Transgenic Mice for a Tamoxifen-Induced, Conditional Expression of the Cre Recombinase in Osteoclasts

Background: Studies on osteoclasts, the bone resorbing cells, have remained limited due to the lack of transgenic mice allowing the conditional knockout of genes in osteoclasts at any time during development or adulthood. Methodology/Principal Finding: We report here on the generation of transgenic mice which specifically express a tamoxifen-inducible Cre recombinase in osteoclasts. These mice, generated on C57BL/6 and FVB background, express a fusion Cre recombinase-ERT2 protein whose expression is driven by the promoter of cathepsin K (CtsK), a gene highly expressed in osteoclasts. We tested the cellular specificity of Cre activity in CtsKCreERT2 strains by breeding with Rosa26LacZ reporter mice. PCR and histological analyses of the CtsKCreERT2LacZ positive adult mice and E17.5 embryos show that Cre activity is restricted largely to bone tissue. In vitro, primary osteoclasts derived from the bone marrow of CtsKCreERT2+/2LacZ+/2 adult mice show a Cre-dependent b-galactosidase activity after tamoxifen stimulation

DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62 % similar overall (28 % identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-lik

Urbano non urbano. Progetto di centro intermodale a Castelvetrano

La proposta progettuale si colloca in un\u2019area di circa 120.000 mq in prossimit\ue0 della stazione ferroviaria di Castelvetrano, tra l\u2019attuale linea ferrata e l\u2019ex sede ferroviaria; una zona che presenta un indebolimento della forma urbana conseguente all\u2019espansione della citt\ue0 dentro il territorio agricolo. Il progetto mira alla riqualificazione di tale area e dove possibile anche alla rifunzionalizzazione di alcuni edifici dismessi appartenenti alla ferrovia. Nell\u2019ambito di un\u2019 eventuale pi\uf9 ampia proposta progettuale di collocare lungo la linea ferrata gli edifici di un centro intermodale volto alla valorizzazione delle vocazioni produttive del comune di Castelvetrano, nonch\ue9 dei comuni limitrofi, un ruolo chiave \ue8 assunto dalla testata di tale centro intermodale, che si collocher\ue0 proprio in quella parte dell\u2019area di progetto particolarmente ibrida, che si pone a cerniera tra il tessuto consolidato e la campagna. Qui trover\ue0 posto il centro direzionale di tale sistema, un edificio che oltre ad avere una funzione pi\uf9 espressamente amministrativa, conterr\ue0 alcuni servizi volti al pubblico, quali una sala conferenze, un ristorante, un cinema, un bar, alcuni negozi; servizi, dunque, volti a un\u2019utenza non necessariamente legata al centro intermodale, ma piuttosto punto di partenza per una progressiva urbanizzazione di tale area. La collocazione planimetrica del centro direzionale si lega inoltre ad un forte elemento strutturante del tessuto urbano di Castelvetrano, costituito dal sistema Villa Comunale - Convento di S. Francesco - Viale Vittorio Veneto e che si spinge in basso fino alla Piazza antistante la Stazione ferroviaria, ponendosi in questo modo come ideale proseguimento del Viale e collegamento tra due parti di citt\ue0 in realt\ue0 divisi dal forte segno della linea ferrata. Proprio l\u2019orientamento di tale asse viario diventa, assieme a quello costituito dalla linea ferrata, elemento generatore della forma dell\u2019edificio che ospiter\ue0 il centro direzionale e della piazza antistante; quest\u2019ultima, in posizione sopraelevata rispetto alla vallata, diventa una sorta di terrazza urbana sulla valle del Belice. Il centro direzionale si presenta come un edificio ibrido, in quanto sistema di elementi funzionali relativamente autonomi e identificabili; esso \ue8 costituito in particolare da tre elementi. Un primo elemento parallelo alla linea ferrata, presenta un corpo basso adibito in parte a magazzino intermodale e in parte a snodo tra i diversi sistemi di circolazione interni all\u2019edificio ed una torre. Questa, in continuit\ue0 rispetto al magazzino, ma con il lato Sud inclinato secondo l\u2019asse del Viale Vittorio Veneto, ospiter\ue0 gli uffici amministrativi, nonch\ue9 una sala conferenze ed un ristorante che occuper\ue0 gli ultimi due livelli. La parte basamentale di questo sistema non presenta soluzioni di continuit\ue0, cosicch\ue8 un ipotetico utente, accedendo dalla zona d\u2019ingresso posta nell\u2019angolo Sud-Est dell\u2019edificio, attraverser\ue0 tutto il primo livello trovando in sequenza l\u2019ampia scalinata di accesso al secondo livello, il centro informazioni, il magazzino intermodale e un\u2019ampia zona di snodo a doppia altezza dalla quale \ue8 possibile accedere al Bar e al cinema, i quali, assieme ad alcuni uffici, occupano il secondo elemento di cui si compone l\u2019edificio. Questo, si pone perpendicolarmente rispetto al sistema torre-magazzino e si sviluppa su tre livelli, delimitando l\u2019ampia piazza antistante, che in parte verr\ue0 coperta dal profondo aggetto della sala cinematografica. Un terzo elemento ospiter\ue0 una serie di negozi ai quali si accede dalla quota della strada che occupa il tracciato dell\u2019ex sede ferroviaria; quest\u2019ultimo elemento si pone in parte parallelamente al primo, ma piega, seguendo l\u2019inclinazione della strada, in corrispondenza della piazza, alla quale si accede mediante un\u2019ampia scalinata, posta lungo il marciapiede alberato antistante i negozi. Completano il progetto la sistemazione a verde delle zone adiacenti all\u2019edificio e la creazione di un parcheggio nell\u2019area antistante l\u2019accesso alla torre

