Suchergebnisse

Jean Hampton (1954-1996) was an influential voice in the landscape of US Philosophy of the second half of the 20th century. The majority of her writings falls within the sphere of Political Philosophy, although her interests ranged from Ethics to the Philosophy of Law, from the Rational Choice Theory to the History of Modern Philosophy and Feminism. In this context, I will analyse Hampton's contractarianism and her view of Liberal Feminism. ; Jean Hampton (1954-1996) è stata una voce influente nel panorama filosofico statunitense della seconda metà del Novecento. La maggioranza dei suoi scritti ricade nell'ambito della filosofia politica, anche se gli interessi della pensatrice spaziarono dall'etica alla filosofia del diritto, dalla teoria della scelta razionale alla storia della filosofia moderna e al femminismo. In questo profilo si approfondisce la sua teoria contrattualistica e la sua proposta di femminismo liberal.

Italian legislation concerning the protection of natural heritage identifies the regional natural parks among the categories of the protected natural areas. Natural parks can include inner land areas, rivers, lakes, and coastal areas endowed with high natural and environmental values which in many cases, are affected by high anthropic pressures. Therefore, planning should consider this problematic dichotomy and guarantee a balance between the conservation objectives and the development needs, according to the sustainability paradigm. Within this framework, the present study proposes a knowledge‐based planning methodology that supports plan‐making processes concerning natural parks, with the first aim to protect and enhance the Park‐related opportunities and identity through the definition of place‐based planning strategies.

Italian legislation concerning the protection of natural heritage identifies the regional natural parks among the categories of the protected natural areas. Natural parks can include inner land areas, rivers, lakes, and coastal areas endowed with high natural and environmental values which, in many cases, are affected by high anthropic pressures. Therefore, planning should consider this problematic dichotomy and guarantee a balance between the conservation objectives and the development needs, according to the sustainability paradigm. Within this framework, the present study proposes a knowledge-based planning methodology that supports plan-making processes concerning natural parks, with the first aim to protect and enhance the Park-related opportunities and identity through the definition of place-based planning strategies.

Abstract
Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates ("calmodulinopathy"). As CaM regulates many key cardiac ion channels, an understanding of disease mechanism associated with CaM variant arrhythmias requires elucidating individual CaM variant effects on distinct channels. One key CaM regulatory target is the KCNQ1 (KV7.1) voltage-gated potassium channel that carries the IKs current. Yet, relatively little is known as to how CaM variants interact with KCNQ1 or affect its function. Here, we take a multipronged approach employing a live-cell fluorescence resonance energy transfer binding assay, fluorescence trafficking assay, and functional electrophysiology to characterize >10 arrhythmia-associated CaM variants for effect on KCNQ1 CaM binding, membrane trafficking, and channel function. We identify one variant (G114W) that exhibits severely weakened binding to KCNQ1 but find that most other CaM variants interact with similar binding affinity to KCNQ1 when compared with CaM wild-type over physiological Ca2+ ranges. We further identify several CaM variants that affect KCNQ1 and IKs membrane trafficking and/or baseline current activation kinetics, thereby delineating KCNQ1 dysfunction in calmodulinopathy. Lastly, we identify CaM variants with no effect on KCNQ1 function. This study provides extensive functional data that reveal how CaM variants contribute to creating a proarrhythmic substrate by causing abnormal KCNQ1 membrane trafficking and current conduction. We find that CaM variant regulation of KCNQ1 is not uniform with effects varying from benign to significant loss of function, suggesting how CaM variants predispose patients to arrhythmia via the dysregulation of multiple cardiac ion channels.
Classification: Biological, Health, and Medical Sciences, Physiology