Functional and cellular analysis of autoimmune regulator (AIRE) protein

Autoimmune diseases are a major health problem. Usually autoimmune disorders are multifactorial and their pathogenesis involves a combination of predisposing variations in the genome and other factors such as environmental triggers. APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) is a rare, recessively inherited, autoimmune disease caused by mutations in a single gene. Patients with APECED suffer from several organ-specific autoimmune disorders, often affecting the endocrine glands. The defective gene, AIRE, codes for a transcriptional regulator. The AIRE (autoimmune regulator) protein controls the expression of hundreds of genes, representing a substantial subset of tissue-specific antigens which are presented to developing T cells in the thymus and has proven to be a key molecule in the establishment of immunological tolerance. However, the molecular mechanisms by which AIRE mediates its functions are still largely obscure. The aim of this thesis has been to elucidate the functions of AIRE by studying the molecular interactions it is involved in by utilizing different cultured cell models. A potential molecular mechanism for exceptional, dominant, inheritance of APECED in one family, carrying a glycine 228 to tryptophan (G228W) mutation, was described in this thesis. It was shown that the AIRE polypeptide with G228W mutation has a dominant negative effect by binding the wild type AIRE and inhibiting its transactivation capacity in vitro. The data also emphasizes the importance of homomultimerization of AIRE in vivo. Furthermore, two novel protein families interacting with AIRE were identified. The importin alpha molecules regulate the nuclear import of AIRE by binding to the nuclear localization signal of AIRE, delineated as a classical monopartite signal sequence. The interaction of AIRE with PIAS E3 SUMO ligases, indicates a link to the sumoylation pathway, which plays an important role in the regulation of nuclear architecture. It was shown that AIRE is not a target for SUMO modification but enhances the localization of SUMO1 and PIAS1 proteins to nuclear bodies. Additional support for the suggestion that AIRE would preferably up-regulate genes with tissue-specific expression pattern and down-regulate housekeeping genes was obtained from transactivation studies performed with two models: human insulin and cystatin B promoters. Furthermore, AIRE and PIAS activate the insulin promoter concurrently in a transactivation assay, indicating that their interaction is biologically relevant. Identification of novel interaction partners for AIRE provides us information about the molecular pathways involved in the establishment of immunological tolerance and deepens our understanding of the role played by AIRE not only in APECED but possibly also in several other autoimmune diseases.

Molecular Characterization of Sclerospora graminicola, the Incitant of Pearl Millet Downy Mildew Using ISSR Markers

The DNA polymorphism among 22 isolates of Sclerospora graminicola, the causal agent of downy mildew disease of pearl millet was assessed using 20 inter simple sequence repeats (ISSR) primers. The objective of the study was to examine the effectiveness of using ISSR markers for unravelling the extent and pattern of genetic diversity in 22 S. graminicola isolates collected from different host cultivars in different states of India. The 19 functional ISSR primers generated 410 polymorphic bands and revealed 89% polymorphism and were able to distinguish all the 22 isolates. Polymorphic bands used to construct an unweighted pair group method of averages (UPGMA) dendrogram based on Jaccard's co-efficient of similarity and principal coordinate analysis resulted in the formation of four major clusters of 22 isolates. The standardized Nei genetic distance among the 22 isolates ranged from 0.0050 to 0.0206. The UPGMA clustering using the standardized genetic distance matrix resulted in the identification of four clusters of the 22 isolates with bootstrap values ranging from 15 to 100. The 3D-scale data supported the UPGMA results, which resulted into four clusters amounting to 70% variation among each other. However, comparing the two methods show that sub clustering by dendrogram and multi dimensional scaling plot is slightly different. All the S. graminicola isolates had distinct ISSR genotypes and cluster analysis origin. The results of ISSR fingerprints revealed significant level of genetic diversity among the isolates and that ISSR markers could be a powerful tool for fingerprinting and diversity analysis in fungal pathogens.

