“Authentic Reproductions”: Staging the “Wild West” in Modern Irish Drama

This article examines two metatheatrical plays written by playwrights from the north of Ireland that bookend the twentieth century. The first is Ulster Literary Theatre (ULT) playwright Gerald MacNamara’s parodic, “proto-Pirandellian”4 The Mist That Does Be on the Bog (1909), which satirizes the peasant aesthetic of the “Abbey play” of the Irish Revival.5 The second is Marie Jones’s international hit, Stones in His Pockets (1999), a “play-full,” postmodern deconstruction of the commodification of Irish culture in the era of the Celtic Tiger. Although separated by exactly ninety years, the two plays can be connected through their critiques of the cultural politics of nationalism and globalization during the periods of the Irish Revival and the Celtic Tiger, respectively. Moreover, both plays are distinguished by their dramaturgical form, as the political critique of each is corporeally embodied in metatheatrical performance.

Chloroquine causes lysosomal dysfunction in neural retina and RPE: Implications for retinopathy

Chronic use of chloroquine has been shown to induce numerous pathophysiological defects in the retina. This drug has the ability to alter pH of intracellular compartments and lysosomal function of the retinal pigment epithelium (RPE) and retinal neurons may constitute the basis of chloroquine retinopathy. The aim of the current study was to investigate pathogenic alterations in retinal cells continuously exposed to chloroquine using appropriate in vivo and in vitro models.

Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer

Predicting long-term outcome after breast-cancer diagnosis remains problematic, particularly for patients with clinically small, axillary lymph node- negative tumours, Evidence suggests that the lectin Helix pomatia agglutinin (HPA) identifies oligosaccharides associated with poor-prognosis cancer. Our aim was to identify oligosaccharides that bind HPA in aggressive breast cancers. Breast-cancer cell lines (MCF-7, BT-549 and BT-20) and a cell line From human milk (HBL-100), which showed a range of HPA-binding intensities, were used to extract HPA-binding glycoproteins, Oligosaccharides were released using anhydrous hydrazine and separated on a range of HPLC matrices. We investigated whether HPA-binding oligosaccharides from cell lines were present in human breast-cancer tissues, using 69 breast-cancer specimens from patients with between 5 and 10 years' follow-up. A monosialylated oligosaccharide was over-expressed in the cell line that bound HPA strongly. Further analysis by normal-phase HPLC showed that the 2-aminobenzamide-conjugated oligosaccharide had a hydrodynamic volume of 4.58 glucose units (HPAgly 1), Increased expression of HPAgly 1 was associated with HPA staining of breast-cancer specimens (Student's t-test p = 0.025). Analysis of oligosaccharide levels and disease-free survival after treatment for breast cancer indicated a shorter disease-free interval for patients with elevated levels of HPAgly 1, This is the first time that histochemical lectin staining has been correlated with biochemical mapping of oligosaccharides, Using this approach, we have identified a monosialylated HPA lectin-binding oligosaccharide present in breast-cancer cells grown in vitro which is elevated in breast-cancer specimens that bind the lectin, (C) 2001 Wiley-Liss, Inc.

Eosinophil peroxidase induces the expression and function of acid-sensing ion channel-3 in allergic rhinitis:in vitro evidence in cultured epithelial cells

BACKGROUND:
Acid-sensing ion channels (ASIC) are a family of acid-activated ligand-gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR.
OBJECTIVES:
The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects.
METHODS:
Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function.
RESULTS:
Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre-treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC-1 was equally expressed in both populations, but ASIC-3 was significantly more highly expressed in AR (P < 0.02). Immunohistochemistry confirmed significantly higher ASIC-3 protein expression on nasal epithelial cells in AR patients than controls (P < 0.01). Immunoreactivity for EPO+ eosinophils in both nasal epithelium and submucosa was more prominent in AR compared with controls. A mechanism of induction of ASIC-3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC-3 in epithelial cells. Furthermore, using a quantitative functional measure of epithelial cell secretory function in vitro, EPO increased the air-surface liquid depth via an ASIC-dependent chloride secretory pathway.
CONCLUSIONS:
This data suggests a possible mechanism for the observed association of eosinophils and rhinorrhoea in AR and is manifested through enhanced ASIC-3 expression.

