Controllo genetico dei regolatori del ciclo cellulare attraverso il complesso SKP2/CKS1 ubiquitina ligasi nel cancro epatico dei roditori e sua associazione con la prognosi dell'epatocarcinoma umano

Previous work showed a genetic control of cell cycle during hepatocarcinogenesis. Evidences indicate a posttranscriptional regulation of oncosuppressors by the ubiquitin ligase SKP1/CUL1/F-box protein (SCF) complex. Here we evaluated the role of SCFSKP2 ubiquitin ligase on cell cycle negative regulators in determining the predisposition to HCC, in F344 and BN rats genetically susceptible/resistant to HCC respectively, and in 2 hHCC subtypes. Rats were treated accordingly the “resistant hepatocytes” protocol, we used human control livers, hHCCs with better (hHCCB) and with poor (hHCCP) prognosis. SKP2 function was studied in hHCC cell lines by silencing or inducing SKP2. SKP2 and cell cycle regulators were determined by IP, WB and qPCR in rats and humans. We showed p21WAF1, p27KIP1, p57KIP2, p130 and RassF1A mRNA increases in F344 fast growing lesions, lower/no increase in BN slowly growing lesions. Opposite results occurred at protein levels. Increase in Cks1-Skp2 ligase and ubiquitination of cell cycle regulators occurred in F344 but not in BN rats. The results of hHCCP are comparable to F344 lesions and those of hHCCB to BN lesions. Proliferation indexes of 60 hHCCs were inversely correlated only with protein levels of cell cycle negative regulators in hHCC, indicating a posttranslational modification. Our results indicate that hHCCP exhibit active ubiquitination of cell cycle negative regulators, suggesting that CKS1-SKP2 ligase might be a promising diagnostic marker

Teoria e pratica dell’aiuto professionale: un’analisi empirica sulla relazione tra domande, risposte e stili relazionali nel servizio sociale

The thesis analyses the idea of “help” typical of professional social work and also goes into its anthropological, psychological and sociological aspects. The research, both bibliographical and empirical, has focused on three aspects: 1) Meaning, emotional - behavioural roots of spontaneous help in ordinary life and possible reciprocal relations with the social worker’s professional help; 2) Client’s help claim analysis, with focus on who, when, how, why and what for someone asks for help to a stranger; 3) Expectations and help relationship quality. This third aspect aims at knowing the clients’ expectations in their help claim and the social workers’ expectation in giving help. It also aims at understanding if the clients’ expectations are somehow affected by their wish of empathy, welcome and love. The empirical research, conducted with a qualitative-type method, was carried out with the shadowing method applied to four social workers belonging to different local social work offices and social/health care offices. The collected documentation, classified in ethnographical notes, was analysed with symbolic interactionism and Goffman’s sociology concepts. A new emergent category “agape action” was also used in the analysis and interpretation of the material. Ritual interaction, bureaucracy, listening, personalization, vulnerability and care are among the relevant topics brought out as significant by the client’s help claims and their respective answers

Improving Dermal Delivery of Rose Bengal by Deformable Lipid Nanovesicles for Topical Treatment of Melanoma

Cutaneous melanoma is one of the most aggressive and metastatic forms of skin cancer. However, current therapeutic options present several limitations, and the annual death rate due to melanoma increases every year. Dermal delivery of nanomedicines can effectively eradicate primary melanoma lesions, avoid the metastatic process, and improve survival. Rose Bengal (RB) is a sono-photosensitizer drug with intrinsic cytotoxicity toward melanoma without external stimuli but the biopharmaceutical profile limits its clinical use. Here, we propose deformable lipid nanovesicles, also known as transfersomes (TF), for the targeted dermal delivery of RB to melanoma lesions to eradicate them in the absence of external stimuli. Considering RB's poor ability to cross the stratum corneum and its photosensitizer nature, transfersomal carriers were selected simultaneously to enhance RB penetration to the deepest skin layers and protect RB from undesired photodegradation. RB-loaded TF dispersion (RB-TF), prepared by a modified reverse-phase evaporation method, were nanosized with a ζ-potential value below -30 mV. The spectrophotometric and fluorimetric analysis revealed that RB efficiently interacted with the lipid phase. The morphological investigations (transmission electron microscopy and small-angle X-ray scattering) proved that RB intercalated within the phospholipid bilayer of TF originating unilamellar and deformable vesicles, in contrast to the rigid multilamellar unloaded ones. Such outcomes agree with the results of the in vitro permeation study, where the lack of a burst RB permeation peak for RB-TF, observed instead for the free drug, suggests that a significant amount of RB interacted with lipid nanovesicles. Also, RB-TF proved to protect RB from undesired photodegradation over 24 h of direct light exposure. The ex vivo epidermis permeation study proved that RB-TF significantly increased RB's amount permeating the epidermis compared to the free drug (78.31 vs 38.31%). Finally, the antiproliferative assays on melanoma cells suggested that RB-TF effectively reduced cell growth compared to free RB at the concentrations tested (25 and 50 μM). RB-TF could potentially increase selectivity toward cancer cells. Considering the outcomes of the characterization and cytotoxicity studies performed on RB-TF, we conclude that RB-TF represents a valid potential alternative tool to fight against primary melanoma lesions via dermal delivery in the absence of light

