Effect of transfection with PLP2 antisense oligonucleotides on gene expression of cadmium-treated MDA-MB231 breast cancer cells

Emerging evidence indicates that cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity in human normal and pathological cells. We have already shown that exposure of MDA-MB231 breast cancer cells to 5 uM CdCl2 for 96 h, apart from affecting significantly mitochondrial metabolism, induces modifications of the expression level of genes coding for members of stress response-, mitochondrial respiration-, MAP kinase-, NF-kB and apoptosis-related pathways. In the present study, we have expanded the knowledge on the biological effects of Cd-breast cancer cell interactions, indicating PLP2 (proteolipid protein-2) as a novel member of the list of Cd-upregulated genes by MDA-MB231 cancer cells and, through the application of transfection techniques with specific antisense oligonucleotides, we have demonstrated that such over-expression may be an upstream event to some of the changes of gene expression levels already observed in Cd-treated cells, thus unveiling new possible molecular relationship between PLP2 and genes linked to the stress- and apoptotic responses

Plastic design of seismic resistant V-braced frames.

In this article, a new method for designing chevron concentrically braced steel frames is presented. The aim of the proposed method is the design of concentrically braced steel frames able to guarantee, under seismic horizontal forces, a collapse mechanism of global type. This result is of great importance in the seismic design of structures, because local failure modes give rise to a worsening of the energy dissipation capacity of structures and, therefore, to an higher probability of failure during severe earthquakes. With reference to the examined structural typology, the global mechanism is characterized by the yielding of tensile bracing diagonals and by the buckling of the compressed diagonals of all the stories. The proposed method is rigorously based on ‘‘capacity design approach’’ which requires that dissipative zones have to be designed to withstand the internal actions due to the seismic design horizontal forces and the vertical loads acting in the seismic load combination; while non dissipative zones have to be designed considering the maximum internal actions that dissipative zones, yielded and strain-hardened, are able to transmit. The new design issue covered by the proposed design procedure is the need to account for the contribution of the compressed diagonals in deriving the design axial force of non dissipative members. The seismic inelastic response of a sample structure is investigated by means of nonlinear dynamic analyses. The results carried out with reference to braced frames designed according to the proposed procedure are compared with those obtained with reference to the same structural schemes designed according to Eurocode 8

Cytotoxicity of the urokinase-plasminogen activator inhibitor carbamimidothioic acid (4-boronophenyl) methyl ester hydrobromide (BC-11) on triple-negative MDA-MB231 breast cancer cells

Abstract: BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding; and (ii) the co-presence of the EGFR inhibitor PD153035 potentiates BC-11’s cytotoxicity. Exposure of cells to a higher concentration of BC-11 corresponding to its ED75 at 72 h (250 μM) caused additional impairment of mitochondrial activity, the production of reactive oxygen species and promotion of apoptosis. Therefore, BC-11 treatment appears to show potential for the development of this class of compounds in the prevention and/or therapy of “aggressive” breast carcinoma

PLASTIC DESIGN OF CB-FRAMES WITH REDUCED SECTION SOLUTION FOR BRACING MEMBERS

The seismic behaviour of concentrically braced frames (CBFs) designed according to the current European provisions is unsatisfactory due to the premature out-of-plane buckling of columns. For this reason, a new design methodology, based on a rigorous application of ``capacity design'' criteria has been recently proposed. In addition, aiming at a reduction of the plastic out of plane deformations of gusset plates due to brace buckling and at the prevention of sudden impact load affecting connections at the end of the straightening phase, Eurocode 8 requires the limitation of the brace slenderness. This limitation leads to the oversizing of diagonals and, consequently, of beams and columns. Therefore, to avoid this problem a new design strategy for bracing members is suggested: the Reduced Section Solution (RSS). It allows the calibration of the diagonal yielding resistance, leaving the brace slenderness practically unchanged. The results of dynamic inelastic analyses carried out with reference to braced frames designed according to the proposed procedure, both with and without RSS, are compared with those obtained with reference to the same structural schemes designed according to Eurocode 8. The obtained results show that the proposed design approaches are able to assure a significant improvement of the seismic performance

Let’s Do It for Real: Making the Ecosystem Service Concept Operational in Regional Planning for Climate Change Adaptation

