Understanding the mechanism of binding between Gab2 and the C terminal SH3 domain from Grb2

Gab2 is a large disordered protein that regulates several cellular signalling pathways and is overexpressed in different forms of cancer. Because of its disordered nature, a detailed characterization of the mechanisms of recognition between Gab2 and its physiological partners is particularly difficult. Here we provide a detailed kinetic characterization of the binding reaction between Gab2 and the C-terminal SH3 domain of the growth factor receptor-bound protein 2 (Grb2). We demonstrate that Gab2 folds upon binding following an induced fit type mechanism, whereby recognition is characterized by the formation of an intermediate, in which Gab2 is primarily disordered. In this scenario, folding of Gab2 into the bound conformation occurs only after binding. However, an alanine scanning of the proline residues of Gab2 suggests that the intermediate contains some degree of native-like structure, which might play a role for the recognition event to take place. The results, which represent a fundamental step forward in the understanding of this functional proteinprotein interaction, are discussed on the light of previous structural works on these proteins

A Giraffe in the Botanic Garden of Pisa (Tuscany, Northern Italy)

The Botanic Garden of Pisa was established in 1543 as a teaching tool and research facility. As with the vast majority of its sister institutions, it focuses on plant collections. However, for a short time in the first half of the XIX century, the Botanic Garden exhibited a living giraffe, a cow, and a calf. Due to the transient nature of the exhibition, it could have easily gone unnoticed but for the fortuitous representation of the animals in a drawing of the same period and for sparse notes archived in the libraries of Pisa University. Furthermore, a XIX-century publication on the morphological and behavioural traits of three antelopes indirectly suggests that those animals had been kept in the Botanic Garden for research purposes. This paper presents the evidence of the living animal display in the Botanic Garden of Pisa and the context in which it was collecte

Modelling the potential distribution of Bemisia tabaci in Europe in light of the climate change scenario

BACKGROUND:Bemisia tabaci is a serious pest of agriculturalandhorticultural crops ingreenhousesandfields aroundtheworld. This paper deals with the distribution of the pest under field conditions. In Europe, the insect is currently found in coastal regions of Mediterranean countries where it is subject to quarantine regulations. To assess the risk presented by B. tabaci to Europe, the area of potential establishment of this insect, in light of the climate change scenario,was assessed by a temperature-dependent physiologically based demographicmodel (PBDM). RESULTS: The simulated potential distribution under current climate conditions has been successfully validated with the available field records of B. tabaci in Europe. Considering climate change scenarios of+1and+2 ∘C, range expansion by B. tabaci is predicted, particularly in Spain, France, Italy, Greece and along the Adriatic coast of the Balkans. Nonetheless, even under the scenario of +2 ∘C, northern European countries are not likely to be at risk of B. tabaci establishment because of climatic limitations. CONCLUSION: Model validation with field observations and evaluation of uncertainties associated with model parameter variability support the reliability of model results. The PBDM developed here can be applied to other organisms and offers significant advantages for assessing the potential distribution of invasive species

MANAGEMENT OF A TERRITORY SUBJECT TO HIGH HYDRO-GEOLOGICAL RISK AND REFLECTIONS ABOUT THE CONSERVATION AND FRUITION OF ITS HERITAGE