La relazione agapica nel servizio sociale

In questo contributo si dà conto degli esiti di una ricerca finalizzata a verificare la possibilità di rilevare tracce di agire agapico nel servizio sociale. In primo luogo, ci si è chiesti se siano riconoscibili, nel lavoro degli assistenti sociali, “azioni agapiche”, cioè azioni che producono eccedenza di dono senza averla messa in conto. Senza attesa né interesse particolare, azioni esperite di volta in volta nel presente, in assenza di progetto e tuttavia capaci di generare nuove realtà sui generis che permangono nel tempo. In secondo luogo, ci si è chiesti se, utilizzando il concetto euristico di “azioni agapiche” sia possibile coglierne la desiderabilità, la riproducibilità, la compatibilità con un approccio professionale. Si tratta di una ricerca di carattere esplorativo sul territorio nazionale con particolare attenzione ai servizi sociali di contrasto all’emarginazione e alla povertà. La scelta metodologica è stata di tipo qualitativo, per cogliere la prospettiva soggettiva degli attori e l’attribuzione di significato da loro conferito alle azioni agapiche e ai loro effetti, mediante interviste e focus group. Si è dunque proceduto dapprima alla somministrazione di interviste semi-strutturate che ripercorre vano, attraverso 11 quesiti, le dimensioni dell’agire agapico rilevabile attraverso l’evocazione di esperienze di relazione d’aiuto ritenute dagli intervistati o dalle intervistate “ben riuscite”, sono state/i ascoltate/i assistenti sociali e cittadini utenti di servizi di quattro diverse regioni italiane e una provincia autonoma. Dopo una prima analisi dei contenuti emersi dalle interviste, sono stati individuati ulteriori quattro quesititi-stimolo da proporre a due focus group formati ciascuno da 6 assistenti sociali provenienti da quattro regioni italiane Questa prima esplorazione non ha portato a scoprire pratiche professionali e azioni innovative o decisamente alternative al social work già consolidato nei servizi, quanto piuttosto a riconoscere e a valorizzabile la dimensione eccedente e originale dell’aiuto che ciascun/a social worker può coltivare senza per questo tralasciare o contraddire i fondamenti teorici e la strumentazione tecnica propria e necessaria per la sua professionalità. Si è avuta evidenza del fatto che le persone e le loro interazioni, anche professionali, appaiono oltre ogni riduttività classificatoria, diagnostica e prescrittiva, si esprimono lungo itinerari esistenziali spesso lunghi e imprevedibili, aprono a nuovi azzardi creativi. Con questa consapevolezza le e gli assistenti sociali possono fare i conti, mettendo in campo non solo tecniche d’azione e assetti organizzativi più o meno controllati ma anche implicazioni esistenziali umane, prossime, rinnovate, condivisibili

Time lag between metamorphism and crystallization of anatectic granites (Córdoba, Argentina)

SHRIMP and LA-ICP-MS analyses carried out on zircons from the Río de los Sauces granite revealed their metamorphic and igneous nature. The metamorphic zircons yielded an age of 537±4.8 (2σ)Ma that probably predates the onset of the anatexis during the Pampean orogeny. By contrast, the igneous zircons yielded a younger age of 529±6 (2σ)Ma and reflected its crystallization age. These data point to a short time lag of ca. 8Myr between the High Temperature (HT) metamorphic peak and the subsequent crystallization age of the granite. Concordia age of 534±3.8 (2σ)Ma, for both types of zircon populations, can be considered as the mean age of the Pampean HT metamorphism in the Sierras de Córdoba

Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

Previous studies showed that YAP1 is over-expressed in hepatocellular carcinoma (HCC). Here we observed higher expression of Yap1/Ctgf axis in dysplastic nodules and HCC chemically-induced in F344 rats, genetically susceptible to hepatocarcinogenesis, than in lesions induced in resistant BN rats. In BN rats, highest increase in Yap1-tyr357, p73 phosphorylation and Caspase 3 cleavage occurred. In human HCCs with poorer prognosis ( 3 years survival; HCCB). In the latter, higher levels of phosphorylated YAP1-ser127, YAP1-tyr357 and p73, YAP1 ubiquitination, and Caspase 3 cleavage occurred. Expression of stemness markers NANOG, OCT-3/4, and CD133 were highest in HCCP and correlated with YAP1 and YAP1-TEAD levels. In HepG2, Huh7, and Hep3B cells, forced YAP1 over-expression led to stem cell markers expression and increased cell viability, whereas inhibition of YAP1 expression by specific siRNA, or transfection of mutant YAP1 which does not bind to TEAD, induced opposite alterations. These changes were associated, in Huh7 cells transfected with YAP1 or YAP1 siRNA, with stimulation or inhibition of cell migration and invasivity, respectively. Furthermore, transcriptome analysis showed that YAP1 transfection in Huh7 cells induces over-expression of genes involved in tumor stemness. In conclusion, Yap1 post-translational modifications favoring its ubiquitination and apoptosis characterize HCC with better prognosis, whereas conditions favoring the formation of YAP1-TEAD complexes are associated with aggressiveness and acquisition of stemness features by HCC cells

Time lag between metamorphism and crystallization of anatectic granites (Córdoba, Argentina)

SHRIMP and LA-ICP-MS analyses carried out on zircons from the Río de los Sauces granite revealed their metamorphic and igneous nature. The metamorphic zircons yielded an age of 537±4.8 (2σ)Ma that probably predates the onset of the anatexis during the Pampean orogeny. By contrast, the igneous zircons yielded a younger age of 529±6 (2σ)Ma and reflected its crystallization age. These data point to a short time lag of ca. 8Myr between the High Temperature (HT) metamorphic peak and the subsequent crystallization age of the granite. Concordia age of 534±3.8 (2σ)Ma, for both types of zircon populations, can be considered as the mean age of the Pampean HT metamorphism in the Sierras de Córdoba

Granitos anatécticos de las Sierras Pampeanas de Córdoba (Argentina): edades U-Pb SHRIMP y estudio LAICP- MS de elementos traza en circón de metamorfismo y cristalización diacrónicos

In this contribution we present new U-Pb SHRIMP ages and in situ LA-ICP-MS trace element geochemistry of zircon crystals from the Río de los Sauces anatectic granite, Córdoba, Argentina. Notable difference in texture and composition allowed us to identify two zircon populations in a single granite sample that are interpreted as reflecting metamorphic and igneous origins. Zircons regarded as restitic crystals entrained during the melt segregation yielded a slightly older concordia age of 537.1 ± 4.8 Ma (2σ) than those interpreted as igneous, dated at 529 ± 6 (2σ) Ma. Inherited metamorphic zircons are interpreted to represent solid-state growth during high temperature metamorphism of the Pampean orogeny at the onset of the anatexis or metamorphic peak. By contrast, igneous zircons would record the crystallization age of Zr within the Río de los Sauces granite. The textural, compositional and geochronological data of both zircon populations suggest that the inception of the anatexis, the melt segregation and crystallization occurred during a short period of time of 8 myEn este trabajo se aportan nuevos datos de edades U-Pb SHRIMP y análisis in situ LA-ICP-MS de elementos traza de circones provenientes del granito Río de los Sauces, Córdoba, Argentina. A partir de marcadas diferencias texturales y composicionales se pudieron identificar dos poblaciones de circones en una misma muestra del granito, las cuales sugieren orígenes metamórficos e ígneos. Las edades concordia obtenidas en los circones metamórficos e ígneos fueron de 537,1 ± 4,8 Ma (2σ) y 529 ± 6 (2σ) Ma, respectivamente. Se interpreta que los circones metamórficos representan el crecimiento en estado sólido durante el metamorfismo de alta temperatura de la orogenia Pampeana, durante el inicio o el clímax de la anatexia. Por su parte, las edades de los circones ígneos representan la edad de cristalización del granito Río de los Sauces. Los datos texturales, composicionales y geocronológicos de ambas poblaciones de circones sugieren que el inicio de la anatexia, la segregación del fundido y la cristalización ocurrieron durante un periodo breve de tiempo de 8 ma

