217 research outputs found
Dissecting the role of Collagen VI at the myotendinous junction by exploiting a mouse model of ColVI-related disorders
No full textCollagen VI (ColVI) is an extracellular matrix (ECM) protein mainly expressed by fibroblasts and known to be expressed in a plethora of tissues. Although it belongs to the collagen family of proteins, its structure is unique in terms of supramolecular assembly, as ColVI tetramers assemble in a beaded microfilament network once secreted into the ECM. Due to its complex assembly (a ColVI monomer is a heterotrimer made of three different α-chains) and its ability to bind several ECM proteins but also membrane-bound receptors, ColVI has many biological functions. ColVI chains are mostly known for being affected in human diseases of the musculoskeletal apparatus. Mutations affecting the assembly, secretion or formation of the beaded microfilament network in the ECM of ColVI results in a mild to severe muscular dystrophy, affecting muscles, tendons, cartilage and bones. Based on the type and severity of symptoms, the diseases caused by mutations in COL6A1, COL6A2, COL6A3 and COL6A6 genes are classified as Bethlem Myopathy (BM), Ullrich Congenital Muscular Distrophy (UCMD) or Myosclerosis Myopathy (MM), different types of ColVI related disorders (ColVI-RD). The underlying pathological mechanisms of disease have been investigated thanks to the use of in vitro models derived from patients’ biopsies or in vivo by generating transgenic mouse lines. In particular, the Col6a1-/- mice (ColVI KO) proved to be a useful loss-of-function model of Bethlem Myopathy, due to its complete incapability of producing ColVI. Thanks to this model many discoveries have been made, such as the mitochondrial dysfunction and the suppression of autophagy in muscle, both targetable processes to develop interventions in humans. Nonetheless a lot of details regarding non.muscle specific features are still unclear. In this context, my PhD project aimed at characterizing potential pathological changes at the myotendinous junction (MTJ) and their contribution to ColVI-RD pathogenesis in the ColVI KO mouse model. The MTJ is the connection site of muscle myofibers with the tendon ECM, and it is characterized by peculiar morphological features of the myofiber tip (forming digit-like protrusions) but also by its specific ECM composition and cellular niche. Due to the great forces applied at this site, the MTJ can undergo rupture in healthy individuals and its contribution to muscular dystrophy is mostly unknown. ColVI was previously shown to be expressed in the human MTJ, but its role in this site has not been addressed yet in the ColVI KO mouse model. I was able to isolate an MTJ-enriched diaphragm region for proteomic analysis which proved to be crucial to dissect the pathological changes at the MTJ in ColVI KO mice. I was able to detect changes in the ECM composition, but also in the mechanical properties of the MTJ ECM. Additionally, proteomic and imaging approaches highlighted cytoskeletal alterations at the myofiber tip, possibly due to the altered mechanical properties and ECM composition. Indeed, decreased focal adhesion signaling activation was highlighted, together with a decreased interdigitation of the myofiber protrusions as shown by electron microscopy. These changes also involved the activation of the mechanosensitive YAP/TAZ signaling pathway, potentially triggering cell proliferation in response to increased stiffness. In support of a proliferative response to an injury-like insult, target genes of the transcriptional repressor HIC1, involved in maintenance of quiescent mesenchymal progenitor cells, were upregulated in ColVI KO MTJ extracts. Overall, we show for the first time the involvement of MTJ-specific pathological alterations in a mouse model of ColVI-RD. Our results pave the way to further deepen our understanding of pathological changes at the MTJ in muscular dystrophies
Scelte, modelli e retoriche della città sportiva. Una riflessione comparata tra Italia ’90 e i processi sistemici oggi in corso
No full textThe cytotoxic effect of slow Loris (nycticebus) venom, on human cancer cells
No full textWithin the Kingdom Mammalia, venom evolution is rare, occurring in only six orders. Arguably the most cryptic, and academically neglected venom occurs within primates among slow lorises (Nycticebus spp.). Venoms comprise novel biological compounds with a potential plethora of proteins and peptides available for utilisation in bio-medical research. We collected samples of slow loris saliva from eight captive-bred pygmy slow lorises (N. pygmaeus) at Paignton Zoo and Shaldon Wildlife Trust UK, given voluntarily as slow lorises chewed on Salimetrics children’s swabs. From January to March 2017, we employed MTT assays, and microscopy assessments to determine cell survival on human epidermal carcinoma cells (A431 line) after the application of concentrations of slow loris salivary venom. Cell survival from both male and female derived saliva was half that of untreated cells. Cytotoxic action is demonstrated in concentrations as low as 0.01% venom. Results demonstrate a cytotoxic effect with ensuing physiological damage on human cancer cells, demonstrating the cytotoxic action of slow loris saliva only, without the admixture of brachial gland exudate. We show that even captive-bred slow loris saliva harbours potentially dangerous substances, with functional applications towards slow loris husbandry. Knowledge of slow loris salivary venom increases understanding of the novel salivary composition and supports discussions of slow loris conservation by proposing a functional narrative to oppose the illegal pet trade, by contradicting their ‘cute and cuddly’ appeal. Evidence of salivary venom shows that cytotoxic effects can result even in the absence of a bite puncturing the skin, and further demonstrates their inappropriateness as pets
