• Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival.

      Creagh, Emma M; Brumatti, Gabriela; Sheridan, Clare; Duriez, Patrick J; Taylor, Rebecca C; Cullen, Sean P; Adrain, Colin; Martin, Seamus J; Molecular Cell Biology Laboratory, Department of Genetics, Smurfit Institute, Trinity College, Dublin, Ireland [corrected] (2009)
      Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a proteomics-based approach to identify proteins that are cleaved by caspases during apoptosis in Drosophila D-Mel2 cells, a subline of the Schneider S2 cell line. This approach identified multiple novel substrates for the fly caspases and revealed that bicaudal/betaNAC is a conserved substrate for Drosophila and mammalian caspases. RNAi-mediated silencing of bicaudal expression in Drosophila D-Mel2 cells resulted in a block to proliferation, followed by spontaneous apoptosis. Similarly, silencing of expression of the mammalian bicaudal homologue, betaNAC, in HeLa, HEK293T, MCF-7 and MRC5 cells also resulted in spontaneous apoptosis. These data suggest that bicaudal/betaNAC is essential for cell survival and is a conserved target of caspases from flies to man.
    • Bicycle helmet wearing in a sample of urban disadvantaged primary school children

      Quirke, MB; McGilloway, S; Comiskey, CM; Wynne, C; O’Sullivan, K; Hollywood, E (Irish Medical Journal, 2013-04)
    • Bifidobacterium animalis AHC7 protects against pathogen-induced NF-kappaB activation in vivo

      O'Mahony, David; Murphy, Sharon; Boileau, Thomas; Park, JeanSoon; O'Brien, Frances; Groeger, David; Konieczna, Patrycja; Ziegler, Mario; Scully, Paul; Shanahan, Fergus; et al. (2010-12-22)
      Abstract Background Bifidobacteria and lactobacilli are among the early and important colonizers of the gastrointestinal tract and are generally considered to be part of a normal, healthy microbiota. It is believed that specific strains within the microbiota can influence host immune-reactivity and may play a role in protection from infection and aberrant inflammatory activity. One such strain, Bifidobacterium animalis AHC7, has been previously shown to protect against Salmonella typhimurium infection in mice and helps resolve acute idiopathic diarrhea in dogs. The aim of this study was to investigate the potential molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7 protective effect. Results Following 4 hours of infection with Salmonella typhimurium, NF-κB activation was significantly elevated in vivo in placebo and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7 consumption significantly attenuated the NF-κB response. In vitro anti-CD3/CD28 stimulated Peyer's patch cells secreted significantly less TNF-α and IFN-γ following Bifidobacterium animalis AHC7 consumption. Stimulated cells released more IL-12p70 but this difference did not reach statistical significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed. No statistically significant change in the cytokine profile of mesenteric lymph node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co-culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic cells resulted in a significant increase in CD25+Foxp3+ T cell numbers. Conclusion Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via the attenuation of pro-inflammatory transcription factor activation in response to an infectious insult associated with modulation of pro-inflammatory cytokine production within the mucosa. The cellular mechanism underpinning Bifidobacterium animalis AHC7 mediated attenuation of NF-κB activation may include recognition of the bacterium by dendritic cells and induction of CD25+Foxp3+ T cells.
    • Bilateral adrenal haemorrhage secondary to intra-abdominal sepsis: a case report

      Egan, Aoife M; Larkin, John O; Ryan, Ronan S; Waldron, Ronan (2009-06-09)
      Abstract Introduction Bilateral adrenal haemorrhage is a rare cause of adrenal failure. Clinical features are non-specific and therefore a high index of suspicion must be maintained in patients at risk. Predisposing factors include infection, malignancy and the post-operative state. Case presentation We report the case of a patient who underwent a left hemicolectomy with primary anastomosis and formation of a defunctioning loop ileostomy for an obstructing colon carcinoma at the splenic flexure. En-bloc splenectomy was performed to ensure an oncologic resection. The patient developed a purulent abdominal collection post-operatively and became septic with hypotension and pyrexia. This precipitated acute bilateral adrenal haemorrhage with consequent adrenal insufficiency. Clinical suspicion was confirmed by radiological findings and a co-syntropin test. Following drainage of the collection, antibiotic therapy and corticosteroid replacement, the patient made an excellent recovery. Conclusion This case highlights the importance of prompt diagnosis and treatment of adrenal failure. In their absence, this condition can rapidly lead to death of the patient.
    • BioCode: Two biologically compatible Algorithms for embedding data in non-coding and coding regions of DNA

