NOVEL IRSP53 (INSULIN RECEPTOR SUBSTRATE PROTEIN OF 53 KDA) FUNCTIONS IN ACTIN CAPPING, FILOPODIA FORMATION AND POLARITY ESTABLISHMENT

IRSp53 (Insulin Receptor Substrate protein of 53 kDa) is a multidomain scaffolding protein that possesses an I-BAR domain (responsible for protein dimerization and membrane deformation), a partial CRIB motif (for the interaction with active CDC42), a SH3 domain (through it binds actin-related proteins) and additional protein interaction modules at the C-terminus. We have studied a previously unknown capping role of IRSp53 and the functional consequences of its interaction with VASP. In particular, we showed that following CDC42 binding and activation, IRSp53 is able to recruit and cluster VASP both in vitro and on the plasma membrane, thus fostering VASP processive elongation activity. The elongation of actin filaments by VASP, together with the membrane-deforming ability of IRSp53, combine to promote filopodia initiation downstream of CDC42. Thus, IRSp53 is essential for coordinating these activities in vitro and in cells in culture. In the second part of this thesis, an IRSp53 role in the polarity program was investigated. We showed that IRSp53 is apically localized in 3-D cyst models of epithelial cells, and IRSp53 depletion leads to a multilumen phenotype in MDCK and Caco2 spheroids. Moreover, using MDCK cysts as a model system, we noted that IRSp53 is enriched early at the prospective lumen initiation site (called AMIS), even before the apical marker podocalyxin. Finally, IRSp53 removal affects podocalyxin localization in MDCK cysts at the early stages. We speculate that IRSp53 might be involved in the trafficking of the apical protein podocalyxin, we are currently investigating the molecular mechanism responsible for this putative role

Flavonoid-inspired vascular disrupting agents: Exploring flavone-8-acetic acid and derivatives in the new century

Naturally occurring flavonoids are found as secondary metabolites in a wide number of plants exploited for both medicine and food and have long been known to be endowed with multiple biological activities, making them useful tools for the treatment of different pathologies. Due to the versatility of the scaffolds and the vast possibilities of appropriate decoration, they have also been regarded as fruitful sources of lead compounds and excellent chemical platforms for the development of bioactive synthetic compounds. Flavone-8-acetic acid (FAA) and 5,6-dimethylxanthone acetic acid (DMXAA) emerged for their antitumour potential due to the induction of cytokines and consequent rapid haemorrhagic necrosis of murine tumour vasculature, and different series of derivatives have been designed thereafter. Although the promising DMXAA failed in phase III clinical trials because of strict species-specificity, a boost in research came from the recent identification of the stimulator of interferon genes (STING), responsible for supporting tumoural innate immune responses, as a possible biological target. Consequently, in the last decade a renewal of interest for these flavonoid-based structures was noticed, and novel derivatives have been synthesised and evaluated for a deeper understanding of the molecular features needed for affecting human cells. Un-doubtedly, these natural-derived molecules deserve further investigation and still appear attractive in an anticancer perspective

Development of an EMG-controlled mobile robot

This paper presents the development of a Robot Operating System (ROS)-based mobile robot control using electromyography (EMG) signals. The proposed robot’s structure is specifically designed to provide modularity and is controlled by a Raspberry Pi 3 running on top of an ROS application and a Teensy microcontroller. The EMG muscle commands are sent to the robot with hand gestures that are captured using a Thalmic Myo Armband and recognized using a k-Nearest Neighbour (k-NN) classifier. The robot’s performance is evaluated by navigating it through specific paths while solely controlling it through the EMG signals and using the collision avoidance approach. Thus, this paper aims to expand the research on the topic, introducing a more accurate classification system with a wider set of gestures, hoping to come closer to a usable real-life applicatio

Modulations of Cortical Power and Connectivity in Alpha and Beta Bands during the Preparation of Reaching Movements

Planning goal-directed movements towards different targets is at the basis of common daily activities (e.g., reaching), involving visual, visuomotor, and sensorimotor brain areas. Alpha (8-13 Hz) and beta (13-30 Hz) oscillations are modulated during movement preparation and are implicated in correct motor functioning. However, how brain regions activate and interact during reaching tasks and how brain rhythms are functionally involved in these interactions is still limitedly explored. Here, alpha and beta brain activity and connectivity during reaching preparation are investigated at EEG-source level, considering a network of task-related cortical areas. Sixty-channel EEG was recorded from 20 healthy participants during a delayed center-out reaching task and projected to the cortex to extract the activity of 8 cortical regions per hemisphere (2 occipital, 2 parietal, 3 peri-central, 1 frontal). Then, we analyzed event-related spectral perturbations and directed connectivity, computed via spectral Granger causality and summarized using graph theory centrality indices (in degree, out degree). Results suggest that alpha and beta oscillations are functionally involved in the preparation of reaching in different ways, with the former mediating the inhibition of the ipsilateral sensorimotor areas and disinhibition of visual areas, and the latter coordinating disinhibition of the contralateral sensorimotor and visuomotor areas

Interplay Between Endocannabinoid System and Neurodegeneration: Focus on Polypharmacology