Range expansion in an invasive small mammal: influence of life-history and habitat quality.

Invasive species pose a major threat to biodiversity but provide an opportunity to describe the processes that lead to changes in a species’ range. The bank vole (Myodes glareolus) is an invasive rodent that was introduced to Ireland in the early twentieth century. Given its continuing range expansion, the substantial empirical data on its spread thus far, and the absence of any eradication program, the bank vole in Ireland represents a unique model system for studying the mechanisms influencing the rate of range expansion in invasive small mammals. We described the invasion using a reaction–diffusion model informed by empirical data on life history traits and demographic parameters. We subsequently modelled the processes involved in its range expansion using a rule-based spatially explicit simulation. Habitat suitability interacted with density-dependent parameters to influence dispersal, most notably the density at which local populations started to donate emigrating individuals, the number of dispersing individuals and the direction of dispersal. Whilst local habitat variability influenced the rate of spread, on a larger scale the invasion resembled a simple reaction–diffusion process. Our results suggest a Type 1 range expansion where the rate of expansion is generally constant over time, but with some evidence for a lag period following introduction. We demonstrate that a two-parameter empirical model and a rule-based spatially explicit simulation are sufficient to accurately describe the invasion history of a species that exhibits a complex, density-dependent pattern of dispersal.

Genome-Wide Association Study of Multiplex Schizophrenia Pedigrees

OBJECTIVE The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs). METHOD The family sample included 2,461 individuals from 631 pedigrees (581 in the primary European-ancestry analyses). Association was tested for single SNPs and genetic pathways. Polygenic scores based on family study results were used to predict case-control status in the Schizophrenia Psychiatric GWAS Consortium (PGC) data set, and consistency of direction of effect with the family study was determined for top SNPs in the PGC GWAS analysis. Within-family segregation was examined for schizophrenia-associated rare CNVs. RESULTS No genome-wide significant associations were observed for single SNPs or for pathways. PGC case and control subjects had significantly different genome-wide polygenic scores (computed by weighting their genotypes by log-odds ratios from the family study) (best p=10-17, explaining 0.4% of the variance). Family study and PGC analyses had consistent directions for 37 of the 58 independent best PGC SNPs (p=0.024). The overall frequency of CNVs in regions with reported associations with schizophrenia (chromosomes 1q21.1, 15q13.3, 16p11.2, and 22q11.2 and the neurexin-1 gene [NRXN1]) was similar to previous case-control studies. NRXN1 deletions and 16p11.2 duplications (both of which were transmitted from parents) and 22q11.2 deletions (de novo in four cases) did not segregate with schizophrenia in families. CONCLUSIONS Many common SNPs are likely to contribute to schizophrenia risk, with substantial overlap in genetic risk factors between multiply affected families and cases in large case-control studies. Our findings are consistent with a role for specific CNVs in disease pathogenesis, but the partial segregation of some CNVs with schizophrenia suggests that researchers should exercise caution in using them for predictive genetic testing until their effects in diverse populations have been fully studied.

Mean shift based gradient vector flow for image segmentation

In recent years, gradient vector flow (GVF) based algorithms have been successfully used to segment a variety of 2-D and 3-D imagery. However, due to the compromise of internal and external energy forces within the resulting partial differential equations, these methods may lead to biased segmentation results. In this paper, we propose MSGVF, a mean shift based GVF segmentation algorithm that can successfully locate the correct borders. MSGVF is developed so that when the contour reaches equilibrium, the various forces resulting from the different energy terms are balanced. In addition, the smoothness constraint of image pixels is kept so that over- or under-segmentation can be reduced. Experimental results on publicly accessible datasets of dermoscopic and optic disc images demonstrate that the proposed method effectively detects the borders of the objects of interest.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.