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  1. Article ; Online: Macrophages exert homeostatic actions in pregnancy to protect against preterm birth and fetal inflammatory injury

    Nardhy Gomez-Lopez / Valeria Garcia-Flores / Peck Yin Chin / Holly M. Groome / Melanie T. Bijland / Kerrilyn R. Diener / Roberto Romero / Sarah A. Robertson

    JCI Insight, Vol 6, Iss

    2021  Volume 19

    Abstract: Macrophages are commonly thought to contribute to the pathophysiology of preterm labor by amplifying inflammation — but a protective role has not previously been considered to our knowledge. We hypothesized that given their antiinflammatory capability in ...

    Abstract Macrophages are commonly thought to contribute to the pathophysiology of preterm labor by amplifying inflammation — but a protective role has not previously been considered to our knowledge. We hypothesized that given their antiinflammatory capability in early pregnancy, macrophages exert essential roles in maintenance of late gestation and that insufficient macrophages may predispose individuals to spontaneous preterm labor and adverse neonatal outcomes. Here, we showed that women with spontaneous preterm birth had reduced CD209+CD206+ expression in alternatively activated CD45+CD14+ICAM3– macrophages and increased TNF expression in proinflammatory CD45+CD14+CD80+HLA-DR+ macrophages in the uterine decidua at the materno-fetal interface. In Cd11bDTR/DTR mice, depletion of maternal CD11b+ myeloid cells caused preterm birth, neonatal death, and postnatal growth impairment, accompanied by uterine cytokine and leukocyte changes indicative of a proinflammatory response, while adoptive transfer of WT macrophages prevented preterm birth and partially rescued neonatal loss. In a model of intra-amniotic inflammation–induced preterm birth, macrophages polarized in vitro to an M2 phenotype showed superior capacity over nonpolarized macrophages to reduce uterine and fetal inflammation, prevent preterm birth, and improve neonatal survival. We conclude that macrophages exert a critical homeostatic regulatory role in late gestation and are implicated as a determinant of susceptibility to spontaneous preterm birth and fetal inflammatory injury.
    Keywords Reproductive biology ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article: CoVaccine HT™ adjuvant is superior to Freund's adjuvants in eliciting antibodies against the endogenous alarmin HMGB1

    Lakhan, Nerissa / John D. Hayball / Kerrilyn R. Diener / Natalie E. Stevens

    Journal of Immunological Methods. 2016,

    2016  

    Abstract: Adjuvants are used to enhance the immune response against specific antigens for the production of antibodies, with the choice of adjuvant most critical for poorly immunogenic and self-antigens. This study quantitatively and qualitatively evaluated ... ...

    Abstract Adjuvants are used to enhance the immune response against specific antigens for the production of antibodies, with the choice of adjuvant most critical for poorly immunogenic and self-antigens. This study quantitatively and qualitatively evaluated CoVaccine HT™ and Freund's adjuvants for eliciting therapeutic ovine polyclonal antibodies targeting the endogenous alarmin, high mobility group box-1 (HMGB1). Sheep were immunised with HMGB1 protein in CoVaccine HT™ or Freund's adjuvants, with injection site reactions and antibody titres periodically assessed. The binding affinity of antibodies for HMGB1 and their neutralisation activity was determined in-vitro, with in vivo activity confirmed using a murine model of endotoxemia. Results indicated that CoVaccine HT™ elicited significantly higher antibody tires with stronger affinity and more functional potency than antibodies induced with Freund's adjuvants. These studies provide evidence that CoVaccine HT™ is superior to Freund's adjuvants for the production of antibodies to antigens with low immunogenicity and supports the use of this alternative adjuvant for clinical and experimental use antibodies.
    Keywords adjuvants ; animal models ; antigens ; binding capacity ; endotoxemia ; immune response ; injection site ; neutralization ; nucleoproteins ; polyclonal antibodies ; sheep ; tires
    Language English
    Size p. .
    Publishing place Elsevier B.V.
    Document type Article
    Note Pre-press version
    ZDB-ID 120142-6
    ISSN 1872-7905 ; 0022-1759
    ISSN (online) 1872-7905
    ISSN 0022-1759
    DOI 10.1016/j.jim.2016.09.008
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Innate Immunity and Biomaterials at the Nexus

    Susan N. Christo / Kerrilyn R. Diener / Akash Bachhuka / Krasimir Vasilev / John D. Hayball

    BioMed Research International, Vol

    Friends or Foes

    2015  Volume 2015

    Abstract: Biomaterial implants are an established part of medical practice, encompassing a broad range of devices that widely differ in function and structural composition. However, one common property amongst biomaterials is the induction of the foreign body ... ...

