ORCID Profile
0000-0001-7640-8326
Current Organisation
Ribomaps
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Publisher: Australian International Academic Centre
Date: 05-02-2016
Publisher: Springer Science and Business Media LLC
Date: 09-05-2012
Publisher: Canadian Science Publishing
Date: 02-2015
Abstract: This study investigated whether the putative physiological benefits induced by growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are countered at supra-physiological concentrations because of an augmentation in the production of mitochondrial-derived free radicals with a subsequent increase in oxidative damage, compromising mitochondrial function. To test this hypothesis, peripheral blood mononuclear cells were incubated for 4 h with either recombinant human GH (rhGH) (range = 0.25–100 μg/L) or recombinant IGF-1 (rIGF-1) (range = 100–600 μg/L) and along with control s les were subsequently analyzed by flow cytometry for the determination of cellular viability, mitochondrial membrane potential (Δψ m ), mitochondrial superoxide (O 2 – ) generation, and mitochondrial permeability transition pore (mtPTP) activity. Results showed levels of mitochondrial O 2 – generation to be significantly reduced compared with control s les (lymphocytes: 21.5 ± 1.6 AU monocytes: 230.2 ± 9.8 AU) following rhGH treatment at both concentrations of 5 μg/L (13.5 ± 1.3 AU, P ≤ 0.05) and 10 μg/L (12.3 ± 1.5 AU, P ≤ 0.05) in lymphocytes and at 10 μg/L (153.4 ± 11.4 AU, P ≤ 0.05) in monocytes. However, no significant effect was found at either higher rhGH concentrations or following treatment with any concentration of rIGF-1. In addition, neither of the 2 hormones had any significant effect on Δψ m , mtPTP activity, or on cellular viability. In conclusion, physiological concentrations of rhGH elicited a protective cellular effect through the reduction of oxidative free radicals within mitochondria. This antioxidant effect was diminished at supra-physiological concentrations but not to a level that would elicit disruption of mitochondrial function.
Publisher: MDPI AG
Date: 05-06-2015
Publisher: Physical Education and Sport Faculty
Date: 28-09-2015
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.IMLET.2016.10.010
Abstract: Exercise immunology research has traditionally focussed on aerobic-exercise, however it has become apparent in more recent years that resistance-exercise can also considerably affect host immunobiology. To date however, no systematic process has been used to establish a dose-response relationship between resistance-exercise and the immune system. The present systematic review was thus conducted to determine the dose-response effects of a bout of resistance-exercise on acute leukocyte counts. In accordance with the PRISMA guidelines, a systematic literature search was conducted in the electronic databases, PubMed, Web of Science, and Google Scholar, over the date range of 1989-2016. Following the PICO elements, eligibility criteria included: i) participants: healthy humans aged 18-40 ii) intervention: a single bout of resistance-exercise iii) comparator: at least one comparator group iv) outcome: acute measures of circulating leukocyte counts. Specific exclusion criteria were also applied. Risk of bias and quality of evidence was assessed using the PEDro scale. Due to the in idual designs of the admitted studies, a qualitative analysis (systematic narrative synthesis) was employed in the present review. The results of the present review demonstrate that a single bout of resistance-exercise induces an acute monocytosis, neutrophilia, and lymphocytosis. It became apparent that the reviewed literature either does not consistently specify, or does not describe with sufficient detail, the time-course between the onset of exercise and the collection of blood. We recommend that researchers consider addressing this in future studies, and also collect blood measures during exercise to aid with comparison of temporal effects. Regarding the determination of a dose-response relationship, an acute neutrophilia, monocytosis and lymphocytosis appears to occur more rapidly and to a greater magnitude following a single bout of high-dose vs low-dose resistance-exercise. Mechanistically, exercise-induced cell trafficking changes are associated with mechanical, metabolic and endocrine factors. Physical aptitude of the host may also affect resistance-exercise-induced lymphocyte trafficking responses.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
Publisher: Springer Science and Business Media LLC
Date: 30-08-2016
Publisher: Springer Science and Business Media LLC
Date: 15-06-2016
DOI: 10.1007/S00421-016-3413-Z
Abstract: Compare capillary and venous blood in the analysis of concentration and function of leucocyte sub-populations. This study hypothesised that capillary s les may be used in a site-specific manner as an alternative source of blood s les for assays of leucocyte concentration and neutrophilic phagocytic function and reactive oxygen species (ROS) production, allowing acquisition of multiple s les to better monitor transient but significant post-exercise immune modulation. Resting blood s les were simultaneously obtained from vein, finger and earlobe of healthy subjects (n = 10, age: 25.1 ± 3.1 years). Leucocyte concentrations were measured using a five-part differential haematological analyser. Leucocyte sub-populations (CD3, CD4, CD8, CD19, CD56, CD14) and granulocytic functional-related (CD11b, CD18, CD16b, CD66b) surface antigen markers, neutrophil phagocytosis (FITC-labelled Escherichia coli) and stimulated ROS production (DHR) were quantified utilizing flow cytometry. A MANOVA (α < 0.05 significance) analysed the effects of the different s ling sites in the concentrations of leucocyte populations, their surface antigen expression and granulocytic functions. Leucocyte concentration and neutrophilic ROS production yielded non-significant differences between s ling sites. Expression of granulocytic surface antigens was increased in both capillary sites compared to venous site (p = 0.008), particularly for adhesion markers CD11b/CD18. The percentage of neutrophils performing phagocytosis was higher in venous s les compared to finger (p = 0.025). Increased number of E. coli ingested was observed in venous s le compared to finger (p = 0.001) and to earlobe (p = 0.006). Whilst attention must be paid for varying neutrophilic surface antigen expression and further studies are needed to establish appropriate reference ranges, this study supports the use of capillary blood s les in a site-specific manner to enhance s ling capabilities field-based research.