      Haughton, David; Balado, Félix (2013-04-09)
      Abstract Background In recent times, the application of deoxyribonucleic acid (DNA) has diversified with the emergence of fields such as DNA computing and DNA data embedding. DNA data embedding, also known as DNA watermarking or DNA steganography, aims to develop robust algorithms for encoding non-genetic information in DNA. Inherently DNA is a digital medium whereby the nucleotide bases act as digital symbols, a fact which underpins all bioinformatics techniques, and which also makes trivial information encoding using DNA straightforward. However, the situation is more complex in methods which aim at embedding information in the genomes of living organisms. DNA is susceptible to mutations, which act as a noisy channel from the point of view of information encoded using DNA. This means that the DNA data embedding field is closely related to digital communications. Moreover it is a particularly unique digital communications area, because important biological constraints must be observed by all methods. Many DNA data embedding algorithms have been presented to date, all of which operate in one of two regions: non-coding DNA (ncDNA) or protein-coding DNA (pcDNA). Results This paper proposes two novel DNA data embedding algorithms jointly called BioCode, which operate in ncDNA and pcDNA, respectively, and which comply fully with stricter biological restrictions. Existing methods comply with some elementary biological constraints, such as preserving protein translation in pcDNA. However there exist further biological restrictions which no DNA data embedding methods to date account for. Observing these constraints is key to increasing the biocompatibility and in turn, the robustness of information encoded in DNA. Conclusion The algorithms encode information in near optimal ways from a coding point of view, as we demonstrate by means of theoretical and empirical (in silico) analyses. Also, they are shown to encode information in a robust way, such that mutations have isolated effects. Furthermore, the preservation of codon statistics, while achieving a near-optimum embedding rate, implies that BioCode pcDNA is also a near-optimum first-order steganographic method.
    • Biofeedback in rehabilitation

      Giggins, Oonagh M; Persson, Ulrik MC; Caulfield, Brian (2013-06-18)
      Abstract This paper reviews the literature relating to the biofeedback used in physical rehabilitation. The biofeedback methods used in rehabilitation are based on biomechanical measurements and measurements of the physiological systems of the body. The physiological systems of the body which can be measured to provide biofeedback are the neuromuscular system, the respiratory system and the cardiovascular system. Neuromuscular biofeedback methods include electromyography (EMG) biofeedback and real-time ultrasound imaging (RTUS) biofeedback. EMG biofeedback is the most widely investigated method of biofeedback and appears to be effective in the treatment of many musculoskeletal conditions and in post cardiovascular accident (CVA) rehabilitation. RTUS biofeedback has been demonstrated effective in the treatment of low back pain (LBP) and pelvic floor muscle dysfunction. Cardiovascular biofeedback methods have been shown to be effective in the treatment of a number of health conditions such as hypertension, heart failure, asthma, fibromyalgia and even psychological disorders however a systematic review in this field has yet to be conducted. Similarly, the number of large scale studies examining the use of respiratory biofeedback in rehabilitation is limited. Measurements of movement, postural control and force output can be made using a number of different devices and used to deliver biomechanical biofeedback. Inertial based sensing biofeedback is the most widely researched biomechanical biofeedback method, with a number of studies showing it to be effective in improving measures of balance in a number of populations. Other types of biomechanical biofeedback include force plate systems, electrogoniometry, pressure biofeedback and camera based systems however the evidence for these is limited. Biofeedback is generally delivered using visual displays, acoustic or haptic signals, however more recently virtual reality (VR) or exergaming technology have been used as biofeedback signals. VR and exergaming technology have been primarily investigated in post-CVA rehabilitation, however, more recent work has shown this type of biofeedback to be effective in improving exercise technique in musculoskeletal populations. While a number of studies in this area have been conducted, further large scale studies and reviews investigating different biofeedback applications in different clinical populations are required.
    • Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.

      Hampel, Harald; Shen, Yong; Walsh, Dominic M; Aisen, Paul; Shaw, Les M; Zetterberg, Henrik; Trojanowski, John Q; Blennow, Kaj; Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience (TCIN), Laboratory of Neuroimaging and Biomarker Research, Trinity College Dublin, Trinity Centre for Health Sciences, The Adelaide and Meath Hospital Incorporating The National Children's Hospital (AMiNCH), Dublin, Ireland; Department of Psychiatry, Alzheimer Memorial Center, Ludwig Maximilian University, Munich, Germany. (2010-06)
      Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer's disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Abeta isoforms (Abeta40/Abeta42), soluble APP isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Abeta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.
    • Bivariate analysis of basal serum anti-Mullerian hormone measurements and human blastocyst development after IVF