Boosting the methanolysis of polycarbonate by the synergy between ultrasound irradiation and task specific ionic liquids

In an attempt to perform polycarbonate chemical recycling in a more sustainable way, we took into consideration the combined use of ultrasound irradiation and task specific ionic liquids. Towards this aim, the methanolysis of polycarbonate, into dimethylcarbonate and bisphenol A, was carried out in the presence of cholinium-based ionic liquids featuring anions derived from amino acids and other eco-friendly species. The target process was optimized in terms of both energy and material amounts as well as in terms of the nature of the catalysts used. The proposed protocol allowed high conversion and yields of bisphenol A to be obtained, under milder conditions compared to the ones so far reported in the literature, perfectly fulfilling green chemistry principles. The best performing catalyst can be reused without significant loss in performance and the methodology can be successfully applied to post-consumer polycarbonate samples. This journal i

Autism Spectrum Disorders: From Candidate Genes to Candidate Ontology Terms

Genetic heterogeneity for a multifactorial disease such as autism would imply that any two patients are unlikely to share the same susceptibility loci. Since different susceptibility loci may affect the same function and since functions may be considered at different levels of analysis, the following question arises: at what phenotypic levels is convergence attained by different genes in autism ? This is an important question to answer in order to shed light on subcellular, cellular or multicellular structures and functions possibly involved in the pathogenesis of autism. Among the various attempts made to answer this question it is worth mentioning the use of the best available genetic information to focus on the formation, structure and function of the glutamatergic synapse. How could we use this working scheme in a more efficient and hopefully fruitful way ? The recent advent of genomic technology offers an unprecedented opportunity to study the biological structure of autism deep into its molecular roots. For example, recent work on structural genomics has led to the identification of many Copy Number Variations in the gene-rich regions of the genome detected in a large number of patients. Interesting advances have also been made by analyzing the global gene-expression profiles in blood cells of autistic patients. The large amount of data generated by these studies is likely to contain precious information about the pathogenesis of autism. In this paper we review the literature on the genomic studies in ASD and present the results of a preliminary study showing how candidate biological processes for ASD can be identified from microarray data using the Gene Ontology database. We also discuss the importance of the transition from a strategy based on the search for candidate genes to the search for candidate ontology terms to expand our current understanding on the biological processes impaired in AS

Progetto di concorso per il Borgo Murattiano a Bari

In occasione del Concorso Internazionale di Idee per il Borgo Murattiano a Bari, il Comune di Bari ha organizzato presso la Chiesa Russa un dibattito, la premiazione e la mostra dei progetti partecipanti. Il progetto Malakos (capogruppo Michele Sbacchi) rientrava tra i cinque segnalati

Synthesis, biological evaluation, and quantitative receptor docking simulations of 2-[(acylamino)ethyl]-1,4-benzodiazepines as novel tifluadom-like ligands with high affinity and selectivity for kappa-opioid receptors

The synthesis and biological evaluation of a series of 2-substitued 5-phenyl-1,4-benzodiazepines, structurally related to tifluadom (5), the only benzodiazepine that acts simultaneously as a kappa-opioid agonist and a cholecystokinin-A (CCK-A) antagonist, are reported. The radioligand binding models used in these studies were [I-125(BH)-CCK-8 in rat pancreas (CCK-A), [H-3]-(MeNLE(28,31))-CCK-8 in guinea pig cerebral cortex (CCK-B), and [H-3]U-69593 (kappa(1)), [H-3]DAMGO (mu), and [H-3]DADLE (delta) in guinea pig brain. All the title compounds were devoid of significant affinity for both CCK-A and CCK-B receptors, while some of them bound with nanomolar affinity and high selectivity for kappa-opioid receptors. In particular, the 2-thienyl derivative 7a (X = H) with a K-i = 0.50 nM represents a clear improvement with respect to tifluadom, showing a comparable potency but higher selectivity. The application of computational simulations and linear regression analysis techniques to the complexes between guinea pig kappa (kappa(1))-receptor and the title compounds allowed the identification of the structural determinants for recognition and quantitative elucidation of the structure-affinity relationships in this class of receptors