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• Journal article
  McKee AJ, Davies JC, Bilton D, Taylor A, Gatzoulis M, Aurora P, Muthurangu V, Balfour-Lynn IMet al., 2011,

  A NOVEL EXERCISE TEST DEMONSTRATES REDUCED STROKE VOLUME AUGMENTATION BUT NO EVIDENCE OF PULMONARY HYPERTENSION IN PATIENTS WITH ADVANCED CYSTIC FIBROSIS

  , PEDIATRIC PULMONOLOGY, Pages: 354-354, ISSN: 8755-6863
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• Journal article
  Malhotra D, Thimmulappa RK, Mercado N, Ito K, Kombairaju P, Kumar S, Ma J, Feller-Kopman D, Barnes P, Biswal Set al., 2011,

  Denitrosylation of HDAC2 by targeting Nrf2 restores glucocorticosteroid sensitivity in macrophages from COPD patients

  , J Clin Invest, Vol: 121, Pages: 4289-4302

  Chronic obstructive pulmonary disease (COPD), which is caused primarily by cigarette smoking, is a major health problem worldwide. The progressive decline in lung function that occurs in COPD is a result of persistent inflammation of the airways and destruction of the lung parenchyma. Despite the key role of inflammation in the pathogenesis of COPD, treatment with corticosteroids - normally highly effective antiinflammatory drugs - has little therapeutic benefit. This corticosteroid resistance is largely caused by inactivation of histone deacetylase 2 (HDAC2), which is critical for the transrepressive activity of the glucocorticoid receptor (GR) that mediates the antiinflammatory effect of corticosteroids. Here, we show that in alveolar macrophages from patients with COPD, S-nitrosylation of HDAC2 is increased and that this abolishes its GR-transrepression activity and promotes corticosteroid insensitivity. Cys-262 and Cys-274 of HDAC2 were found to be the targets of S-nitrosylation, and exogenous glutathione treatment of macrophages from individuals with COPD restored HDAC2 activity. Treatment with sulforaphane, a small-molecule activator of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), was also able to denitrosylate HDAC2, restoring dexamethasone sensitivity in alveolar macrophages from patients with COPD. These effects of sulforaphane were glutathione dependent. We conclude that NRF2 is a novel drug target for reversing corticosteroid resistance in COPD and other corticosteroid-resistant inflammatory diseases.

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• Journal article
  Tse-Laurence MA, Bidartondo MI, 2011,

  Mapping fungi from below ground: online genetic resources and ectomycorrhizal geographic distributions

  , iForest, Vol: 4, Pages: 252-255
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• Conference paper
  Kizawa Y, Kimura G, Ueda K, Ito K, Barnes PJ, Kusama Tet al., 2011,

  p38MAPKγ is involved in the corticosteroid refractory airway inflammation and AHR in cigarette smoke exposed and poly(I:C) treated mice

  , 84th Annual Meeting of the Japanese-Pharmacological-Society/11th Southeast Asian Western Pacific Regional Meeting of Pharmacologists, Publisher: JAPANESE PHARMACOLOGICAL SOC, Pages: 215P-215P, ISSN: 1347-8613
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• Journal article
  Simwami SP, Khayhan K, Henk DA, Aanensen DM, Boekhout T, Hagen F, Brouwer AE, Harrison TS, Donnelly CA, Fisher MCet al., 2011,

  Low Diversity Cryptococcus neoformans Variety grubii Multilocus Sequence Types from Thailand Are Consistent with an Ancestral African Origin

  , Plos Pathog, Vol: 7, ISSN: 1553-7366

  The global burden of HIV-associated cryptococcal meningitis is estimated at nearly one million cases per year, causing up to a third of all AIDS-related deaths. Molecular epidemiology constitutes the main methodology for understanding the factors underpinning the emergence of this understudied, yet increasingly important, group of pathogenic fungi. Cryptococcus species are notable in the degree that virulence differs amongst lineages, and highly-virulent emerging lineages are changing patterns of human disease both temporally and spatially. Cryptococcus neoformans variety grubii (Cng, serotype A) constitutes the most ubiquitous cause of cryptococcal meningitis worldwide, however patterns of molecular diversity are understudied across some regions experiencing significant burdens of disease. We compared 183 clinical and environmental isolates of Cng from one such region, Thailand, Southeast Asia, against a global MLST database of 77 Cng isolates. Population genetic analyses showed that Thailand isolates from 11 provinces were highly homogenous, consisting of the same genetic background (globally known as VNI) and exhibiting only ten nearly identical sequence types (STs), with three (STs 44, 45 and 46) dominating our sample. This population contains significantly less diversity when compared against the global population of Cng, specifically Africa. Genetic diversity in Cng was significantly subdivided at the continental level with nearly half (47%) of the global STs unique to a genetically diverse and recombining population in Botswana. These patterns of diversity, when combined with evidence from haplotypic networks and coalescent analyses of global populations, are highly suggestive of an expansion of the Cng VNI clade out of Africa, leading to a limited number of genotypes founding the Asian populations. Divergence time testing estimates the time to the most common ancestor between the African and Asian populations to be 6,920 years ago (95% HPD 122.96 - 27,177.76

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• Journal article
  Davies JC, Alton EWFW, 2011,

  Design of Gene Therapy Trials in CF Patients

  , CYSTIC FIBROSIS: DIAGNOSIS AND PROTOCOLS, VOL I: APPROACHES TO STUDY AND CORRECT CFTR DEFECTS, Vol: 741, Pages: 55-68, ISSN: 1064-3745
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  • Citations: 3
• Conference paper
  Coughlan CA, Reeves EP, Bergsson G, Greene CM, Chotirmall SH, Kavanagh K, McElvaney NGet al., 2011,

  GLIOTOXIN SECRETION IS RESPONSIBLE FOR VITAMIN D RECEPTOR DOWN-REGULATION AND A HEIGHTENED T-HELPER 2 RESPONSE IN <i>ASPERGILLUS FUMIGATUS</i> COLONISED CYSTIC FIBROSIS AIRWAYS

  , Publisher: WILEY-BLACKWELL, Pages: 266-267, ISSN: 8755-6863
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• Book chapter
  Lee K-Y, Delille A, Bismarck A, 2011,

  Greener Surface Treatments of Natural Fibres for the Production of Renewable Composite Materials

  , CELLULOSE FIBERS: BIO- AND NANO-POLYMER COMPOSITES, Editors: Kalia, Kaith, Kaur, Publisher: SPRINGER-VERLAG BERLIN, Pages: 155-178, ISBN: 978-3-642-17369-1
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  • Citations: 35
• Book chapter
  Xu J, Manosuthi W, Banerjee U, Zhu L-P, Chen J, Kohno S, Izumikawa K, Chen Y, Sungkanuparph S, Harrison TS, Fisher Met al., 2011,

  Cryptococcosis in Asia

  , CRYPTOCOCCUS: FROM HUMAN PATHOGEN TO MODEL YEAST, Editors: Heitman, Kozel, KwonChung, Perfect, Casadevall, Publisher: AMER SOC MICROBIOLOGY, Pages: 287-297, ISBN: 978-1-55581-501-1
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  • Citations: 8
• Conference paper
  Molyneaux PL, Mallia P, Duff RM, Moffatt MF, Cookson WO, Johnston SLet al., 2011,

  Investigating The Role Of Rhinovirus Infection In Precipitating Bacterial Infections In COPD Using Culture Independent Molecular Microbiology

  , Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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  • Citations: 1

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