Epithelial sodium channel in airway epithelium of the newborn infant : Implications for postnatal pulmonary adaptation

The aim of the present thesis was to study the role of the epithelial sodium channel (ENaC) in clearance of fetal lung fluid in the newborn infant by measurement of airway epithelial expression of ENaC, of nasal transepithelial potential difference (N-PD), and of lung compliance (LC). In addition, the effect of postnatal dexamethasone on airway epithelial ENaC expression was measured in preterm infants with bronchopulmonary dysplasia (BPD). The patient population was formed of selected term newborn infants born in the Department of Obstetrics (Studies II-IV) and selected preterm newborn infants treated in the neonatal intensive care unit of the Hospital for Children and Adolescents (Studies I and IV) of the Helsinki University Central Hospital in Finland. A small population of preterm infants suffering from BPD was included in Study I. Studies I, III, and IV included airway epithelial measurement of ENaC and in Studies II and III, measurement of N-PD and LC. In Study I, ENaC expression analyses were performed in the Research Institute of the Hospital for Sick Children in Toronto, Ontario, Canada. In the following studies, analyses were performed in the Scientific Laboratory of the Hospital for Children and Adolescents. N-PD and LC measurements were performed at bedside in these hospitals. In term newborn infants, the percentage of amiloride-sensitive N-PD, a surrogate for ENaC activity, measured during the first 4 postnatal hours correlates positively with LC measured 1 to 2 days postnatally. Preterm infants with BPD had, after a therapeutic dose of dexamethasone, higher airway epithelial ENaC expression than before treatment. These patients were subsequently weaned from mechanical ventilation, probably as a result of the clearance of extra fluid from the alveolar spaces. In addition, we found that in preterm infants ENaC expression increases with gestational age (GA). In preterm infants, ENaC expression in the airway epithelium was lower than in term newborn infants. During the early postnatal period in those born both preterm and term airway epithelial βENaC expression decreased significantly. Term newborn infants delivered vaginally had a significantly smaller airway epithelial expression of αENaC after the first postnatal day than did those delivered by cesarean section. The functional studies showed no difference in N-PD between infants delivered vaginally and by cesarean section. We therefore conclude that the low airway epithelial expression of ENaC in the preterm infant and the correlation of N-PD with LC in the term infant indicate a role for ENaC in the pathogenesis of perinatal pulmonary adaptation and neonatal respiratory distress. Because dexamethasone raised ENaC expression in preterm infants with BPD, and infants were subsequently weaned from ventilator therapy, we suggest that studies on the treatment of respiratory distress in the preterm infant should include the induction of ENaC activity.

Limiting the Extent of the RDN1 Heterochromatin Domain by a Silencing Barrier and Sir2 Protein Levels in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, transcriptional silencing occurs at the cryptic mating-type loci (HML and HMR), telomeres, and ribosomal DNA ( rDNA; RDN1). Silencing in the rDNA is unusual in that polymerase II (Pol II) promoters within RDN1 are repressed by Sir2 but not Sir3 or Sir4. rDNA silencing unidirectionally spreads leftward, but the mechanism of limiting its spreading is unclear. We searched for silencing barriers flanking the left end of RDN1 by using an established assay for detecting barriers to HMR silencing. Unexpectedly, the unique sequence immediately adjacent to RDN1, which overlaps a prominent cohesin binding site (CARL2), did not have appreciable barrier activity. Instead, a fragment located 2.4 kb to the left, containing a tRNA(Gln) gene and the Ty1 long terminal repeat, had robust barrier activity. The barrier activity was dependent on Pol III transcription of tRNA(Gln), the cohesin protein Smc1, and the SAS1 and Gcn5 histone acetyltransferases. The location of the barrier correlates with the detectable limit of rDNA silencing when SIR2 is overexpressed, where it blocks the spreading of rDNA heterochromatin. We propose a model in which normal Sir2 activity results in termination of silencing near the physical rDNA boundary, while tRNA(Gln) blocks silencing from spreading too far when nucleolar Sir2 pools become elevated.

Common past, divided memories: historical memory of the Polish minority members in Lithuania

The Master’s thesis examines historical memory of the Polish minority members in Lithuania with regard to how their interpretation of the common Polish-Lithuanian history reiterates or differs from the official Polish and Lithuanian narratives conveyed by the school textbooks. History teaching in high schools carries a crucial state-supported role of “identity building policies” – it maintains a national narrative of memory, which might be exclusive to minorities and their peculiar understanding of history. Lithuanians Poles, in this regard, represent a national minority, which is exposed to two conflicting national narratives of the common past – Polish and Lithuanian. As members of the Polish nation, their understanding of the common Polish-Lithuanian history is conditioned by the Polish historical narrative, acquired as part of the collective memory of the family and/or different minority organizations. On the other hand, they encounter Lithuanian historical narrative of the Polish-Lithuanian past throughout the secondary school history education, where the curriculum, even if taught in Polish, largely represents the Lithuanian point of view. The concept of collective memory is utilized to refer to collective representations of national memory (i.e. publicly articulated narratives and images of collective past in history textbooks) as well as to socially framed individual memories (i.e. historical memory of minority members, where individual remembering is framed by the social context of their identity). The thesis compares the official national historical narratives in Lithuania and Poland, as conveyed by the Polish and Lithuanian history textbooks. The consequent analysis of qualitative interviews with the Polish minority members in Lithuania offers insights into historical memory of Lithuanian Poles and its relation to the official Polish and Lithuanian national narratives of the common past. Qualitative content analysis is applied in both parts of the analysis. The narratives which emerge from the interview data could be broadly grouped into two segments. First, a more pronounced view on the past combines the following elements: i) emphasis on the value of multicultural and diverse past of Lithuania, ii) contestation of “Lithuanocentricity” of the Lithuanian narrative and iii) rejection of the term “occupation”, based on the cultural presuppositions – the dominant position of Polish culture and language in the Vilnius region, symbolic belonging and “Lithuanianness” of the local Poles. While the opposition to the term of “occupation” is in accord with the official Polish narrative conveyed by the textbooks, the former two elements do not neatly adhere to either Polish or Lithuanian textbook narratives. They should rather be considered as an expression of claims for inclusion of plural pasts into Lithuanian collective memory and hence as claims for symbolic enfranchisement into the Lithuanian “imagined community”. The second strand of views, on the other hand, does not exclude assertions about the historically dominant position of Polish culture in Lithuania, but at the same time places more emphasis on the political and historical continuity of the Lithuanian state and highlights a long-standing symbolic connectedness of Vilnius and Lithuania, thus, striking a middle way between the Polish and Lithuanian interpretations of the past.