    Abstract Biomaterial implants are an established part of medical practice, encompassing a broad range of devices that widely differ in function and structural composition. However, one common property amongst biomaterials is the induction of the foreign body response: an acute sterile inflammatory reaction which overlaps with tissue vascularisation and remodelling and ultimately fibrotic encapsulation of the biomaterial to prevent further interaction with host tissue. Severity and clinical manifestation of the biomaterial-induced foreign body response are different for each biomaterial, with cases of incompatibility often associated with loss of function. However, unravelling the mechanisms that progress to the formation of the fibrotic capsule highlights the tightly intertwined nature of immunological responses to a seemingly noncanonical “antigen.” In this review, we detail the pathways associated with the foreign body response and describe possible mechanisms of immune involvement that can be targeted. We also discuss methods of modulating the immune response by altering the physiochemical surface properties of the biomaterial prior to implantation. Developments in these areas are reliant on reproducible and effective animal models and may allow a “combined” immunomodulatory approach of adapting surface properties of biomaterials, as well as treating key immune pathways to ultimately reduce the negative consequences of biomaterial implantation.
    Keywords Medicine ; R
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Transient dominant host-range selection using Chinese hamster ovary cells to generate marker-free recombinant viral vectors from vaccinia virus

    Liang Liu / Tamara Cooper / Preethi Eldi / Pablo Garcia-Valtanen / Kerrilyn R. Diener / Paul M. Howley / John D. Hayball

    BioTechniques, Vol 62, Iss 4, Pp 183-

    2017  Volume 187

    Abstract: Recombinant vaccinia viruses (rVACVs) are promising antigen-delivery systems for vaccine development that are also useful as research tools. Two common methods for selection during construction of rVACV clones are (i) co-insertion of drug resistance or ... ...

    Abstract Recombinant vaccinia viruses (rVACVs) are promising antigen-delivery systems for vaccine development that are also useful as research tools. Two common methods for selection during construction of rVACV clones are (i) co-insertion of drug resistance or reporter protein genes, which requires the use of additional selection drugs or detection methods, and (ii) dominant host-range selection. The latter uses VACV variants rendered replication-incompetent in host cell lines by the deletion of host-range genes. Replicative ability is restored by co-insertion of the host-range genes, providing for dominant selection of the recombinant viruses. Here, we describe a new method for the construction of rVACVs using the cowpox CP77 protein and unmodified VACV as the starting material. Our selection system will expand the range of tools available for positive selection of rVACV during vector construction, and it is substantially more high-fidelity than approaches based on selection for drug resistance.
    Keywords Vaccinia ; CHO ; CP77 ; host-range factor ; recombinant virus construction ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher Future Science Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes

    Natalie E. Stevens / Marianne J. Chapman / Cara K. Fraser / Tim R. Kuchel / John D. Hayball / Kerrilyn R. Diener

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 14

    Abstract: Abstract Sepsis remains a significant health burden and a major clinical need exists for therapeutics to dampen the excessive and uncontrolled immune activation. Nuclear protein high mobility group box protein 1 (HMGB1) is released following cell death ... ...