Numerosi studi mettono in luce trend preoccupanti a livello nazionale che parlano di un eccessivo consumo di suolo con conseguente artificializzazione. Altrettanti mettono in guardia sul suo impatto in contesti caratterizzati (per “costituzione strutturale”) da un’elevata propensione al rischio ambientale (che trova espressione in forme molteplici). Col presente lavoro si è voluto approfondire un’indagine già condotta su scala provinciale (province di Verona e Vicenza) e che ha portato a sottolineare i trend di consumo di suolo nell’ultimo trentennio. L’obiettivo è stato quello di approfondire il rapporto tra consumo di suolo e presenza di beni culturali/naturali, come anche delle eventuali aree di criticità nella loro gestione. Identificazione e rappresentazione sono, infatti, elementi sui quali innestare diverse e più attente politiche di tutela e valorizzazione dell’una e dell’altra tipologia di bene. Il caso di studio – per le caratteristiche paradigmatiche della porzione di territorio esaminato (i bacini del Chiampo e dell’Alpone) – ben si presta a rappresentare dinamiche in atto in contesti più ampi, permettendo di dare conferma del fenomeno menzionato. La porzione del territorio citata (sita in comuni pianeggianti, fortemente antropizzati, ad alta densità urbana, infrastrutturale e di popolazione) nel 2010 – ma anche in passato – è stata interessata da fenomeni alluvionali [espressione ultima di una pericolosità idraulica nel tempo sottovalutata e mal gestita]. Per meglio analizzare la distribuzione del rischio legata a queste aree critiche si sono utilizzati concetti quali prossimità geografica e distanza, che forniscono una cornice interpretativa. Mediante l’utilizzo di strumenti GIS si è mirato a rappresentare i cambiamenti, concentrando l’attenzione sui riflessi che la gestione del rischio idrogeologico e del territorio ha sulla fruizione e sulla conservazione/integrità del bene culturale (convinti che il corpus di conoscenza derivante dall’analisi geografica e cartografico-spaziale sia imprescindibile per prevenire il rischio e ri-orientare la politica e l’agire sociale). A tal fine si è condotta un’analisi di vicinanza per testare i risultati precedentemente ottenuti sull’area complessiva provinciale e dei bacini (e che avevano avuto come esito la produzione di carte d’uso suolo, della permeabilità e il calcolo di indici vegetazionali come anche della portata dei cambiamenti intercorsi tra il 1984 e il 2011). Tale analisi si innesta sull’elaborazione di carte sulla distribuzione dei beni e del patrimonio culturale e architettonico più in generale nei bacini indagati.Several studies highlight worrying trends at a national level concerning extreme land use and consequent anthropization. Also, many others warn against such an impact in contexts characterized (due to their structure) by a high propensity for environmental risk. Our investigation intends to add more detailed information to research previously carried out at a provincial level (the Provinces of Verona and Vicenza) that underlines trends in land use over the last thirty years. Our aim is to investigate the relationship between land use and cultural and natural heritage, as well as the possible critical areas in their management. Identification and description are in fact elements on which to base different and more thorough policies of conservation and valorisation of both kinds of heritage resources. This case study (due to the paradigmatic peculiarities of the areas examined (the Chiampo and Alpone basins) offers ample proof of the dynamics prevalent in wider contexts, allowing us to confirm the above-mentioned phenomenon. The district examined (lying on the plain, with significant anthropization and a high density of urbanization, infrastructures and population) was affected in 2010 – but also in the past – by floods (the latest example of water risk that has been badly managed and underestimated over the years). In order to analyse better the risk distribution in these critical areas, concepts such as geographical proximity and distance have been used in the present paper; these provide a framework for interpretation. Using GIS tools, we have sought to show changes in land use, focusing on the effects management of hydro-geological risk and of the district’s natural assets have on the fruition/conservation of cultural heritage sites (convinced as we are that knowledge based on geographical and cartographical/ spatial analysis is fundamental for preventing risks and redirecting policy and social behaviour). To this end, we conducted a proximity analysis to test the results previously obtained in the overall area and in that of these basins. (This also resulted in the production of land use and permeability maps and the calculation of vegetation indexes, as well as displaying the effects of the changes made between 1984 and 2011). Our analysis overlaps with the creation of maps showing the distribution of cultural and architectural heritage sites in the basins under discussion

Behavioral macromodeling of high-speed drivers via compressed tensor representations

This paper addresses the behavioral modeling of digital drivers for Signal and Power Integrity co-simulations. State-of-the-art two-piece model representations are combined with a compact description of the device static characteristics. The latter are considered as multivariate mappings that are functions of the device electrical variables, and of additional parameters defining process corners and device settings. Overall model complexity is reduced through a compressed tensor representation obtained via a high-order singular value decomposition. Several application examples demonstrate the feasibility and the advantages of the proposed approac

Biodiversity impacts of ship movement, noise, grounding and anchoring

Marine life in the Mediterranean Sea is threatened by intensive human activities such as fisheries, ship traffic, pollution and coastal development. Cetaceans and other vertebrates are affected not only by chemical pollution, but also by noise pollution (Richardson et al., 1995; Simmonds et al., 2004). Noise has become a ubiquitous form of marine pollution, especially in areas of heavy maritime traffic and along developed coasts. Intense underwater noise is generated by airguns, widely used for geophysical exploration in the oil and gas industry as well as for academic and government research purposes; by high power sonar, either military or civilian; by ship traffic; by shoreline and offshore construction works; and by a number of other commercial, scientific, military and industrial sources. The most powerful noises (from airguns, sonars, and explosions) may directly injure animals in the vicinity of the source. General ship traffic, heavy industries on the coast and a variety of other human activities generally do not generate such intense noise, but the acoustic pollution they produce is constant over time and may affect large areas. It may be a serious hazard not only to individual animals, but also to entire populations. Such increased background noise affects underwater life just as airborne noise affects terrestrial animals, including human beings.peer-reviewe

