Dysregulation of principal cell miRNAs facilitates epigenetic regulation of AQP2 and results in nephrogenic diabetes insipidus

Background MicroRNAs (miRNAs), formed by cleavage of pre-microRNA by the endoribonuclease Dicer, are critical modulators of cell function by post-transcriptionally regulating gene expression. Methods Selective ablation of Dicer in AQP2-expressing cells (DicerAQP2Cre1 mice) was used to investigate the role of miRNAs in the kidney collecting duct of mice. Results The mice had severe polyuria and nephrogenic diabetes insipidus, potentially due to greatly reduced AQP2 and AQP4 levels. Although epithelial sodium channel levels were decreased in cortex and increased in inner medulla, amiloride-sensitive sodium reabsorption was equivalent in DicerAQP2Cre1 mice and controls. Small-RNA sequencing and proteomic analysis revealed 31 and 178 significantly regulated miRNAs and proteins, respectively. Integrated bioinformatic analysis of the miRNAome and proteome suggested alterations in the epigenetic machinery and various transcription factors regulating AQP2 expression in DicerAQP2Cre1 mice. The expression profile and function of three miRNAs (miR-7688-5p, miR-8114, and miR-409-3p) whose predicted targets were involved in epigenetic control (Phf2, Kdm5c, and Kdm4a) or transcriptional regulation (GATA3, GATA2, and ELF3) of AQP2 were validated. Luciferase assays could not demonstrate direct interaction of AQP2 or the three potential transcription factors with miR-7688-5p, miR-8114, and miR-409-3p. However, transfection of respective miRNA mimics reduced AQP2 expression. Chromatin immunoprecipitation assays demonstrated decreased Phf2 and significantly increased Kdm5c interactions at the Aqp2 gene promoter in DicerAQP2Cre1 mice, resulting in decreased RNA Pol II association. Conclusions Novel evidence indicates miRNA-mediated epigenetic regulation of AQP2 expression

La riforma del Trasporto Pubblico Locale (TPL) in Italia: il quadro normativo di riferimento

I recenti sviluppi normativi (D. Lgs. 422/97 e successive modifiche) hanno prodotto numerose trasformazioni nel Trasporto Pubblico Locale quali: il decentramento delle mansioni, la programmazione dei servizi minimi, la trasformazione delle modalità di affidamento, la stipula dei contratti di servizio, il monitoraggio. In questo articolo gli autori hanno esaminato la normativa vigente a livello comunitario, nazionale e regionale mettendo in evidenza soprattutto le differenze e le analogie tra le diverse leggi regionali

A passenger-oriented optimization model for implementing energy-saving strategies in railway contexts

Rail and metro systems are characterized by high-performing and environmentally friendly features that make them a crucial factor for driving modal split towards public transport modes, thus reducing private car use and related externalities (such as air and noise pollution, traffic congestion and accidents). Within this framework, the implementation of suitable energy-saving policies, allowing to reduce energy consumption, but, at the same time, preserving timetable stability and passengers’ satisfaction, may turn out to be imperative. In particular, this study aims to develop an analytical framework for properly supporting the implementation of eco-driving strategies in a passenger-oriented perspective. An application to a rail line in southern Italy is performed so as to demonstrate the usefulness of the proposed approach in determining the optimal compromise between energy reductions and travel time increases

Railway system design by adopting the Merry-Go-Round (MGR) paradigm

Public transport systems can be characterised by a schedule-based or a frequency-based framework according to the kind of service to be operated. In the former case, specific departure and arrival times are set for each run and disclosed to the users; in the latter, instead, it is necessary to maintain a certain headway between two successive runs, rather than a specific timetable structure. This paper focuses on modelling frequency-based systems, which can be described by means of the so-called Merry-Go-Round (MGR) paradigm. The paradigm is first discussed and the related an-alytical formulation is presented; the role of the terminal station layout is then investigated within this framework. Finally, in order to show the effectiveness of the proposed formulation, it was implemented in the case of a real-scale metro line

Energy-saving applications in the case of rolling stock failures

Current sustainable policies, adopted by most of the world’s governments, have shown the necessity to promote the use of public transportation systems which provide lower external costs (such as congestion, accidents, air and noise pollution) compared to road transportation systems. In this context, the rail and metro systems allow to achieve further two objectives: the increase in efficiency (i.e. operational costs for real/potential carried passengers) and the delocalization of energy production centres (i.e. large industrial plants out of population centres). The above-mentioned positive aspects may be further increased by applying suitable energy-saving and energy-recovery strategies, generally based on the on the adoption of suitable driving profiles and/or installation of on-board/lineside storage devices. In this context, our proposal is based on the investigation of the effects of rolling-stock failures (for breakdowns, maintenance or under-sized fleet) on the effectiveness of energy-saving/energy-recovery measures within a multi-objective framework which combines the reduction in energy consumption with a passenger-oriented perspective. A regional rail line in the south of Italy has been analysed as case-study in order to show the feasibility of the proposed approach

I sistemi di supporto alle decisioni per la pianificazione, la progettazione e la gestione dei sistemi di trasporto

Il lavoro rappresenta uno stato dell'arte relativo ai sistemi di supporto alle decisioni utilizzati nella pianificazione, nella progettazione e nella gestione dei sistemi di trasporto

Predictive methodology for supply disruptions

Energy supply disruptions do not suddenly arise in a full-blown fashion. Lags in the energy system provide a time horizon which allows for the prediction of a possible supply problem. A simple model is described which can be used to provide a set of indicators for the possible onset of an energy emergency. The methodology was tested on the gasoline shortage of 1979, and the results are presented

Passengers’ satisfaction in the case of energy-saving strategies: A rail system application

Rail and metro systems are characterised by high-performing and environmentally-friendly features which make them a crucial factor for driving modal split towards public transport modes, thus reducing private car use and related externalities (such as air and noise pollution, traffic congestion and accidents). Within this framework, the implementation of suitable energy-saving policies, allowing to reduce energy consumption, but, at the same time, preserving timetable stability and passengers’ satisfaction, may turn out to be imperative. In particular, our proposal consists in developing an analytical framework for properly supporting the implementation of eco-driving strategies in a passenger-oriented perspective. An application to a rail line in southern Italy is performed so as to demonstrate the usefulness of the proposed approach

Stato dell'arte sulle tecniche di progetto di reti di TPL

In questa nota si esamina lo stato dell'arte relativo alla progettazione delle reti di trasporto collettivo; i diversi lavori ritrovati in letteratura sono stati classificati in funzione dell'approccio risolutivo al problema

A Total Cost Approach (TCA) for optimising energy-saving measures in disruption conditions

Power supply required for operating rail convoys represents a great cost item for train companies which are paying increasing attention to energy-saving and energy-recovery measures aimed at reducing traction energy consumption and maximising the sustainability of railway system. Indeed, such a transport mode is able to move large volumes of passengers with high energy efficiency and low environmental impact. However, energy saving strategies affect both rail operations and passengers’ satisfaction, and have to be properly implemented in the case of disruption conditions. Specifically, the paper analyses the implementation of energy-efficient speed profiles in a perturbed condition characterised by fleet unavailability and provides a rescheduling methodology based on an ad-hoc optimisation framework, taking into account the trade-off between service providers and service customers’ needs. Indeed, on one hand, the lower the number of operating convoys, the lower the energy consumption; but, on the other hand, this implies a reduction in service frequency with an increase in passenger waiting times. Finally, the proposed approach has been applied in the case of a regional rail line in the south of Italy, in order to point out its usefulness