The application of ecosystem service (ES) knowledge to planning processes and decision-making can lead to more effective climate change adaptation. Despite the increased attention given to the ES concept, its degree of integration and use in spatial planning processes are still below the expectations of those who are promoting this concept. Barriers hindering its operationalisation cover a span of aspects ranging from theoretical to procedural and methodological issues. Overall, there is a general lack of guidance on how and at what point ES knowledge should be integrated into planning processes. This study aims to promote the inclusion of ES knowledge into spatial planning practices and decision-making processes to enhance climate change adaptation. A replicable GIS-based methodology is proposed. First, the potential supply of ESs that can support climate change adaptation (ESCCAs) is defined, mapped, and quantified. Then, a need for an ESCCA supply is identified, and territorial capacities to respond to the expected climate change impacts on natural and socio-economic sectors are assessed. The methodology is applied to the Friuli Venezia Giulia Autonomous Region (Italy) as an illustrative case study. The results reveal that areas with similar geomorphological characteristics tend to respond similarly. Forest ecosystems, inland wetlands and specifically salt marshes can potentially supply a greater variety of ESCCAs. In the case study area, about 62% of the supplied ESCCAs can contribute to reducing the impacts in more than 50% of the impacted sectors. The territory of the study site generally shows good preparedness for expected impacts in most of the analysed sectors; less prepared areas are characterised by agricultural ecosystems. This reading approach based on land cover analyses can thus assist in developing policies to enhance different territorial capacities, ultimately leading to better and more sustainable decision-making

Let’s Do It for Real: Making the Ecosystem Service Concept Operational in Regional Planning for Climate Change Adaptation

The application of ecosystem service (ES) knowledge to planning processes and decision-making can lead to more effective climate change adaptation. Despite the increased attention given to the ES concept, its degree of integration and use in spatial planning processes are still below the expectations of those who are promoting this concept. Barriers hindering its operationalisation cover a span of aspects ranging from theoretical to procedural and methodological issues. Overall, there is a general lack of guidance on how and at what point ES knowledge should be integrated into planning processes. This study aims to promote the inclusion of ES knowledge into spatial planning practices and decision-making processes to enhance climate change adaptation. A replicable GIS-based methodology is proposed. First, the potential supply of ESs that can support climate change adaptation (ESCCAs) is defined, mapped, and quantified. Then, a need for an ESCCA supply is identified, and territorial capacities to respond to the expected climate change impacts on natural and socio-economic sectors are assessed. The methodology is applied to the Friuli Venezia Giulia Autonomous Region (Italy) as an illustrative case study. The results reveal that areas with similar geomorphological characteristics tend to respond similarly. Forest ecosystems, inland wetlands and specifically salt marshes can potentially supply a greater variety of ESCCAs. In the case study area, about 62% of the supplied ESCCAs can contribute to reducing the impacts in more than 50% of the impacted sectors. The territory of the study site generally shows good preparedness for expected impacts in most of the analysed sectors; less prepared areas are characterised by agricultural ecosystems. This reading approach based on land cover analyses can thus assist in developing policies to enhance different territorial capacities, ultimately leading to better and more sustainable decision-making

The project No one is left behind: teaching educational research

School closures due to COVID-19 have brought significant disruptions to education. Service-learning interventions have offered significant opportunities to reduce and reverse the long-term negative effects and to empower the recovery process of pupils in difficulty. The study was carried out with 869 students enrolled in the Primary Education Sciences master's degree course at the University of Palermo. The participants have been involved in the planning and implementation of targeted educational courses designed for the "fragile" pupils from 33 different schools in Palermo. The primary level pupils were provided with a total of 60,000 hours of recovery and learning enhancement activities in remote mode. Challenging teaching activities fostered cognitive and learning development of the pupils and responsibility in teaching educational research. Il progetto Nessuno resta indietro: formazione alla ricerca didattica. La chiusura delle scuole che ha provocato un incremento significativo della povertà educativa ha sollecitato l'opportunità di progettare interventi integrati di service learning per favorire il recupero e il potenziamento dei minori in difficoltà. 869 studenti del Corso di Laurea Magistrale in Scienze della Formazione Primaria dell'Università degli Studi di Palermo, sono stati coinvolti nella progettazione e nella realizzazione di percorsi didattici mirati, rivolti agli alunni "fragili" di 33 scuole palermitane. Complessivamente sono state erogate 60,000 ore in DAD di attività di recupero e di potenziamento dell'apprendimento di alunni della scuola primaria di Palermo. Le attività didattiche sfidanti hanno favorito la stimolazione cognitiva e lo sviluppo della motivazione per l'apprendimento degli alunni e la responsabilità nella formazione alla ricerca didattica