473 research outputs found
No Need to Stick Together to Be Connected: Multiple Types of Enhancers’ Networking
No full textThe control of gene expression at a transcriptional level requires a widespread landscape of regulatory elements. Central to these regulatory circuits are enhancers (ENHs), which are defined as cis-acting DNA elements able to increase the transcription of a target gene in a distance- and orientation-independent manner. ENHs are not independent functional elements but work in a complex and dynamic cooperative network, constituting the building blocks of multimodular domains of gene expression regulation. The information from each of these elements converges on the target promoter, contributing to improving the precision and sharpness of gene modulation. ENHs’ interplay varies in its nature and extent, ranging from an additive to redundant effect depending on contexts. Moving from super-enhancers that drive the high expression levels of identity genes, to shadow-enhancers, whose redundant functions contribute to buffering the variation in gene expression, this review aims to describe the different modalities of ENHs’ interaction and their role in the regulation of complex biological processes like cancer development
Economic factors affecting obesity: an application in Italy
No full textThe World Health Organization has stated that obesity is spreading around the world like a “global epidemic”. In 2004 the percentage of obese people in the Italian population was 9%, but the trend s increasing in recent years. Focusing on this country, the purpose of the paper is to analyze the socio-economic variables affecting obesity by means of a survey conducted in a consumer sample. Our analysis is based on a survey conducted in Italy, and the sample was composed of 999 consumers. We used a binary logit model and the dependent variable is body mass index (BMI), expressed in a dichotomic way (seriously overweight and obese, value 1, and normal weight, value 0). The results show that the condition of the seriously overweight and obese increases with age, especially in people over 65 of age. Also gender is correlated with the pathology: being seriously overweight and obese is far more likely for men than for women. An inverse relation was shown between obesity and education, and between obesity and the level of food knowledge. The results highlight that disadvantaged social categories are more susceptible to the problem of overweight and obesity. A policy implication of the analysis, to limit the spread of obesity, could lie in programs aimed at improving health and food awareness and focused on these minority groups.economics of obesity, BMI and consumer, logit model, Food Consumption/Nutrition/Food Safety, Health Economics and Policy,
Demand Side Management in the built environment by means of heat pumps
No full textIl Demand Side Management (DSM) raggruppa un insieme di pratiche ed attività progettate per influenzare la domanda energetica di un consumatore in termini di tempo e/o distribuzione con il fine di individuare come utilizzare l’energia elettrica in modo più efficiente. Il DSM diminuisce il costo per il soddisfacimento della richiesta del consumatore in termini energetici tramite investimenti in efficienza energetica e in gestione dei carichi del consumatore, fornendo flessibilità e riconfigurando il mercato dell'elettricità. Gli obiettivi del DSM sono vari ed includono la diminuzione delle emissioni di CO2 nonché un uso più efficiente di energia, inoltre le misure del DSM mirano ad instaurare un sistema più stabile di tariffazione elettrica. Un altro fondamentale obiettivo del DSM è la gestione dei carichi elettrici, ovvero dei profili di carico del consumatore. Le combinazioni tra i profili di carico sono molte e svariate, tra le categorie più impiegate troviamo il Load Shifting ed il Peak Clipping poiché sono di semplice applicazione e realizzazione, inoltre non richiedono l'impiego di tecnologie avanzate. Per questo motivo, questi due profili di carico sono stati i più indagati nei lavori presentati nel manoscritto. Tra le opportunità più interessanti dell'applicazione del DSM troviamo l'impiego di tali strategie nei dispositivi elettrici, per citarne uno tra tanti, nel campo delle pompe di calore. Il modo più promettente di combinare queste due realtà consiste nell'applicare strategie di load management. A tal fine, ci si serve di strumenti in grado di consentire la gestione dei carichi energetici: tra i tanti, uno dei più validi è sicuramente lo stoccaggio di energia termica (TES). Nei programmi di DSM, il TES viene impiegato in modo da spostare la richiesta per il riscaldamento/raffrescamento dai periodi di maggiore richiesta (on-peak) notoriamente più gravosi a livello economico, ai periodi di bassa richiesta (off-peak) dove solitamente la tariffa oraria è più conveniente. L'impiego dei TES nel DSM aggiunge flessibilità alla gestione dei carichi energetici come ampliamente dimostrato da un vasto numero di lavori in letteratura ed è il nostro campo di ricerca. La novità di quanto qui presentato consiste nell'applicazione delle strategie di DSM al settore dell'edilizia residenziale ed industriale, nello specifico applicando il DSM a casi reali nei quali fossero integrate energie rinnovabili. Si parte dal ricostruire il caso reale in un ambiente di simulazione dinamica per simularne il comportamento sul lungo periodo. I modelli di simulazione sono stati progettati per studiare l'integrazione delle strategie di DSM negli edifici e per analizzare gli effetti dei carichi termici sui consumi elettrici e sulle prestazioni degli involucri. I risultati avuti confermano come le strategie di DSM possano agire positivamente sulle prestazioni