Effetto della modifica bidirezionale della cascata della MAP chinasi sulla memoria di riconoscimento visivo e sulla plasticità sinaptica della corteccia peririnale

E’ stato proposto che la formazione di tracce di memoria richieda l’attivazione di vie di segnalazione intracellulare, che regolino lo stato di attività di proteine importanti per la trasmissione sinaptica (recettori, proteine coinvolte nel rilascio del trasmettitore) e la sintesi proteica. Una delle vie di segnalazione coinvolte è quella che coinvolge ERK1,2 (anche denominate p42/44 MAP chinasi), difatti interferenze farmacologiche con i meccanismi di segnalazione che coinvolgono le ERK inibiscono i fenomeni di plasticità sinaptica (LTP e LTD) e causano deficit di consolidamento delle tracce di memoria in modelli animali. Nell’uomo mutazioni genetiche che coinvolgono i suoi fattori sono responsabili di molte patologie che comportano ritardo mentale. Nel presente studio abbiamo cercato di verificare se le ERK siano importanti per i fenomeni di memoria di riconoscimento visivo ed in particolare di valutare gli effetti dell’iper- e ipo-attivabilità di questa via, nel consolidamento di tracce di memoria visiva e nella plasticità sinaptica. Nella prima fase del nostro lavoro, abbiamo utilizzato due tipi di topi mutanti per osservarne le loro prestazioni in un test comportamentale (Object Recognition Test) di memoria visiva. In un mutante era stato inattivato il gene che codifica per rasGRF1, un attivatore calcio-dipendente delle ERK, in modo da ridurre l’attività della cascata in risposta a stimolazione sinaptica. In un’altra linea di mutanti invece, era stato deleto il gene che codifica per ERK1 con il risultato di indurre un ipercompensazione da parte di ERK2 che rendeva questa chinasi più attivabile del normale. In questo test l’animale è stato inizialmente posto di fronte a due oggetti uguali perché si verifichi una familiarizzazione. Successivamente dopo un periodo di un’ora, il topo è stato messo davanti a due oggetti diversi di cui, uno corrispondeva a quelli visti nella familiarizzazione e l’altro era un oggetto nuovo. Lo stesso procedimento è stato ripetuto anche a distanza di 1,24, 48, 72 e 96 ore. Dal momento che questi animali per comportamento naturale tendono ad esplorare maggiormente oggetti ancora sconosciuti, abbiamo valutato la capacità di consolidamento delle tracce di memoria misurando il tempo trascorso ad esplorare il nuovo oggetto rispetto a quello già visto. I risultati del test hanno mostrato delle differenze tra i gruppi: a distanza di 24 ore dalla fase di familiarizzazione i mutanti rasGRF1, con ipoattivabilità delle ERK, mostravano deficit di memoria rispetto ai wild type. Un fenotipo opposto era osservato nei mutanti ERK1 con iperattivabilità di ERK infatti la traccia di memoria si manteneva più a lungo (72 ore) che nei wild type. Questo suggerisce che la via di ERK costituisca un punto di regolazione importante dei meccanismi di consolidamento delle tracce di memoria visiva. E’ risaputo che nel riconoscimento visivo gioca un ruolo fondamentale la corteccia peririnale. Numerosi esperimenti hanno dimostrato che ratti in cui questa zona è stata lesionata, presentano forti deficit nei test che implicano il riconoscimento di oggetti. Disturbi analoghi sono stati osservati anche nell’uomo, nel caso di soggetti che hanno subito traumi o interventi che l’hanno lesionata. Nella seconda fase del lavoro quindi, abbiamo cercato di capire il ruolo di rasGRF1 e di ERK1 nei fenomeni di plasticità sinaptica della corteccia peririnale. Abbiamo eseguito registrazioni di potenziali di campo da fettine di corteccia peririnale per valutare la plasticità sinaptica (LTP e LTD) in questa struttura nei mutanti rasGRF1 e ERK1. Dal momento che recenti studi dimostrano che l’attività colinergica sia una modulazione particolarmente influente sui neuroni della peririnale, abbiamo deciso di studiare l’LTD indotto da carbacolo, un’agonista colinergico. L’ LTP è stato indotto da treni di stimoli di frequenza theta. Gli esperimenti hanno evidenziato una forte riduzione dell’ LTD sui mutanti rasGRF1 rispetto ai wild type di controllo e dati preliminari suggeriscono anche una riduzione dell‘LTP. Ciò dimostra come l’assenza di Ras GRF1 limiti molto questi fenomeni di plasticità, e che questi siano effettivamente dipendenti dalla cascata della MAP chinasi a livello della corteccia peririnale. Nel caso di ERK1 risultati preliminari suggeriscono invece che non vi siano differenze significative rispetto al controllo. La differenza fenotipica dei mutanti ERK1 tra plasticità sinaptica e il prolungamento della traccia di memoria di riconoscimento visivo osservata comportamentalmente potrebbe dipendere da un azione di ERK a stadi più tardivi del consolidamento, non compresi nel nostro protocollo di sperimentazione elettrofisiologica, oppure da un coinvolgimento di altre aree cerebrali nelle fasi tardive del consolidamento della memoria visiva

