Rikottu hiljaisuus : Intialaisten sanomalehtien normista poikkeavia seksuaalisuuksia ja sukupuolia käsittelevät artikkelit heteromatriisin horjuttajina ja tabun uudelleenjärjestäjinä

Tutkielmassa tarkastellaan niitä tapoja, joilla intialaisissa englanninkielisissä sanomalehdissä käsitellään normista poikkeavia seksuaalisuuksia ja sukupuolia. Aineistona ovat vuosina 2003-2006 seuraavissa lehdissä ilmestyneet kirjoitukset: The Hindu, The Telegraph, Deccan Herald ja The Times of India kaupunkiliitteineen. Lisäksi aineistoon kuuluu yksi artikkeli The Statesman -lehdestä. Aineisto on jaettu kuuteen aiheryhmään: 1. Intian rikoslain 377. pykälä ja homoseksuaalisuuden dekriminalisointi, 2. hijrat, 3. Pushkin Chandran murha, 4. parisuhde, perhe ja avioliitto, 5. elokuvat ja lesbous, 6. homojen elämää. Ryhmien ulkopuolelle jää kuusi artikkelia, joita analysoidaan erikseen. Tutkielman lähtökohtana ja kysymyksenasettelun taustalla vaikuttaa queer-teoria. Tähän liittyy ajatus, ettei ole mitään muuttumatonta, olemuksellista sukupuolta, vaan sukupuoli on kulttuurista fiktiota, joka syntyy toiston ja tavoittamattoman ideaalin jäljittelyn kautta. Tutkielmassa tarkastellaan heteroseksuaalista matriisia - sitä kulttuuristen ymmärrysten verkkoa, jossa tietyt ruumiit, sukupuolet ja halut luonnollistuvat - Mary Douglasin kulttuurijärjestelmiä ja saastumista käsittelevien teorioiden sekä tabun käsitteen avulla. Aineistoa analysoidaan retoriseen diskurssianalyysiin tukeutuen. Analyysissa keskitytään artikkeleiden kielenkäyttöön ymmärrettäviksi tarkoitettuina argumentteina ja huomioidaan samalla rivien välistä luettavat merkitykset. Artikkeleita, joista suurin osa puolustaa homoseksuaalisuuden dekriminalisointia, tarkastellaan tabun uudelleenjärjestäjinä ja heteroseksuaalisen matriisin huojuttajina: ne pyrkivät homoseksuaalisuuden tabuun liittyvän hiljaisuuden rikkomisella kyseenalaistamaan vallitsevan järjestyksen, jossa vain heteroseksuaaliset halut hyväksytään. Toisaalta ne pyrkivät luomaan uudenlaisen järjestyksen, jonka katveisiin myös jää sopimatonta materiaalia. Silmiinpistävin uuteen järjestykseen sopimaton ihmisryhmä ovat hijrat, joilla on entisessä järjestelmässä ollut määrätty paikkansa järjestelmää ylläpitävänä anomaliana. Hijroja tarkastellaan artikkeleissa sekä osana transsukupuolisuuden teemaa että intialaista mytologiaa. Pyrkiessään muokkaamaan yleisön asenteita suvaitsevammiksi seksuaalista ja sukupuolista monimuotoisuutta kohtaan artikkelit käyttävät monenlaisia retorisia keinoja. Seksuaali- ja sukupuolivähemmistöjen edustajat pyritään esittämään niin sankareina kuin uhreinakin. Seksuaalivähemmistöihin pyritään liittämään luonnollisuuden ja normaaliuden määreet. Hijrojen kohdalla muistutetaan heidänkin olevan ihmisiä. Suvaitsevaisuuden puolesta käytetään argumenttina niin intialaista perinnettä kuin modernia länsimaista kulttuuria. Nyky-Intian homofobiasta ja kolonialistisesta perinnöstä sen sijaan pyritään erottautumaan.

