biological drugs, such as, TNF blockers. Rheumatic disorders and their experimental therapy are reproducible in mice. This study revealed systemically increased levels of IL-6 in developing arthritis caused by transfer of pathogenic antibodies, as well as the effects of IL-6 neutralization by monoclonal antibodies against murine IL-6. Our results suggest a pathogenic role of the two cytokines, TNF and IL-6, in experimental arthritis induced by passive transfer of anti-collagen antibodies.

  16. Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K

    2012-01-01

    The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor...... microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment...... its activity by suppressing stroma cell recruitment to the site of the growing tumor. Our epitope mapping studies suggested that the antibody recognition site overlaps with the target binding interface of human S100A4. We conclude here that this antibody could serve as a solid basis for development...

  17. Health Promotion Education Politics and Schooling: The Greek Case

    Science.gov (United States)

    Ifanti, Amalia A.; Argyriou, Andreas A.; Kalofonos, Haralabos P.

    2011-01-01

    This paper seeks to explore the politics of health promotion as a continual process of public health globally and locally. Our main objective in this study is to present the health promotion education initiatives taken by the World Health Organization (WHO) at an international level and also to examine the politics of health promotion in Greece,…

  18. Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Kazuko Shichijo; Kazuya Makiyama; Chun-Yang Wen; Mutsumi Matsuu; Toshiyuki Nakayama; Masahiro Nakashima; Makoto Ihara; Ichiro Sekine

    2005-01-01

    AIM: To produce an antibody against rat eosinophil cationic protein (ECP) and to examine the effects of the antibody in rats with dextran sulfate sodium (DSS)-induced colitis.METHODS: An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were exarmined histologically and correlated with clinical symptoms.Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation.RESULTS: The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa.Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms (diarrhea and/or blood-stained stool). Body weight gain was significantly greater and the colon length was significantly longer in anti-ECP-treated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor (MIF) in anti-ECP-treated rats.CONCLUSION: Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response,and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis (UC).

  19. Health Promotion in a Military Hospital: Personal Behaviors, Attitudes, Beliefs and Practices of Hospital Nurses

    Science.gov (United States)

    2007-11-02

    Current federal and state reform initiatives address the significant cost savings of prevention and health promotion services and consider these... health promotion services these nurses provide. The purpose of this study is to: (1) examine and describe the personal health promoting lifestyle... promotion activities in professional nursing practice; and (3) examine and describe the professional health promotion practices of nurses within the inpatient

  20. RICE SUCROSE SYNTHASE PROMOTER

    DEFF Research Database (Denmark)

    2000-01-01

    A promoter is described. The promoter comprises a nucleotide sequence corresponding to that shown as SEQ ID No. 1 or a variant, homologue or derivative thereof.......A promoter is described. The promoter comprises a nucleotide sequence corresponding to that shown as SEQ ID No. 1 or a variant, homologue or derivative thereof....

  1. Initiating Teachers' Action Research: Empowering Teachers' Voices

    Science.gov (United States)

    Bognar, Branko

    2013-01-01

    The role of a teacher as an action researcher in Croatia is still insufficiently appreciated and promoted in initial teachers' training, school students learning and in the employed teachers' professional post-qualification development. In this country, teachers are most frequently perceived as mediators or technicians whose task is to prepare and…

  2. Opsonization of Treponema pallidum is mediated by immunoglobulin G antibodies induced only by pathogenic treponemes.

    OpenAIRE

    Shaffer, J. M.; Baker-Zander, S A; Lukehart, S A

    1993-01-01

    Rabbit antisera to Leptospira interrogans, Borrelia hermsii, and Treponema phagedenis biotype Reiter, reactive to shared spirochetal antigens, failed to enhance phagocytosis of Treponema pallidum by macrophages, while immunoglobulin G to Treponema pallidum subsp. pertenue and Treponema paraluiscuniculi promoted phagocytosis. Opsonic antibodies are directed to pathogen-restricted, not shared spirochetal, antigens.

  3. Phenotypic screening: the future of antibody discovery.

    Science.gov (United States)

    Gonzalez-Munoz, Andrea L; Minter, Ralph R; Rust, Steven J

    2016-01-01

    Most antibody therapeutics have been isolated from high throughput target-based screening. However, as the number of validated targets diminishes and the target space becomes increasingly competitive, alternative strategies, such as phenotypic screening, are gaining momentum. Here, we review successful phenotypic screens, including those used to isolate antibodies against cancer and infectious agents. We also consider exciting advances in the expression and phenotypic screening of antibody repertoires in single cell autocrine systems. As technologies continue to develop, we believe that antibody phenotypic screening will increase further in popularity and has the potential to provide the next generation of therapeutic antibodies.

  4. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    their mothers in many studies (e.g., Ashwood & Van deWater, 2004; Jyonouchi et al., 2005; Molloy et al., 2006; Braunschweig et al., 2013). Systemic...against brain and CNS proteins. For example, both abnormalities in serum antibody concentrations and T cells have been reported for ASD compared to...Accomplishments: - Nearly all serum samples have been obtained and processed. - Two unique peptoid libraries have been synthesized and validated. - The peptoid

  5. When "Other" Initiate Repair.

    Science.gov (United States)

    Schegloff, Emanuel A.

    2000-01-01

    Elaborates on the locus of other-initiated repair, and reports on a number of environments in which others initiate repair turns later than the one directly following the trouble-source turn. Describes several ways that other initiation of repair, which occurs in next-turn position, may be delayed within that position. (Author/VWL)

  6. Preparation of thiophilic paramagnetic adsorbent for separation of antibodies

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The micron-sized mierospheres with superparamagnetic property were synthesized with vinyl acetate and divinylbenzene by microsuspension polymerization. After the complete alcoholysis, these hydroxyl-functionalized microspheres were activated by divinylfone and modified with mercaptoethanol to prepare the thiophilic magnetic adsorbent, which was used to specifically isolate immunoglobulin G (IgG) from human serum. This thiophilic magnetic adsorbent performed an evident salt-dependent adsorption behavior for IgG. Due to their salt-promoted adsorption towards IgG under high salt concentration, the absorbed antibodies could be extracted in low salt concentration with high purity.

  7. Broadly Neutralizing Antibodies for HIV Eradication.

    Science.gov (United States)

    Stephenson, Kathryn E; Barouch, Dan H

    2016-02-01

    Passive transfer of antibodies has long been considered a potential treatment modality for infectious diseases, including HIV. Early efforts to use antibodies to suppress HIV replication, however, were largely unsuccessful, as the antibodies that were studied neutralized only a relatively narrow spectrum of viral strains and were not very potent. Recent advances have led to the discovery of a large portfolio of human monoclonal antibodies that are broadly neutralizing across many HIV-1 subtypes and are also substantially more potent. These antibodies target multiple different epitopes on the HIV envelope, thus allowing for the development of antibody combinations. In this review, we discuss the application of broadly neutralizing antibodies (bNAbs) for HIV treatment and HIV eradication strategies. We highlight bNAbs that target key epitopes, such as the CD4 binding site and the V2/V3-glycan-dependent sites, and we discuss several bNAbs that are currently in the clinical development pipeline.

  8. 9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Erysipelothrix Rhusiopathiae Antibody... REQUIREMENTS Antibody Products § 113.452 Erysipelothrix Rhusiopathiae Antibody. Erysipelothrix Rhusiopathiae Antibody is a specific antibody product containing antibodies directed against one or more somatic...

  9. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies

    Science.gov (United States)

    Cheeseman, Hannah M.; Olejniczak, Natalia J.; Rogers, Paul M.; Evans, Abbey B.; King, Deborah F. L.; Ziprin, Paul; Liao, Hua-Xin; Haynes, Barton F.

    2016-01-01

    ABSTRACT Definition of the key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue may prove critical to effective vaccine development and the prophylactic use of monoclonal antibodies. Although direct antibody-mediated neutralization is highly effective against cell-free virus, antibodies targeting different sites of envelope vulnerability may display differential activity against mucosal infection. Nonneutralizing antibodies (nnAbs) may also impact mucosal transmission events through Fc-gamma receptor (FcγR)-mediated inhibition. In this study, a panel of broadly neutralizing antibodies (bnAbs) and nnAbs, including those associated with protection in the RV144 vaccine trial, were screened for the ability to block HIV-1 acquisition and replication across a range of cellular and mucosal tissue models. Neutralization potency, as determined by the TZM-bl infection assay, did not fully predict activity in mucosal tissue. CD4-binding site (CD4bs)-specific bnAbs, in particular VRC01, were consistent in blocking HIV-1 infection across all cellular and tissue models. Membrane-proximal external region (MPER) (2F5) and outer domain glycan (2G12) bnAbs were also efficient in preventing infection of mucosal tissues, while the protective efficacy of bnAbs targeting V1-V2 glycans (PG9 and PG16) was more variable. In contrast, nnAbs alone and in combinations, while active in a range of cellular assays, were poorly protective against HIV-1 infection of mucosal tissues. These data suggest that tissue resident effector cell numbers and low FcγR expression may limit the potential of nnAbs to prevent establishment of the initial foci of infection. The solid protection provided by specific bnAbs clearly demonstrates their superior potential over that of nonneutralizing antibodies for preventing HIV-1 infection at the mucosal portals of infection. IMPORTANCE Key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal

  10. Advances in monoclonal antibody application in myocarditis

    Institute of Scientific and Technical Information of China (English)

    Li-na HAN; Shuang HE; Yu-tang WANG; Li-ming YANG; Si-yu LIU; Ting ZHANG

    2013-01-01

    Monoclonal antibodies have become a part of daily preparation technologies in many laboratories.Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases,inflammatory diseases,cancer,and other immune-associated diseases.This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis,an inflammatory disease of the heart,could be a novel approach in the future.In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis,we,through a significant amount of literature research both domestic and abroad,developed a systematic elaboration of monoclonal antibodies,pathogenesis of myocarditis,and application of monoclonal antibodies in myocarditis.This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future.Under conventional therapy,myocarditis is typically associated with congestive heart failure as a progressive outcome,indicating the need for alternative therapeutic strategies to improve long-term results.Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis,we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above.However,several issues remain.The technology on howto make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues.If we are to further stimulate

  11. How have health promotion frameworks considered gender?

    Science.gov (United States)

    Gelb, Karen; Pederson, Ann; Greaves, Lorraine

    2012-12-01

    This paper provides an overview of five key internationally recognized health promotion frameworks and assesses their consideration of gender. This analysis was conducted as part of the Promoting Health in Women project, a Canadian initiative focused on generating a framework for effective health promotion for women. To date, no review of health promotion frameworks has specifically focused on assessing the treatment of gender. This analysis draws on a comprehensive literature review that covered available literature on gender and health promotion frameworks published internationally between 1974 and 2010. Analysis of five key health promotion frameworks revealed that although gender was at times mentioned as a determinant of health, gender was never identified and integrated as a factor critical to successful health promotion. This superficial attention to the role of gender in health promotion is problematic as it limits our capacity to understand how gender influences health, health contexts and health promotion, as well as our ability to integrate gender into future comprehensive health promotion strategies.

  12. HNF-4α regulates expression of human ornithin carbamoyltransferase through interaction with two positive cis-acting regulatory elements located in the proximal promoter.

    Science.gov (United States)

    Lukšan, O; Dvořáková, L; Jirsa, M

    2014-01-01

    OTC encodes ornithine carbamoyltransferase, mitochondrial matrix enzyme involved in the synthesis of urea. The tissue-specific expression of OTC in the liver and intestine is dependent on the interaction of OTC promoter with an upstream enhancer. HNF-4 and C/EBPβ are crucial for this interaction in the rat and mouse. In the present study we focused on characterization of elements involved in the regulation of OTC transcription in human. Using a set of 5'-deleted promoter mutants in a reporter assay we identified two positive cis-acting regulatory elements located at c.-105 and c.-136 within the human OTC promoter. Both are essential for the transcriptional activity of the promoter itself and for the interaction with the enhancer. Protein binding at the corresponding sites was confirmed by DNase I footprinting. Electromobility shift assay with a specific competitor and anti-HNF-4α antibody identified the DNA-protein binding sites as HNF-4α recognition motifs. A third HNF-4α binding site has been found at the position c.-187. All three HNF-4α binding sites are located within 35 bp upstream of the transcription start sites at positions c.-95, c.-119 (major) and c.-169 (minor). A series of C/EBPβ recognition motifs was identified within the enhancer. Involvement of C/EBPβ and HNF-4α in the promoter-enhancer interaction is further supported by a massive DNAprotein interaction observed in the footprinting and EMSA assays. Since the OTC promoter lacks general core promoter elements such as TATA-box or initiators in standard positions, HNF-4α most likely plays an essential role in the initiation of OTC transcription in human.