degli edifici e dell'intero sistema, incrementandone flessibilità ed efficienza energetica. Inoltre, tali strategie di DSM hanno influito sulla riduzione dei consumi energetici e delle bollette elettriche dei casi studiati, soprattutto qualora siano in atto tariffe elettriche che variano su scala oraria, tutto ciò senza intaccare il comfort interno degli edifici e degli occupanti. Le strategie di DSM risultano essere economicamente vantaggiose qualora vengano integrati sistemi di stoccaggio di energia termica; questi permettono di spostare la richiesta energetica nelle fasce orarie di bassa tariffazione, andando ad attivarsi nei periodi di on-peak, ovvero quando il costo dell'elettricità è più alto. I lavori presentati dimostrano come lo stoccaggio non sia sempre la soluzione energeticamente più vantaggiosa poiché questi necessita di cariche preventive e successive scariche che vanno ad influire sui consumi. Tuttavia, lo stoccaggio permette di allontanare i consumi dai periodi di on-peak e quando presenti delle strategie di DSM, viene confermato come lo stoccaggio sia di aiuto nella riduzione dei costi. Nei lavori viene dimostrato come un contesto Cinese di tariffazione elettrica possa rendere lo stoccaggio un'applicazione di successo, questo poiché i prezzi durante l'off-peak sono sensibilmente più bassi dei prezzi della fascia on-peak. Inoltre, si dimostra come misure semplici di DSM siano solitamente sufficienti a migliorare l'efficienza energetica, questo è dovuto al fatto che il settore edilizio non ha bisogno di grandi stravolgimenti qualora siano impiegate tariffe variabili su scala oraria e soprattutto energie rinnovabili
Cytoskeleton Dynamics in Peripheral T Cell Lymphomas: An Intricate Network Sustaining Lymphomagenesis.
No full textDefects in cytoskeleton functions support tumorigenesis fostering an aberrant proliferation and promoting inappropriate migratory and invasive features. The link between cytoskeleton and tumor features has been extensively investigated in solid tumors. However, the emerging genetic and molecular landscape of peripheral T cell lymphomas (PTCL) has unveiled several alterations targeting structure and function of the cytoskeleton, highlighting its role in cell shape changes and the aberrant cell division of malignant T cells. In this review, we summarize the most recent evidence about the role of cytoskeleton in PTCLs development and progression. We also discuss how aberrant signaling pathways, like JAK/STAT3, NPM-ALK, RhoGTPase, and Aurora Kinase, can contribute to lymphomagenesis by modifying the structure and the signaling properties of cytoskeleton
HELLS: the transcriptional sentinel
No full textThe role of the chromatin remodeler HELicase Lymphoid Specific (HELLS) has been historically associated with DNA methylation and DNA damage repair. However, recent studies have shed light on an unexpected, multimodal, and direct participation of HELLS in transcriptional regulation. This forum article aims to discuss how, through different and context-specific mechanisms, HELLS modulates the expression of functionally related genes favoring transcriptional plasticity and phenotypic adaptation, ultimately safeguarding the genome organization and stability
Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive Factor RUNX2.
No full textAberrant reactivation of embryonic pathways occurs commonly in cancer. The transcription factor RUNX2 plays a fundamental role during embryogenesis and is aberrantly reactivated during progression and metastasization of different types of human tumors. In this study, we attempted to dissect the molecular mechanisms governing RUNX2 expression and its aberrant reactivation. We identified a new regulatory enhancer element, located within the RUNX2 gene, which is responsible for the activation of the RUNX2 promoter and for the regulation of its expression in cancer cells. Furthermore, we have shown that treatment with the anticancer compounds histone deacetylase inhibitor (HDACi) results in a profound inhibition of RUNX2 expression, which is determined by the disruption of the transcription-activating complex on the identified enhancer. These data envisage a possible targeting strategy to counteract the oncongenic function of RUNX2 in cancer cells and provide evidence that the cytotoxic activity of HDACi in cancer is not only dependent on the reactivation of silenced oncosuppressors but also on the repression of oncogenic factors that are necessary for survival and progression
Author response
No full textDetecting pathogens and mounting immune responses upon infection is crucial for animal health. However, these responses come at a high metabolic price (McKean and Lazzaro, 2011, Kominsky et al., 2010), and avoiding pathogens before infection may be advantageous. The bacterial endotoxins lipopolysaccharides (LPS) are important immune system infection cues (Abbas et al., 2014), but it remains unknown whether animals possess sensory mechanisms to detect them prior to infection. Here we show that Drosophila melanogaster display strong aversive responses to LPS and that gustatory neurons expressing Gr66a bitter receptors mediate avoidance of LPS in feeding and egg laying assays. We found the expression of the chemosensory cation channel dTRPA1 in these cells to be necessary and sufficient for LPS avoidance. Furthermore, LPS stimulates Drosophila neurons in a TRPA1-dependent manner and activates exogenous dTRPA1 channels in human cells. Our findings demonstrate that flies detect bacterial endotoxins via a gustatory pathway through TRPA1 activation as conserved molecular mechanism.sponsorship: Vlaams Instituut voor Biotechnologie Alessia Soldano Luis Franco Guangda Liu Natalia Mora Emre Yaksi Bassem A