Positional cloning and pathway analysis of the asthma susceptibility gene, NPSR1

In the present study, we identified a novel asthma susceptibility gene, NPSR1 (neuropeptide S receptor 1) on chromosome 7p14.3 by the positional cloning strategy. An earlier significant linkage mapping result among Finnish Kainuu asthma families was confirmed in two independent cohorts: in asthma families from Quebec, Canada and in allergy families from North Karelia, Finland. The linkage region was narrowed down to a 133-kb segment by a hierarchial genotyping method. The observed 77-kb haplotype block showed 7 haplotypes and a similar risk and nonrisk pattern in all three populations studied. All seven haplotypes occur in all three populations at frequences > 2%. Significant elevated relative risks were detected for elevated total IgE (immunoglobulin E) or asthma. Risk effects of the gene variants varied from 1.4 to 2.5. NPSR1 belongs to the G protein-coupled receptor (GPCR) family with a topology of seven transmembrane domains. NPSR1 has 9 exons, with the two main transcripts, A and B, encoding proteins of 371 and 377 amino acids, respectively. We detected a low but ubiquitous expression level of NPSR1-B in various tissues and endogenous cell lines while NPSR1-A has a more restricted expression pattern. Both isoforms were expressed in the lung epithelium. We observed aberrant expression levels of NPSR1-B in smooth muscle in asthmatic bronchi as compared to healthy. In an experimental mouse model, the induced lung inflammation resulted in elevated Npsr1 levels. Furthermore, we demonstrated that the activation of NPSR1 with its endogenous agonist, neuropeptide S (NPS), resulted in a significant inhibition of the growth of NPSR1-A overexpressing stable cell lines (NPSR1-A cells). To determine which target genes were regulated by the NPS-NPSR1 pathway, NPSR1-A cells were stimulated with NPS, and differentially expressed genes were identified using the Affymetrix HGU133Plus2 GeneChip. A total of 104 genes were found significantly up-regulated and 42 down-regulated 6 h after NPS administration. The up-regulated genes included many neuronal genes and some putative susceptibility genes for respiratory disorders. By Gene Ontology enrichment analysis, the biological process terms, cell proliferation, morphogenesis and immune response were among the most altered. The expression of four up-regulated genes, matrix metallopeptidase 10 (MMP10), INHBA (activin A), interleukin 8 (IL8) and EPH receptor A2 (EPHA2), were verified and confirmed by quantitative reverse-transcriptase-PCR. In conclusion, we identified a novel asthma susceptibility gene, NPSR1, on chromosome 7p14.3. NPS-NPSR1 represents a novel pathway that regulates cell proliferation and immune responses, and thus may have functional relevance in the pathogenesis of asthma.

Iodine Brachytherapy for Large Uveal Melanomas

Uveal melanoma is the most common primary intraocular malignancy in adults. Vision in the affected eye is threatened by both the tumor and side-effects from the treatments currently available. Poor prognosis for saving vision increases with tumor size and, consequently, enucleation has been the treatment of choice for large uveal melanomas in most centers. However, increasing evidence suggests that no survival benefit is gained (nor lost) by enucleation as compared to eye-conserving methods. The Helsinki University Eye Hospital has since 1990 offered episcleral iodine-125 plaque brachytherapy (IBT) for all patients unwilling to undergo enucleation for a large uveal melanoma. The primary aim of this study was to assess survival, local tumor recurrence and preservation of the eye and vision after IBT in a population-based series of 97 patients with uveal melanomas classified as large by the Collaborative Ocular Melanoma Study (COMS) criteria. Further aims included reporting the incidence of side-effects and assessing the role of intraocular dose distribution and clinical risk factors in their development. Finally, means to improve the current treatment were investigated by using computer models to compare existing plaques with collimating ones and by comparing the outcome of a subgroup of 54 IBT patients with very thick tumors with 33 patients with similarly-sized tumors managed with transscleral local resection (TSR) in Liverpool, United Kingdom. Kaplan-Meier estimates of all-cause and melanoma-specific survival at 5 years after IBT were 62% and 65%, respectively, and visually comparable with the survival experience of patients reported after enucleation by the COMS. Local recurrence developed in 6% of eyes and 84% of eyes were conserved at 5 years. Visual prognosis was guarded with 11% avoiding loss of 20/70 vision and 26% avoiding loss of 20/400 vision in the tumor eye at 2 years. Large tumor height and short distance from the posterior pole were independently associated with loss of vision. Using cumulative incidence analysis to account for competing risks, such as enucleation and metastatic death, the 5-year incidence of cataract after IBT was 79%, glaucoma 60%, optic neuropathy 46%, maculopathy 52%, persistent or recurring retinal detachment (RD) 25%, and vitreous hemorrhage 36%. In multivariate competing risks regression models, increasing tumor height was associated with cataract, iris neovascularization and RD. Maculopathy and optic neuropathy were associated with distance from the tumor to the respective structure. Median doses to the tumor apex, macula and optic disc were 81 Gy (range, 40-158), 79 Gy (range, 12-632), and 83 Gy (range, 10-377), respectively. Dose to the optic disc was independently associated with optic neuropathy, and both dose to the optic disc and dose to the macula predicted vision loss after IBT. Simulated treatment using collimating plaques resulted in clinically meaningful reduction in both optic disc (median reduction, 30 Gy) and macular (median reduction, 36 Gy) doses as compared to the actual treatment with standard plaques. In the subgroup of patients with uveal melanomas classified as large because of tumor height, cumulative incidence analysis revealed that while long-term preservation of 20/70 vision was rare after both IBT and TSR, preservation of 20/400 vision was better after TSR (32% vs. 5% at 5 years). In multivariate logistic regression models, TSR was independently associated with better preservation of 20/400 vision (OR 0.03 at 2 years, P=0.005) No cases of secondary glaucoma were observed after TSR and optic neuropathy was rare. However, local tumor recurrence was more common after TSR than it was after IBT (Cumulative incidence 41% vs. 7% at 5 years, respectively). In terms of survival, IBT seems to be a safe alternative to enucleation in managing large uveal melanomas. Local tumor control is no worse than with medium-sized tumors and the chances of avoiding secondary enucleation are good. Unfortunately, side-effects from radiotherapy are frequent, especially in thick tumors, and long-term prognosis of saving vision is consequently guarded. Some complications can be limited by using collimating plaques and by managing uveal melanomas that are large because of tumor height with TSR instead of IBT. However, the patient must be willing to accept a substantial risk of local tumor recurrence after TSR and it is best suited for cases in which the preservation of vision in the tumor eye is critical.