  13. Monoclonal antibodies to intermediate filament proteins of human cells: unique and cross-reacting antibodies.

    Science.gov (United States)

    Gown, A M; Vogel, A M

    1982-11-01

    Monoclonal antibodies were generated against the intermediate filament proteins of different human cells. The reactivity of these antibodies with the different classes of intermediate filament proteins was determined by indirect immunofluorescence on cultured cells, immunologic indentification on SDS polyacrylamide gels ("wester blot" experiments), and immunoperoxidase assays on intact tissues. The following four antibodies are described: (a) an antivimentin antibody generated against human fibroblast cytoskeleton; (b), (c) two antibodies that recognize a 54-kdalton protein in human hepatocellular carcinoma cells; and (d) an antikeratin antibody made to stratum corneum that recognizes proteins of molecular weight 66 kdaltons and 57 kdaltons. The antivimentin antibody reacts with vimentin (58 kdaltons), glial fibrillary acidic protein (GFAP), and keratins from stratum corneum, but does not recognize hepatoma intermediate filaments. In immunofluorescence assays, the antibody reacts with mesenchymal cells and cultured epithelial cells that express vimentin. This antibody decorates the media of blood vessels in tissue sections. One antihepatoma filament antibody reacts only with the 54 kdalton protein of these cells and, in immunofluorescence and immunoperoxidase assays, only recognizes epithelial cells. It reacts with almost all nonsquamous epithelium. The other antihepatoma filament antibody is much less selective, reacting with vimentin, GFAP, and keratin from stratum corneum. This antibody decorates intermediate filaments of both mesenchymal and epithelial cells. The antikeratin antibody recognizes 66-kdalton and 57-kdalton proteins in extracts of stratum corneum and also identifies proteins of similar molecular weights in all cells tested. However, by immunofluorescence, this antibody decorates only the intermediate filaments of epidermoid carcinoma cells. When assayed on tissue sections, the antibody reacts with squamous epithelium and some, but not all

  14. Affinity enhancement of antibodies: how low-affinity antibodies produced early in immune responses are followed by high-affinity antibodies later and in memory B-cell responses.

    Science.gov (United States)

    Eisen, Herman N

    2014-05-01

    The antibodies produced initially in response to most antigens are high molecular weight (MW) immunoglobulins (IgM) with low affinity for the antigen, while the antibodies produced later are lower MW classes (e.g., IgG and IgA) with, on average, orders of magnitude higher affinity for that antigen. These changes, often termed affinity maturation, take place largely in small B-cell clusters (germinal center; GC) in lymphoid tissues in which proliferating antigen-stimulated B cells express the highly mutagenic cytidine deaminase that mediates immunoglobulin class-switching and sequence diversification of the immunoglobulin variable domains of antigen-binding receptors on B cells (BCR). Of the large library of BCR-mutated B cells thus rapidly generated, a small minority with affinity-enhancing mutations are selected to survive and differentiate into long-lived antibody-secreting plasma cells and memory B cells. BCRs are also endocytic receptors; they internalize and cleave BCR-bound antigen, yielding peptide-MHC complexes that are recognized by follicular helper T cells. Imperfect correlation between BCR affinity for antigen and cognate T-cell engagement may account for the increasing affinity heterogeneity that accompanies the increasing average affinity of antibodies. Conservation of mechanisms underlying mutation and selection of high-affinity antibodies over the ≈200 million years of evolution separating bird and mammal lineages points to the crucial role of antibody affinity enhancement in adaptive immunity.

  15. A robust robotic high-throughput antibody purification platform.

    Science.gov (United States)

    Schmidt, Peter M; Abdo, Michael; Butcher, Rebecca E; Yap, Min-Yin; Scotney, Pierre D; Ramunno, Melanie L; Martin-Roussety, Genevieve; Owczarek, Catherine; Hardy, Matthew P; Chen, Chao-Guang; Fabri, Louis J

    2016-07-15

    Monoclonal antibodies (mAbs) have become the fastest growing segment in the drug market with annual sales of more than 40 billion US$ in 2013. The selection of lead candidate molecules involves the generation of large repertoires of antibodies from which to choose a final therapeutic candidate. Improvements in the ability to rapidly produce and purify many antibodies in sufficient quantities reduces the lead time for selection which ultimately impacts on the speed with which an antibody may transition through the research stage and into product development. Miniaturization and automation of chromatography using micro columns (RoboColumns(®) from Atoll GmbH) coupled to an automated liquid handling instrument (ALH; Freedom EVO(®) from Tecan) has been a successful approach to establish high throughput process development platforms. Recent advances in transient gene expression (TGE) using the high-titre Expi293F™ system have enabled recombinant mAb titres of greater than 500mg/L. These relatively high protein titres reduce the volume required to generate several milligrams of individual antibodies for initial biochemical and biological downstream assays, making TGE in the Expi293F™ system ideally suited to high throughput chromatography on an ALH. The present publication describes a novel platform for purifying Expi293F™-expressed recombinant mAbs directly from cell-free culture supernatant on a Perkin Elmer JANUS-VariSpan ALH equipped with a plate shuttle device. The purification platform allows automated 2-step purification (Protein A-desalting/size exclusion chromatography) of several hundred mAbs per week. The new robotic method can purify mAbs with high recovery (>90%) at sub-milligram level with yields of up to 2mg from 4mL of cell-free culture supernatant.

  16. Generation of monospecific antibodies based on affinity capture of polyclonal antibodies.

    Science.gov (United States)

    Hjelm, Barbara; Forsström, Björn; Igel, Ulrika; Johannesson, Henrik; Stadler, Charlotte; Lundberg, Emma; Ponten, Fredrik; Sjöberg, Anna; Rockberg, Johan; Schwenk, Jochen M; Nilsson, Peter; Johansson, Christine; Uhlén, Mathias

    2011-11-01

    A method is described to generate and validate antibodies based on mapping the linear epitopes of a polyclonal antibody followed by sequential epitope-specific capture using synthetic peptides. Polyclonal antibodies directed towards four proteins RBM3, SATB2, ANLN, and CNDP1, potentially involved in human cancers, were selected and antibodies to several non-overlapping epitopes were generated and subsequently validated by Western blot, immunohistochemistry, and immunofluorescence. For all four proteins, a dramatic difference in functionality could be observed for these monospecific antibodies directed to the different epitopes. In each case, at least one antibody was obtained with full functionality across all applications, while other epitope-specific fractions showed no or little functionality. These results present a path forward to use the mapped binding sites of polyclonal antibodies to generate epitope-specific antibodies, providing an attractive approach for large-scale efforts to characterize the human proteome by antibodies.

  17. Low prevalence of antibodies and other plasma factors binding to CC chemokines and IL-2 in HIV-positive patients

    DEFF Research Database (Denmark)

    Meyer, C N; Svenson, M; Larsen, Carsten Schade;

    2000-01-01

    Neutralizing cytokine antibodies are found in healthy and diseased individuals, including patients treated with recombinant cytokines. Identification of CCR-5 as co-receptor for HIV has focused interest on CC chemokines and their potential therapeutic use. Chemokine-binding components in plasma...... of HIV-infected patients were therefore assessed by radioimmunoassay and radioreceptor assay. IgG from 4/505 HIV patients and 9/2000 healthy controls (p>0.05) bound rMIP-1alpha and rMIP-1beta, but not rRANTES. No other plasma factors bound the chemokines. The antibodies inhibited receptor binding of both...... chemokines. There was no association between presence of antibodies and disease stage or HIV progression rate. Three of 11 patients treated with rIL-2 developed IgG antibodies suppressing cellular binding and growth promotion of rIL-2. Hence, circulating factors, including antibodies MIP-1alpha/MIP-1beta...

  18. WSSV ie1 promoter is more efficient than CMV promoter to express H5 hemagglutinin from influenza virus in baculovirus as a chicken vaccine

    Directory of Open Access Journals (Sweden)

    Yu Li

    2008-12-01

    Full Text Available Abstract Background The worldwide outbreak of influenza A (H5N1 viruses among poultry species and humans highlighted the need to develop efficacious and safe vaccines based on efficient and scaleable production. Results White spot syndrome virus (WSSV immediate-early promoter one (ie1 was shown to be a stronger promoter for gene expression in insect cells compared with Cytomegalovirus immediate-early (CMV promoter in luciferase assays. In an attempt to improve expression efficiency, a recombinant baculovirus was constructed expressing hemagglutinin (HA of H5N1 influenza virus under the control of WSSV ie1 promoter. HA expression in SF9 cells increased significantly with baculovirus under WSSV ie1 promoter, compared with CMV promoter based on HA contents and hemagglutination activity. Further, immunization with baculovirus under WSSV ie1 promoter in chickens elicited higher level anti-HA antibodies compared to CMV promoter, as indicated in hemagglutination inhibition, virus neutralization and enzyme-linked immunosorbent assays. By immunohistochemistry, strong HA antigen expression was observed in different chicken organs with vaccination of WSSV ie1 promoter controlled baculovirus, confirming higher efficiency in HA expression by WSSV ie1 promoter. Conclusion The production of H5 HA by baculovirus was enhanced with WSSV ie1 promoter, especially compared with CMV promoter. This contributed to effective elicitation of HA-specific antibody in vaccinated chickens. This study provides an alternative choice for baculovirus based vaccine production.

  19. Structural basis for quinine-dependent antibody binding to platelet integrin αIIbβ3.

    Science.gov (United States)

    Zhu, Jianghai; Zhu, Jieqing; Bougie, Daniel W; Aster, Richard H; Springer, Timothy A

    2015-10-29

    Drug-induced immune thrombocytopenia (DITP) is caused by antibodies that react with specific platelet-membrane glycoproteins when the provoking drug is present. More than 100 drugs have been implicated as triggers for this condition, quinine being one of the most common. The cause of DITP in most cases appears to be a drug-induced antibody that binds to a platelet membrane glycoprotein only when the drug is present. How a soluble drug promotes binding of an otherwise nonreactive immunoglobulin to its target, leading to platelet destruction, is uncertain, in part because of the difficulties of working with polyclonal human antibodies usually available only in small quantities. Recently, quinine-dependent murine monoclonal antibodies were developed that recognize a defined epitope on the β-propeller domain of the platelet integrin αIIb subunit (GPIIb) only when the drug is present and closely mimic the behavior of antibodies found in human patients with quinine-induced thrombocytopenia in vitro and in vivo. Here, we demonstrate specific, high-affinity binding of quinine to the complementarity-determining regions (CDRs) of these antibodies and define in crystal structures the changes induced in the CDR by this interaction. Because no detectable binding of quinine to the target integrin could be demonstrated in previous studies, the findings indicate that a hybrid paratope consisting of quinine and reconfigured antibody CDR plays a critical role in recognition of its target epitope by an antibody and suggest that, in this type of drug-induced immunologic injury, the primary reaction involves binding of the drug to antibody CDRs, causing it to acquire specificity for a site on a platelet integrin.

  20. Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay

    Directory of Open Access Journals (Sweden)

    Mason Helen D

    2005-09-01

    Full Text Available Abstract Background We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF. Methods A synthetic single-chain antibody (Tomlinson J phage display library was bio-panned with partially purified GnSAF produced by cultured human granulosa/luteal cells. The initial screening with a simple binding immunoassay resulted in 8 clones that were further screened using our in-vitro rat monolayer bioassay for GnSAF. Initially the antibodies were screened as pooled phage forms and subsequently as individual, soluble, single-chain antibody (scAbs forms. Then, in order to improve the stability of the scAbs for immunopurification purposes, and to widen the range of labelled secondary antibodies available, these were engineered into full-length human immunoglobulins. The immunoglobulin with the highest affinity for GnSAF and a previously described rat anti-GnSAF polyclonal antiserum was then used to immunopurify bioactive GnSAF protein. The two purified preparations were electrophoresed on 1-D gels and on 7 cm 2-D gels (pH 4–7. The candidate GnSAF protein bands and spots were then excised for peptide mass mapping. Results Three of the scAbs recognised GnSAF bioactivity and subsequently one clone of the purified scAb-derived immunoglobulin demonstrated high affinity for GnSAF bioactivity, also binding the molecule in such as way as to block its bioactivity. When used for repeated immunopurification cycles and then Western blot, this antibody enabled the isolation of a GnSAF-bioactive protein band at around 66 kDa. Similar results were achieved using the rat anti-GnSAF polyclonal antiserum. The main candidate molecules identified from the immunopurified material by excision of 2-D gel protein spots was human serum albumin precursor and variants. Conclusion This study demonstrates that the combination of

  1. An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre.

    Science.gov (United States)

    Huda, S; Wong, S H; Pettingill, P; O'Connell, D; Vincent, A; Steiger, M

    2015-02-01

    Acquired diseases classically associated with VGKC-complex antibodies include peripheral nerve hyperexcitability (PNH), Morvan's syndrome, limbic encephalitis (LE), and epilepsy. However, not all such patients have VGKC-complex antibodies and antibodies have been reported in patients without a defined immune-mediated syndrome. To analyse the clinical relevance of positive VGKC-complex antibodies requested on the basis of initial clinical suspicion. We retrospectively analysed patients with positive VGKC-complex antibodies (>100 pM) referred to our institution between 2001 and 2011. 1,614 VGKC-complex assays were performed in 1,298 patients. Titres >100 pM were detected in 57/1,298 (4 %) patients. A classic VGKC-complex channelopathy (60 %) was associated with VGKC-complex antibody titres >400 pM (p = 0.0004). LGI1 or CASPR2 antibodies were only detected in classic VGKC-complex channelopathies (LE; n = 3/4 and PNH; n = 1/5). VGKC-complex antibody titres VGKC-complex antibodies was higher than the age-matched national incidence of malignancy (OR 19.9, 95 % CI 8.97-44.0 p400 pM can help determine VGKC-complex antibody relevance. Antibody titres <400 pM are associated with PNH but also a more heterogeneous clinical spectrum. The antibody association in the latter is of doubtful clinical relevance. The rate of malignancy was significantly higher than the national incidence irrespective of titre.