Magma chamber growth models in the upper crust: A review of the hydraulic and inertial constraints

Finite volumes of magma moving in confinement, store hydraulic potential energy for the generation, control and transmission of power. The Pascal´s principle in a hydraulic jack arrangement is used to model the vertical and lateral growth of sills. The small input piston of the hydraulic jack is equivalent to the feeder dike, the upper large expansible piston equivalent to the magmatic chamber and the inertial force of the magma in the dike is the input force. This arrangement is particularly relevant to the case of sills expanding with blunt tips, for which rapid fracture propagation is inhibited. Hydraulic models concur with experimental data that show that lateral expansion of magma into a sill is promoted when the vertical ascent of magma through a feeder dike reaches the bottom contact with an overlying, flat rigid-layer. At this point, the magma is forced to decelerate, triggering a pressure wave through the conduit caused by the continued ascent of magma further down (fluid-hammer effect). This pressure wave can provide overpressure enough to trigger the initial hydraulic lateral expansion of magma into an incipient sill, and still have enough input inertial force left to continue feeding the hydraulic system. The lateral expansion underneath the strong impeding layer, causes an area increase and thus, further hydraulic amplification of the input inertial force on the sides and roof of the incipient sill, triggering further expansion in a self-reinforcing process. Initially, the lateral pressure increase is larger than that in the roof allowing the sill to expand. However, expansion eventually increases the total integrated force on the roof allowing its uplift into either a laccolith, if the roof preserves continuity, or into a piston bounded by a circular set of fractures. Hydraulic models for shallow magmatic chambers, also suggest that laccolith-like intrusions require the existence of a self-supported chamber roof. In contrast, if the roof of magmatic chambers loses the self-supporting capacity, lopoliths and calderas should be expected for more or less dense magmas, respectively, owing to the growing influence of the density contrast between the host rock and the magma.Fil: Aragon, Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: D'eramo, Fernando Javier. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Pinotti, Lucio Pedro. Universidad Nacional de Río Cuarto; ArgentinaFil: Demartis, Manuel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Tubía Martinez, José María. Universidad del Pais Vasco - Euskal Herriko Unibertsitatea, Campus Bizkaia;Fil: Weinberg, Roberto F.. Monash University; AustraliaFil: Coniglio, Jorge Enrique. Universidad Nacional de Río Cuarto; Argentin

Granite emplacement by crustal boudinage: example of the Calmayo and El Hongo plutons (Córdoba, Argentina)

This study deals with the structure and emplacement of the Calmayo and El Hongo trondhjemite plutons (Famatinian belt of Córdoba, Argentina). It provides structural data from the granites and the country rocks and a study of the magnetic fabric in the plutons. New U/Pb geochronological data yield intrusion ages of 512.1 ± 3.4 Ma and 500.6 ± 4.5 Ma for the Calmayo and El Hongo plutons respectively. The El Hongo massif and the southern part of the Calmayo trondhjemite preserve magmatic structures, whereas the northern domain of Calmayo shows the imprint of solid-state deformation. The main foliation in the country rocks outlines a boudin-like pattern at the map scale and the granites are located along boudin necks, suggesting that the emplacement of these trondhjemite plutons was linked to large-scale boudinage of the country rocks.Fil: D'eramo, Fernando Javier. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tubía, José M.. Universidad del País Vasco; EspañaFil: Pinotti, Lucio Pedro. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vegas, Néstor. Universidad del País Vasco; EspañaFil: Coniglio, Jorge Enrique. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Demartis, Manuel. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aranguren, Aitor. Universidad del País Vasco; EspañaFil: Basei, Miguel. Universidade de Sao Paulo; Brasi