785 research outputs found

    PUK9 COST-EFFECTIVENESS OF PARICALCITOL IN THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM: THE EXPERIENCE IN ITALY

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    SYSTEM FOR AUTOMATIC DETECTION OF CLUSTERED MICROCALCIFICATIONS IN DIGITAL MAMMOGRAMS

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    In this paper, we investigate the performance of a Computer Aided Diagnosis (CAD) system for the detection of clustered microcalcifications in mammograms. Our detection algorithm consists of the combination of two different methods. The first, based on difference-image techniques and gaussianity statistical tests, finds out the most obvious signals. The second, is able to discover more subtle microcalcifications by exploiting a multiresolution analysis by means of the wavelet transform. We can separately tune the two methods, so that each one of them is able to detect signals with similar features. By combining signals coming out from the two parts through a logical OR operation, we can discover microcalcifications with different characteristics. Our algorithm yields a sensitivity of 91.4% with 0.4 false positive cluster per image on the 40 images of the Nijmegen database

    Praja1 E3 ubiquitin ligase promotes skeletal myogenesis through degradation of EZH2 upon p38α activation

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    Polycomb proteins are critical chromatin modifiers that regulate stem cell differentiation via transcriptional repression. In skeletal muscle progenitors Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), contributes to maintain the chromatin of muscle genes in a repressive conformation, whereas its down-regulation allows the progression through the myogenic programme. Here, we show that p38α kinase promotes EZH2 degradation in differentiating muscle cells through phosphorylation of threonine 372. Biochemical and genetic evidence demonstrates that the MYOD-induced E3 ubiquitin ligase Praja1 (PJA1) is involved in regulating EZH2 levels upon p38α activation. EZH2 premature degradation in proliferating myoblasts is prevented by low levels of PJA1, its cytoplasmic localization and the lower activity towards unphosphorylated EZH2. Our results indicate that signal-dependent degradation of EZH2 is a prerequisite for satellite cells differentiation and identify PJA1 as a new player in the epigenetic control of muscle gene expression

    X‐ray Tomography Unveils the Construction Technique of Un‐Montu’s Egyptian Coffin (Early 26th Dynasty)

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    The Bologna Archaeological Museum, in cooperation with prestigious Italian universities, institutions, and independent scholars, recently began a vast investigation programme on a group of Egyptian coffins of Theban provenance dating to the first millennium BC, primarily the 25th–26th Dynasty (c. 746–525 BC). Herein, we present the results of the multidisciplinary investigation car-ried out on one of these coffins before its restoration intervention: the anthropoid wooden coffin of Un‐Montu (Inv. MCABo EG1960). The integration of radiocarbon dating, wood species identifica-tion, and CT imaging enabled a deep understanding of the coffin’s wooden structure. In particular, we discuss the results of the tomographic investigation performed in situ. The use of a transportable X‐ray facility largely reduced the risks associated with the transfer of the large object (1.80 cm tall) out of the museum without compromising image quality. Thanks to the 3D tomographic imaging, the coffin revealed the secrets of its construction technique, from the rational use of wood to the employment of canvas (incamottatura), from the use of dowels to the assembly procedure

    Intraring allostery controls the function and assembly of a hetero‐oligomeric class II chaperonin

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    Class II chaperonins are essential multisubunit complexes that aid the folding of nonnative proteins in the cytosol of archaea and eukarya. They use energy derived from ATP to drive a series of structural rearrangements that enable polypeptides to fold within their central cavity. These events are regulated by an elaborate allosteric mechanism in need of elucidation. We employed mutagenesis and experimental analysis in concert with in silico molecular dynamics simulations and interface-binding energy calculations to investigate the class II chaperonin from Thermoplasma acidophilum. Here we describe the effects on the asymmetric allosteric mechanism and on hetero-oligomeric complex formation in a panel of mutants in the ATP-binding pocket of the α and ÎČ subunits. Our observations reveal a potential model for a nonconcerted folding mechanism optimized for protecting and refolding a range of nonnative substrates under different environmental conditions, starting to unravel the role of subunit heterogeneity in this folding machine and establishing important links with the behavior of the most complex eukaryotic chaperonins.—Shoemark, D. K., Sessions, R. B., Brancaccio, A., Bigotti, M. G. Intraring allostery controls the function and assembly of a hetero-oligomeric class II chaperonin