    Abstract Abstract Sepsis remains a significant health burden and a major clinical need exists for therapeutics to dampen the excessive and uncontrolled immune activation. Nuclear protein high mobility group box protein 1 (HMGB1) is released following cell death and is a late mediator in sepsis pathogenesis. While approaches targeting HMGB1 have demonstrated reduced mortality in pre-clinical models of sepsis, the impact of HMGB1 blockade on the complex septic inflammatory milieu and the development of subsequent immunosuppression remain enigmatic. Analysis of plasma samples obtained from septic shock patients established an association between increased HMGB1 and non-survival, higher APACHE II scores, and increased pro-inflammatory cytokine responses. Pre-clinically, administration of neutralising ovine anti-HMGB1 polyclonal antibodies improved survival in murine endotoxaemia and caecal ligation and puncture-induced sepsis models, and altered early cytokine profiles to one which corresponded to patterns observed in the surviving patient cohort. Additionally, anti-HMGB1 treated murine sepsis survivors were significantly more resistant to secondary bacterial infection and exhibited altered innate immune cell phenotypes and cytokine responses. These findings demonstrate that anti-HMGB1 antibodies alter inflammation in murine sepsis models and reduce sepsis mortality without potentiating immunosuppression.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2017-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: It takes a community to conceive

    Sophie G.E. Kedzior / Tina Bianco-Miotto / James Breen / Kerrilyn R. Diener / Martin Donnelley / Kylie R. Dunning / Megan A.S. Penno / John E. Schjenken / David J. Sharkey / Nicolette A. Hodyl / Tod Fullston / Maria Gardiner / Hannah M. Brown / Alice R. Rumbold

    Reproductive Biomedicine & Society Online, Vol 9, Iss , Pp 48-

    an analysis of the scope, nature and accuracy of online sources of health information for couples trying to conceive

    2019  Volume 63

    Abstract: This study examined the nature and accuracy of information available across online platforms for couples trying to conceive. A consumer simulation-based investigation of English websites and social media (Facebook, Twitter, Instagram) was undertaken ... ...

    Abstract This study examined the nature and accuracy of information available across online platforms for couples trying to conceive. A consumer simulation-based investigation of English websites and social media (Facebook, Twitter, Instagram) was undertaken using common search terms identified in a pilot study. Claims about fertility and pregnancy health were then extracted from the results and analysed thematically. The accuracy of each claim was assessed independently by six fertility and conception experts, rated on a scale of 1 (not factual) to 4 (highly factual), with scores collated to produce a median rating. Claims with a median score <3 were classified as inaccurate. The use of the terms 'trying to conceive' and '#TTC' were common identifiers on online platforms. Claims were extracted predominantly from websites (n = 89) rather than social media, with Twitter and Instagram comprising commercial elements and Facebook focused on community-based support. Thematic analysis revealed three major themes among the claims across all platforms: conception behaviour and monitoring, lifestyle and exposures, and medical. Fact-checking by the experts revealed that 40% of the information assessed was inaccurate, and that inaccuracies were more likely to be present in the conception behaviour and monitoring advice, the topics most amenable to modification. Since online information is a readily accessible and commonly utilized resource, there is opportunity for improved dissemination of evidence-based material to reach interested couples. Further cross-disciplinary and consumer-based research, such as a user survey, is required to understand how best to provide the 'trying to conceive' community with accurate information. Keywords: internet, social media, conception, fertility, accuracy
    Keywords Reproduction ; QH471-489 ; Social sciences (General) ; H1-99
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Cytolytic DNA vaccine encoding lytic perforin augments the maturation of- and antigen presentation by- dendritic cells in a time-dependent manner

    Danushka K. Wijesundara / Wenbo Yu / Ben J. C. Quah / Preethi Eldi / John D. Hayball / Kerrilyn R. Diener / Ilia Voskoboinik / Eric J. Gowans / Branka Grubor-Bauk

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 8

    Abstract: Abstract The use of cost-effective vaccines capable of inducing robust CD8+ T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA ... ...