  2. Surface activity of a monoclonal antibody.

    Science.gov (United States)

    Mahler, Hanns-Christian; Senner, Frank; Maeder, Karsten; Mueller, Robert

    2009-12-01

    The development of high concentration antibody formulations presents a major challenge for the formulation scientist, as physical characteristics and stability behavior change compared to low concentration protein formulations. The aim of this study was to investigate the potential correlation between surface activity and shaking stress stability of a model antibody-polysorbate 20 formulation. The surface activities of pure antibody and polysorbate 20 were compared, followed by a study on the influence of a model antibody on the apparent critical micelle concentration (CMC) of polysorbate 20 over a protein concentration range from 10 to 150 mg/mL. In a shaking stress experiment, the stability of 10, 75, and 150 mg/mL antibody formulations was investigated containing different concentrations of polysorbate 20, both below and above the CMC. The antibody increased significantly the apparent CMC of antibody-polysorbate 20 mixtures in comparison to the protein-free buffer. However, the concentration of polysorbate required for stabilization of the model antibody in a shaking stress experiment did not show dependence on the CMC. A polysorbate 20 level of 0.005% was found sufficient to stabilize both at low and high antibody concentration against antibody aggregation and precipitation.

  3. Are Onconeural Antibodies a Clinical Phenomenology in Paraneoplastic Limbic Encephalitis?

    Directory of Open Access Journals (Sweden)

    Hongliang Zhang

    2013-01-01

    Full Text Available Paraneoplastic neurological syndromes (PNSs occur in patients with cancer and can cause clinical symptoms and signs of dysfunction of the nervous system that are not due to a local effect of the tumor or its metastases. Most of these clinical syndromes in adults are associated with lung cancer, especially small cell lung cancer (SCLC, lymphoma, and gynecological tumors. The finding of highly specific antibodies directed against onconeural antigens has revolutionized the diagnosis and promoted the understanding of these syndromes and led to the current hypothesis of an autoimmune pathophysiology. Accumulating data strongly suggested direct pathogenicity of these antibodies. The field of PNS has expanded rapidly in the past few years with the discovery of limbic encephalitis associated with glutamic acid decarboxylase (GAD 65, the voltage (VGKC-gated potassium channel complex, the methyl (N-NMDA-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, and gamma aminobutyric acid (GABA (B receptors, and so forth. Despite this, the clinical spectrum of these diseases has not yet been fully investigated. The clinical importance of these conditions lies in their frequent response to immunotherapies and, less commonly, their association with distinctive tumors. This review provides an overview on the pathogenesis and diagnosis of PNS, with emphasis on the role of antibodies in limbic encephalitis.

  4. Fayette County Better Buildings Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Capella, Arthur [County of Fayette, Uniontown, PA (United States)

    2015-03-04

    The Fayette County Better Buildings Initiative represented a comprehensive and collaborative approach to promoting and implementing energy efficiency improvements. The initiative was designed to focus on implementing energy efficiency improvements in residential units, while simultaneously supporting general marketing of the benefits of implementing energy efficiency measures. The ultimate goal of Fayette County’s Better Buildings Initiative was to implement a total of 1,067 residential energy efficiency retrofits with a minimum 15% estimated energy efficiency savings per unit. Program partners included: United States Department of Energy, Allegheny Power, and Private Industry Council of Westmoreland-Fayette, Fayette County Redevelopment Authority, and various local partners. The program was open to any Fayette County residents who own their home and meet the prequalifying conditions. The level of assistance offered depended upon household income and commitment to undergo a BPI – Certified Audit and implement energy efficiency measures, which aimed to result in at least a 15% reduction in energy usage. The initiative was designed to focus on implementing energy efficiency improvements in residential units, while simultaneously supporting general marketing of the benefits of implementing energy efficiency measures. Additionally, the program had components that involved recruitment and training for employment of persons in the energy sector (green jobs), as well as marketing and implementation of a commercial or community facilities component. The residential component of Fayette County’s Better Buildings Initiative involved a comprehensive approach, providing assistance to low- moderate- and market-rate homeowners. The initiative will also coordinate activities with local utility providers to further incentivize energy efficiency improvements among qualifying homeowners. The commercial component of Fayette County’s Better Building Initiative involved grants

  5. Interaction of the transcription start site core region and transcription factor YY1 determine ascorbate transporter SVCT2 exon 1a promoter activity.

    Directory of Open Access Journals (Sweden)

    Huan Qiao

    Full Text Available Transcription of the ascorbate transporter, SVCT2, is driven by two distinct promoters in exon 1 of the transporter sequence. The exon 1a promoter lacks a classical transcription start site and little is known about regulation of promoter activity in the transcription start site core (TSSC region. Here we present evidence that the TSSC binds the multifunctional initiator-binding protein YY1. Electrophoresis shift assays using YY1 antibody showed that YY1 is present as one of two major complexes that specifically bind to the TSSC. The other complex contains the transcription factor NF-Y. Mutations in the TSSC that decreased YY1 binding also impaired the exon 1a promoter activity despite the presence of an upstream activating NF-Y/USF complex, suggesting that YY1 is involved in the regulation of the exon 1a transcription. Furthermore, YY1 interaction with NF-Y and/or USF synergistically enhanced the exon 1a promoter activity in transient transfections and co-activator p300 enhanced their synergistic activation. We propose that the TSSC plays a vital role in the exon 1a transcription and that this function is partially carried out by the transcription factor YY1. Moreover, co-activator p300 might be able to synergistically enhance the TSSC function via a "bridge" mechanism with upstream sequences.

  6. [Liver diseases with microsomal antibodies. Frequency, clinical and immunological findings and course observations (author's transl)].

    Science.gov (United States)

    Schmidt, G; Kienle, J; Schmidt, D S; Wolf, H

    1978-08-01

    Microsomal antibodies (LKM-antibodies) differ in the indirect immunfluorescence by use of rat organ sections (kidney, stomach, and liver) from mitochondrial antibodies by there reaction with proximal renal tubules and hepatocytes while parietal cells usually fail to stain. In contrast to other humoral autoantibodies LKM-antibodies are rare. In a prospective study on 930 adults and 33 children with two third chronic hepatitis resp. cirrhosis frequency in the first group amounts to 0.38% and in the latter to 6.9% of all liver diseases. Among six patients with LKW-antibodies and chronic active hepatitis there were three children aged 4-13 and three adults between 45-55 years. On common results two children showed beside LKM-antibodies by absence of other immunphenomenons a rise of gamma-globulins in the electrophoresis and immunglobulin G as well as a chronic active hepatitis with necrosis leading in spite of initial rapid progression and persistent antibodies into inactive postnecrotiv cirrhosis. The other four patients showed no common course in respect to clinical, histological and immunological findings.

  7. Anti-DNA antibodies cross-react with C1q.

    Science.gov (United States)

    Franchin, Giovanni; Son, Myoungsun; Kim, Sun Jung; Ben-Zvi, Ilan; Zhang, Jie; Diamond, Betty

    2013-08-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder that involves multiple organ systems and typically presents as a chronic inflammatory disease. Antibodies to double-stranded (ds) DNA are present in approximately 70% of patients and form nucleic acid containing immune complexes which activate dendritic cells through engagement of toll-like receptors, leading to a pro-inflammatory, pro-immunogenic milieu. In addition, anti-dsDNA antibodies deposit in kidneys to initiate glomerulonephritis. Antibodies to C1q have also been implicated in lupus nephritis and are found in 30-50% of patients. C1q is a known suppressor of immune activation and C1q deficiency is the strongest risk factor for SLE. We previously identified a subset of anti-DNA antibodies that binds the N-methyl-D-aspartate receptor. We now show that both mouse and human anti-DNA antibodies with this specificity bind C1q. These antibodies bind to Clq in glomeruli and exhibit decreased glomerular deposition in the absence of C1q. We propose that this subset of anti-DNA antibodies participates in lupus pathogenesis through direct targeting of C1q on glomeruli and also through removal of soluble C1q thereby limiting the ability of C1q to mediate immune homeostasis.

  8. Preparation and characterization of polyclonal antibody against Kaposi's sarcoma-associated herpesvirus lytic gene encoding RTA.

    Science.gov (United States)

    Fan, Weifei; Tang, Qiao; Shen, Chenyou; Qin, Di; Lu, Chun; Yan, Qin

    2015-11-01

    Replication and transcription activator (RTA) is a critical lytic protein encoded by Kaposi's sarcoma-associated herpesvirus (KSHV). To prepare rabbit polyclonal antibody against RTA, three antigenic polypeptides of KSHV RTA were initially synthesized. The fragment of RTA was cloned into p3FlagBsd to construct the recombinant plasmid, pRTA-Flag. 293 T and EA.hy926 cells were transfected with pRTA-Flag to obtain RTA-Flag fusion protein, which was detected using anti-Flag antibody. Next, New Zealand white rabbits were immunized with keyhole limpet hemocyanin-conjugated peptides to generate polyclonal antibodies against RTA. Enzyme-linked immunosorbent assays were performed to characterize the polyclonal antibodies, and the titers of the polyclonal antibodies against RTA were greater than 1:11,000. Western blotting and immunofluorescence assay revealed that the prepared antibody reacted specifically with the RTA-Flag fusion protein as well as the native viral protein in KSHV-infected primary effusion lymphoma cells. Collectively, our work successfully constructed the recombinant expression vector, pRTA-Flag, and prepared the polyclonal antibody against RTA, which was valuable for investigating the biochemical and biological functions of the critical KSHV lytic gene.

  9. Sustainable Agricultural Marketing Initiatives

    OpenAIRE

    Hakan Adanacıoğlu

    2015-01-01

    Sustainable marketing is a holistic approach that puts equal emphasis on environmental, social equity, and economic concerns in the development of marketing strategies. The purpose of the study is to examine and discuss the sustainable agricultural marketing initiatives practiced throughout the World and Turkey, and to put forth suggestions to further improve the performance of agricultural marketing initiatives in Turkey. Some of the sustainable agricultural marketing initiatives practiced a...

  10. Health Promotion at the Ballpark.

    Science.gov (United States)

    Hodges, Bonni C

    2017-03-01

    The arrival of a new summer collegiate baseball league franchise to a small central New York city was seen as an opportunity for health promotion. The initiative was set up to explore two overarching questions: (1) Are summer collegiate baseball events acceptable to local public health organizations as viable places for health promotion activities addressing local health issues? (2) Are summer collegiate baseball organizations amenable to health promotion activities built in to their fan and/or player experiences? Planning and implementation were guided by precede-proceed, social cognitive theory, social marketing, and diffusion of innovations constructs. Environmental changes were implemented to support healthy eating and nontobacco use by players and fans; four health awareness nights were implemented at home games corresponding to local public health priorities and included public service announcements, between inning quizzes, information dissemination at concession and team market locations, and special guests. Sales and fan feedback support mostly healthy concession offerings and a tobacco-free ballpark; postseason evaluations from team staff and public health partners support continuing the trials of this sports event as a venue for health promotion.

  11. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tongqing; Georgiev, Ivelin; Wu, Xueling; Yang, Zhi-Yong; Dai, Kaifan; Finzi, Andrés; Kwon, Young Do; Scheid, Johannes F.; Shi, Wei; Xu, Ling; Yang, Yongping; Zhu, Jiang; Nussenzweig, Michel C.; Sodroski, Joseph; Shapiro, Lawrence; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D. (NIH); (Rockefeller); (DFCI)

    2010-08-26

    During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.

  12. Belgian recommendations on ANA, anti-dsDNA and anti-ENA antibody testing.

    Science.gov (United States)

    Van Blerk, M; Bossuyt, X; Humbel, R; Mewis, A; Servais, G; Tomasi, J P; Van Campenhout, C; Van Hoovels, L; Vercammen, M; Damoiseaux, J; Coucke, W; Van de Walle, P

    2014-04-01

    Autoantibodies to nuclear antigens, i.e. antinuclear antibodies (ANA), antibodies to double-stranded DNA (dsDNA) and extractable nuclear antigens (ENA), are useful as diagnostic markers for a variety of autoimmune diseases. In March 2010, the Belgian national External Quality Assessment Scheme sent a questionnaire on ANA, anti-dsDNA and anti-ENA antibody testing designed by the Dutch EASI (European Autoimmunity Standardization Initiative) team, to all clinical laboratories performing ANA testing. Virtually all laboratories completed the questionnaire (97·7%, 127/130). This paper discusses the results of this questionnaire and provides valuable information on the state-of-the-art of ANA, anti-dsDNA and anti-ENA antibody testing as practiced in the Belgian laboratories. In addition, this work presents practical recommendations developed by the members of the advisory board of the scheme as a result of the outcome of this study.

  13. Emerging Pathogens Initiative (EPI)

    Data.gov (United States)

    Department of Veterans Affairs — The Emerging Pathogens Initiative (EPI) database contains emerging pathogens information from the local Veterans Affairs Medical Centers (VAMCs). The EPI software...