An investigation of interregional trade network structures

We provide empirical evidence on the network structure of trade flows between European regions and discuss the theoretical underpinning of such a structure. First, we analyze EU regional trade data using Social Network Analysis. We describe the topology of this network and compute local and global centrality measures. Finally, we consider the distribution of higher order statistics, through the analysis of local clustering and main triadic structures in the triad census of interregional trade flows. In the theoretical part, we explore the relationship between trade costs and trade links. As shown by Behrens (2004, 2005a, 2005b) in a two-region linear new economic geography (NEG) model, trade costs and the local market size determine, even with finite trade costs, unconditional autarky and unilateral trade, that is, a one-directional flow from one region to the other. Following these contributions and guided by the empirical evidence, we clarify the relationship between market competition, trade costs and the patterns of trade in a three-region NEG model. We identify a larger set of trade network configurations other the three elementary ones that occur at the dyadic level between two regions (no trade, one-way trade, reciprocated two-way trade), and relate the model with the triad census

Pyridostigmine in pediatric Intestinal pseudo-obstruction. case report of a 2-year old girl and literature review

Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, longacting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility

Bridging thermodynamics and metrology in non-equilibrium Quantum Thermometry

Single-qubit thermometry presents the simplest tool to measure the temperature of thermal baths with reduced invasivity. At thermal equilibrium, the temperature uncertainty is linked to the heat capacity of the qubit, however the best precision is achieved outside equilibrium condition. Here, we discuss a way to generalize this relation in a non-equilibrium regime, taking into account purely quantum effects such as coherence. We support our findings with an experimental photonic simulation.Comment: 7 pages, 4 figure

Investigation of Mechanical Properties of Aluminum Tailor Welded Blanks

Nowadays, the reduction of CO2 emissions and the decrease in energy consumption are the main aims of several industries, especially in the automotive sector. To comply with the increasingly restrictive regulations, the automotive industry is constantly looking for innovative techniques to produce lighter, more efficient, and less polluting vehicles. One of the latest technologies, and still developing, is based on the fabrication of the body-in-white and car parts through the stamping of aluminum Tailor Welded Blanks. Tailor Welded Blanks (TWBs) are generally the combination of two/three metal sheets with different thicknesses and/or mechanical strengths, which are commonly butt-welded together by laser sources. The use of aluminum TWBs has several advantages such as low density and corrosion resistance adequate. However, their use is still limited by the lower formability with respect to the parent materials and the more intrinsic difficulty of laser welding of aluminum sheets (i.e., internal porosity) that, although its use in automated industries is constantly growing, remains a process to be further developed and improved. This study has investigated the effect of the main laser welding process parameters (laser power, welding speed, and focal distance) on the mechanical properties of aluminum TWBs made of 6xxx series. The research results show that a narrow weldability window can be found to ensure welded joints with high strength and limited or no porosity