Genetic Mechanisms Underlying Autism Spectrum Disorders

Autism is a childhood-onset developmental disorder characterized by deficits in reciprocal social interaction, verbal and non-verbal communication, and dependence on routines and rituals. It belongs to a spectrum of disorders (autism spectrum disorders, ASDs) which share core symptoms but show considerable variation in severity. The whole spectrum affects 0.6-0.7% of children worldwide, inducing a substantial public health burden and causing suffering to the affected families. Despite having a very high heritability, ASDs have shown exceptional genetic heterogeneity, which has complicated the identification of risk variants and left the etiology largely unknown. However, recent studies suggest that rare, family-specific factors contribute significantly to the genetic basis of ASDs. In this study, we investigated the role of DISC1 (Disrupted-in-schizophrenia-1) in ASDs, and identified association with markers and haplotypes previously associated with psychiatric phenotypes. We identified four polymorphic micro-RNA target sites in the 3 UTR of DISC1, and showed that hsa-miR-559 regulates DISC1 expression in vitro in an allele-specific manner. We also analyzed an extended autism pedigree with genealogical roots in Central Finland reaching back to the 17th century. To take advantage of the beneficial characteristics of population isolates to gene mapping and reduced genetic heterogeneity observed in distantly related individuals, we performed a microsatellite-based genome-wide screen for linkage and linkage disequilibrium in this pedigree. We identified a putative autism susceptibility locus on chromosome 19p13.3 and obtained further support for previously reported loci at 1q23 and 15q11-q13. To follow-up these findings, we extended our study sample from the same sub-isolate and initiated a genome-wide analysis of homozygosity and allelic sharing using high-density SNP markers. We identified a small number of haplotypes shared by different subsets of the genealogically connected cases, along with convergent biological pathways from SNP and gene expression data, which highlighted axon guidance molecules in the pathogenesis of ASDs. In conclusion, the results obtained in this thesis show that multiple distinct genetic variants are responsible for the ASD phenotype even within single pedigrees from an isolated population. We suggest that targeted resequencing of the shared haplotypes, linkage regions, and other susceptibility loci is essential to identify the causal variants. We also report a possible micro-RNA mediated regulatory mechanism, which might partially explain the wide-range neurobiological effects of the DISC1 gene.

Global capitalism meets national spirit: Discourses in media texts on a cross-border acquisition

In this article, the authors explore media coverage of a recent acquisition across national borders. Their starting point is that the media represent a key arena of “discursive strategizing” for actors such as corporate managers. They illustrate and specify how global capitalism, as discourse relying on economic and financial rationale and exemplified here by the acquiring firm’s attempts to expand, meets national spirit, exemplified here by the complexity in selling the acquisition target to foreigners. The main contribution of this study lies in identifying how key actors draw on and mobilize rationalistic and nationalistic discourses in public discussion. The analysis illustrates that the same actors can draw on different—even contradictory—discourses at different points in time. Furthermore, different actors—even with opposing objectives—may draw on the same discourse in legitimizing their positions and pursuing specific ends.