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  • Journal article
    Comninos A, Jayasena C, Nijher G, Abbara A, De Silva A, Veldhuis J, Ratnasabapathy R, Izzi-Engbeaya C, Lim A, Patel D, Ghatei M, Bloom S, Dhillo Wet al., 2014,

    The effects of kisspeptin administration on the menstrual cycle in healthy women

    , LANCET, Vol: 383, Pages: 37-37, ISSN: 0140-6736
  • Journal article
    Kim MJ, Turner CM, Hewitt R, Smith J, Bhangal G, Pusey CD, Unwin RJ, Tam FWKet al., 2014,

    Exaggerated renal fibrosis in P2X4 receptor-deficient mice following unilateral ureteric obstruction

    , Nephrology Dialysis Transplantation, Vol: 29, Pages: 1350-1361, ISSN: 1460-2385

    Background. The ATP-sensitive P2X7 receptor (P2X7R) hasbeen shown to contribute to renal injury in nephrotoxic nephritis,a rodent model of acute glomerulonephritis, and in unilateral uretericobstruction (UUO), a rodent model of chronic interstitialinflammation and fibrosis. Renal tubular cells, endothelial cellsand macrophages also express the closely related P2X4 receptor(P2X4R), which is chromosomally co-located with P2X7R andhas 40% homology; it is also pro-inflammatory and has beenshown to interact with P2X7R to modulate its pro-apoptotic andpro-inflammatory effects. Therefore, we chose to explore the functionof P2X4R in the UUO model of renal injury using knockoutmice. We hypothesized that UUO-induced tubulointerstitialdamage and fibrosis would also be attenuated in P2X4R−/− mice.Method. P2X4R−/− and wild-type (WT) mice were subjectedto either UUO or sham operation. Kidney samples taken onDays 7 and 14 were evaluated for renal inflammation and fi-brosis, and expression of pro-fibrotic factors.Results. To our surprise, the obstructed kidney in P2X4R−/−mice showed more severe renal injury, more collagen deposition( picrosirius red staining, increase of 53%; P < 0.05) andmore type I collagen staining (increase of 107%; P < 0.01), aswell as increased mRNA for TGF-β (increase of 102%, P <0.0005) and CTGF (increase of 157%; P < 0.05) by Day 14,compared with the UUO WT mice.Conclusion. These findings showed that lack of P2X4Rexpression leads to increased renal fibrosis, and increasedexpression of TGF-β and CTGF in the UUO model.

  • Journal article
    Kiguli S, Akech SO, Mtove G, Opoka RO, Engoru C, Olupot-Olupot P, Nyeko R, Evans J, Crawley J, Prevatt N, Reyburn H, Levin M, George EC, South A, Babiker AG, Gibb DM, Maitland Ket al., 2014,

    WHO GUIDELINES ON FLUID RESUSCITATION IN CHILDREN Concerns about intravenous fluids given to critically ill children Reply

    , BMJ-BRITISH MEDICAL JOURNAL, Vol: 348, ISSN: 1756-1833
  • Journal article
    Gurung P, Anand PK, Malireddi RKS, Walle LV, Van Opdenbosch N, Dillon CP, Weinlich R, Green DR, Lamkanfi M, Kanneganti T-Det al., 2014,

    FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes

    , Journal of Immunology, Vol: 192, Pages: 1835-1846, ISSN: 0022-1767

    The Nlrp3 inflammasome is critical for host immunity, but the mechanisms controlling its activation are enigmatic. In this study, we show that loss of FADD or caspase-8 in a RIP3-deficient background, but not RIP3 deficiency alone, hampered transcriptional priming and posttranslational activation of the canonical and noncanonical Nlrp3 inflammasome. Deletion of caspase-8 in the presence or absence of RIP3 inhibited caspase-1 and caspase-11 activation by Nlrp3 stimuli but not the Nlrc4 inflammasome. In addition, FADD deletion prevented caspase-8 maturation, positioning FADD upstream of caspase-8. Consequently, FADD- and caspase-8–deficient mice had impaired IL-1β production when challenged with LPS or infected with the enteropathogen Citrobacter rodentium. Thus, our results reveal FADD and caspase-8 as apical mediators of canonical and noncanonical Nlrp3 inflammasome priming and activation.