Workers’ Aging Management—Human Fatigue at Work: An Experimental Offices Study

The aging issue in the work context is becoming a significant element of the future sustainability of service and industrial companies. It is well known that with increasing worker age the problem of maintaining the performance and the safety level when fatigue increases is a crucial point, and fatigue increases with the age. Due to social and political developments, especially in Western countries, the retirement age is increasing and companies operate with a higher workforce mean age. Therefore, the problem of recognizing and measuring fatigue has become a key aspect in the management of aging. Note that in the scientific engineering field, the problem of fatigue evaluation when a worker is performing his/her work activities is an important issue in the industrial and service world and especially in the context of the researchers that are investigating the human reliability assessment. As it is clear from the literature, the industrial operations management are suffering from some misleading concepts that only the medicine scientific context can clarify. Therefore, the aim of this paper is to define what are the open issues and the misleading concepts present in the classical fatigue evaluation methods, and second to define two experimental curves of fatigue that will help the decision makers to minimize the impact of fatigue on the workers, thus maximizing the sustainability of the working tasks assigned. This aim is achieved by examining the medical literature about the measurement of a particular kind of fatigue related to the circadian cycle, i.e., the cognitive one; after that, a survey about the possible technologies for measurements is performed. On the basis of technology selection, an experiment on real work activities is performed and some remarkable results about the fatigue in the workers observed and the technology use and its limitations are defined

Leptin levels predict the development of left ventricular hypertrophy in a sample of adult men: the Olivetti Heart Study

A higher leptin (LPT) is associated with a greater cardiometabolic risk. Some studies also showed a positive association between LPT and cardiovascular organ damage but no consistent data are available about a predictive role of LPT on cardiac remodelling. Hence, the aim of this study was to evaluate the potential role of LPT on the incidence of left ventricular hypertrophy (LVH) in a sample of adult men

Assessment of blood perfusion quality in laparoscopic colorectal surgery by means of Machine Learning

An innovative algorithm to automatically assess blood perfusion quality of the intestinal sector in laparoscopic colorectal surgery is proposed. Traditionally, the uniformity of the brightness in indocyanine green-based fluorescence consists only in a qualitative, empirical evaluation, which heavily relies on the surgeon's subjective assessment. As such, this leads to assessments that are strongly experience-dependent. To overcome this limitation, the proposed algorithm assesses the level and uniformity of indocyanine green used during laparoscopic surgery. The algorithm adopts a Feed Forward Neural Network receiving as input a feature vector based on the histogram of the green band of the input image. It is used to (i) acquire information related to perfusion during laparoscopic colorectal surgery, and (ii) support the surgeon in assessing objectively the outcome of the procedure. In particular, the algorithm provides an output that classifies the perfusion as adequate or inadequate. The algorithm was validated on videos captured during surgical procedures carried out at the University Hospital Federico II in Naples, Italy. The obtained results show a classification accuracy equal to [Formula: see text], with a repeatability of [Formula: see text]. Finally, the real-time operation of the proposed algorithm was tested by analyzing the video streaming captured directly from an endoscope available in the OR

Adoption of Machine Learning Techniques to Enhance Classification Performance in Reactive Brain-Computer Interfaces

This paper proposes the adoption of an innovative algorithm to enhance the performance of highly wearable, reactive Brain-Computer Interfaces (BCIs), which exploit the Steady-State Visually Evoked Potential (SSVEP) paradigm. In particular, a combined time-domain/frequency-domain processing is performed in order to reduce the number of features of the brain signals acquired. Successively, these features are classified by means of an Artificial Neural Network (ANN) with a learnable activation function. In this way, the user intention can be translated into commands for external devices. The proposed algorithm was initially tested on a benchmark data set, composed by 35 subjects and 40 simultaneous flickering stimuli, obtaining performance comparable with the state of the art. Successively, the algorithm was also applied to a data set realized with highly wearable BCI equipment. In particular, (i) Augmented Reality (AR) smart glasses were used to generate the flickering stimuli necessary to the SSVEPs elicitation, and (ii) a single-channel EEG acquisition was conducted for each volunteer. The obtained results showed that the proposed strategy provides a significant enhancement in SSVEPs classification with respect to other state-of-the-art algorithms. This can contribute to improve reliability and usability of brain computer interfaces, thus favoring the adoption of this technology also in daily-life applications