Low loss and frequency (1 kHz-1 MHz) independent dielectric characteristics of 3BaO-3TiO(2)-B2O3 glasses

X-ray powder diffraction along with differential thermal analysis carried out on the as-quenched samples in the 3BaO-3TiO(2)-B2O3 system confirmed their amorphous and glassy nature, respectively. The dielectric constants in the 1 kHz-1 MHz frequency range were measured as a function of temperature (323-748 K). The dielectric constant and loss were found to be frequency independent in the 323-473 K temperature range. The temperature coefficient of dielectric constant was estimated using Havinga's formula and found to be 16 ppm K-1. The electrical relaxation was rationalized using the electric modulus formalism. The dielectric constant and loss were 17 +/- 0.5 and 0.005 +/- 0.001, respectively at 323 K in the 1 kHz-1 MHz frequency range which may be of considerable interest to capacitor industry.

Identification of genetic susceptibility loci for migraine

Migraine is the common cause of chronic episodic headache, affecting 12%-15% of the Caucasian population (41 million Europeans and some half a million Finns), and causes considerable loss of quality of life to its sufferers, as well as being linked to increased risk for a wide range of conditions, from depression to stroke. Migraine is the 19th most severe disease in terms of disability-adjusted life years, and 9th among women. It is characterized by attacks of headache accompanied by sensitivity to external stimuli lasting 4-72 hours, and in a third of cases by neurological aura symptoms, such as loss of vision, speech or muscle function. The underlying pathophysiology, including what triggers migraine attacks and why they occur in the first place, is largely unknown. The aim of this study was to identify genetic factors associated with the hereditary susceptibility to migraine, in order to gain a better understanding of migraine mechanisms. In this thesis, we report the results of genetic linkage and association analyses on a Finnish migraine patient collection as well as migraineurs from Australia, Denmark, Germany, Iceland and the Netherlands. Altogether we studied genetic information of nearly 7,000 migraine patients and over 50,000 population-matched controls. We also developed a new migraine analysis method called the trait component analysis, which is based on individual patient responses instead of the clinical diagnosis. Using this method, we detected a number of new genetic loci for migraine, including on chromosome 17p13 (HLOD 4.65) and 10q22-q23 (female-specific HLOD 7.68) with significant evidence of linkage, along with five other loci (2p12, 8q12, 4q28-q31, 18q12-q22, and Xp22) detected with suggestive evidence of linkage. The 10q22-q23 locus was the first genetic finding in migraine to show linkage to the same locus and markers in multiple populations, with consistent detection in six different scans. Traditionally, ion channels have been thought to play a role in migraine susceptibility, but we were able to exclude any significant role for common variants in a candidate gene study of 155 ion transport genes. This was followed up by the first genome-wide association study in migraine, conducted on 2,748 migraine patients and 10,747 matched controls followed by a replication in 3,209 patients and 40,062 controls. In this study, we found interesting results with genome-wide significance, providing targets for future genetic and functional studies. Overall, we found several promising genetic loci for migraine providing a promising base for future studies in migraine.

An update on the thermodynamics of Ta2O5

Using a solid-state electrochemical cell incorporating yttria-doped thoria (YDT) as the electrolyte and a mixture of (Mn + MnO) as the reference electrode, standard Gibbs free energy of formation of beta-Ta2O5 has been determined as a function of temperature in the range (1000 to 1300) K. The solid-state electrochemical cell used can be represented as (-)Pt,Ta +Ta2O5//(Y2O3)ThO2//Mn + MnO, Pt(+) Combining the reversible e.m.f. of the cell with recent data on the free energy of formation of MnO, standard Gibbs free energy of formation of Ta2O5 from Ta metal and diatomic oxygen gas (O-2) in the temperature range (1000 to 1300) K is obtained: Delta fG degrees +/- 0.35/(kJ.mol(-1)) = -2004.376 + 0.40445(T/K). Because of the significant solid solubility of oxygen in tantalum, a small correction for the activity of Ta in the metal phase in equilibrium with Ta2O5 is applied. An analysis of the results obtained in this study and other free energy data reported in the literature by the "third law" method suggests the need for refining data for Ta2O5 reported in thermodynamic compilations. Used in the analysis is a revised value for standard entropy of Ta2O5 based on more recent low-temperature heat capacity measurements. An improved set of thermodynamic properties of ditantalum pentoxide (Ta2O5) are presented in the temperature range (298.15 to 2200) K. (C) 2008 Elsevier Ltd. All rights reserved.