  14. Sustainable Forest Bioenergy Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Breger, Dwayne; Rizzo, Rob

    2011-09-20

    associated with biomass usage, an understanding of forest management trends including harvesting and fuel processing methods, and the carbon profile of utilizing forest based woody biomass for the emerging biomass markets. Each of the tasks and subtasks have provided an increased level of understanding to support new directives, policies and adaptation of existing regulations within Massachusetts. The project has provided the essential information to allow state policymakers and regulators to address emerging markets, while ensuring forest sustainability and understanding the complex science on CO2 accounting and impacts as a result of biomass harvesting for power generation. The public at large and electricity ratepayers in Massachusetts will all benefit from the information garnered through this project. This is a result of the state’s interest to provide financial incentives to only biomass projects that demonstrate an acceptable carbon profile, an efficient use of the constrained supply of fuel, and the harvest of biomass to ensure forest sustainability. The goals of the Massachusetts Sustainable Forest Bioenergy Initiative as proposed in 2006 were identified as: increase the diversity of the Massachusetts energy mix through biomass; promote economic development in the rural economy through forest industry job creation; help fulfill the state’s energy and climate commitments under the Renewable Energy Portfolio Standard and Climate Protection Plan; assist the development of a biomass fuel supply infrastructure to support energy project demands; provide education and outreach to the public on the benefits and impacts of bioenergy; improve the theory and practice of sustainable forestry in the Commonwealth. Completed project activities summarized below will demonstrate the effectiveness of the project in meeting the above goals. In addition, as discussed above, Massachusetts DOER needed to make some modifications to its work plan and objectives during the term of this

  15. Controlled delivery of antibodies from injectable hydrogels.

    Science.gov (United States)

    Fletcher, Nathan A; Babcock, Lyndsey R; Murray, Ellen A; Krebs, Melissa D

    2016-02-01

    Therapeutic antibodies are currently used for the treatment of various diseases, but large doses delivered systemically are typically required. Localized controlled delivery techniques would afford major benefits such as decreasing side effects and required doses. Injectable biopolymer systems are an attractive solution due to their minimally invasive potential for controlled release in a localized area. Here, alginate-chitosan hydrogels are demonstrated to provide controlled delivery of IgG model antibodies and also of Fab antibody fragments. Also, an alternate delivery system comprised of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with antibodies and encapsulated in alginate was shown to successfully provide another level of control over release. These biopolymer systems that offer controlled delivery for antibodies and antibody fragments will be promising for many applications in drug delivery and regenerative medicine.

  16. 7 CFR 1219.32 - Initial nomination and appointment of importer members and alternates.

    Science.gov (United States)

    2010-01-01

    ...), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order The Hass Avocado Board § 1219.32 Initial nomination and appointment of...

  17. 7 CFR 1219.31 - Initial nomination and appointment of producer members and alternates.

    Science.gov (United States)

    2010-01-01

    ...), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order The Hass Avocado Board § 1219.31 Initial nomination and appointment of...

  18. Promoting preschool reading

    OpenAIRE

    2013-01-01

    The thesis titled Promoting preschool reading consists of a theoretiral and an empirical part. In the theoretical part I wrote about reading, the importance of reading, types of reading, about reading motivation, promoting reading motivation, internal and external motivation, influence of reading motivation on the child's reading activity, reading and familial literacy, the role of adults in promotion reading literacy, reading to a child and promoting reading in pre-school years, where I ...

  19. Epithelial nuclear factor-κB signaling promotes lung carcinogenesis via recruitment of regulatory T lymphocytes.

    Science.gov (United States)

    Zaynagetdinov, R; Stathopoulos, G T; Sherrill, T P; Cheng, D-S; McLoed, A G; Ausborn, J A; Polosukhin, V V; Connelly, L; Zhou, W; Fingleton, B; Peebles, R S; Prince, L S; Yull, F E; Blackwell, T S

    2012-06-28

    The mechanisms by which chronic inflammatory lung diseases, particularly chronic obstructive pulmonary disease, confer enhanced risk for lung cancer are not well-defined. To investigate whether nuclear factor (NF)-κB, a key mediator of immune and inflammatory responses, provides an interface between persistent lung inflammation and carcinogenesis, we utilized tetracycline-inducible transgenic mice expressing constitutively active IκB kinase β in airway epithelium (IKTA (IKKβ trans-activated) mice). Intraperitoneal injection of ethyl carbamate (urethane), or 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) was used to induce lung tumorigenesis. Doxycycline-treated IKTA mice developed chronic airway inflammation and markedly increased numbers of lung tumors in response to urethane, even when transgene expression (and therefore epithelial NF-κB activation) was begun after exposure to carcinogen. Studies using a separate tumor initiator/promoter model (MCA+BHT) indicated that NF-κB functions as an independent tumor promoter. Enhanced tumor formation in IKTA mice was preceded by increased proliferation and reduced apoptosis of alveolar epithelium, resulting in increased formation of premalignant lesions. Investigation of inflammatory cells in lungs of IKTA mice revealed a substantial increase in macrophages and lymphocytes, including functional CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs). Importantly, Treg depletion using repetitive injections of anti-CD25 antibodies limited excessive tumor formation in IKTA mice. At 6 weeks following urethane injection, antibody-mediated Treg depletion in IKTA mice reduced the number of premalignant lesions in the lungs in association with an increase in CD8 lymphocytes. Thus, persistent NF-κB signaling in airway epithelium facilitates carcinogenesis by sculpting the immune/inflammatory environment in the lungs.

  20. Antibody-directed targeting of lysostaphin adsorbed onto polylactide nanoparticles increases its antimicrobial activity against S. aureus in vitro

    Science.gov (United States)

    Satishkumar, R.; Vertegel, A. A.

    2011-12-01

    The objective of this paper was to study the effect of antibody-directed targeting of S. aureus by comparing the activities of lysostaphin conjugated to biodegradable polylactide nanoparticles (NPs) in the presence and in the absence of co-immobilized anti-S. aureus antibody. Lysostaphin-antibody-NP conjugates were synthesized through physical adsorption at different enzyme:antibody:NP ratios. The synthesized enzyme-NP conjugates were characterized by means of dynamic light scattering and zeta potential analysis, and the total protein binding yield on the NPs was characterized using Alexa Fluor 350 and 594 dyes for the S. aureus antibody and lysostaphin respectively. We observed enhanced antimicrobial activity for both enzyme-coated and enzyme-antibody-coated NPs for lysostaphin coatings corresponding to ~ 40% of the initial monolayer and higher compared to the free enzyme case (p < 0.05). At the highest antibody coating concentration, bacterial lysis rates for antibody-coated samples were significantly higher than for lysostaphin-coated samples lacking the antibody (p < 0.05). Such enzyme-NP conjugates thus have the potential for becoming novel therapeutic agents for treating antibiotic-resistant S. aureus infections.

  1. Antibody response to measles immunization in India*

    OpenAIRE

    Job, J. S.; John, T J; Joseph, A.

    1984-01-01

    Antibody response to measles vaccine was measured in 238 subjects aged 6-15 months. Seroconversion rates ranged from 74% at 6 months of age to 100% at 13-15 months; the differences in age-specific rates were not statistically significant. The postimmunization antibody titres increased with increasing age of the vaccinee. Seroconversion rates and antibody titres in 49 subjects with grades I and II malnutrition were not significantly different from those in the 189 normal subjects.

  2. Plug-in Hybrid Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Angie; Moore, Ray; Rowden, Tim

    2013-09-27

    Our main project objective was to implement Plug-in Electric Vehicles (PEV) and charging infrastructure into our electric distribution service territory and help reduce barriers in the process. Our research demonstrated the desire for some to be early adopters of electric vehicles and the effects lack of education plays on others. The response of early adopters was tremendous: with the initial launch of our program we had nearly 60 residential customers interested in taking part in our program. However, our program only allowed for 15 residential participants. Our program provided assistance towards purchasing a PEV and installation of Electric Vehicle Supply Equipment (EVSE). The residential participants have all come to love their PEVs and are more than enthusiastic about promoting the many benefits of driving electric.

  3. CoSMoS unravels mysteries of transcription initiation.

    Science.gov (United States)

    Gourse, Richard L; Landick, Robert

    2012-02-17

    Using a fluorescence method called colocalization single-molecule spectroscopy (CoSMoS), Friedman and Gelles dissect the kinetics of transcription initiation at a bacterial promoter. Ultimately, CoSMoS could greatly aid the study of the effects of DNA sequence and transcription factors on both prokaryotic and eukaryotic promoters.

  4. CoSMoS Unravels Mysteries of Transcription Initiation

    OpenAIRE

    Gourse, Richard L.; Landick, Robert

    2012-01-01

    Using a fluorescence method called colocalization single-molecule spectroscopy (CoSMoS), Friedman and Gelles dissect the kinetics of transcription initiation at a bacterial promoter. Ultimately, CoSMoS could greatly aid the study of the effects of DNA sequence and transcription factors on both prokaryotic and eukaryotic promoters.

  5. Developing a Promotional Video

    Science.gov (United States)

    Epley, Hannah K.

    2014-01-01

    There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…

  6. Antiphospholipid Antibodies and Systemic Scleroderma

    Directory of Open Access Journals (Sweden)

    Awa Oumar Touré

    2013-03-01

    Full Text Available Objective: Antiphospholipid antibodies (APLs could be associated with an increased risk of vascular pathologies in systemic scleroderma. The aim of our study was to search for APLs in patients affected by systemic scleroderma and to evaluate their involvement in the clinical manifestations of this disease. Materials and Methods: We conducted a cross-sectional descriptive study, from January 2009 until August 2010, with patients received at the Department of Dermatology (Dakar, Senegal. Blood samples were taken at the hematology laboratory and were analyzed for the presence of APLs. Results: Forty patients were recruited. Various types of either isolated or associated APLs were found in 23 patients, i.e. 57.5% of the study population. The most frequently encountered antibody was IgG anti-β2 GPI (37.5% of the patients, followed by anticardiolipins (17.5% and lupus anticoagulants (5%. No statistically significant association of positive antiphospholipid-related tests to any of the scleroderma complications could be demonstrated. Conclusion: A high proportion of patients showing association of systemic scleroderma and APLs suggests the presence of a morbid correlation between these 2 pathologies. It would be useful to follow a cohort of patients affected by systemic scleroderma in order to monitor vascular complications following confirmation of the presence of antiphospholipid syndrome.

  7. Antibody engineering and therapeutics, The Annual Meeting of the Antibody Society: December 8-12, 2013, Huntington Beach, CA.

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul W H I; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates.

  8. 6th Annual European Antibody Congress 2010

    Science.gov (United States)

    2011-01-01

    The 6th European Antibody Congress (EAC), organized by Terrapinn Ltd., was held in Geneva, Switzerland, which was also the location of the 4th and 5th EAC.1,2 As was the case in 2008 and 2009, the EAC was again the largest antibody congress held in Europe, drawing nearly 250 delegates in 2010. Numerous pharmaceutical and biopharmaceutical companies active in the field of therapeutic antibody development were represented, as were start-up and academic organizations and representatives from the US Food and Drug Administration (FDA). The global trends in antibody research and development were discussed, including success stories of recent marketing authorizations of golimumab (Simponi®) and canakinumab (Ilaris®) by Johnson & Johnson and Novartis, respectively, updates on antibodies in late clinical development (obinutuzumab/GA101, farletuzumab/MORAb-003 and itolizumab/T1 h, by Glycart/Roche, Morphotek and Biocon, respectively) and success rates for this fast-expanding class of therapeutics (Tufts Center for the Study of Drug Development). Case studies covering clinical progress of girentuximab (Wilex), evaluation of panobacumab (Kenta Biotech), characterization of therapeutic antibody candidates by protein microarrays (Protagen), antibody-drug conjugates (sanofi-aventis, ImmunoGen, Seattle Genetics, Wyeth/Pfizer), radio-immunoconjugates (Bayer Schering Pharma, Université de Nantes) and new scaffolds (Ablynx, AdAlta, Domantis/GlaxoSmithKline, Fresenius, Molecular Partners, Pieris, Scil Proteins, Pfizer, University of Zurich) were presented. Major antibody structural improvements were showcased, including the latest selection engineering of the best isotypes (Abbott, Pfizer, Pierre Fabre), hinge domain (Pierre Fabre), dual antibodies (Abbott), IgG-like bispecific antibodies (Biogen Idec), antibody epitope mapping case studies (Eli Lilly), insights in FcγRII receptor (University of Cambridge), as well as novel tools for antibody fragmentation (Genovis). Improvements

  9. Isoimmunization with anti-U antibody.

    Science.gov (United States)

    Turner, R J; Holder, W T; McCord, D L

    1984-03-01

    Isoimmunization with anti-U antibody is a rare but significant cause of hemolytic disease in black newborns. In this case report, an lgG antibody stimulated by fetomaternal transfusion produced a positive direct Coombs' test on cord blood but not neonatal hyperbilirubinemia. A review of the literature suggests the pathophysiology is similar to Rh isoimmunization. The anti-U antibody may develop as a result of pregnancy or blood transfusion in the 1.2 percent of American blacks who are at risk for developing the antibody. The principles of treatment employed in Rh isoimmunization can be successfully used in isoimmunization due to anti-U.

  10. Exceptional Antibodies Produced by Successive Immunizations.

    Directory of Open Access Journals (Sweden)

    Patricia J Gearhart

    2015-12-01

    Full Text Available Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing activation-induced deaminase, which unleashes a tsunami of mutations in the immunoglobulin loci. This produces random DNA substitutions, followed by selection for the highest affinity antibodies. We may be able to manipulate the process to produce better antibodies by expanding the repertoire of specific B cells through successive vaccinations.

  11. Single-domain antibodies for biomedical applications.

    Science.gov (United States)

    Krah, Simon; Schröter, Christian; Zielonka, Stefan; Empting, Martin; Valldorf, Bernhard; Kolmar, Harald

    2016-01-01

    Single-domain antibodies are the smallest antigen-binding units of antibodies, consisting either only of one variable domain or one engineered constant domain that solely facilitates target binding. This class of antibody derivatives comprises naturally occurring variable domains derived from camelids and sharks as well as engineered human variable or constant antibody domains of the heavy or light chain. Because of their high affinity and specificity as well as stability, small size and benefit of multiple re-formatting opportunities, those molecules emerged as promising candidates for biomedical applications and some of these entities have already proven to be successful in clinical development.

