507 research outputs found

    A POU homeo domain protein related to dPOU-19/pdm-1 binds to the regulatory DNA necessary for vital expression of the Drosophila choline acetyltransferase gene

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    Expression of the choline acetyltransferase (ChAT) gene in Drosophila melanogaster is responsible for production of the neurotransmitter acetylcholine and is necessary for viability. In previous studies, we have shown that the regulatory region for normal ChAT expression is large and composed of multiple regulatory elements (Kitamoto et al., 1992; Kitamoto and Salvaterra, 1993). In this study, using various lengths of 5′ flanking DNA fused to wild type ChAT cDNA, we have defined a 0.3 kilobase (kb) region of the cis-regulatory DNA, which is essential for restoring viability of Cha lethal mutants. DNase I footprinting analysis of this 0.3 kb DNA revealed a protected 22 bp sequence that contains an octamer-like motif (ATTCAAAT) with one base difference from the consensus octamer motif (ATGCAAAT). Electrophoretic mobility shift assays and Southwestern blot analysis confirmed the presence of specific binding factor(s) for the 22 bp sequence in embryo nuclear extracts, and competition studies established the importance of the octamer-like motif for high-affinity binding. Using the 22-mer as a probe, we have isolated a cDNA clone encoding the Drosophila POU homeo domain protein, dPOU-19/pdm-1, whose target genes and specific binding sequences have not been identified. We propose that vital expression of the Drosophila ChAT gene is regulated by a member of the dPOU-19/pdm-1 putative transcription factor family.</jats:p

    History and state of the art of PrP-res “typing” in Creutzfeldt-Jakob disease

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    Much progress has been made in understanding the molecular basis of phenotypic variability in Creutzfeldt-Jakob disease (CJD) in the last ten years. The most significant advance was the discovery that the genotype at polymorphic codon 129 of PRNP and the “type” of the protease-resistant prion protein fragment, PrP-res, have a major influence on the disease phenotype in all forms of CJD, irrespective of their etiology. The most widely accepted CJD classification includes six clinico-pathological phenotypes and two major types of PrP-res, types 1 and 2, which can be distinguished on the basis of a ∼2 kDa difference in relative molecular mass of the protein fragment. However, alternative classifications of human PrP-res types distinguished three patterns of PrP-res molecular mass instead of two, thereby creating significant confusion in the field. Fortunately, progress has been recently made in clarifying these disparities. Most significant in this regard, has been the finding that pH variation among CJD brain homogenates in standard buffers influences the size of PrP-res. Thus, some of the PrP-res heterogeneity used to identify putative strain-specific PrP-res types simply represents a technical “artefact” related to the experimental conditions. On the other hand, recent data have also shown that PrP-res types 1 and 2 are heterogeneous biological species, which can be further distinguished into molecular subtypes that fit the current histopathological classification of sporadic CJD in 6 subtypes. Finally, novel truncated PrP-res fragments of smaller size than PrP-res types 1 and 2 have recently been identified in CJD. Although more studies are needed to fully characterize the presence, characteristics and biological significance of these peptides, preliminary results indicate that their search and characterization may be useful in the molecular diagnostics of CJD subtypes

    Relations between x-ray timing features and spectral parameters of galactic black hole x-ray binaries

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    We present a study of correlations between spectral and timing parameters for a sample of black hole X-ray binary candidates. Data are taken from GX 339-4, H 1743-322, and XTE J1650-500, as the Rossi X-ray Timing Explorer (RXTE) observed complete outbursts of these sources. In our study we investigate outbursts that happened before the end of 2009 to make use of the high-energy coverage of the HEXTE detector and select observations that show a certain type of quasi-periodic oscillations (type-C QPOs). The spectral parameters are derived using the empirical convolution model simpl to model the Comptonized component of the emission together with a disc blackbody for the emission of the accretion disc. Additional spectral features, namely a reflection component, a high-energy cut-off, and excess emission at 6.4 keV, are taken into account. Our investigations confirm the known positive correlation between photon index and centroid frequency of the QPOs and reveal an anti-correlation between the fraction of up-scattered photons and the QPO frequency. We show that both correlations behave as expected in the “sombrero” geometry. Furthermore, we find that during outburst decay the correlation between photon index and QPO frequency follow a general track, independent of individual outbursts

    The characterization of AD/PART co-pathology in CJD suggests independent pathogenic mechanisms and no cross-seeding between misfolded Aβ and prion proteins

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    Current evidence indicating a role of the human prion protein (PrP) in amyloid-beta (Aβ) formation or a synergistic effect between Aβ and prion pathology remains controversial. Conflicting results also concern the frequency of the association between the two protein misfolding disorders and the issue of whether the apolipoprotein E gene (APOE) and&nbsp;the prion protein gene (PRNP), the major modifiers of Aβ- and PrP-related pathologies, also have a pathogenic role in other proteinopathies, including tau neurofibrillary degeneration. Here, we thoroughly characterized the Alzheimer's disease/primary age-related tauopathy (AD/PART) spectrum in a series of 450 cases with definite sporadic or genetic Creutzfeldt-Jakob disease (CJD). Moreover, we analyzed: (i) the effect of variables known to affect CJD pathogenesis and the co-occurring Aβ- and tau-related pathologies; (II) the influence of APOE genotype on CJD pathology, and (III) the effect of AD/PART co-pathology on the clinical CJD phenotype. AD/PART characterized 74% of CJD brains, with 53.3% and 8.2% showing low or intermediate-high levels of AD pathology, and 12.4 and 11.8% definite or possible PART. There was no significant correlation between variables affecting CJD (i.e., disease subtype, prion strain, PRNP genotype) and those defining the AD/PART spectrum (i.e., ABC score, Thal phase, prevalence of CAA and Braak stage), and no difference in the distribution of APOE ε4 and ε2 genotypes among CJD subtypes. Moreover, AD/PART co-pathology did not significantly affect the clinical presentation of typical CJD, except for a tendency to increase the frequency of cognitive symptoms. Altogether, the present results seem to exclude an increased prevalence AD/PART co-pathology in sporadic and genetic CJD, and indicate that largely independent pathogenic mechanisms drive AD/PART and CJD pathology even when they coexist in the same brain

    Microvariability of SS 0716+714; a gamma-Ray Blazar

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    Simultaneous optical multiband observations of the Blazar S5 0716 +714 were performed using the 70 cm telescope of the University of Roma (Italy), the 70 cm of the Collurania-Teramo Observatory, the 50 cm of the Vallinfreda Station (Roma, Italy) and the 40 cm of the University of Perugia (Italy). Standard B,V,R,I and narrow band at 720, 800, 860 and 990 nm filters of the Arizona system were used. Using several telescopes it is possible to achieve a very tight temporal sampling in a number of spectral bands and to look for possible different behaviours of the light curves at different wave-lengths. Even intranight trends as small as a few hundredth of magnitude can be unambiguously detected. The results of several days of observations are shown and discussed in the framework of current models
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