Inhibition of peroxidase-catalyzed protein tyrosine nitration by antithyroid drugs and their analogues

In this paper, we describe the effect of some commonly used thiourea-based antithyroid drugs and their analogues on the peroxidase-catalyzed nitration reactions. The nitration of bovine serum albumin (BSA) and cytochrome c was studied using the antibody against 3-nitro-L-tyrosine. This study reveals that the thione-based antithyroid drugs effectively inhibit lactoperoxidase (LPO)-catalyzed nitration of BSA. These compounds show very weak inhibition towards the nitration of cytochrome c. Some of these compounds also inhibit myeloperoxidase (MPO)-catalyzed nitration of L-tyrosine. A structure-activity correlation study on the peroxidase-catalyzed nitration of L-tyrosine reveals that the presence of thione/selone moiety is important for the inhibition. Although the presence of a free N-H group adjacent to C=S moiety is necessary for most of the thiones to inhibit the LPO-catalyzed nitration, the corresponding selones do not require the presence of any free N-H group for their activity. Furthermore, experiments with different concentrations of H2O2 suggest that the antithyroid drugs and related thiones inhibit the nitration reaction mainly by coordinating to the Fe(III)-center of the enzyme active site as previously proposed for the inhibition of peroxidase-catalyzed iodination. On the other hand, the selenium compounds inhibit the nitration by scavenging H2O2 without interacting with the enzyme active site. This assumption is based on the observations that catalase effectively inhibits tyrosine nitration by scavenging H2O2, which is one of the substrates for the nitration. In contrast, superoxide dismutase (SOD) does not alter the nitration reactions, indicating the absence of superoxide radical anion (O-2 center dot(-)) during the peroxidase-catalyzed nitration reactions. (C) 2010 Elsevier B.V. All rights reserved.

Synthesis and characterization of barium bis(citrato) oxozirconate(iv) tetrahydrate--A new molecular precursor for fine particle BaZrO3

Barium metazirconate (BaZrO3) fine powder has been produced by thermally decomposing a molecular precursor, barium bis(citrato)oxozirconate(IV) tetrahydrate at about 700-degrees-C. The precursor, Ba[ZrO(C6H6O7)2] . 4H2O (BZO) has been synthesized and characterized by employing a combination of spectroscopic and thermoanalytical techniques. The precursor undergoes thermal decomposition in three major stages: (i) dehydration to give an anhydrous barium zirconyl citrate, (ii) decomposition of the anhydrous citrate in a multistep process to form an ionic oxycarbonate intermediate, Ba2Zr2O5CO3, and (iii) decomposition of the oxycarbonate to produce BaZrO3 fine powder. The particle size of the resultant BaZrO3 is about 0.2 mum, and the surface area is found to be 4.0 m2 g-1.

Extended Huckel molecular orbital calculations on hydroxobridged heterotrinuclear cobalt(III) complexes

EHT calculations on heterotrinuclear cobalt(III) complexes of the type [Cu{(OH)(2)Co(L(4))}(2)](4+) where L(4) denotes (en)(2) or (NH3)(4), en = ethylenediamine and their component species have been carried out. The results regarding bonding and structure for the trinuclear complexes are compared with those for the monomer components such as [Co(en)(2)(OH)(2)](+), [Co(NH3)(4)(OH)(2)](+) and [Cu(OH)(4)](2-) are discussed.

Mean-field theory of charge ordering and phase transitions in the colossal-magnetoresistive manganites

We study phase transitions in the colossal-magnetoresistive manganites by using a mean-field theory both at zero and non-zero temperatures. Our Hamiltonian includes double-exchange, superexchange, and Hubbard terms with on-site and nearest-neighbour Coulomb interaction, with the parameters estimated from earlier density-functional calculations. The phase diagrams show magnetic and charge-ordered (or charge-disordered) phases as a result of the competition between the double-exchange, superexchange, and Hubbard terms, the relative effects of which are sensitively dependent on parameters such as doping, bandwidth, and temperature. In accord with the experimental observations, several important features are reproduced from our model, namely, (i) a phase transition from an insulating, charge-ordered antiferromagnetic to a metallic, charge-disordered ferromagnetic state near dopant concentration x = 1/2, (ii) the reduction of the transition temperature TAF-->F by the application of a magnetic field, (iii) melting of the charge order by a magnetic field, and (iv) phase coexistence for certain values of temperature and doping. An important feature, not reproduced in our model, is the antiferromagnetism in the electron-doped systems, e.g., La1-xCaxMnO3 over the entire range of 0.5 less than or equal to x less than or equal to 1, and we suggest that a multi-band model which includes the unoccupied t(2g) orbitals might be an important ingredient for describing this feature.