Complete genome sequence of Colocasia bobone disease-associated virus, a putative cytorhabdovirus infecting taro

We report the first genome sequence of a Colocasia bobone disease-associated virus (CBDaV) derived from bobone-affected taro [Colocasia esculenta L. Schott] from Solomon Islands. The negative-strand RNA genome is 12,193 nt long, with six major open reading frames (ORFs) with the arrangement 3′-N-P-P3-M-G-L-5′. Typical of all rhabdoviruses, the 3′ leader and 5′ trailer sequences show complementarity to each other. Phylogenetic analysis indicated that CBDaV is a member of the genus Cytorhabdovirus, supporting previous reports of virus particles within the cytoplasm of bobone-infected taro cells. The availability of the CBDaV genome sequence now makes it possible to assess the role of this virus in bobone, and possibly alomae disease of taro and confirm that this sequence is that of Colocasia bobone disease virus (CBDV).

How to measure sustainable progress

In September, the United Nations General Assembly adopted Sustainable Development Goals (SDGs), to be met by the year 2030. These important goals range from poverty eradication and improvements in education and health to the protection of global assets, including the oceans and a stable climate. Unfortunately, neither the SDGs nor their background documents explain how governments should judge whether the development programs they undertake to meet the goals are sustainable.

Studies on some metal monothiobenzoates

Monothiobenzoate (MTB) (Chemical Equation Presented) complexes with the molecular formulas Cr(MTB)3, [Ni(MTB)2]n, [Zn(MTB)2]n, [Cd(MTB)2]n, [Hg(MTB)2]n, [Cu(MTB)]n, and [Ag(MTB)]n have been prepared and studied. All the complexes are nonionic in acetonitrile. Only the chromium complex is soluble in nitrobenzene and found to be monomeric cryoscopically. The thiobenzoate ligand appears to be asymmetrically chelated in Cr(III) and Cd(II) complexes, with stronger oxygen and sulfur coordination, respectively, while practically symmetrically coordinated in Ni(II) and Zn(II) complexes. These four complexes are assigned distorted octahedral structures around the metal ion. The coordination in Hg(II), Cu(I), and Ag(I) complexes is mainly through sulfur indicating the monodentate nature of the thiobenzoate ligand in these complexes. The coordination of monothiobenzoate ion in the complexes has been rationalized in terms of "hard" and "soft" acid-base concept.

Identification of genetic susceptibility loci for migraine

Migraine is the common cause of chronic episodic headache, affecting 12%-15% of the Caucasian population (41 million Europeans and some half a million Finns), and causes considerable loss of quality of life to its sufferers, as well as being linked to increased risk for a wide range of conditions, from depression to stroke. Migraine is the 19th most severe disease in terms of disability-adjusted life years, and 9th among women. It is characterized by attacks of headache accompanied by sensitivity to external stimuli lasting 4-72 hours, and in a third of cases by neurological aura symptoms, such as loss of vision, speech or muscle function. The underlying pathophysiology, including what triggers migraine attacks and why they occur in the first place, is largely unknown. The aim of this study was to identify genetic factors associated with the hereditary susceptibility to migraine, in order to gain a better understanding of migraine mechanisms. In this thesis, we report the results of genetic linkage and association analyses on a Finnish migraine patient collection as well as migraineurs from Australia, Denmark, Germany, Iceland and the Netherlands. Altogether we studied genetic information of nearly 7,000 migraine patients and over 50,000 population-matched controls. We also developed a new migraine analysis method called the trait component analysis, which is based on individual patient responses instead of the clinical diagnosis. Using this method, we detected a number of new genetic loci for migraine, including on chromosome 17p13 (HLOD 4.65) and 10q22-q23 (female-specific HLOD 7.68) with significant evidence of linkage, along with five other loci (2p12, 8q12, 4q28-q31, 18q12-q22, and Xp22) detected with suggestive evidence of linkage. The 10q22-q23 locus was the first genetic finding in migraine to show linkage to the same locus and markers in multiple populations, with consistent detection in six different scans. Traditionally, ion channels have been thought to play a role in migraine susceptibility, but we were able to exclude any significant role for common variants in a candidate gene study of 155 ion transport genes. This was followed up by the first genome-wide association study in migraine, conducted on 2,748 migraine patients and 10,747 matched controls followed by a replication in 3,209 patients and 40,062 controls. In this study, we found interesting results with genome-wide significance, providing targets for future genetic and functional studies. Overall, we found several promising genetic loci for migraine providing a promising base for future studies in migraine.