Il progetto “Energie Sisma Emilia”
No full textI disastri naturali, come quelli che si sono verificati in Italia nel secondo dopoguerra e, in particolare, eventi sismici, alluvioni, frane ed esondazioni, richiamano in misura crescente l’attenzione (e non solo quella degli studiosi) sulla fragilità del territorio e sulla necessità di interventi di prevenzione per mitigare i loro effetti economici e sociali. Accanto alla prevenzione, si segnala da più parti, dalle Nazioni Unite alla Commissione Europea, la necessità di far leva sulle capacità di resilienza delle comunità colpite da calamità naturali, agendo quindi sui fattori endogeni dello sviluppo
The challenges in integrating ESG factors into banks’ credit department: a knowledge management enhanced framework
No full textPurpose
Assuming that knowledge management is a pivotal issue in business to improve and maintain competitive advantages, this paper aims to investigate how knowledge management is useful to face challenges about the integration of environment, social and governance (ESG) factors, filling the gap in the literature regarding knowledge management and ESG in the banking world by considering a real case.
Design/methodology/approach
Starting from the analysis of the more relevant literature on the topic, this paper describes an illustrative real case through interviews with the credit department of an Italian bank that has adopted a specific sustainability approach. This paper discusses this case in the context of the outlined theoretical background to explore the trends and challenges of ESG integration. The case study allows us to evaluate and expand our theoretical framework, leading to a greater understanding of the complex phenomenon under investigation.
Findings
Based on the analysis of the literature combined with the insights that emerged from the experience of the real case, this study shows that there are three primary factors to consider: data issues, competencies and workflow. This study outlines an enhanced knowledge management framework displaying the complexity emerging from the integration of ESG into a bank’s credit department and identify the best practices to pursue.
Practical implications
Given the increasing pressure toward the incorporation of ESG factors into the banking sector, the practical implications of the study are relevant as they provide guidelines for action. Specifically, the practical problems highlighted by the real case, like the priority on themes such as questionnaires, the need for ad hoc commissions and workflow, drive the attention of decision-makers on key aspects to effectively adopt an advanced knowledge management approach aimed at improving the ESG integration. Considering the effect of the banking system on the economy, the best practices this study has identified can also have a positive impact on society as a whole.
Originality/value
The proposed enhanced knowledge management framework offers a guideline to orchestrate ESG integration into banks’ credit departments, considering the increasing need to frame a sustainability-oriented strategic approach that emerges from academic and practical enquiries. This research represents an initial attempt to investigate the integration of ESG factors in the banking system through the lens of knowledge management. The strategic nature of the ESG approach clearly appears in a dynamic environment where stakeholder pressures and regulatory evolutions are strong
Attractiveness In The Eu Policy Debate And A Research Field for Territorial Cohesion
No full textstatus: Publishe
Multiple Tank Explosions in an Edible-Oil Refinery Plant: A Case Study
No full textMultiple explosions occurred when five workers were acting on a footbridge structure at the top of crude olive pomace oil tanks. Welding on the tank roofs was performed without previously cleaning the tanks stopping their operation. First, one of the several approximate to 650-m3 reservoirs exploded, provoking a pool fire that spread throughout the tank farm. Roughly 1h later, two other reservoirs exploded causing the launching of missiles to a distance of 60-80m and a huge fire that extended throughout the entire tank farm. Four workers were killed instantaneously. The explosion was caused by the unusually high content of hexane in the crude olive pomace oil and, hence, by the inefficiency of the desolventization process which creates a flammable and explosive oil from a combustible one
Territorial attractiveness in EU urban and spatial policy: A critical review and future research agenda
No full textThe paper introduces the concept of territorial assets and discusses their role for regional development. Focusing on European societies and taking into account different strands of the literature on place and territorial capital, we argue that the endowment with - and mobilization of - such territorial assets could be seen as a key aspect of regional policy, producing changes in the attraction (and/or retention) of specific segments of population and, in a longer-term perspective, influencing sustainable development strategies. In this light, 'territorial attractiveness' - characterized in this paper in both conceptual and operational terms - is presented as a powerful element in European spatial policy, allowing regional development strategies to be more systematically integrated under an overall objective of territorial cohesion, while taking into account their implications in terms of human mobility. © The Author(s) 2011.sponsorship: ESPON project: ATTREGstatus: Publishe
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