  12. In Vitro Trypanocidal Activity of Antibodies to Bacterially Ex­pressed Trypanosoma brucei Tubulin

    Directory of Open Access Journals (Sweden)

    GW Lubega

    2012-09-01

    Full Text Available Background: There are only four drugs for treating African trypanosomiasis, a devastating disease in sub-Saharan Africa. With slow discovery of better drugs, vaccination is viewed as the best method of control. We previously showed that antibodies to native Trypanosoma brucei brucei tubulin inhibit the growth of trypanosomes in culture. Here, we aimed to determine the effect of antibodies to bacte­rially expressed trypanosome tubulin on T. brucei brucei growth. Methods: T. brucei brucei alpha and beta tubulin genes were individually expressed in Escherichia coli under the tryptophan promoter. Monoclonal tubulin antibodies reacted specifically with the ex­pressed tubulins with no cross-reaction with the opposite tubulin. Rabbits were immunized with 450μg each of the concentrated recombinant tubulin, and production of antibodies assessed by ELISA and Western blotting. The effect of polyclonal antibodies on trypanosome growth was deter­mined by culturing bloodstream T. brucei brucei in up to 25% of antisera. Results: Low antisera dilutions (25% from the immunized rabbits inhibited trypanosome growth. The most cytotoxic antisera were from one rabbit immunized with a mixture of both alpha and beta tubulins. However, the result was not reproduced in other rabbits and there was no apparent effect on growth at higher antisera dilutions. Conclusion: Antibodies to bacterially expressed trypanosome tubulin are not effective at killing cul­tured bloodstream trypanosomes.

  13. Antinuclear antibodies in rheumatic disease: a proposal for a function-based classification.

    Science.gov (United States)

    Pisetsky, D S

    2012-09-01

    Antinuclear antibodies (ANAs) are a diverse group of autoantibodies that bind macromolecular components of the cell nucleus. While some ANAs occur in normal individuals, others are expressed almost exclusively in patients with rheumatic disease and serve as markers for diagnosis and prognosis. Despite the clinical associations of ANAs, the relationship of these antibodies to specific disease manifestations is often unknown because the target antigens are intracellular molecules that are ubiquitously expressed. In systemic lupus erythematosus, the role of ANAs in disease manifestations is better understood, especially for antibodies to DNA and related nucleosomal antigens. These antibodies can promote nephritis by the formation of immune complexes that are deposited in the kidney. In addition, anti-DNA, along with antibodies to RNA-binding proteins such as anti-Sm, can induce non-specific immune abnormalities based on the induction of type interferon 1 by plasmacytoid dendritic cells. Despite ANA expression in rheumatic disease, studies in animal models of inflammation and tissue injury indicate that antibodies to certain nuclear molecules such as HMGB1 have protective effects. Together, these considerations suggest a function-based classification of ANAs based on their expression in normal and autoimmune individuals as well as their capacity to induce or attenuate immunological disturbances. This classification provides a framework to elucidate the serological features of rheumatic disease and the often uncertain relationship between ANA expression and disease manifestations.

  14. Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Stang, Espen, E-mail: espsta@rr-research.no [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)

    2012-12-10

    The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: Black-Right-Pointing-Pointer Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. Black-Right-Pointing-Pointer Antibody combination causes internalization of EGFR by macropinocytosis. Black-Right-Pointing-Pointer Antibody-induced internalization of EGFR is independent of EGFR kinase activity. Black-Right-Pointing-Pointer Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

  15. An efficient method for isolating antibody fragments against small peptides by antibody phage display

    DEFF Research Database (Denmark)

    Duan, Zhi; Siegumfeldt, Henrik

    2010-01-01

    We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do....... The scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....

  16. On the Meaning of Affinity Limits in B-Cell Epitope Prediction for Antipeptide Antibody-Mediated Immunity

    Directory of Open Access Journals (Sweden)

    Salvador Eugenio C. Caoili

    2012-01-01

    Full Text Available B-cell epitope prediction aims to aid the design of peptide-based immunogens (e.g., vaccines for eliciting antipeptide antibodies that protect against disease, but such antibodies fail to confer protection and even promote disease if they bind with low affinity. Hence, the Immune Epitope Database (IEDB was searched to obtain published thermodynamic and kinetic data on binding interactions of antipeptide antibodies. The data suggest that the affinity of the antibodies for their immunizing peptides appears to be limited in a manner consistent with previously proposed kinetic constraints on affinity maturation in vivo and that cross-reaction of the antibodies with proteins tends to occur with lower affinity than the corresponding reaction of the antibodies with their immunizing peptides. These observations better inform B-cell epitope prediction to avoid overestimating the affinity for both active and passive immunization; whereas active immunization is subject to limitations of affinity maturation in vivo and of the capacity to accumulate endogenous antibodies, passive immunization may transcend such limitations, possibly with the aid of artificial affinity-selection processes and of protein engineering. Additionally, protein disorder warrants further investigation as a possible supplementary criterion for B-cell epitope prediction, where such disorder obviates thermodynamically unfavorable protein structural adjustments in cross-reactions between antipeptide antibodies and proteins.

  17. Isolated Central Nervous System Vasculitis Associated with Antiribonuclear Protein Antibody

    Directory of Open Access Journals (Sweden)

    Amer M. Awad

    2011-01-01

    Full Text Available We describe the case of a young woman who was referred to a tertiary care center with unexplained subacute progressive encephalopathy preceded by long-standing severe headaches. Her extensive workup was remarkable for abnormal intracranial angiography suggestive of small- and medium-vessel vasculitis, persistently elevated protein in the cerebrospinal fluid and persistently high titers of antiribonuclear protein antibody. The patient showed a modest response to intravenous high-dose steroids. We propose that the patient's neurologic disease is secondary to immune-mediated central nervous system vasculitis, possibly as an initial manifestation of mixed connective tissue disease.

  18. Pregnancies in women with systemic lupus erythematosus and antiphospholipid antibodies

    DEFF Research Database (Denmark)

    Schreiber, K

    2016-01-01

    Systemic lupus erythematosus (SLE) has preponderance in women in their childbearing years; consequently pregnancy has always been an important issue of concern for the patient and the treating physician. Based upon numerous reports on successful pregnancy outcomes in the past decades, the initial...... of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE) study, so far the largest multicentre cohort study of pregnant women with underlying stable SLE, has given some important answers to long-discussed questions. Future studies on data collected from...

  19. Health Promotion Education

    DEFF Research Database (Denmark)

    Lehn-Christiansen, Sine

    The paper discusses the implications of health promotion in education. The paper is based on my PhD project entitled “Health promotion education seen through a power/knowledge and subjectification perspective” (in prep). The PhD project explores how professional health promotion skills...... are conceived in a specific educational setting; namely the Danish social and health education programme. Here, health promotion is formally conceived as a qualification aimed at citizens and patients - and not at the students themselves. However, as the paper will demonstrate, conceptions of student...... health promotion workers should ideally act as health promotion role models. This claim leads to a series of educational and morally anchored dilemmas and challenges. Inspired by Foucault and others who have developed this line of thinking (eg. Signild Vallgårde) health promotion is viewed as a heartfelt...

  20. The production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi

    NARCIS (Netherlands)

    Joosten, V.; Lokman, C.; Hondel, C.A.M.J.J. van den; Punt, P.J.

    2003-01-01

    In this review we will focus on the current status and views concerning the production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi. We will focus on single-chain antibody fragment production (scFv and VHH) by these lower eukaryotes and the possible applications

  1. Initiation of Meiotic Recombination in Mammals

    Directory of Open Access Journals (Sweden)

    Rajeev Kumar

    2010-12-01

    Full Text Available Meiotic recombination is initiated by the induction of programmed DNA double strand breaks (DSBs. DSB repair promotes homologous interactions and pairing and leads to the formation of crossovers (COs, which are required for the proper reductional segregation at the first meiotic division. In mammals, several hundred DSBs are generated at the beginning of meiotic prophase by the catalytic activity of SPO11. Currently it is not well understood how the frequency and timing of DSB formation and their localization are regulated. Several approaches in humans and mice have provided an extensive description of the localization of initiation events based on CO mapping, leading to the identification and characterization of preferred sites (hotspots of initiation. This review presents the current knowledge about the proteins known to be involved in this process, the sites where initiation takes place, and the factors that control hotspot localization.

  2. Antibodies to watch in 2017.

    Science.gov (United States)

    Reichert, Janice M

    Over 50 investigational monoclonal antibody (mAb) therapeutics are currently undergoing evaluation in late-stage clinical studies, which is expected to drive a trend toward first marketing approvals of at least 6-9 mAbs per year in the near-term. In the United States (US), a total of 6 and 9 mAbs were granted first approvals during 2014 and 2015, respectively; all these products are also approved in the European Union (EU). As of December 1, 2016, 6 mAbs (atezolizumab, olaratumab, reslizumab, ixekizumab, bezlotoxumab, oblitoxaximab) had been granted first approvals during 2016 in either the EU or US. Brodalumab, was granted a first approval in Japan in July 2016. Regulatory actions on marketing applications for brodalumab in the EU and US are not expected until 2017. In 2017, first EU or US approvals may also be granted for at least nine mAbs (ocrelizumab, avelumab, Xilonix, inotuzumab ozogamicin, dupilumab, sirukumab, sarilumab, guselkumab, romosozumab) that are not yet approved in any country. Based on announcements of company plans for regulatory submissions and the estimated completion dates for late-stage clinical studies, and assuming the study results are positive, marketing applications for at least 6 antibody therapeutics (benralizumab, tildrakizumab, emicizumab, galcanezumab, ibalizumab, PRO-140) that are now being evaluated in late-stage clinical studies may be submitted during December 2016* or 2017. Other 'antibodies to watch' in 2017 include 20 mAbs are undergoing evaluation in pivotal studies that have estimated primary completion dates in late 2016 or during 2017. Of these, 5 mAbs are for cancer (durvalumab, JNJ-56022473, ublituximab, anetumab ravtansine, glembatumumab vedotin) and 15 mAbs are for non-cancer indications (caplacizumab, lanadelumab, roledumab, tralokinumab, risankizumab, SA237, emapalumab, suptavumab, erenumab, eptinezumab, fremanezumab, fasinumab, tanezumab, lampalizumab, brolucizumab). Positive results from these studies may

  3. Membrane adsorbers as purification tools for monoclonal antibody purification.

    Science.gov (United States)

    Boi, Cristiana

    2007-03-15

    Downstream purification processes for monoclonal antibody production typically involve multiple steps; some of them are conventionally performed by bead-based column chromatography. Affinity chromatography with Protein A is the most selective method for protein purification and is conventionally used for the initial capturing step to facilitate rapid volume reduction as well as separation of the antibody. However, conventional affinity chromatography has some limitations that are inherent with the method, it exhibits slow intraparticle diffusion and high pressure drop within the column. Membrane-based separation processes can be used in order to overcome these mass transfer limitations. The ligand is immobilized in the membrane pores and the convective flow brings the solute molecules very close to the ligand and hence minimizes the diffusional limitations associated with the beads. Nonetheless, the adoption of this technology has been slow because membrane chromatography has been limited by a lower binding capacity than that of conventional columns, even though the high flux advantages provided by membrane adsorbers would lead to higher productivity. This review considers the use of membrane adsorbers as an alternative technology for capture and polishing steps for the purification of monoclonal antibodies. Promising industrial applications as well as new trends in research will be addressed.

  4. An alternative chemical redox method for the production of bispecific antibodies: implication in rapid detection of food borne pathogens.

    Directory of Open Access Journals (Sweden)

    Mohammad Owais

    Full Text Available Bi-functional antibodies with the ability to bind two unrelated epitopes have remarkable potential in diagnostic and bio-sensing applications. In the present study, bispecific antibodies that recognize human red blood cell (RBC and the food borne pathogen Listeria monocytogenes (L. monocytogenes were engineered. The procedure involves initial reduction of a mixture of anti-RBC and anti-Listeria antibodies followed by gradual re-oxidation of the reduced disulphides. This facilitates association of the separated antibody chains and formation of hybrid immunoglobulins with affinity for the L. monocytogenes and human RBC. The bispecific antibodies caused the agglutination of the RBCs only in the presence of L. monocytogenes cells. The agglutination process necessitated the specific presence of L. monocytogenes and the red colored clumps formed were readily visible with naked eyes. The RBC agglutination assay described here provides a remarkably simple approach for the rapid and highly specific screening of various pathogens in their biological niches.

  5. 21 CFR 866.3290 - Gonococcal antibody test (GAT).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gonococcal antibody test (GAT). 866.3290 Section... antibody test (GAT). (a) Identification. A gonococcal antibody test (GAT) is an in vitro device that..., indirect fluorescent antibody, or radioimmunoassay, antibodies to Neisseria gonorrhoeae in sera...

  6. The Yekaterinburg headache initiative

    DEFF Research Database (Denmark)

    Lebedeva, Elena R; Olesen, Jes; Osipova, Vera V

    2013-01-01

    for a demonstrational interventional project in Russia, undertaken within the Global Campaign against Headache. The initiative proposes three actions: 1) raise awareness of need for improvement; 2) design and implement a three-tier model (from primary care to a single highly specialized centre with academic affiliation...... of a health-care needs assessment, and as a model for all Russia. We present and discuss early progress of the initiative, justify the investment of resources required for implementation and call for the political support that full implementation requires. The more that the Yekaterinburg headache initiative...