    Transannular patching is a valid alternative for tetralogy of Fallot and complete atrioventricular septal defect repair

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    Objective: We report our experience with repair of tetralogy of Fallot associated with complete atrioventricular septal defect, addressing in particular the need for a pulmonary valve in the right ventricular outflow tract. Methods: Between 1992 and 2006, 33 children with tetralogy of Fallot and complete atrioventricular septal defect were admitted; 26 had Down’s syndrome (79%). Thirty-two children had complete repair (18 primary, 14 staged); of the 15 who received initial palliation, 1 died before complete repair. Right ventricular outflow tract obstruction was relieved by transannular patch in 14 cases (42%), infundibular patch with preservation of the pulmonary valve in 7 (21%), and right ventricle–to–pulmonary artery conduit in 11 (33%). Results: There were no hospital deaths. Actuarial survival was 96% 3.9% at 5 years and 85.9 1.1% at 10 years. Multivariate analysis showed that type of relief of right ventricular outflow tract obstruction did not influence survival (P ÂŒ .16), nor did the choice to use a valved conduit (P ÂŒ .82). Primary correction (P ÂŒ .05) and lower weight at repair (P ÂŒ .05) were associated with higher probability of survival. Mean follow-up was 69.3 5.9 months (range 0.2–282 months). There were 2 late deaths. Overall freedom from reoperation was 69% at 5 years and 38%at 10 years. Right ventricular outflow tract reconstruction without use of a valved conduit allowed a significantly higher freedom from reinterventions (P<.05). Conclusions: Tetralogy of Fallot associated with complete atrioventricular septal defect can be corrected at low risk with favorable intermediate survival. Use of right ventricle–to–pulmonary artery conduit can be avoided in two thirds of patients with no impact on survival, possibly improving overall freedom from reintervention

    Transannular patching is a valid alternative for tetralogy of Fallot and complete atrioventricular septal defect repair

    Get PDF
    Objective: We report our experience with repair of tetralogy of Fallot associated with complete atrioventricular septal defect, addressing in particular the need for a pulmonary valve in the right ventricular outflow tract. Methods: Between 1992 and 2006, 33 children with tetralogy of Fallot and complete atrioventricular septal defect were admitted; 26 had Down’s syndrome (79%). Thirty-two children had complete repair (18 primary, 14 staged); of the 15 who received initial palliation, 1 died before complete repair. Right ventricular outflow tract obstruction was relieved by transannular patch in 14 cases (42%), infundibular patch with preservation of the pulmonary valve in 7 (21%), and right ventricle–to–pulmonary artery conduit in 11 (33%). Results: There were no hospital deaths. Actuarial survival was 96% 3.9% at 5 years and 85.9 1.1% at 10 years. Multivariate analysis showed that type of relief of right ventricular outflow tract obstruction did not influence survival (P ÂŒ .16), nor did the choice to use a valved conduit (P ÂŒ .82). Primary correction (P ÂŒ .05) and lower weight at repair (P ÂŒ .05) were associated with higher probability of survival. Mean follow-up was 69.3 5.9 months (range 0.2–282 months). There were 2 late deaths. Overall freedom from reoperation was 69% at 5 years and 38%at 10 years. Right ventricular outflow tract reconstruction without use of a valved conduit allowed a significantly higher freedom from reinterventions (P<.05). Conclusions: Tetralogy of Fallot associated with complete atrioventricular septal defect can be corrected at low risk with favorable intermediate survival. Use of right ventricle–to–pulmonary artery conduit can be avoided in two thirds of patients with no impact on survival, possibly improving overall freedom from reintervention
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