    Abstract Abstract The use of cost-effective vaccines capable of inducing robust CD8+ T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8+ T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8+ T cell immunity. In vitro data showed that transfection of HEK293T cells with the cytolytic DNA resulted in the release of lactate dehydrogenase, indicative of necrotic/lytic cell death. In vitro exposure of this lytic cell debris to purified DCs from naïve C57BL/6 mice resulted in maturation of DCs as determined by up-regulation of CD80/CD86. Using activation/proliferation of adoptively transferred OT-I CD8+ T cells to measure antigen presentation by DCs in vivo, it was determined that cytolytic DNA immunisation resulted in a time-dependent increase in the proliferation of OT-I CD8+ T cells compared to canonical DNA immunisation. Overall, the data suggest that the cytolytic DNA vaccine increases the activity of DCs which has important implications for the design of DNA vaccines to improve their translational prospects.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2017-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT™ is functionally superior to Freund's adjuvant.

    Natalie E Stevens / Cara K Fraser / Mohammed Alsharifi / Michael P Brown / Kerrilyn R Diener / John D Hayball

    PLoS ONE, Vol 8, Iss 7, p e

    2013  Volume 68895

    Abstract: Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the ... ...

    Abstract Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund's adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund's adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.
    Keywords Medicine ; R ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Hybrid core/shell microparticles and their use for understanding biological processes

    Bachhuka, Akash / Agnieszka Mierczynska / Alex Cavallaro / Jim Manavis / John D. Hayball / Kerrilyn R. Diener / Krasimir Vasilev / Louise E. Smith / Romeo Marian / Susan N. Christo

    Journal of colloid and interface science. 2015 Nov. 01, v. 457

    2015  

    Abstract: Hybrid micro and nanoparticles have become a topic of intense research in recent years. This is due to the special properties of these materials that open new avenues in advanced applications. Herein, we report a novel method for the generation of hybrid ...

    Abstract Hybrid micro and nanoparticles have become a topic of intense research in recent years. This is due to the special properties of these materials that open new avenues in advanced applications. Herein, we report a novel method for the generation of hybrid particles utilising plasma polymerization. Poly (methyl methacrylate) (PMMA) beads were first coated with a thin allylamine based plasma polymer layer. Gold nanoparticles of engineered size and surface structure were then attached in a controlled manner to the plasma polymer coated beads. To generate uniform chemistry on the outermost surface and to preserve the nanotopography, we deposited a 5–10nm thin layer of Acpp. We demonstrated that these particles can be utilized in in vivo models to interrogate important biological phenomena. Specifically, we used them in mice to study the inflammatory and foreign body responses to surface nanotopography. The data strongly indicates that surface nanotopography and chemistry can modulate collagen production and the number of adhering immune cells. The method for generating hybrid particles reported here is solvent free and can open new opportunities in fields such as tissue engineering, drug delivery, biosensors, and regenerative medicine.
    Keywords biological properties and phenomena ; biosensors ; collagen ; drugs ; medicine ; methodology ; mice ; microparticles ; models ; nanogold ; nanoparticles ; polymerization ; polymethylmethacrylate ; solvents ; tissue engineering
    Language English
    Dates of publication 2015-1101
    Size p. 9-17.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 241597-5
    ISSN 1095-7103 ; 0021-9797
    ISSN (online) 1095-7103
    ISSN 0021-9797
    DOI 10.1016/j.jcis.2015.06.040
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: A vaccinia-based single vector construct multi-pathogen vaccine protects against both Zika and chikungunya viruses

    Natalie A. Prow / Liang Liu / Eri Nakayama / Tamara H. Cooper / Kexin Yan / Preethi Eldi / Jessamine E. Hazlewood / Bing Tang / Thuy T. Le / Yin Xiang Setoh / Alexander A Khromykh / Jody Hobson-Peters / Kerrilyn R. Diener / Paul M. Howley / John D. Hayball / Andreas Suhrbier

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 12

    Abstract: Zika and chikungunya virus are co-circulating in many regions and currently there is no approved vaccine for either virus. Here, the authors engineer one vaccinia virus based vaccine for both, Zika and chikungunya, and show protection from infection and ... ...

    Abstract Zika and chikungunya virus are co-circulating in many regions and currently there is no approved vaccine for either virus. Here, the authors engineer one vaccinia virus based vaccine for both, Zika and chikungunya, and show protection from infection and pathogenesis in mice.
    Keywords Science ; Q
    Language English
    Publishing date 2018-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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