  7. 2-(ω-Carboxyethyl)pyrrole Antibody as a New Inhibitor of Tumor Angiogenesis and Growth.

    Science.gov (United States)

    Wu, Chunying; Wang, Xizhen; Tomko, Nicholas; Zhu, Junqing; Wang, William R; Zhu, Jinle; Wang, Yanming; Salomon, Robert G

    2016-09-22

    Angiogenesis is a fundamental process in the progression, invasion, and metastasis of tumors. Therapeutic drugs such as bevacizumab and ranibuzumab have thus been developed to inhibit vascular endothelial growth factor (VEFG)-promoted angiogenesis. While these anti-angiogenic drugs have been commonly used in the treatment of cancer, patients often develop significant resistance that limits the efficacy of anti-VEGF therapies to a short period of time. This is in part due to the fact that an independent pathway of angiogenesis exists, which is mediated by 2-(ω-carboxyethyl)pyrrole (CEP) in a TLR2 receptor-dependent manner that can compensate for inhibition of the VEGF-mediated pathway. In this work, we evaluated a CEP antibody as a new tumor growth inhibitor that blocks CEP-induced angiogenesis. We first evaluated the effectiveness of a CEP antibody as a monotherapy to impede tumor growth in two human tumor xenograft models. We then determined the synergistic effects of bevacizumab and CEP antibody in a combination therapy, which demonstrated that blocking of the CEP-mediated pathway significantly enhanced the anti-angiogenic efficacy of bevacizumab in tumor growth inhibition indicating that CEP antibody is a promising chemotherapeutic drug. To facilitate potential translational studies of CEP-antibody, we also conducted longitudinal imaging studies and identified that FMISO-PET is a non-invasive imaging tool that can be used to quantitatively monitor the anti-angiogenic effects of CEP-antibody in the clinical setting. That treatment with CEP antibody induces hypoxia in tumor tissue was indicated by 43% higher uptake of [18F]FMISO in CEP antibody-treated tumor xenografs than in the control PBS-treated littermates.

  8. Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis

    NARCIS (Netherlands)

    Tervaert, JWC; Stegeman, CA; Kallenberg, CGM

    2001-01-01

    High-dose corticosteroids in combination with cytotoxic drugs are universally accepted as the initial approach in vasculitides that are associated with anti-neutrophil cytoplasmic antibodies. Cyclophosphamide is the most effective cytotoxic drug and is used in more severe cases. Because cyclophospha

  9. Photonic crystal fiber based antibody detection

    DEFF Research Database (Denmark)

    Duval, A; Lhoutellier, M; Jensen, J B

    2004-01-01

    An original approach for detecting labeled antibodies based on strong penetration photonic crystal fibers is introduced. The target antibody is immobilized inside the air-holes of a photonic crystal fiber and the detection is realized by the means of evanescent-wave fluorescence spectroscopy...

  10. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    1989-01-01

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia. Antibod

  11. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  12. Methods for Selecting Phage Display Antibody Libraries.

    Science.gov (United States)

    Jara-Acevedo, Ricardo; Diez, Paula; Gonzalez-Gonzalez, Maria; Degano, Rosa Maria; Ibarrola, Nieves; Gongora, Rafael; Orfao, Alberto; Fuentes, Manuel

    2016-01-01

    The selection process aims sequential enrichment of phage antibody display library in clones that recognize the target of interest or antigen as the library undergoes successive rounds of selection. In this review, selection methods most commonly used for phage display antibody libraries have been comprehensively described.

  13. Receptor antibodies as novel therapeutics for diabetes

    DEFF Research Database (Denmark)

    Ussar, Siegfried; Vienberg, Sara Gry; Kahn, C Ronald

    2011-01-01

    Antibodies to receptors can block or mimic hormone action. Taking advantage of receptor isoforms, co-receptors, and other receptor modulating proteins, antibodies and other designer ligands can enhance tissue specificity and provide new approaches to the therapy of diabetes and other diseases....

  14. Antibody-drug conjugates: Intellectual property considerations.

    Science.gov (United States)

    Storz, Ulrich

    2015-01-01

    Antibody-drug conjugates are highly complex entities that combine an antibody, a linker and a toxin. This complexity makes them demanding both technically and from a regulatory point of view, and difficult to deal with in their patent aspects. This article discusses different issues of patent protection and freedom to operate with regard to this promising new class of drugs.

  15. Photonic crystal fiber based antibody detection

    OpenAIRE

    Duval, A.; Lhoutellier, M; Jensen, J. B.; Hoiby, P E; Missier, V; Pedersen, L. H.; Hansen, Theis Peter; Bjarklev, Anders Overgaard; Bang, Ole

    2004-01-01

    An original approach for detecting labeled antibodies based on strong penetration photonic crystal fibers is introduced. The target antibody is immobilized inside the air-holes of a photonic crystal fiber and the detection is realized by the means of evanescent-wave fluorescence spectroscopy and the use of a transversal illumination setup.

  16. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  17. Anti-influenza M2e antibody

    Science.gov (United States)

    Bradbury, Andrew M.

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  18. Bioconjugation of antibodies to horseradish peroxidase (hrp)

    Science.gov (United States)

    The bioconjugation of an antibody to an enzymatic reporter such as horseradish peroxidase (HRP) affords an effective mechanism by which immunoassay detection of a target antigen can be achieved. The use of heterobifunctional cross—linkers to covalently link antibodies to HRP provides a simple and c...

  19. "Unconventional" Neutralizing Activity of Antibodies Against HIV

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Neutralizing antibodies are recognized to be one of the essential elements of the adaptive immune response that must be induced by an effective vaccine against HIV. However, only a limited number of antibodies have been identified to neutralize a broad range of primary isolates of HIV-1 and attempts to induce such antibodies by immunization were unsuccessful. The difficulties to generate such antibodies are mainly due to intrinsic properties of HIV-1 envelope spikes, such as high sequence diversity, heavy glycosylation, and inducible and transient nature of certain epitopes. In vitro neutralizing antibodies are identified using "conventional" neutralization assay which uses phytohemagglutinin (PHA)-stimulated human PBMCs as target cells. Thus, in essence the assay evaluates HIV-1 replication in CD4+ T cells. Recently, several laboratories including us demonstrated that some monoclonal antibodies and HIV-1-specific polyclonal IgG purified from patient sera, although they do not have neutralizing activity when tested by the "conventional" neutralization assay, do exhibit potent and broad neutralizing activity in "unconventional" ways. The neutralizing activity of these antibodies and IgG fractions is acquired through post-translational modifications, through opsonization of virus particles into macrophages and immature dendritic cells (iDCs), or through expression of antibodies on the surface of HIV-1-susceptible cells. This review will focus on recent findings of this area and point out their potential applications in the development of preventive strategies against HIV.

  20. RAS Initiative - Events

    Science.gov (United States)

    The NCI RAS Initiative has organized multiple events with outside experts to discuss how the latest scientific and technological breakthroughs can be applied to discover vulnerabilities in RAS-driven cancers.

  1. Prairie Reconstruction Initiative Project

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of the Prairie Reconstruction Initiative Advisory Team (PRIAT) is to identify and take steps to resolve uncertainties in the process of prairie...

  2. Surgical Critical Care Initiative

    Data.gov (United States)

    Federal Laboratory Consortium — The Surgical Critical Care Initiative (SC2i) is a USU research program established in October 2013 to develop, translate, and validate biology-driven critical care....

  3. Quality Initiatives - General Information

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS has developed a standardized approach for the development of quality measures that it uses in its quality initiatives. Known as the Measures Management System...

  4. RAS Initiative - Community Outreach

    Science.gov (United States)

    Through community and technical collaborations, workshops and symposia, and the distribution of reference reagents, the RAS Initiative seeks to increase the sharing of knowledge and resources essential to defeating cancers caused by mutant RAS genes.

  5. Nursing Home Quality Initiative

    Data.gov (United States)

    U.S. Department of Health & Human Services — This Nursing Home Quality Initiative (NHQI) website provides consumer and provider information regarding the quality of care in nursing homes. NHQI discusses quality...

  6. Prairie Reconstruction Initiative

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of the Prairie Reconstruction Initiative Advisory Team (PRIAT) is to identify and take steps to resolve uncertainties in the process of prairie...

  7. Nursing Home Quality Initiative

    Data.gov (United States)

    U.S. Department of Health & Human Services — This Nursing Home Quality Initiative (NHQI) website provides consumer and provider information regarding the quality of care in nursing homes. NHQI discusses...

  8. Trace of antibody to myeloperoxidase with nanocrystal quantum dot labeled antibody recognizing activating neutrophils

    Science.gov (United States)

    Hoshino, Akiyoshi; Nagao, Tomokazu; Yamamoto, Kenji; Suzuki, Kazuo

    2006-02-01

    It is assumed that activated neutrophils contribute to the development of anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitis due to the association of myelopeoxidase(MPO)-ANCA with MPO expressed on the surface of activated neutrophils. FITC-labeled antibody (Ab) used widely are not suitable for neutrophil examination because of the labile fluorescence emission of FITC. Therefore, it is necessary to develop specific fluorescent probes for MPO detection in neutrophils in vivo. Recently, fluorescent nanocrystal quantum dots (QDs) have been used for biotechnological and medical applications because of their greater and far longer fluorescence in. QDs have several advantages over organic fluorophores: high luminescence, far longer stability against photobleaching, and a range of fluorescence wavelengths from blue to infrared, depending on particle size. Thus, we examined the role of MPO and the Ab to MPO in the pathogenesis of glomerulonephritis associated with MPO-ANCA in experimental glomerulonephritis mice using QDs. We demonstrated the QD-conjugated anti-MPO Ab visualized the expression of MPO on the neutrophil surface after stimulation with proinflammatory cytokines. In addition, QD immuno-conjugates with anti-recombinant murine MPO (rmMPO) Ab revealed the trafficking of MPO-ANCA in vivo. Deceleration of blood flow in kidney vessels occurred in model mice, in which serum proteins including anti-rmMPO Ab were leaked out from collapsed glomeruli into the proximal tubule. Thus, sustained MPO expression on the neutrophil surface was significantly related to glomerulonephritis. These results indicate that the expressed MPO on the activated neutrophils with anti-MPO Ab may coordinately play essential roles in the initial steps for the development of glomerulonephritis.

  9. Promotion of Sustainable Renovation in Europe

    DEFF Research Database (Denmark)

    Fokaides, Paris A.; Kanarachos, Andreas; Kanarachos, Georgette

    2013-01-01

    pressing the energy renovation of buildings. Both the obstacles and the contribution of national regulations will be discussed, towards promotion of sustainable renovation in Europe today. This study is also expected to report on research initiatives currently being undertaken in Europe on the energy...

  10. Healthy Universities: Mapping Health-Promotion Interventions

    Science.gov (United States)

    Sarmiento, Juan Pablo

    2017-01-01

    Purpose: The purpose of this paper is to map out and characterize existing health-promotion initiatives at Florida International University (FIU) in the USA in order to inform decision makers involved in the development of a comprehensive and a long-term healthy university strategy. Design/methodology/approach: This study encompasses a narrative…

  11. School Health Promotion and Teacher Professional Identity

    Science.gov (United States)

    Jourdan, Didier; Simar, Carine; Deasy, Christine; Carvalho, Graça S.; McNamara, Patricia Mannix

    2016-01-01

    Purpose: Health and education are inextricably linked. Health promotion sits somewhat uncomfortably within schools, often remaining a marginal aspect of teachers' work. The purpose of this paper is to examine the compatibility of an HP-initiative with teacher professional identity. Design/methodology/approach: A qualitative research design was…

  12. Promoting the female condom to refugees

    Directory of Open Access Journals (Sweden)

    Jacqueline Papo

    2006-05-01

    Full Text Available UNHCR and its partners have been providing male condoms since the late 1990s. However, uptake remains alarmingly low. Will the agency be more successful in promoting the female condom, a female-initiated barrier method of contraception and disease prevention?

  13. Anti-miroestrol polyclonal antibodies: a comparison of immunogen preparations used to obtain desired antibody properties.

    Science.gov (United States)

    Kitisripanya, Tharita; Jutathis, Kamonthip; Inyai, Chadathorn; Komaikul, Jukrapun; Udomsin, Orapin; Yusakul, Gorawit; Tanaka, Hiroyuki; Putalun, Waraporn

    2016-04-01

    Immunogen quality is one important factor that contributes to desirable antibody characteristics. Highly specific antibodies against miroestrol can be used to develop a quality control immunoassay for Pueraria candollei products. In this study, we investigated how various immunogen preparations affect antibody properties. The results show that immunogen prepared using the Mannich reaction provides antibodies with higher specificity and sensitivity against miroestrol than immunogen prepared with the periodate reaction. The results suggest the Mannich reaction maintains the original structure of miroestrol and generates useful antibodies for developing immunoassays.

  14. Progress in Initiator Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Hrousis, C A; Christensen, J S

    2009-05-04

    There is great interest in applying magnetohydrodynamic (MHD) simulation techniques to the designs of electrical high explosive (HE) initiators, for the purpose of better understanding a design's sensitivities, optimizing its performance, and/or predicting its useful lifetime. Two MHD-capable LLNL codes, CALE and ALE3D, are being used to simulate the process of ohmic heating, vaporization, and plasma formation in the bridge of an initiator, be it an exploding bridgewire (EBW), exploding bridgefoil (EBF) or slapper type initiator. The initiation of the HE is simulated using Tarver Ignition & Growth reactive flow models. 1-D, 2-D and 3-D models have been constructed and studied. The models provide some intuitive explanation of the initiation process and are useful for evaluating the potential impact of identified aging mechanisms (such as the growth of intermetallic compounds or powder sintering). The end product of this work is a simulation capability for evaluating margin in proposed, modified or aged initiation system designs.