Spectrophotometric determination of copper with piperidinium piperidyl dithioformate

The reagent piperidinium piperidyl dithioformate forms with copper in aqueous solution a yellowish brown complex which can be extracted with carbon tetrachloride. The copper-PPDF complex in carbon tetrachloride solution has maximum absorption at 434 nm. A spectrophotometric method for determining copper has been developed as the reagent has been shown to form a definite complex.

Dielectric Studies of laser ablated Ca doped BaTiO3 thin films

Recently, there has been growing interest in Ca modified BaTiO3 structures due to their larger electro-optic coefficients for their use in optical storage of information over conventional BaTiO3 crystals. Barium Calcium Titanate (BCT) shows promising applications in advanced laser systems, optical interconnects and optical storage devices. BaTiO3 thin films of varied Ca (3 at. % - 15 at. %) doping were deposited using pulsed laser ablation (KrF excimer laser) technique over Pt/Si substrates. The stoichiometric and the compositional analysis were carried out using EDAX and SIMS. The dielectric studies were done at the frequency regime of 40 Hz to 100 kHz at different ambient temperatures from 200 K to 600 K. The BCT thin films exhibited diffuse phase transition, which was of a typical non lead relaxor behavior and had high dielectric constant and low dielectric loss. The phase transition for the different compositions of BCT thin films was near the room temperature, showing a marked departure from the bulk phase transition. The C - V and the hysteresis behavior confirmed the ferroelectric nature below the phase transition and paraelectric at the room temperature.

MFIS and MFS structures using SrBi2Ta2O9 thin films for the FRAM applications

Recently there is an increasing demand and extensive research on high density memories, in particular to the ferroelectric random access memory composed of 1T/1C (1 transistor/1 capacitor) or 2T/2C. FRAM's exhibit fast random acess in read/write mode, non - volatility and low power for good performance. An integration of the ferroelectric on Si is the key importance and in this regard, there had been various models proposed like MFS, MFIS, MFMIS structure etc., Choosing the proper insulator is very essential for the better performance of the device and to exhibit excellent electrical characteristics. ZrTiO4 is a potential candidate because of its excellent thermal stability and lattice match on the Si substrate. SrBi2Ta2O9 and ZrTiO4 thin films were prepared on p - type Si substrate by pulsed excimer laser ablation technique. Optimization of both ZT and SBT thin films in MFS and MFIS structure had been done based on the annealing, oxygen partial pressures and substrate temperatures to have proper texture of the thin films. The dc leakage current, P - E hysteresis, capacitance - voltage and conductance - voltage measurement were carried out. The effect of the frequency dependence on MFIS structure was observed in the C – V curve. It displays a transition of C - V curve from high frequency to low frequency curve on subjection to varied frequencies. Density of interface states has been calculated using Terman and high - low frequency C - V curve. The effect of memory window in the C - V hysteresis were analysed in terms of film thickness and annealing temperatures. DC conduction mechanism were analysed in terms of poole - frenkel, Schottky and space charge limited conduction separately on MFS, MIS structure.

Field Induced Dielectric Properties of 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 Thin Films

DC electric field induced dielectric properties of 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMN-PT) thin films were studied as a function of frequency at different temperatures. It was observed that the dielectric constant (ε) and dissipation factor (tanδ) were decreased in presence of bias field. The temperature of dielectric maxima was found to increase with increasing bias level. The low temperature (