CLIMA: a weather generator framework

Abstract: Weather generators (WG) can be defined as collections of models to estimate site specific weather data and derived variables. Their use spans from providing inputs to a variety of biophysical models to deriving weather indices. Also, using either global circulation models or local area models inputs, sets of parameters calculated from long term weather series specific to a site can be modified to reproduce via WG synthetic series representing climate change scenarios. Finally, models implemented in WG are used for estimating missing data and to perform quality control on data collected from sensors in weather stations. The models implemented in WG vary from purely empirical to physically based. There are several models to either estimate or to generate each weather variable, with different input requirements. New models are continuously being proposed, and, whether some models to estimate specific variables are commonly accepted as reference methods, the lack of some inputs requires at times using alternate approaches. Currently available WG are applications which implement a predefined set of modelling options, in software implementations which do not allow for independent extensions by third parties. The CLIMA weather generator is a component based application which consist of a set of reusable graphical user interface (GUI) components, and of a set of extensible model components. The latter are subdivided into six namespaces to estimate variables related to air temperature, rainfall, solar radiation, evapotranspiration, wind, and leaf wetness. The time characteristic of the variables estimated varies from a day to ten minutes. Another library allows estimating climatic indices from one year of daily data at the time. The current implementation consists of a total of more than 300 models. Components are usable either via the CLIMA GUI, or via custom developed applications in a client-server architecture. The architecture of components is based on the composite and strategy as keystone design patterns. Models are implemented as single approaches (simple strategies), and as composite models (composite strategies) which are associated to models of finer granularity. Another type of model unit is represented by context strategies, which implement logic to select within associated models. Finally, the GUI allows building composite models which can be saved as libraries, to be reused both within CLIMA for weather series generation, or independently by other applications. The components are implemented as .NET libraries. They implement the test of pre- and post-conditions, and a scalable tracing via .NET listeners. All variables and parameters are documented via a description, units, default, maximum, and minimum values. Components are extensible: new models can be added independently by third parties and detected by the CLIMA application, which can also use them for data generation via building new composite libraries. Each component is made available via a software development kit which includes the code of two sample projects, either to extend or to reuse the component. CLIMA and its model components are freely available for reuse in no-profit applications.JRC.DG.G.3-Monitoring agricultural resource

I am Me:Brain systems integrate and segregate to establish a multidimensional sense of self

Humans experience a sense of self, which is proposed to emerge from the integration of intrinsic and extrinsic self-processing through the propagation of information across brain systems. Using a novel functional magnetic resonance imaging (fMRI) paradigm, we tested this hypothesis in a non-clinical sample by modulating the intrinsic and extrinsic self-relatedness of auditory action consequences in terms of identity and agency, respectively. In addition, the relevance of individual traits associated with altered self-experiences (e.g., psychosis-like experiences) was examined. The task-evoked fMRI results showed distinctive associations between the neural coding of identity and negative affect traits, and between agency and psychosis-like experiences. Most importantly, regarding the functional connectivity analysis, graph theoretical measures demonstrated that the simultaneous processing of identity and agency relies on the functional integration and segregation of default mode, sensorimotor, language, and executive brain networks. Finally, cross-network interactions mediated by executive and sensorimotor regions were negatively associated with psychosis-like experiences when the intrinsic and extrinsic self-relatedness of action consequences conflicted. These findings provide evidence that the self is a multidimensional phenomenon rooted in the functional interactions between large-scale neuronal networks. Such interactions may have particular relevance for self-experience alterations

Imprinting-Deprinting-Reimprinting: A Process Theory of Intergenerational Learning and Spin-off Entry

New entrants very often spin out from established firms and because they set on a course at founding, their learning and capabilities become inextricably linked to their organizational and technological heritage. But while this heritage may provide an initial advantage, it can also generate inertia and resistance to change, unless the new company is able to unlearn some practices from the parent company and learn something new in order to establish its own sources of competitive uniqueness. This tension between inherited path and new trajectory, imprinted past and search for newness is the object of this paper. Building on an in depth case study of Acorn Computers and ARM semiconductors we show that while there are strong influences from the parent company on the spinoff, these imprinted organizational effects can be overridden. We use the term deprinting to stress the reversible nature of this process in contrast with the irreversibility embodied by the classic imprinting notion. This is followed by a phase of intense learning efforts whereby the spinoff establishes its competitive identity based on a blending of retained routines, repeated improvisation and feedbacks from the market. We refer to this process with the term reimprinting, to emphasize the metamorphosis experienced by the spinoff as it sets on a new distinctive trajectory

Hybrid Magnetic Nanovectors Promote Selective Glioblastoma Cell Death through a Combined Effect of Lysosomal Membrane Permeabilization and Chemotherapy

Glioblastoma multiforme is the most aggressive brain tumor, due to its high invasiveness and genetic heterogeneity. Moreover, the blood-brain barrier prevents many drugs from reaching a therapeutic concentration at the tumor site, and most of the chemotherapeutics lack in specificity toward cancer cells, accumulating in both healthy and diseased tissues, with severe side effects. Here, we present in vitro investigations on lipid-based nanovectors encapsulating a drug, nutlin-3a, and superparamagnetic iron oxide nanoparticles, to combine the proapoptotic action of the drug and the hyperthermia mediated by superparamagnetic iron oxide nanoparticles stimulated with an alternating magnetic field. The nanovectors are functionalized with the peptide angiopep-2 to induce receptor-mediated transcytosis through the blood-brain barrier and to target a receptor overexpressed by glioma cells. The glioblastoma multiforme targeting efficiency and the blood-brain barrier crossing abilities were tested through in vitro fluidic models, where different human cell lines were placed to mimic the tumor microenvironment. These nanovectors successfully cross the blood-brain barrier model, maintaining their targeting abilities for glioblastoma multiforme with minimal interaction with healthy cells. Moreover, we showed that nanovector-assisted hyperthermia induces a lysosomal membrane permeabilization that not only initiates a caspase-dependent apoptotic pathway, but also enhances the anticancer efficacy of the drug