      Sills, E Scott; Collins, Gary S; Brady, Adam C; Walsh, David J; Marron, Kevin D; Peck, Alison C; Wash, Anthony PH; Salem, Rifaat D (2011-12-02)
      Abstract Background To report on relationships among baseline serum anti-Müllerian hormone (AMH) measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles. Methods Pre-treatment AMH was measured in patients undergoing IVF (n = 79) and retrospectively correlated to in vitro embryo development noted during culture. Results Mean (+/- SD) age for study patients in this study group was 36.3 ± 4.0 (range = 28-45) yrs, and mean (+/- SD) terminal serum estradiol during IVF was 5929 +/- 4056 pmol/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44) was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol/l; p = 0.029). Conclusions While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation.
    • Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures

      Nic An Ultaigh, Sinead; Saber, Tajvur P; McCormick, Jennifer; Connolly, Mary; Dellacasagrande, Jerome; Keogh, Brian; McCormack, William; Reilly, Mary; O'Neill, Luke A; McGuirk, Peter; et al. (2011-02-23)
      Abstract Introduction The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells. Methods RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg/ml), an anti-TLR2 antibody (OPN301, 1 μg/ml) or an immunoglobulin G (IgG) (1 μg/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology. Results Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab. Conclusions These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.
    • Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures

      Nic An Ultaigh, Sinead; Saber, Tajvur P; McCormick, Jennifer; Connolly, Mary; Dellacasagrande, Jerome; Keogh, Brian; McCormack, William; Reilly, Mary; O'Neill, Luke A; McGuirk, Peter; et al. (2011-02-23)
      Abstract Introduction The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells. Methods RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg/ml), an anti-TLR2 antibody (OPN301, 1 μg/ml) or an immunoglobulin G (IgG) (1 μg/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology. Results Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab. Conclusions These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.
    • Blue care: a systematic review of blue space interventions for health and wellbeing.

      Britton, Easkey; Kindermann, Gesche; Domegan, Christine; Carlin, Caitriona (Health Promotion International, 2018-12-18)
      There is increasing interest in the potential use of outdoor water environments, or blue space, in the promotion of human health and wellbeing. However, therapeutic nature-based practices are currently outpacing policy and the evidence base for health or wellbeing benefits of therapeutic interventions within blue space has not been systematically assessed. This systematic review aims to address the gap in understanding the impacts of blue space within existing interventions for targeted individuals. A systematic review was carried out, searching Google Scholar, SCOPUS, PubMed, etc. through to August 2017. Only blue space interventions were included that were specifically designed and structured with a therapeutic purpose for individuals with a defined need and did not include nature-based promotion projects or casual recreation in the outdoors. Thirty-three studies met the inclusion criteria and were assessed. Overall, the studies suggest that blue care can have direct benefit for health, especially mental health and psycho-social wellbeing. The majority of papers found a positive or weak association between blue care and health and wellbeing indicators. There was also some evidence for greater social connectedness during and after interventions, but results were inconsistent and mixed across studies with very few findings for physical health. This is the first systematic review of the literature on blue care. In summary, it has been shown that mental health, especially psycho-social wellbeing, can be improved with investment in blue spaces. Key areas for future research include improving understanding of the mechanisms through which blue care can improve public health promotion.
    • Body mass index and height over three generations: evidence from the Lifeways cross-generational cohort study

      Murrin, Celine M; Kelly, Gabrielle E; Tremblay, Richard E; Kelleher, Cecily C (2012-01-25)
      Abstract Background Obesity and its measure of body mass index are strongly determined by parental body size. Debate continues as to whether both parents contribute equally to offspring body mass which is key to understanding the aetiology of the disease. The aim of this study was to use cohort data from three generations of one family to examine the relative maternal and paternal associations with offspring body mass index and how these associations compare with family height to demonstrate evidence of genetic or environmental cross-generational transmission. Methods 669 of 1082 families were followed up in 2007/8 as part of the Lifeways study, a prospective observational cross-generation linkage cohort. Height and weight were measured in 529 Irish children aged 5 to 7 years and were self-reported by parents and grandparents. All adults provided information on self-rated health, education status, and indicators of income, diet and physical activity. Associations between the weight, height, and body mass index of family members were examined with mixed models and heritability estimates computed using linear regression analysis. Results Self-rated health was associated with lower BMI for all family members, as was age for children. When these effects were accounted for evidence of familial associations of BMI from one generation to the next was more apparent in the maternal line. Heritability estimates were higher (h2 = 0.40) for mother-offspring pairs compared to father-offspring pairs (h2 = 0.22). In the previous generation, estimates were higher between mothers-parents (h2 = 0.54-0.60) but not between fathers-parents (h2 = -0.04-0.17). Correlations between mother and offspring across two generations remained significant when modelled with fixed variables of socioeconomic status, health, and lifestyle. A similar analysis of height showed strong familial associations from maternal and paternal lines across each generation. Conclusions This is the first family cohort study to report an enduring association between mother and offspring BMI over three generations. The evidence of BMI transmission over three generations through the maternal line in an observational study corroborates the findings of animal studies. A more detailed analysis of geno and phenotypic data over three generations is warranted to understand the nature of this maternal-offspring relationship.
    • Body Piercing involving Intraoral sites

      McNamara, C; Field, D; Ryan, D; McNamara, CM (2007)
    • Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group

      ten Broek, Richard P G; Krielen, Pepijn; Di Saverio, Salomone; Coccolini, Federico; Biffl, Walter L; Ansaloni, Luca; Velmahos, George C; Sartelli, Massimo; Fraga, Gustavo P; Kelly, Michael D; et al. (2018-06-19)
      Abstract Background Adhesive small bowel obstruction (ASBO) is a common surgical emergency, causing high morbidity and even some mortality. The adhesions causing such bowel obstructions are typically the footprints of previous abdominal surgical procedures. The present paper presents a revised version of the Bologna guidelines to evidence-based diagnosis and treatment of ASBO. The working group has added paragraphs on prevention of ASBO and special patient groups. Methods The guideline was written under the auspices of the World Society of Emergency Surgery by the ASBO working group. A systematic literature search was performed prior to the update of the guidelines to identify relevant new papers on epidemiology, diagnosis, and treatment of ASBO. Literature was critically appraised according to an evidence-based guideline development method. Final recommendations were approved by the workgroup, taking into account the level of evidence of the conclusion. Recommendations Adhesion formation might be reduced by minimally invasive surgical techniques and the use of adhesion barriers. Non-operative treatment is effective in most patients with ASBO. Contraindications for non-operative treatment include peritonitis, strangulation, and ischemia. When the adhesive etiology of obstruction is unsure, or when contraindications for non-operative management might be present, CT is the diagnostic technique of choice. The principles of non-operative treatment are nil per os, naso-gastric, or long-tube decompression, and intravenous supplementation with fluids and electrolytes. When operative treatment is required, a laparoscopic approach may be beneficial for selected cases of simple ASBO. Younger patients have a higher lifetime risk for recurrent ASBO and might therefore benefit from application of adhesion barriers as both primary and secondary prevention. Discussion This guideline presents recommendations that can be used by surgeons who treat patients with ASBO. Scientific evidence for some aspects of ASBO management is scarce, in particular aspects relating to special patient groups. Results of a randomized trial of laparoscopic versus open surgery for ASBO are awaited.
    • Bone ageing and HIV

      Mallon, Patrick (2010-05-11)
      null
    • Bone morphogenetic proteins enhance an epithelial-mesenchymal transition in normal airway epithelial cells during restitution of a disrupted epithelium

      McCormack, Natasha; Molloy, Emer L; O’Dea, Shirley (2013-03-19)
      Abstract Background Mechanisms of airway repair are poorly understood. It has been proposed that, following injury, progenitor populations such as club cells (Clara) become undifferentiated, proliferate and re-differentiate to re-epithelialise the airway. The exact phenotype of such cells during repair is unknown however. We hypothesised that airway epithelial cells (AECs) undergo some degree of epithelial-mesenchymal transition (EMT) in order to migrate over a denuded airway and effect re-epithelialisation. Furthermore, based on our previous findings that BMP signalling is an early event in AECs following injury in vivo and that BMP4 down-regulates E-cadherin expression and enhances migration in AECs in vitro, we hypothesised that BMPs could play a role in inducing such a phenotypic switch. Methods Normal AECs were isolated from mouse lungs and analysed in a model of a disrupted epithelium. EMT marker expression and BMP signalling were examined by immunofluorescence, Western blotting and RT-PCR. Results Following generation of a wound area, AECs at the wound edge migrated and acquired a mesenchymal-like morphology. E-cadherin expression was reduced in migrating cells while vimentin and α-smooth muscle actin (α-SMA) expression was increased. Re-expression of membrane E-cadherin was subsequently observed in some cells in the wound area following re-establishment of the monolayer. A transient increase in the incidence of nuclear phosphorylated Smad1/5/8 was observed in migrating cells compared with confluent cells, indicating active BMP signalling during migration. BMP antagonists noggin and gremlin inhibited cell migration, confirming the involvement of BMP signalling in migration and indicating autocrine signalling, possibly involving BMP7 or BMP4 which were expressed in AECs. Exogenous BMP2, BMP4 and BMP7 induced a mesenchymal-like morphology in AECs, enhanced the rate of cell migration and increased α-SMA protein expression in AECs. Conclusions Following disruption of an intact epithelium, migrating AECs at the wound edge acquire an EMT-like phenotype involving altered expression of E-cadherin, vimentin and α-SMA. BMP signalling is involved in AEC migration and is likely to mediate the switch towards an EMT-like phenotype by altering protein expression to facilitate cell migration and wound closure. We propose therefore that acquisition of an EMT-like phenotype by AECs is a normal aspect of wound repair. Furthermore, we suggest that diseases involving fibrosis may arise because the EMT phase of repair is prolonged by chronic injury/inflammation, rather than being caused by it, as is the current paradigm.
    • Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes

      Whan, Vicki; Hobbs, Matthew; McWilliam, Sean; Lynn, David J; Strandberg Lutzow, Ylva; Khatkar, Mehar; Barendse, William; Raadsma, Herman; Tellam, Ross L (2010-11-23)
      Abstract Background About forty human diseases are caused by repeat instability mutations. A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation is also apparent in human poly-Q encoding genes from normal individuals. As these coding sequence repeats are subject to selection in mammals, it has been suggested that normal variations in some of these typically highly conserved genes are implicated in morphological differences between species and phenotypic variations within species. At present, poly-Q encoding genes in non-human mammalian species are poorly documented, as are their functions and propensities for polymorphic variation. Results The current investigation identified 178 bovine poly-Q encoding genes (Q ≥ 5) and within this group, 26 genes with orthologs in both human and mouse that did not contain poly-Q repeats. The bovine poly-Q encoding genes typically had ubiquitous expression patterns although there was bias towards expression in epithelia, brain and testes. They were also characterised by unusually large sizes. Analysis of gene ontology terms revealed that the encoded proteins were strongly enriched for functions associated with transcriptional regulation and many contributed to physical interaction networks in the nucleus where they presumably act cooperatively in transcriptional regulatory complexes. In addition, the coding sequence CAG repeats in some bovine genes impacted mRNA splicing thereby generating unusual transcriptional diversity, which in at least one instance was tissue-specific. The poly-Q encoding genes were prioritised using multiple criteria for their likelihood of being polymorphic and then the highest ranking group was experimentally tested for polymorphic variation within a cattle diversity panel. Extensive and meiotically stable variation was identified. Conclusions Transcriptional diversity can potentially be generated in poly-Q encoding genes by the impact of CAG repeat tracts on mRNA alternative splicing. This effect, combined with the physical interactions of the encoded proteins in large transcriptional regulatory complexes suggests that polymorphic variations of proteins in these complexes have strong potential to affect phenotype.
    • The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection.

      Haedicke, Juliane; Brown, Craig; Naghavi, Mojgan H; Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland. (2009-08-18)
      Neurons are one of the few cell types in the human body that do not support HIV type-1 (HIV-1) replication. Although the lack of key receptors is a major obstacle to infection, studies suggest that additional functions inhibit virus replication to explain the exquisite resistance of neurons to HIV-1. However, specific neuronal factors that may explain this resistance remain to be discovered. In a screen for antiviral factors using a fibroblast line chemically mutagenized and selected for resistance to retroviral infection, we recently identified induction of rat FEZ1 (fasciculation and elongation protein zeta-1), a brain-specific protein, as the cause of this resistance. When exogenously expressed in nonneuronal cell lines rat FEZ1 blocked nuclear entry of retroviral DNA. Here, we demonstrate that among human brain cells, neurons naturally express high levels of FEZ1 compared to astrocytes or microglia cells and are correspondingly less susceptible to infection with pseudotyped HIV-1 that bypasses receptor-mediated viral entry. Demonstrating that endogenous FEZ1 was functionally important in the resistance of neurons to HIV-1 infection, siRNA-mediated knockdown of endogenous FEZ1 increased the infectivity of neurons while sensitive brain cell types like microglia became more resistant upon FEZ1 overexpression. In addition, FEZ1 expression was not induced in response to IFN treatment. As such, in contrast to other widely expressed, IFN-inducible antiviral factors, FEZ1 appears to represent a unique neuron-specific determinant of cellular susceptibility to infection in a cell type that is naturally resistant to HIV-1.
    • Breakage of endodontic instruments

      Patel, Shreeti (Irish Dental Assocation (IDA), 2016-08)