Sebastiano Serlio e la Sicilia. Modelli per porte e finestre

Serlio and Sicily. Models for Portals and Windows. More than once historiography has highlighted the role played in Sicilian architecture by Sebastiano Serlio's books. We deal with a clear phenomenon wich is recognizable in many outlines, sometimes in early cases. The spread of these books was synchronous and encompassed the whole half of the 16th century. It seem, from the architectural rsults, that a greater success was obtained by the Libri III and IV, and by the Extraordinario. Withing few decades, many workshop in all Sicily began to reproduced architectural elements based on them; above all gates and windows (the series of works here displayed represents just a selection). The fortune of Serlio's models has deeply modified the portal's motif managing to combine those qualities which best represent the wish of modernity and variety of clients

BIAXIAL CURVATURE AND DUCTILITY CAPACITY OF RC COLUMN BASE CROSS SECTIONS

The deformation performance of the base cross sections of reinforced concrete buildings is fundamental when large seismic events occur allowing the structure to have large excursions in nonlinear field and guaranteeing an overall ductile behaviour. It is well known that the axial force acting on columns significantly reduces the curvature capacity of the sections and for this reason the technical codes give design criteria stating a limitation in order to preserve the displacement capacity. It is also recognized that when biaxial bending occur the cross section undergo a loss in strength capacity. Starting the study of from Bresler (1960), which provided suitable expression to predict 3D limit interaction surfaces, several numerical and analytical models were developed to take into account the biaxial interaction in strength. Simultaneously it is noteworthy to point out that the presence of biaxial bending also influences the deformation capacity of sections causing in most of the cases a relevant loss of the curvature and ductility available with respect to the one owned along the principal axes. This important issue is not faced by technical codes and not exhaustively treated in scientific literature as it was done for strength. Moreover nonlinear structural models based on lumped plasticity do not take into account these interaction aspects when defining plastic hinge properties in terms of curvature capacity. The paper presents a numerical study in which the deformation capacity of RC cross sections subjected to axial load and biaxial bending is investigated by means of a fiber discretization. A procedure for the numerical definition of biaxial domains of ultimate curvature, yielding curvature and curvature ductility is provided and the sensitivity of the biaxial deformation performance to some geometrical and mechanical parameters (aspect ratio, concrete strength and confinement efficacy) is discussed.The deformation performance of the base cross sections of reinforced concrete buildings is fundamental when large seismic events occur allowing the structure to have large excursions in nonlinear field and guaranteeing an overall ductile behaviour. It is well known that the axial force acting on columns significantly reduces the curvature capacity of the sections and for this reason the technical codes give design criteria stating a limitation in order to preserve the displacement capacity. It is also recognized that when biaxial bending occur the cross section undergo a loss in strength capacity. Starting the study of from Bresler (1960), which provided suitable expression to predict 3D limit interaction surfaces, several numerical and analytical models were developed to take into account the biaxial interaction in strength. Simultaneously it is noteworthy to point out that the presence of biaxial bending also influences the deformation capacity of sections causing in most of the cases a relevant loss of the curvature and ductility available with respect to the one owned along the principal axes. This important issue is not faced by technical codes and not exhaustively treated in scientific literature as it was done for strength. Moreover nonlinear structural models based on lumped plasticity do not take into account these interaction aspects when defining plastic hinge properties in terms of curvature capacity. The paper presents a numerical study in which the deformation capacity of RC cross sections subjected to axial load and biaxial bending is investigated by means of a fiber discretization. A procedure for the numerical definition of biaxial domains of ultimate curvature, yielding curvature and curvature ductility is provided and the sensitivity of the biaxial deformation performance to some geometrical and mechanical parameters (aspect ratio, concrete strength and confinement efficacy) is discussed

Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Recently we found that acute treatment with Oxotremorine (Oxo), a non-selective mAChRs agonist, up-regulates heat shock proteins and activates their transcription factor heat shock factor 1 in the rat hippocampus. Here we aimed to investigate: a) if acute treatment with Oxo may regulate pro-inflammatory or anti-inflammatory cytokines and oxidative stress in the rat hippocampus; b) if chronic restraint stress (CRS) induces inflammatory or oxidative alterations in the hippocampus and whether such alterations may be affected by chronic treatment with Oxo. In the acute experiment, rats were injected with single dose of Oxo (0.4 mg/kg) and sacrificed at 24 h, 48 h and 72 h. In the CRS experiment, the rats were exposed for 21 days to the CRS and then were treated with Oxo (0.2 mg/kg) for further 10 days. The acute Oxo treatment showed an ability to significantly reduce reactive oxygen species (ROS), singlet oxygen (1O2), pro-inflammatory cytokines levels (IL-1β and IL-6) and phosphorylated NF-κB-p65. Acute Oxo treatment also increased superoxide dismutase (SOD)-2 protein levels and stimulated SOD activity. No differences were detected in the anti-inflammatory cytokine levels, including IL-10 and TGF-β1. In the group of rats exposed to the CRS were found increased hippocampal IL-1β and IL-6 levels, together with a reduction of SOD activity level. These changes produced by CRS were counteracted by chronic Oxo treatment. In contrast, the upregulation of ROS and 1O2 levels in the CRS group was not counteracted by chronic Oxo treatment. The results revealed a hippocampal anti-inflammatory and antioxidant effect of Oxo treatment in both basal conditions and anti-inflammatory in the CRS rat model

Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation

An increased burden of rare exonic variants in NRXN1 microdeletion carriers is likely to enhance the penetrance for autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of a subset of cases (~15%-30%) presenting a rare large-effect variant. However, clinical interpretation in these cases is often complicated by incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent the prototype of such ASD-associated susceptibility variants. From chromosomal microarrays analysis of 104 ASD individuals, we identified an inherited NRXN1 deletion in a trio family. We carried out whole-exome sequencing and deep sequencing of mitochondrial DNA (mtDNA) in this family, to evaluate the burden of rare variants which may contribute to the phenotypic outcome in NRXN1 deletion carriers. We identified an increased burden of exonic rare variants in the ASD child compared to the unaffected NRXN1 deletion-transmitting mother, which remains significant if we restrict the analysis to potentially deleterious rare variants only (P = 6.07 7 10-5 ). We also detected significant interaction enrichment among genes with damaging variants in the proband, suggesting that additional rare variants in interacting genes collectively contribute to cross the liability threshold for ASD. Finally, the proband's mtDNA presented five low-level heteroplasmic mtDNA variants that were absent in the mother, and two maternally inherited variants with increased heteroplasmic load. This study underlines the importance of a comprehensive assessment of the genomic background in carriers of large-effect variants, as penetrance modulation by additional interacting rare variants to might represent a widespread mechanism in neurodevelopmental disorders

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

Giorgio Vasari a Palazzo Abatellis. Percorsi del Rinascimento in Sicilia

La mostra si inserisce nell'ambito delle celebrazioni per i 500 anni della nascita di Giorgio Vasari (1511-2011), ricorrenza che, nel corso dell'anno, \ue8 stata oggetto di numerosi eventi culturali italiani e internazionali. L'iniziativa nasce dalla collaborazione tra la Biblioteca Centrale della Regione siciliana "A. Bombace", la sezione "Sfera" del Dipartimento di Architettura dell'Universit\ue0 degli Studi di Palermo, e la Galleria Interdisciplinare Regionale della Sicilia, istituzione che custodisce, nella prestigiosa sede di Palazzo Abatellis, due grandi dipinti su tavola di Vasari, costituenti le ricurve parti laterali del trittico della "Caduta della manna" realizzato nel 1545 per il refettorio di Santa Maria di Monteoliveto a Napoli. Le lunette vasariane, esposte in modo permanente dal 2009 ma ancora quasi del tutto sconosciute a studiosi e pubblico, per l'occasione sono state ricollocate secondo gli originali rapporti dimensionali con il perduto quadro centrale e poste in relazione con il disegno preparatorio dello stesso Vasari, oggi custodito presso l'Ecole nationale superieure des beaux-arts di Parigi. Il percorso analitico, che si \ue8 avvalso anche del prezioso contributo di Claudia Conforti, tra le pi\uf9 autorevoli studiose dell'artista aretino, e delle competenze tecniche dell'Associazione culturale LapiS, \ue8 stato svolto secondo tre tematiche connesse alla poliedrica attivit\ue0 vasariana e al suo contesto culturale: la pittura e l'arte del disegno, la produzione letteraria, l'architettura. Al patrimonio pittorico e grafico della Galleria, riconducibile a quella che lo stesso Vasari definisce \uabmaniera moderna\ubb, sono stati quindi associati preziosi volumi a stampa, a partire dalla rara edizione del 1568 delle "Vite de' pi\uf9 eccellenti architetti, pittori e scultori italiani", e pannelli illustrativi riferiti a opere siciliane di architetti e scultori citati nelle "Vite" vasariane, costituenti alcune pregnanti testimonianze del Rinascimento in Sicili

Molecular Epidemiology of HIV-1 Transmission in a Cohort of HIV-1 Concordant Heterosexual Couples from Dakar, Senegal

BACKGROUND: A large number of HIV-1 infections in Africa occur in married couples. The predominant direction of intracouple transmission and the principal external origins of infection remain important issues of debate. METHODS: We investigated HIV-1 transmission in 46 HIV-1 concordant positive couples from Dakar, Senegal. Intracouple transmission was confirmed by maximum-likelihood phylogenetic analysis and pairwise distance comparisons of HIV-1 env gp41 sequences from both partners. Standardized interview data were used to deduce the direction as well as the external sources of the intracouple transmissions. RESULTS: Conservative molecular analyses showed linked viruses in 34 (74%) couples, unlinked viruses in 6 (13%) couples, and indeterminate results for 6 (13%) couples. The interview data corresponded completely with the molecular analyses: all linked couples reported internal transmission and all unlinked couples reported external sources of infection. The majority of linked couples (93%) reported the husband as internal source of infection. These husbands most frequently (82%) reported an occasional sexual relationship as external source of infection. Pairwise comparisons of the CD4 count, antiretroviral therapy status, and the proportion of gp41 ambiguous base pairs within transmission pairs correlated with the reported order of infection events. CONCLUSIONS: In this suburban Senegalese population, a majority of HIV-1 concordant couples showed linked HIV-1 transmission with the husband as likely index partner. Our data emphasize the risk of married women for acquiring HIV-1 as a result of the occasional sexual relationships of their husbands

Mitochondrial Uncoupling Protein-2 (UCP2) Mediates Leptin Protection Against MPP+ Toxicity in Neuronal Cells

Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity