Ferritin Decorated PLGA/Paclitaxel Loaded Nanoparticles Endowed with an Enhanced Toxicity Toward MCF-7 Breast Tumor Cells

PolyLactic and Glycolic Acid nanoparticles (PLGA-NPs), coated with L-Ferritin,are exploited for the simultaneous delivery of paclitaxel and an amphiphilic Gd based MRI contrast agent into breast cancer cells (MCF7). L-Ferritin has been covalently conjugated to the external surface of PLGA-NPs exploiting NHS activated carboxylic groups. The results confirmed that nanoparticles decorated with L-Ferritin have many advantages with respect both albumin-decorated and non-decorated particles. Ferritin moieties endow PLGA-NPs with targeting capability, exploiting SCARA5 receptors overexpressed by these tumour cells, that results in an increased paclitaxel cytotoxicity. Moreover, protein coating increased nanoparticle stability thus reducing the fast and aspecific drug release before reaching the target. The theranostic potentiality of the nanoparticles has been demonstrated by evaluating the signal intensity enhancement on T1-weighted MRI images of labelled MCF7 cells. The results werecompared with that obtained with MDA cells used as negative control due to their lower SCARA5 expression.Fil: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Ruggiero, Maria R.. Universita di Torino; ItaliaFil: Stefanìa, Rachele. Universita di Torino; ItaliaFil: Cutrin, Juan C.. Universita di Torino; ItaliaFil: Aime, Silvio. Universita di Torino; ItaliaFil: Geninatti Crich, Simonetta. Universita di Torino; Itali

Taken by strum: ukuleles and participatory music-making in Hamilton, Aotearoa/New Zealand

Ethnographic study of ukulele playing in Hamilton, N

Seismotectonic analysis of a complex fault system in Italy: the "Garfagnana-North" (Northern Tuscany) line

We present the results obtained combining different techniques to determine the seismotectonic character of the Garfagnana region (northern Tuscany). There, the existence of a rather complex fault system is acknowledged and somewhat mapped, but apart from the geological evidences, very little is known about its extension with depth and the regime. The seismic potential of the system is also well known. The area was characterized, in the past, by destructive earthquakes; in particular a major event (Ms=6.4) struck the Lunigiana-Garfagnana area in September 1920, but many others have been reported. Therefore, the seismicity is under constant monitoring by the national seismic network (RSNC – National Central Seismic Network) and a pool of local stations, belonging to a regional network (RSLG – Regional Seimic network of Lunigiana and Garfagnana). These additional stations account for the lower magnitude seismicity. Such a concentration of seismic stations, and the consequent availability of several seismograms, makes likely to record and localize earthquakes down to a very low magnitude threshold (inferior to Ml = 2.0) with extremely narrow hypocentral parameter errors . Making use of the resulting databases, several analyses were conducted to determine the shape, size, extension with depth of the fault and the associated seismicity. The methodology consists in seismic tomography (1D and 3D velocity models), precise location algorithms NonLinLoc and HypoDD (very constrained and reliable locations) and computation of focal mechanisms (fault orientation and source), all combined with the constraints provided by the geology. The main findings of the study are that the concentration of the recent seismic activity is close to the likely location of the most relevant historical events. In particular the earthquakes are distributed along a plane in the range 0 – 20 km depth dipping 30° NE. All focal mechanisms show a transtensive character

H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC.

H-Prune hydrolyzes short-chain polyphosphates (PPase activity) together with an hitherto cAMP-phosphodiesterase (PDE), the latest influencing different human cancers by its overexpression. H-Prune promotes cell migration in cooperation with glycogen synthase kinase-3 (Gsk-3β). Gsk-3β is a negative regulator of canonical WNT/β-catenin signaling. Here, we investigate the role of Gsk-3β/h-Prune complex in the regulation of WNT/β-catenin signaling, demonstrating the h-Prune capability to activate WNT signaling also in a paracrine manner, through Wnt3a secretion. In vivo study demonstrates that h-Prune silencing inhibits lung metastasis formation, increasing mouse survival. We assessed h-Prune levels in peripheral blood of lung cancer patients using ELISA assay, showing that h-Prune is an early diagnostic marker for lung cancer. Our study dissects out the mechanism of action of h-Prune in tumorigenic cells and also sheds light on the identification of a new therapeutic target in non-small-cell lung cancer

Processes and experiences of creative cognition in seven Western classical composers

In a qualitative study, we explored the range of reflections and experiences involved in the composition of score-based music by administering a 15-item, open-ended, questionnaire to seven professional composers from Europe and North America. Adopting a grounded theory approach, we organized six different codes emerging from our data into two higher-order categories ( the act of composing and establishing relationships). Our content analysis, inspired by the theoretical resources of 4E cognitive science, points to three overlapping characteristics of creative cognition in music composition: it is largely exploratory, it is grounded in bodily experience, and it emerges from the recursive dialogue of agents and their environment. More generally, such preliminary findings suggest that musical creativity may be advantageously understood as a process of constant adaptation – one in which composers enact their musical styles and identities by exploring novel interactivities hidden in their contingent and historical milieux

Towards a sociocultural understanding of children’s voice

While ‘voice’ is frequently invoked in discussions of pupils’ agency and empowerment, less attention has been paid to the dialogic dynamics of children’s voices and the sociocultural features shaping their emergence. Drawing on linguistic ethnographic research involving recent recordings of ten and eleven year-old children’s spoken language experience across the school day, this article examines how pupils’ voices are configured within institutional interactional contexts which render particular kinds of voice more or less hearable, and convey different kinds of value. Analysis shows how children appropriate and reproduce the authoritative voices of education, popular culture and parents in the course of their induction into social practices. At the same time they also express varying degrees of commitment to these voices and orchestrate their own and other people’s voices within accounts and anecdotes, making voice appropriation an uneven, accumulative process shot through with the dynamics of personal and peer-group experience. The examination of children’s dialogue from different contexts across the school day highlights the situated semiotics of voice and the heteroglossic development of children’s speaking consciousness

Il terremoto del 21 giugno 2013 in Lunigiana. Le attività del coordinamento Sismiko

Il 21 giugno 2013 alle ore 10.33 UTC è stato registrato dalla Rete Sismica Nazionale (RSN) [Amato e Mele, 2008; Delladio, 2011] dell’Istituto Nazionale di Geofisica e Vulcanologia (INGV) un terremoto di magnitudo (ML) 5.2 nel distretto sismico1 denominato “Alpi Apuane” tra i comuni di Minucciano in provincia di Lucca e Fivizzano e Casola in provincia di Massa e Carrara, zona conosciuta come “Lunigiana”. L’evento sismico, localizzato dai sismologi in turno presso la sala di sorveglianza sismica di Roma [Basili, 2011] con coordinate 44.153°N e 10.135° E e una profondità di circa 5 km è stato ben risentito in tutta la penisola centro-settentrionale ed è stato seguito in poche ore da numerosi eventi anche di ML ≥ 3.0 (16 nelle prime 72 ore). Storicamente l’area oggetto della sequenza sismica è stata interessata da numerosi terremoti di magnitudo superiore a 5.0 il più grande dei quali quello avvenuto nel 1920 nella zona della Garfagnana (fonte dati: Catalogo Parametrico dei Terremoti Italiani - CPTI11 [Rovida et al., 2011]), ad una distanza di circa 12 km dal mainshock odierno, interessata anch’essa da una piccola sequenza sismica a gennaio del 2013. In considerazione dell’entità dell’evento e seguendo le procedure definite per le situazioni di emergenza internamente all’INGV anche in accordo con l’Allegato A2 della Convenzione vigente 2012- 20203 fra l’ente e il Dipartimento di Protezione Civile (DPC), è stata attivata la Rete Sismica Mobile della sede INGV di Roma (Re.Mo. [Moretti et al., 2010]). Nell’arco di tempo di poco più un’ora dall’accadimento del mainshock è stata disposta l’installazione di una rete sismica temporanea costituita da sei stazioni a integrazione delle reti sismiche permanenti già presenti in area epicentrale (RSN e Regional Seismic network of North-Western Italy – RSNI [Ferretti et al., 2008; 2010; Eva et al., 2010; Pasta et al., 2011]). Nel contempo sono stati consultati tramite e-mail i referenti delle unità di rete sismica mobile delle altre sedi INGV che nell’ambito del coordinamento “Sismiko” [Moretti et al., 2012] negli ultimi due anni hanno dato la propria disponibilità, in termini di personale e strumentazione, ad intervenire in caso di emergenza sismica; sono stati inoltre contattati i colleghi del Dipartimento di Scienze della Terra, dell’Ambiente e della Vita, dell’Università degli Studi di Genova (DISTAV) i più vicini all’area epicentrale e gestori della RSNI che hanno comunicato loro stessi l’intenzione di installare due stazioni temporanee, una in real-time e una in configurazione stand-alone. In questo lavoro viene descritta l’attività compiuta dalla Rete Sismica Mobile INGV, la tempistica dell’intervento effettuato in sinergia con i colleghi dell’Università di Genova, i dettagli circa l'installazione e la gestione delle stazioni sismiche temporanee nel primo mese di attività e una valutazione del dataset acquisito