Pharmacological treatment of complex pathologies, such as neurodegenerative diseases still represents a major challenge, due to the networked pathways involved in their onset and progression that may require equally complex therapeutic approaches. Polypharmacology, based on the simultaneous modulation of multiple targets involved in the disease, may offer the potential to increase effectiveness and reduce the drawbacks related to the use of drug combinations. Clearly, this approach requires both the knowledge of the systems responsible for disease development and the discovery of new attractive targets to be exploited to design a multitarget drug. Over the last years, an ever increasing interest has focused on the endocannabinoid system, implicated in the modulation of several physiological functions, among which neuroinflammation, a crucial process for most neurodegenerative diseases. In this respect, the cannabinoid receptor subtype 2 represents a promising therapeutic target, being overexpressed in microglia cells and thus involved in neuroinflammation. The indirect modulation of this system through the inhibition of the main enzymes responsible for endocannabinoids metabolism, namely fatty acid amide hydrolase and monoacylglycerol lipase, may also significantly affect neurodegenerative processes. The aim of this review is to give an overview of the opportunities posed by the endocannabinoid system for neurodegenerative diseases management, mainly focusing on the potential for a multitarget strategy

A BGK model for reactive mixtures of polyatomic gases with continuous internal energy

Versão dos autores para esta publicação.In this paper we derive a BGK relaxation model for a mixture of polyatomic gases with a continuous structure of internal energies. The emphasis of the paper is on the case of a quaternary mixture undergoing a reversible chemically reaction of bimolecular type. For such a mixture we prove an H-theorem and characterize the equilibrium solutions with related mass action law of chemical kinetics. Further, a Chapman-Enskog asymptotic analysis is performed in view of computing the first-order non-equilibrium corrections to the distribution functions and investigating the transport properties of the reactive mixture. The chemical reaction rate is explicitly derived at the first-order and the balance equations for the constituent number densities are derived at the Euler level.The paper is partially supported by the Italian National Group GNFM of INdAM and by the Portuguese Funds FCT Project UID/MAT/00013/2013. One of the Authors (AJS) thanks the Italian institution for the financial support given in her visiting professor program in Italy.info:eu-repo/semantics/publishedVersio

The strong and the hungry: Bias in capture methods for mountain hares (Lepus timidus).

Estimating density, age and sex structure of wild populations is a key objective in wildlife management. Live trapping is frequently used to collect data on populations of small and medium-sized mammals. Ideally, sampling mammal populations by live capturing of individuals provides a random and representative sample of the target population. Trapping data may, however, be biased. We used live-capture data from mountain hares Lepus timidus in Scotland to assess sampling bias between two different capture methods.Wecaptured hares using baited cage traps and long nets on five study areas in the Scottish Highlands. After controlling for the effects of body size, individuals caught in traps were lighter than individuals caught using long nets, suggesting that the body condition of hares differed between the capture methods. This tendency may reflect an increased risk-taking of individuals in poorer body condition and less aversion to entering traps in order to benefit from eating bait. Overall, we caught more adult hares than juveniles and more female hares than males. Our results show that estimates of density and population structure of mountain hares using livecapture data could be affected by the capture method used. We suggest that live-capture studies employ more than one capture method and test for heterogeneity in capture probability to minimise potential bias and achieve reliable estimates of population parameters

Experimental and numerical analysis of a CO2 dual-source heat pump with PVT evaporators for residential heating applications

Multi-source energy systems are a promising solution to lower the environmental impact of the heating and cooling sector and enhance the exploitation of renewable energy sources. In this context, dual-source solar-assisted heat pumps exploit solar energy and air as the low-temperature heat sources. However, the efficiency of solar-based systems is strictly related to weather conditions, location, and time. Therefore, there is a need for accurate models to be used in dynamic simulations of these systems and perform detailed performance analyses and study the involved energy flows. This paper presents an experimental and numerical investigation of a direct-expansion solar-assisted heat pump (DX-SAHP) operating with CO2 as the refrigerant. The heat pump prototype can work with an air-finned coil heat exchanger or photovoltaic-thermal (PVT) solar collectors as the evaporator. The solar-mode configuration allows the exploitation of the heat from solar radiation to evaporate the refrigerant and to improve the photovoltaic electricity production due to the cooling of the cells up to 8%. A numerical heat pump model, integrated with novel gas-cooler and PVT collectors models, has been developed and implemented as a TRNSYS type for dynamic simulations of the system. The model has been validated with continuous measurements during the heat pump operation in solar and air modes. The proposed model can be used for performing seasonal simulations of a heat pump operating with a transcritical CO2 cycle. Moreover, the outcomes of the analysis show how the configuration of a CO2 heat pump with a direct-expansion air-finned coil heat exchanger or PVT can be used to enhance the performance of the heat pump and increase the electrical efficiency of the photovoltaic cells

Tanaka Theorem for Inelastic Maxwell Models

We show that the Euclidean Wasserstein distance is contractive for inelastic homogeneous Boltzmann kinetic equations in the Maxwellian approximation and its associated Kac-like caricature. This property is as a generalization of the Tanaka theorem to inelastic interactions. Consequences are drawn on the asymptotic behavior of solutions in terms only of the Euclidean Wasserstein distance

On Proper Polynomial Maps of C2.\mathbb{C}^2.

Two proper polynomial maps $f_1, f_2 \colon \mathbb{C}^2 \longrightarrow \mathbb{C}^2$ are said to be \emph{equivalent} if there exist $\Phi_1, \Phi_2 \in \textrm{Aut}(\mathbb{C}^2)$ such that $f_2=\Phi_2 \circ f_1 \circ \Phi_1$. We investigate proper polynomial maps of arbitrary topological degree $d \geq 2$ up to equivalence. Under the further assumption that the maps are Galois coverings we also provide the complete description of equivalence classes. This widely extends previous results obtained by Lamy in the case $d=2$.Comment: 15 pages. Final version, to appear in Journal of Geometric Analysi