  15. Choice of initial therapy

    Directory of Open Access Journals (Sweden)

    Manuel Battegay

    2014-11-01

    Full Text Available Current international and national treatment guidelines such as EACS, BHIVA, DHHS or IAS update regularly recommendations on the choice of initial combination antiretroviral treatment (cART regimens. Preferred cART regimens include a backbone with two nucleoside (nucleotide reverse transcriptase inhibitors combined either with one non-nucleoside reverse transcriptase inhibitor or one ritonavir boosted protease inhibitor or more recently one integrase inhibitor. Response rates according to viral load measurements increased in recent years, in particular due to better tolerability. The choice of initial therapy is flexible and influenced by several factors such as height of viral load, genotypic resistance testing, CD4 cell count, co-morbidities, interactions, potential adverse events, (potential for pregnancy, convenience, adherence, costs as well as physician's and patient's preferences. Diverse highly potent initial cART regimens exist. Following the many possibilities, the choice of a regimen is based on a mixture of evidence-informed data and individualized concepts, some of the latter only partly supported by strong evidence. For example, different perceptions and personal experiences exist about boosted protease inhibitors compared to non-nucleoside reverse transcriptase inhibitors or integrase inhibitors and vice versa which may influence the initial choice. This lecture will discuss choices of initial cART in view of international guidelines and the evidence for individualization of initial HIV therapy.

  16. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J

    2006-09-01

    Multiple options are now available for the treatment of chronic lymphocytic leukemia. Over the last 10 years, monoclonal antibodies have become an integral part of the management of this disease. Alemtuzumab has received approval for use in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab has been investigated extensively in chronic lymphocytic leukemia both as a single agent and in combination with chemotherapy and other monoclonal antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the early phase of clinical development. This article will review the monoclonal antibodies more commonly used to treat chronic lymphocytic leukemia, the results obtained with monoclonal antibodies as single agents and in combination with chemotherapy, and other biological agents and newer compounds undergoing clinical trials.

  17. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies...... are powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors...... such as structure, accessibility and amino acid composition are crucial. Since small peptides tend not to be immunogenic, it may be necessary to conjugate them to carrier proteins in order to enhance immune presentation. Several strategies for conjugation of peptide-carriers applied for immunization exist...

  18. Antiphospholipid antibody: laboratory, pathogenesis and clinical manifestations

    Directory of Open Access Journals (Sweden)

    T. Ziglioli

    2011-06-01

    Full Text Available Antiphospholipid antibodies (aPL represent a heterogeneous group of antibodies that recognize various antigenic targets including beta2 glycoprotein I (β2GPI, prothrombin (PT, activated protein C, tissue plasminogen activator, plasmin and annexin A2. The most commonly used tests to detect aPL are: lupus anticoagulant (LAC, a functional coagulation assay, anticardiolipin antibody (aCL and anti-β2GPI antibody (anti-β2GPI, which are enzyme-linked immunoassay (ELISA. Clinically aPL are associated with thrombosis and/or with pregnancy morbidity. Apparently aPL alone are unable to induce thrombotic manifestations, but they increase the risk of vascular events that can occur in the presence of another thrombophilic condition; on the other hand obstetrical manifestations were shown to be associated not only to thrombosis but mainly to a direct antibody effect on the trophoblast.

  19. Antibody-based resistance to plant pathogens.

    Science.gov (United States)

    Schillberg, S; Zimmermann, S; Zhang, M Y; Fischer, R

    2001-01-01

    Plant diseases are a major threat to the world food supply, as up to 15% of production is lost to pathogens. In the past, disease control and the generation of resistant plant lines protected against viral, bacterial or fungal pathogens, was achieved using conventional breeding based on crossings, mutant screenings and backcrossing. Many approaches in this field have failed or the resistance obtained has been rapidly broken by the pathogens. Recent advances in molecular biotechnology have made it possible to obtain and to modify genes that are useful for generating disease resistant crops. Several strategies, including expression of pathogen-derived sequences or anti-pathogenic agents, have been developed to engineer improved pathogen resistance in transgenic plants. Antibody-based resistance is a novel strategy for generating transgenic plants resistant to pathogens. Decades ago it was shown that polyclonal and monoclonal antibodies can neutralize viruses, bacteria and selected fungi. This approach has been improved recently by the development of recombinant antibodies (rAbs). Crop resistance can be engineered by the expression of pathogen-specific antibodies, antibody fragments or antibody fusion proteins. The advantages of this approach are that rAbs can be engineered against almost any target molecule, and it has been demonstrated that expression of functional pathogen-specific rAbs in plants confers effective pathogen protection. The efficacy of antibody-based resistance was first shown for plant viruses and its application to other plant pathogens is becoming more established. However, successful use of antibodies to generate plant pathogen resistance relies on appropriate target selection, careful antibody design, efficient antibody expression, stability and targeting to appropriate cellular compartments.

  20. Brazilian obesity prevention and control initiatives.

    Science.gov (United States)

    Jaime, P C; da Silva, A C F; Gentil, P C; Claro, R M; Monteiro, C A

    2013-11-01

    Obesity prevalence in the Brazilian adult population is 12.5% among men and 16.9% among women. Obesity control has been a subject of concern in Brazilian health policies since the publication of the National Food and Nutrition Policy in 1999. The initiatives include a comprehensive national intersectorial plan for obesity prevention and control focused on confronting its social and environmental causes, development of a food and nutrition education framework aimed at intersectorial public policies in the food and nutritional security field, promotion and provision of healthy food in school environments (linked to family farming), structuring nutrition actions in primary healthcare in the national healthcare system, promoting community physical activity, food regulation and control, and encouragement of public participation and food control. We conclude that several initiatives have been developed in Brazil to deal with the challenge of implementing an intergovernmental, intersectorial response to reverse the rising overweight and obesity rates. The success of this response will depend on a governance model that promotes joint and integrated action by different sectors and active participation of society to consolidate the actions, places and laws that protect health and promote healthy lifestyles.

  1. Functional Characterization of an scFv-Fc Antibody that Immunotherapeutically Targets the Common Cancer Cell Surface Proteoglycan CSPG4

    OpenAIRE

    Wang, Xinhui; Katayama, Akihiro; Wang, Yangyang; YU Ling; Favoino, Elvira; Sakakura, Koichi; Favole, Alessandra; Tsuchikawa, Takahiro; Silver, Susan; Watkins, Simon C.; Kageshita, Toshiro; Ferrone, Soldano

    2011-01-01

    Cell surface chondroitin sulfate proteoglycan 4 (CSPG4) is an attractive target for antibody-based cancer immunotherapy because of its role in tumor cell biology, its high expression on malignant cells including cancer-initiating cells, and its restricted distribution in normal tissues. The clinical use of CSPG4 has been hampered by the lack of a CSPG4-specific chimeric, humanized, or fully human monoclonal antibody. To overcome this limitation, we generated a CSPG4-specific fully human singl...

  2. Is Lamb Promotion Working?

    OpenAIRE

    Capps, Oral, Jr.; Williams, Gary W.

    2007-01-01

    This objective of this study is to determine whether the advertising and promotion dollars collected and spent by the American Lamb Board on lamb promotion since the inception of the Lamb Checkoff Program have effectively increased lamb consumption in the United States. The main conclusion is that program has resulted in roughly 7.6 additional pounds of total lamb consumption per dollar spent on advertising and promotion and $41.59 in additional lamb sales per dollar spent on advertising and ...

  3. A novel antibody against human properdin inhibits the alternative complement system and specifically detects properdin from blood samples.

    Directory of Open Access Journals (Sweden)

    Diana Pauly

    Full Text Available The complement system is an essential part of the innate immune system by acting as a first line of defense which is stabilized by properdin, the sole known positive regulator of the alternative complement pathway. Dysregulation of complement can promote a diversity of human inflammatory diseases which are treated by complement inhibitors. Here, we generated a novel blocking monoclonal antibody (mAb against properdin and devised a new diagnostic assay for this important complement regulator. Mouse mAb 1340 specifically detected native properdin from human samples with high avidity. MAb 1340 inhibited specifically the alternative complement mediated cell lysis within a concentration range of 1-10 µg/mL. Thus, in vitro anti-properdin mAb 1340 was up to fifteen times more efficient in blocking the complement system as compared to anti-C5 or anti-Ba antibodies. Computer-assisted modelling suggested a three-dimensional binding epitope in a properdin-C3(H2O-clusterin complex to be responsible for the inhibition. Recovery of properdin in a newly established sandwich ELISA using mAb 1340 was determined at 80-125% for blood sample dilutions above 1∶50. Reproducibility assays showed a variation below 25% at dilutions less than 1∶1,000. Systemic properdin concentrations of healthy controls and patients with age-related macular degeneration or rheumatic diseases were all in the range of 13-30 µg/mL and did not reveal significant differences. These initial results encourage further investigation into the functional role of properdin in the development, progression and treatment of diseases related to the alternative complement pathway. Thus, mAb 1340 represents a potent properdin inhibitor suitable for further research to understand the exact mechanisms how properdin activates the complement C3-convertase and to determine quantitative levels of properdin in biological samples.

  4. The Mechanism of Hydrogen-facilitating Initiation of Voids

    Institute of Scientific and Technical Information of China (English)

    褚武扬; 蒋兴钢; 肖纪美

    1994-01-01

    By combining the hydrogen-induced local plastic deformation theory with the decohesive theory and the hydrogen pressure theory, a new mechanism of hydrogen-facilitating initiation of voids has been proposed. Through facilitating the local plastic deformation and reducing the cohesive strength, hydrogen promotes both initiating a nanocrack and blunting the nanocrack into a void, resulting in hydrogen-promoting initiation of the void. On the other hand, hydrogen can enhance the stability of the void through reducing the cohesive strength and forming a hydrogen pressure in the void.

  5. Radiohalogenated half-antibodies and maleimide intermediate therefor

    Science.gov (United States)

    Kassis, A.I.; Khawli, L.A.

    1991-02-19

    N-(m-radiohalophenyl) maleimide can be conjugated with a reduced antibody having a mercapto group to provide a radiolabeled half-antibody having immunological specific binding characteristics of whole antibody. No Drawings

  6. Identification of distinct antibody epitopes and mimotopes from a peptide array of 5520 randomly generated sequences.

    Science.gov (United States)

    Reineke, Ulrich; Ivascu, Claudia; Schlief, Marén; Landgraf, Christiane; Gericke, Seike; Zahn, Grit; Herzel, Hanspeter; Volkmer-Engert, Rudolf; Schneider-Mergener, Jens

    2002-09-01

    We used a relatively small library of 5520 randomly generated single 15-mer peptides prepared by SPOT synthesis as an array of 28.5x19.0 cm to identify epitopes for three distinct monoclonal antibodies, namely anti-p24 (human immunodeficiency virus (HIV)-1) monoclonal anibody (mab) CB4-1, anti-interleukin-10 (IL-10) mab CB/RS/13, and anti-transforming growth factor alpha (TGFalpha) mab Tab2. Initially identified peptide ligands mostly had very low affinities for the antibodies with dissociation constants around 10(-4) M. Subsequent identification of residues critical for the antibody interactions involved complete L-amino acid substitutional analyses. Several substitutions resulted in analogs with dissociation constants in the low micromolar and high nanomolar range. Specifically binding peptides with key residue patterns matching the wild-type epitopes were identified for all three antibodies. In addition, for antibody CB4-1 mimotopes that showed no homology to the known epitope were selected. Our results suggest that a very limited library diversity, although far from covering the entire sequence repertoire, can suffice to rapidly and economically select peptidic antibody epitopes and mimotopes.

  7. Hepatitis C virus antibodies in patients with liver disease. The western Cape experience.

    Science.gov (United States)

    Robson, S C; du Toit, J M; Brice, E A; Bird, A R; Brink, N S

    1991-09-21

    Hepatitis C virus (HCV) is a recently characterised non-A, non-B hepatitis (NANBH) agent, which appears to be important in both parenteral and sporadic NANBH. HCV infection has been associated with the development of chronic liver disease, cirrhosis and hepatoma. Groups of patients in the western Cape with chronic liver disease and hepatoma were screened for antibodies to HCV and the results were confirmed by standard neutralisation tests. Three of 19 patients with cirrhosis secondary to alcohol abuse or classic auto-immune chronic active hepatitis were considered to have antibodies to HCV at initial screening. All of these were false-positive results. Five of 20 patients with presumptive chronic NANBH were considered possibly to have antibodies to HCV. Only 1 patient with post-transfusional NANBH was confirmed to have specific HCV antibodies. Two of 30 patients with hepatoma had specific anti-HCV antibodies in contrast to 11 others with serum HBsAg positivity. One hundred blood transfusion donors and 25 antenatal patients were tested concurrently and shown to be negative for anti-HCV. Specific antibodies to HCV were present in very few patients with cirrhosis, presumptive NANBH and hepatoma tested in this local survey. False-positive reactions appeared to occur at a higher rate than true-positive results.