Hereditary alpha-1-antitrypsin deficiency and its clinical consequences

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally grave

Group Singing as a Resource for the Development of a Healthy Public

A growing body of evidence points to a wide range of benefits arising from participation in group singing. Group singing requires participants to engage with each other in a simultaneous musical dialogue in a pluralistic and emergent context, creating a coherent cultural expression through the reflexive negotiation of (musical) meaning manifest in the collective power of the human voice. As such, group singing might be taken – both literally and figuratively – as a potent form of ‘healthy public’, creating an ‘ideal’ community which participants can subsequently mobilise as a positive resource for everyday life. The experiences of a group of singers (n=78) who had participated in an outdoor singing project were collected and analysed using a three-layer research design consisting of: distributed data generation and interpretation, considered against comparative data from other singing groups (n=88); a focus group workshop (n=11); an unstructured interview (n=2). The study confirmed an expected perception of the social bonding effect of group singing, highlighting affordances for interpersonal attunement and attachment alongside a powerful individual sense of feeling ‘uplifted’. This study presents a novel perspective on group singing, highlighting the importance of participant experience as a means of understanding music as a holistic and complex adaptive system. It validates findings about group singing from previous studies - in particular the stability of the social bonding effect as a less variant characteristic in the face of environmental and other situational influences, alongside its capacity for mental health recovery. It establishes a subjective sociocultural and musical understanding of group singing, by expanding on these findings to centralise the importance of individual experience, and the consciousness of that experience as descriptive self-awareness. The ways in which participants describe and discuss their experiences of group singing and its benefits points to a complex interdependence between a number of musical, neurobiological and psychosocial mechanisms which might be independently and objectively analysed. An emerging theory is that at least some of the potency of group singing is as a resource where people can rehearse and perform ‘healthy’ relationships, further emphasising its potential as a resource for healthy publics

Elevated serum neutrophil elastase is related to prehypertension and airflow limitation in obese women

<p>Abstract</p> <p>Background</p> <p>Neutrophil elastase level/activity is elevated in a variety of diseases such as atherosclerosis, systolic hypertension and obstructive pulmonary disease. It is unknown whether obese individuals with prehypertension also have elevated neutrophil elastase, and if so, whether it has a deleterious effect on pulmonary function. Objectives: To determine neutrophil elastase levels in obese prehypertensive women and investigate correlations with pulmonary function tests.</p> <p>Methods</p> <p>Thirty obese prehypertensive women were compared with 30 obese normotensive subjects and 30 healthy controls. The study groups were matched for age. Measurements: The following were determined: body mass index, waist circumference, blood pressure, lipid profile, high sensitivity C-reactive protein, serum neutrophil elastase, and pulmonary function tests including forced expiratory volume in one second (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio.</p> <p>Results</p> <p>Serum neutrophil elastase concentration was significantly higher in both prehypertensive (405.8 ± 111.6 ng/ml) and normotensive (336.5 ± 81.5 ng/ml) obese women than in control non-obese women (243.9 ± 23.9 ng/ml); the level was significantly higher in the prehypertensive than the normotensive obese women. FEV1, FVC and FEV1/FVC ratio in both prehypertensive and normotensive obese women were significantly lower than in normal controls, but there was no statistically significant difference between the prehypertensive and normotensive obese women. In prehypertensive obese women, there were significant positive correlations between neutrophil elastase and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low density lipoprotein cholesterol, high sensitivity C-reactive protein and negative correlations with high density lipoprotein cholesterol, FEV1, FVC and FEV1/FVC.</p> <p>Conclusion</p> <p>Neutrophil elastase concentration is elevated in obese prehypertensive women along with an increase in high sensitivity C-reactive protein which may account for dyslipidemia and airflow dysfunction in the present study population.</p