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Journal articleChatterjee J, Howden S, Saso S, et al., 2016,
Metastatic low-grade fibromyxoid sarcoma of the broad ligament: A case report and literature review.
, Journal of Obstetrics and Gynaecology, Pages: 1-3, ISSN: 1364-6893 -
Journal articleElbediwy A, Vincent-Mistiaen ZI, Spencer-Dene B, et al., 2016,
Integrin signalling regulates YAP and TAZ to control skin homeostasis
, DEVELOPMENT, Vol: 143, Pages: 1674-1687, ISSN: 0950-1991- Author Web Link
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- Citations: 222
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Journal articleBertram CD, Macaskill C, Moore Jr JE, 2016,
Pump function curve shape for a model lymphatic vessel
, Medical Engineering & Physics, Vol: 38, Pages: 656-663, ISSN: 1873-4030The transport capacity of a contractile segment of lymphatic vessel is defined by its pump function curve relating mean flow-rate and adverse pressure difference. Numerous system characteristics affect curve shape and the magnitude of the generated flow-rates and pressures. Some cannot be varied experimentally, but their separate and interacting effects can be systematically revealed numerically. This paper explores variations in the rate of change of active tension and the form of the relation between active tension and muscle length, factors not known from experiment to functional precision. Whether the pump function curve bends toward or away from the origin depends partly on the curvature of the passive pressure-diameter relation near zero transmural pressure, but rather more on the form of the relation between active tension and muscle length. A pump function curve bending away from the origin defines a well-performing pump by maximum steady output power. This behaviour is favoured by a length/active-tension relationship which sustains tension at smaller lengths. Such a relationship also favours high peak mechanical efficiency, defined as output power divided by the input power obtained from the lymphangion diameter changes and active-tension time-course. The results highlight the need to pin down experimentally the form of the active tension/length relationship.
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Conference paperOjo OO, Wiegman C, Chung K, et al., 2016,
Necroptosis signalling in lung epithelial cells modulates mitochondrial function and reactive oxygen species generation in healthy and asthmatic airway smooth muscle (ASM) cells
, International Conference of the American Thoracic Society (ATS), Publisher: American Thoracic Society, ISSN: 1535-4970 -
Journal articleHolt RJ, Vandiedonck C, Willis-Owen SA, et al., 2016,
A functional AT/G polymorphism in the 5'-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14.
, Genes Immun, Vol: 18, Pages: 57-57 -
Journal articleDe Guio F, Jouvent E, Biessels GJ, et al., 2016,
Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease.
, Journal of Cerebral Blood Flow & Metabolism, Vol: 36, Pages: 1319-1337, ISSN: 0271-678XBrain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.
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Journal articleCheeseman HM, Carias AM, Evans AB, et al., 2016,
Expression profile of human Fc receptors in mucosal tissue: implications for antibody-dependent cellular effector functions targeting HIV-1 transmission
, PLOS One, Vol: 11, ISSN: 1932-6203The majority of new Human Immunodeficiency Virus (HIV)-1 infections are acquired via sexual transmission at mucosal surfaces. Partial efficacy (31.2%) of the Thai RV144 HIV-1 vaccine trial has been correlated with Antibody-dependent Cellular Cytotoxicity (ADCC) mediated by non-neutralizing antibodies targeting the V1V2 region of the HIV-1 envelope. This has led to speculation that ADCC and other antibody-dependent cellular effector functions might provide an important defense against mucosal acquisition of HIV-1 infection. However, the ability of antibody-dependent cellular effector mechanisms to impact on early mucosal transmission events will depend on a variety of parameters including effector cell type, frequency, the class of Fc-Receptor (FcR) expressed, the number of FcR per cell and the glycoslyation pattern of the induced antibodies. In this study, we characterize and compare the frequency and phenotype of IgG (CD16 [FcγRIII], CD32 [FcγRII] and CD64 [FcγRI]) and IgA (CD89 [FcαR]) receptor expression on effector cells within male and female genital mucosal tissue, colorectal tissue and red blood cell-lysed whole blood. The frequency of FcR expression on CD14+ monocytic cells, myeloid dendritic cells and natural killer cells were similar across the three mucosal tissue compartments, but significantly lower when compared to the FcR expression profile of effector cells isolated from whole blood, with many cells negative for all FcRs. Of the three tissues tested, penile tissue had the highest percentage of FcR positive effector cells. Immunofluorescent staining was used to determine the location of CD14+, CD11c+ and CD56+ cells within the three mucosal tissues. We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria. The potential implication of the observed FcR expression patterns on the effectiveness of FcR-dependent cellular effector functions to impact on the ini
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Journal articleArmstrong-James DPH, 2016,
Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death
, American Journal of Respiratory and Critical Care Medicine, Vol: 194, Pages: 1127-1139, ISSN: 1535-4970Rationale: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis.Objectives: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants.Methods: We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies.Measurements and Main Results: Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell–cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape.Conclusions: These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.