  8. Asthmatic persons are prone to the persistence of Chlamydia pneumoniae antibodies.

    Science.gov (United States)

    Paldanius, Mika; Juvonen, Raija; Leinonen, Maija; Bloigu, Aini; Silvennoinen-Kassinen, Sylvi; Saikku, Pekka

    2007-10-01

    Acute Chlamydia pneumoniae infection may initiate asthma or worsen asthmatic symptoms. In crowded conditions, such as military service, young men are susceptible to respiratory infections, including C. pneumoniae. We recruited 127 asthmatic and 391 nonasthmatic military conscripts, followed up their respiratory tract infections and the kinetics of serum C. pneumoniae antibodies, and assessed the association between C. pneumoniae and asthma during 6 months of military service in 2 intake groups. During the 6-month period, in the July intake group, IgG antibody prevalence decreased from 60.3% to 43.8% in asthmatic and from 55.6% to 22.6% in nonasthmatic conscripts. In the January intake group, IgG antibody prevalence increased from 38.3% to 48.4% in asthmatic and from 37.2% to 43% in nonasthmatic recruits. IgG and IgA antibodies persisted more often in the asthmatic groups. In conclusion, the prevalence of IgG antibodies showed seasonal variation. Military recruits seem to be most vulnerable to C. pneumoniae infections during the period from January to June. The antibody titer changes were more rapid than previously thought.

  9. Selecting an acceptable and safe antibody detection test can present a dilemma.

    Science.gov (United States)

    Combs, M R; Bredehoeft, S J

    2001-01-01

    The Transfusion Service at Duke University Hospital has changed antibody detection methods from the use of albumin in indirect antiglobulin tests to low-ionic-strength solution (LISS), and from LISS to polyethylene glycol (PEG) in an effort to enhance the rapid detection of clinically significant antibodies. In 1996, staffing issues required the consideration of automation. Although previous studies indicated that the gel test was not as sensitive as PEG for detection of clinically significant antibodies, we chose to implement the gel test to be used with the Tecan MegaFlex-ID. We performed a retrospective analysis of identified antibodies and transfusion reactions to compare the outcomes of one year's experience with gel and PEG. We found comparable detection of potentially clinically significant antibodies by both methods and significantly fewer unwanted or clinically insignificant antibodies detected with the use of gel. Fewer delayed serologic transfusion reactions and no transfusion-associated hemolytic events occurred in the year that gel was used. Although we initially found the selection of the gel test to be a dilemma, our ultimate decision appears to have successfully protected patient safety and balanced sensitivity with specificity.

  10. Simplifying complex sequence information: a PCP-consensus protein binds antibodies against all four Dengue serotypes.

    Science.gov (United States)

    Bowen, David M; Lewis, Jessica A; Lu, Wenzhe; Schein, Catherine H

    2012-09-14

    Designing proteins that reflect the natural variability of a pathogen is essential for developing novel vaccines and drugs. Flaviviruses, including Dengue (DENV) and West Nile (WNV), evolve rapidly and can "escape" neutralizing monoclonal antibodies by mutation. Designing antigens that represent many distinct strains is important for DENV, where infection with a strain from one of the four serotypes may lead to severe hemorrhagic disease on subsequent infection with a strain from another serotype. Here, a DENV physicochemical property (PCP)-consensus sequence was derived from 671 unique sequences from the Flavitrack database. PCP-consensus proteins for domain 3 of the envelope protein (EdomIII) were expressed from synthetic genes in Escherichia coli. The ability of the purified consensus proteins to bind polyclonal antibodies generated in response to infection with strains from each of the four DENV serotypes was determined. The initial consensus protein bound antibodies from DENV-1-3 in ELISA and Western blot assays. This sequence was altered in 3 steps to incorporate regions of maximum variability, identified as significant changes in the PCPs, characteristic of DENV-4 strains. The final protein was recognized by antibodies against all four serotypes. Two amino acids essential for efficient binding to all DENV antibodies are part of a discontinuous epitope previously defined for a neutralizing monoclonal antibody. The PCP-consensus method can significantly reduce the number of experiments required to define a multivalent antigen, which is particularly important when dealing with pathogens that must be tested at higher biosafety levels.

  11. Analysis of promotions

    Directory of Open Access Journals (Sweden)

    V.V. Bozhkova

    2011-03-01

    Full Text Available Article describes the classification of promotions and determining the effectiveness of specific measures to stimulate sales (which isnt possible practically in most advertising companies.

  12. Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice.

    Science.gov (United States)

    Krishnan, Meera R; Wang, Congmiao; Marion, Tony N

    2012-07-01

    The strongest serological correlate for lupus nephritis is antibody to double-stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane-binding anti-DNA antibody. Basement membrane-binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis.

  13. Laser-Initiated Free Radical Chain Reactions: Synthesis Of Hydroperoxides

    Science.gov (United States)

    Bray, R. G.; Chou, M. S.

    1984-05-01

    We have investigated the advantages of using laser-initiation for the synthesis of cumenehydroperoxide and t-butylhydroperoxide. Laser-initiation significantly improves the oxidation rates of cumene in the liquid phase and iso-butane in the vapor phase (using HBr promoters) with moderate photoefficiencies (418 and 490 respectively). The primary effect of laser-initiation is to reduce the induction period of the reaction. For the oxidation of cumene the beneficial effect of laser initiation is strongly dependent on laser wavelength, alternately enhancing (at 351 nm) or inhibiting (at 249 nm) the oxidation rate. For isobutane oxidation, laser-initiation also minimizes the HBr depletion rate relative to oxidation rate.

  14. Venturing into schools: Locating mental health initiatives in complex environments

    OpenAIRE

    Helen Askell-Williams; Lawson, Michael J.; Phillip T. Slee

    2009-01-01

    Schools provide viable settings for mental health promotion initiatives, such as programs to develop students’ social and emotional capabilities (SEC). Complexity in the school environments into which initiatives are introduced, such as diverse student capabilities, school structures, and teachers’ knowledge and confidence, will play an integral role in the success of those initiatives. This paper investigates the environments of schools about to receive the KidsMatter mental heath prom...

  15. Trypanosoma brucei: a putative RNA polymerase II promoter.

    Science.gov (United States)

    Bayele, Henry K

    2009-12-01

    RNA polymerase II (pol II) promoters are rare in the African trypanosome Trypanosoma brucei because gene regulation in the parasite is complex and polycistronic. Here, we describe a putative pol II promoter and its structure-function relationship. The promoter has features of an archetypal eukaryotic pol II promoter including putative canonical CCAAT and TATA boxes, and an initiator element. However, the spatial arrangement of these elements is only similar to yeast pol II promoters. Deletion mapping and transcription assays enabled delineation of a minimal promoter that could drive orientation-independent reporter gene expression suggesting that it may be a bidirectional promoter. In vitro transcription in a heterologous nuclear extract revealed that the promoter can be recognized by the basal eukaryotic transcription complex. This suggests that the transcription machinery in the parasite may be very similar to those of other eukaryotes.

  16. Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society December 7-10, 2015, San Diego, CA, USA.

    Science.gov (United States)

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M; Lund-Johansen, Fridtjof; Bradbury, Andrew R M; Carter, Paul J; Melis, Joost P M

    2016-01-01

    The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6-10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on "Antibodies to watch" in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries.

  17. Tissue-specific and pathogen-inducible expression of a fusion protein containing a Fusarium-specific antibody and a fungal chitinase protects wheat against Fusarium pathogens and mycotoxins.

    Science.gov (United States)

    Cheng, Wei; Li, He-Ping; Zhang, Jing-Bo; Du, Hong-Jie; Wei, Qi-Yong; Huang, Tao; Yang, Peng; Kong, Xian-Wei; Liao, Yu-Cai

    2015-06-01

    Fusarium head blight (FHB) in wheat and other small grain cereals is a globally devastating disease caused by toxigenic Fusarium pathogens. Controlling FHB is a challenge because germplasm that is naturally resistant against these pathogens is inadequate. Current control measures rely on fungicides. Here, an antibody fusion comprised of the Fusarium spp.-specific recombinant antibody gene CWP2 derived from chicken, and the endochitinase gene Ech42 from the biocontrol fungus Trichoderma atroviride was introduced into the elite wheat cultivar Zhengmai9023 by particle bombardment. Expression of this fusion gene was regulated by the lemma/palea-specific promoter Lem2 derived from barley; its expression was confirmed as lemma/palea-specific in transgenic wheat. Single-floret inoculation of independent transgenic wheat lines of the T3 to T6 generations revealed significant resistance (type II) to fungal spreading, and natural infection assays in the field showed significant resistance (type I) to initial infection. Gas chromatography-mass spectrometry analysis revealed marked reduction of mycotoxins in the grains of the transgenic wheat lines. Progenies of crosses between the transgenic lines and the FHB-susceptible cultivar Huamai13 also showed significantly enhanced FHB resistance. Quantitative real-time PCR analysis revealed that the tissue-specific expression of the antibody fusion was induced by salicylic acid drenching and induced to a greater extent by F. graminearum infection. Histochemical analysis showed substantial restriction of mycelial growth in the lemma tissues of the transgenic plants. Thus, the combined tissue-specific and pathogen-inducible expression of this Fusarium-specific antibody fusion can effectively protect wheat against Fusarium pathogens and reduce mycotoxin content in grain.

  18. Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system.

    Science.gov (United States)

    Cho, Sung Hoon; Raybuck, Ariel L; Stengel, Kristy; Wei, Mei; Beck, Thomas C; Volanakis, Emmanuel; Thomas, James W; Hiebert, Scott; Haase, Volker H; Boothby, Mark R

    2016-09-08

    Germinal centres (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen-activated B cells proliferate, express high-affinity antibodies, promote antibody class switching, and yield B cell memory. Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class, both cell-autonomous and extrinsic metabolic programming have emerged as modulators of T-cell-mediated immunity. Here we show in mice that GC light zones are hypoxic, and that low oxygen tension () alters B cell physiology and function. In addition to reduced proliferation and increased B cell death, low impairs antibody class switching to the pro-inflammatory IgG2c antibody isotype by limiting the expression of activation-induced cytosine deaminase (AID). Hypoxia induces HIF transcription factors by restricting the activity of prolyl hydroxyl dioxygenase enzymes, which hydroxylate HIF-1α and HIF-2α to destabilize HIF by binding the von Hippel-Landau tumour suppressor protein (pVHL). B-cell-specific depletion of pVHL leads to constitutive HIF stabilization, decreases antigen-specific GC B cells and undermines the generation of high-affinity IgG, switching to IgG2c, early memory B cells, and recall antibody responses. HIF induction can reprogram metabolic and growth factor gene expression. Sustained hypoxia or HIF induction by pVHL deficiency inhibits mTOR complex 1 (mTORC1) activity in B lymphoblasts, and mTORC1-haploinsufficient B cells have reduced clonal expansion, AID expression, and capacities to yield IgG2c and high-affinity antibodies. Thus, the normal physiology of GCs involves regional variegation of hypoxia, and HIF-dependent oxygen sensing regulates vital functions of B cells. We propose that the restriction of oxygen in lymphoid organs, which can be altered in pathophysiological states, modulates humoral immunity.

  19. Antiphospholipid Antibodies in Lupus Nephritis.

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    Ioannis Parodis

    Full Text Available Lupus nephritis (LN is a major manifestation of systemic lupus erythematosus (SLE. It remains unclear whether antiphospholipid antibodies (aPL alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204 or without (n = 294 LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous, before and after induction treatment (short-term outcomes. Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR and the Chronic Kidney Disease (CKD stage, after a median follow-up of 11.3 years (range: 3.3-18.8. Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all, but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1-2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are

  20. [Results of Booster Vaccination in Children with Primary Vaccine Failure after Initial Varicella Vaccination].

    Science.gov (United States)

    Ozakiv, Takao; Nishimura, Naoko; Gotoh, Kensei; Funahashi, Keiji; Yoshii, Hironori; Okuno, Yoshinobu

    2016-05-01

    In October 2014, the varicella vaccination policy in Japan was changed from a single voluntary inoculation to two routine inoculations. This paper reports the results of booster vaccination in children who did not show seroconversion after initial vaccination (i.e., primary vaccine failure : PVF) over a 7-year period prior to the introduction of routine varicella vaccination. Between November 2007 and May 2014, 273 healthy children aged between 1.1 and 14.5 years (median : 1.7 years) underwent varicella vaccination. Before and 4 to 6 weeks after vaccination, the antibody titers were measured using an immune adherence hemagglutination (IAHA) assay and a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). In addition, side reactions were examined during the four-week period after vaccination. Children who did not show IAHA seroconversion (PVF) were recommended to receive a booster vaccination, and the measurement of antibody titers and an assessment of side reactions were performed after the booster dose. In May 2015, a questionnaire was mailed to each of the 273 participants to investigate whether they had developed varicella and/or herpes zoster after vaccination. After initial vaccination, the IAHA seroconversion rate was 75% and the mean antibody titer (Log2) with seroconversion was 4.7, while the gpELISA seroconversion rate was 84% and the mean antibody titer (Log10) with seroconversion was 2.4. Among children with PVF, 54 received booster vaccination within 81 to 714 days (median : 139 days) after the initial vaccination. After booster vaccination, the IAHA seroconversion rate was 98% and the mean antibody titer (Log2) with seroconversion was 5.8. Both the seroconversion rate and the antibody titer were higher compared with the values after the initial vaccination (p vaccination, the gpELISA seropositive rate was 100% and the mean positive antibody titer (Log 10) was 3.6 ; similar results were obtained for the IAHA assay, with a significantly higher