Hassanr Fonds Wetenschappelijk Onderzoek G.0702.12 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0077.15 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0680.10 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0681.10 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0503.12 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0654.15 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0761.10N Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0596.12 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar Fonds Wetenschappelijk Onderzoek G.0565.07 Alessia Soldano Yeranddy A Alpizar Brett Boonen Alejandro Lopez-Requena Natalia Mora Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar KU Leuven GOA/14/011 Alessia Soldano Yeranddy A Alpizar Brett Boonen Luis Franco Alejandro Lopez-Requena Guangda Liu Natalia Mora Emre Yaksi Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar European Commission IUAP P7/13 Alessia Soldano Yeranddy A Alpizar Brett Boonen Luis Franco Alejandro Lopez-Requena Guangda Liu Natalia Mora Emre Yaksi Thomas Voets Rudi Vennekensr KU Leuven OT/12/091 Alessia Soldano Yeranddy A Alpizar Brett Boonen Luis Franco Alejandro Lopez-Requena Guangda Liu Natalia Mora Emre Yaksi Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talaverar KU Leuven PF-TRPLe Alessia Soldano Yeranddy A Alpizar Brett Boonen Luis Franco Alejandro Lopez-Requena Guangda Liu Natalia Mora Emre Yaksi Thomas Voets Rudi Vennekens Bassem A Hassan Karel Talavera (Vlaams Instituut voor Biotechnologie, Fonds Wetenschappelijk Onderzoek|G.0702.12, Fonds Wetenschappelijk Onderzoek|G.0077.15, Fonds Wetenschappelijk Onderzoek|G.0680.10, Fonds Wetenschappelijk Onderzoek|G.0681.10, Fonds Wetenschappelijk Onderzoek|G.0503.12, Fonds Wetenschappelijk Onderzoek|G.0654.15, Fonds Wetenschappelijk Onderzoek|G.0761.10N, Fonds Wetenschappelijk Onderzoek|G.0596.12, KU Leuven|GOA/14/011, KU Leuven|OT/12/091, European Commission|IUAP P7/13, KU Leuven PF-TRPLe)status: Publishe
Molecular and Histopathological Characterization of Metastatic Cutaneous Squamous Cell Carcinomas: A Case–Control Study
No full textSimple Summary This study investigates the characteristics of metastatic cutaneous squamous cell carcinoma (cSCC) to improve patient risk stratification. By comparing patients with metastatic and non-metastatic cSCC, we analyzed cSCC skin samples for histological parameters and gene expression profiles. Out of 770 genes tested, 67 were differentially expressed in metastatic cSCC. These were mainly related to immune regulation, skin integrity, angiogenesis, cell migration, and proliferation. The findings suggest that combining histological and molecular profiles can help identify features specific to metastatic cSCC, potentially enhancing patient risk assessment.Abstract Background: A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The study aims to identify specific histological and molecular parameters characterizing metastatic cSCC. Methods: Patients affected by metastatic and non-metastatic cSCC (controls) were included in the present study and matched for clinical and histological characteristics. Skin samples from primary tumors were revised for several histological parameters and also underwent gene expression profiling with a commercially available panel testing 770 different genes. Results: In total, 48 subjects were enrolled in the study (24 cases, 24 controls); 67 genes were found to be differentially expressed between metastatic and non-metastatic cSCC. Most such genes were involved in immune regulation, skin integrity, angiogenesis, cell migration and proliferation. Conclusion: The combination of histological and molecular profiles of cSCCs allows the identification of features specific to metastatic cSCC, with potential implications for more precise patient risk stratification
Thermal energy storage coupled with PV panels for demand side management of industrial building cooling loads
No full textDue to their non-deterministic behaviour, renewable energies are defined as non-dispatchable energies and are largely coupled with energy storage systems to overcome the problem of matching energy production and demand. Hence, in the energy efficiency and conservation field there is growing interest towards energy storage systems, especially when combined with the demand side management (DSM) concept, representing DSM the possibility of shaping end user electricity consumption. In this work an existing installation of a thermal energy storage (TES) system coupled with heat pumps in an industrial building is presented and a dynamic simulation model is built to represent its behaviour. Simulations are performed to show the load shifting potential of such storage and costs and energy use are assessed for different configurations, in order to evaluate the viability of this TES application. In particular the demand side strategy considered is aimed at shifting energy demand for cooling to weekend daytime to recover surplus PV electricity or otherwise to off peak hours to profit from lower electricity tariffs. It is found that the use of TES implies increased energy demand, while costs can decrease when electricity tariffs with a considerable difference between on peak and off peak rates are applied. Furthermore the integration with renewable sources for electricity production, such as PV panels, makes the installation of TES economically interesting independently of the electricity tariff in place. However the more relevant aspect for the overall economic feasibility of such installation is the initial capital investment
Assessment of the Energy Performance of an Air Source Heat Pump by Response Surface Methodology
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