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Journal articleCosgrove CA, Lacey CJ, Cope AV, et al., 2016,
Comparative immunogenicity of HIV-1 gp140 vaccine delivered by parenteral, and mucosal routes in female volunteers; MUCOVAC2, a randomized two centre study
, PLOS One, Vol: 11, ISSN: 1932-6203BackgroundDefining optimal routes for induction of mucosal immunity represents an important research priority for the HIV-1 vaccine field. In particular, it remains unclear whether mucosal routes of immunization can improve mucosal immune responses.MethodsIn this randomized two center phase I clinical trial we evaluated the systemic and mucosal immune response to a candidate HIV-1 Clade C CN54gp140 envelope glycoprotein vaccine administered by intramuscular (IM), intranasal (IN) and intravaginal (IVAG) routes of administration in HIV negative female volunteers. IM immunizations were co-administered with Glucopyranosyl Lipid Adjuvant (GLA), IN immunizations with 0.5% chitosan and IVAG immunizations were administered in an aqueous gel.ResultsThree IM immunizations of CN54 gp140 at either 20 or 100 μg elicited significantly greater systemic and mucosal antibodies than either IN or IVAG immunizations. Following additional intramuscular boosting we observed an anamnestic antibody response in nasally primed subjects. Modest neutralizing responses were detected against closely matched tier 1 clade C virus in the IM groups. Interestingly, the strongest CD4 T-cell responses were detected after IN and not IM immunization.ConclusionsThese data show that parenteral immunization elicits systemic and mucosal antibodies in women. Interestingly IN immunization was an effective prime for IM boost, while IVAG administration had no detectable impact on systemic or mucosal responses despite IM priming.
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Journal articleLaskowski J, Renner B, Le Quintrec M, et al., 2016,
Distinct roles for the complement regulators factor H and Crry in protection of the kidney from injury
, Kidney International, Vol: 90, Pages: 109-122, ISSN: 1523-1755Mutations in the complement regulatory proteins are associated with several different diseases. Although these mutations cause dysregulated alternative pathway activation throughout the body, the kidneys are the most common site of injury. The susceptibility of the kidney to alternative pathway-mediated injury may be due to limited expression of complement regulatory proteins on several tissue surfaces within the kidney. To examine the roles of the complement regulatory proteins factor H and Crry in protecting distinct renal surfaces from alternative pathway mediated injury, we generated mice with targeted deletions of the genes for both proteins. Surprisingly, mice with combined genetic deletions of factor H and Crry developed significantly milder renal injury than mice deficient in only factor H. Deficiency of both factor H and Crry was associated with C3 deposition at multiple locations within the kidney, but glomerular C3 deposition was lower than that in factor H alone deficient mice. Thus, factor H and Crry are critical for regulating complement activation at distinct anatomic sites within the kidney. However, widespread activation of the alternative pathway reduces injury by depleting the pool of C3 available at any 1 location.
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