  • Journal article
    Dionne MS, 2014,

    Immune-metabolic interaction in <i>Drosophila</i>

    , FLY, Vol: 8, Pages: 75-79, ISSN: 1933-6934
  • Journal article
    Ssemaganda A, Kindinger L, Bergin P, Nielsen L, Mpendo J, Ssetaala A, Kiwanuka N, Munder M, Teoh TG, Kropf P, Mueller Iet al., 2014,

    Characterization of neutrophil subsets in healthy human pregnancies

    , PLOS One, Vol: 9, ISSN: 1932-6203

    We have previously shown that in successful pregnancies increased arginase activity is a mechanism that contributes to the suppression of the maternal immune system. We identified the main type of arginase-expressing cells as a population of activated low-density granulocytes (LDGs) in peripheral blood mononuclear cells and in term placentae. In the present study, we analyzed the phenotype of LDGs and compared it to the phenotype of normal density granulocytes (NDGs) in maternal peripheral blood, placental biopsies and cord blood. Our data reveal that only LDGs but no NDGs could be detected in placental biopsies. Phenotypically, NDGs and LDGs from both maternal and cord blood expressed different levels of maturation, activation and degranulation markers. NDGs from the maternal and cord blood were phenotypically similar, while maternal, cord and placental LDGs showed different expression levels of CD66b. LDGs present in cord blood expressed higher levels of arginase compared to maternal and placental LDGs. In summary, our results show that in maternal and cord blood, two phenotypically different populations of neutrophils can be identified, whereas in term placentae, only activated neutrophils are present.

  • Journal article
    Findlay EG, Danks L, Madden J, Cavanagh MM, McNamee K, McCann F, Snelgrove RJ, Shaw S, Feldmann M, Taylor PC, Horwood NJ, Hussell Tet al., 2014,

    OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis

    , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 111, Pages: 2289-2294, ISSN: 0027-8424
  • Journal article
    Bower M, Dalla Pria A, Coyle C, Andrews E, Tittle V, Dhoot S, Nelson Met al., 2014,

    Prospective Stage-Stratified Approach to AIDS-Related Kaposi's Sarcoma

    , JOURNAL OF CLINICAL ONCOLOGY, Vol: 32, Pages: 409-414, ISSN: 0732-183X
  • Journal article
    Van der Watt JJ, Wilkinson KA, Wilkinson RJ, Heckmann JMet al., 2014,

    Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study

    , BMC INFECTIOUS DISEASES, Vol: 14, ISSN: 1471-2334
  • Journal article
    Moreira FTC, Sharma S, Dutra RAF, Noronha JPC, Cass AEG, Sales MGFet al., 2014,

    Protein-responsive polymers for point-of care detection of cardiac biomarker

    , Sensors and Actuators B: Chemica

    This work describes a novel use for the polymeric film, Poly (o-aminophenol) (PAP) that was made responsive to a specific protein. This was achieved through templated electropolymerization of aminophenol (AP) in the presence of protein. The procedure involved adsorbing protein on the electrode surface and thereafter electroploymerizing the aminophenol. Proteins embedded at the outer surface of the polymeric film were digested by proteinase K and then washed away thereby creating vacant sites. The capacity of the template film to specifically rebind protein was tested with Myoglobin (Myo), a cardiac biomarker for ischemia. The films acted as biomimetic artificial antibodies and were produced on a gold (Au) screen printed electrode (SPE), as a step towards disposable sensors to enable point-of-care applications.Raman spectroscopy was used to follow the surface modification of the Au-SPE. The ability of the material to rebind Myo was measured by electrochemical techniques, namely electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). The devices displayed linear responses to Myo in EIS and SWV assays down to 4.0 μg/mL and 3.5 μg/mL, respectively, with detection limits of 1.5 and 0.8 μg/mL. Good selectivity was observed in the presence of troponin T (TnT) and creatine kinase (CKMB) in SWV assays, and accurate results were obtained in applications to spiked serum. The sensor described in this work is a potential tool for screening Myo in point-of-care due to the simplicity of fabrication, disposability, short time response, low cost, good sensitivity and selectivity.

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