Publisher: American Society for Clinical Investigation
Date: 25-01-2021
Publisher: Springer Science and Business Media LLC
Date: 02-02-2021
DOI: 10.1186/S40168-020-00962-2
Abstract: Microbial endocrinology, which is the study of neuroendocrine-based interkingdom signaling, provides a causal mechanistic framework for understanding the bi-directional crosstalk between the host and microbiome, especially as regards the effect of stress on health and disease. The importance of the cecal microbiome in avian health is well-recognized, yet little is understood regarding the mechanisms underpinning the avian host-microbiome relationship. Neuroendocrine plasticity of avian tissues that are focal points of host-microbiome interaction, such as the gut and lung, has likewise received limited attention. Avian in vivo models that enable the study of the neuroendocrine dynamic between host and microbiome are needed. As such, we utilized Japanese quail (Coturnix japonica) that erge in corticosterone response to stress to examine the relationship between stress-related neurochemical concentrations at sites of host-microbe interaction, such as the gut, and the cecal microbiome. Our results demonstrate that birds which contrast in corticosterone response to stress show profound separation in cecal microbial community structure as well as exhibit differences in tissue neurochemical concentrations and structural morphologies of the gut. Changes in neurochemicals known to be affected by the microbiome were also identified in tissues outside of the gut, suggesting a potential relationship in birds between the cecal microbiome and overall avian physiology. The present study provides the first evidence that the structure of the avian cecal microbial community is shaped by selection pressure on the bird for neuroendocrine response to stress. Identification of unique region-dependent neurochemical changes in the intestinal tract following stress highlights environmental stressors as potential drivers of microbial endocrinology-based mechanisms of avian host-microbiome dialogue. Together, these results demonstrate that tissue neurochemical concentrations in the avian gut may be related to the cecal microbiome and reveal the Japanese quail as a novel avian model in which to further examine the mechanisms underpinning these relationships.
Publisher: Springer Science and Business Media LLC
Date: 04-07-2016
Publisher: Springer Science and Business Media LLC
Date: 28-05-2011
Abstract: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers) in CFS/ME patients. We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK) and CD8 + T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4 + T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2), levels of NK phenotypes (CD56 bright and CD56 dim ) and regulatory T cells expressing FoxP3 transcription factor. Compared to healthy in iduals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4 + CD25 + T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8 + T cells and NK phenotypes, in particular the CD56 bright NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients. Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.
Publisher: EMBO
Date: 06-2021
Publisher: Cold Spring Harbor Laboratory
Date: 05-02-2019
DOI: 10.1101/540146
Abstract: Spatial organization and gene expression of mammalian chromosomes are maintained and regulated in conjunction with cell cycle progression. This is however disturbed once cells enter senescence and the highly abundant HMGB1 protein is depleted from senescent cell nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we know little about the positioning of HMGB1 on chromatin or about its roles in the nucleus. To address this, we mapped HMGB1 binding genome-wide in different primary cells using a tailored protocol. We integrated ChIP-seq and Hi-C data with a graph theory approach to uncover HMGB1 demarcation of a subset of topologically-associating domains (TADs) that harbor genes required for paracrine senescence. Moreover, using sCLIP, knock-down and overexpression experiments, we now show that HMGB1 is a bona fide RNA-binding protein (RBP) bound to senescence-relevant mRNAs and affecting splicing. HMGB1 also has an interactome rich in RBPs, many of which are implicated in senescence regulation. The mRNAs of many of these RBPs are directly bound by HMGB1 and concertedly regulate the availability of SASP-relevant transcripts. Our findings highlight a broader than hitherto assumed role for HMGB1. It coordinates chromatin folding and RNA homeostasis as part of a feedforward loop controlling both cell-autonomous and paracrine senescence inside and outside of cells.
Start Date: 2019
End Date: 2021
Funder: Irish Research Council
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