Detection of Ligand-induced Conformational Changes in the Activation Loop of Aurora-A Kinase by PELDOR Spectroscopy.

The structure of protein kinases has been extensively studied by protein crystallography. Conformational movement of the kinase activation loop is thought to be crucial for regulation of activity; however, in many cases the position of the activation loop in solution is unknown. Protein kinases are an important class of therapeutic target and kinase inhibitors are classified by their effect on the activation loop. Here, we report the use of pulsed electron double resonance (PELDOR) and site-directed spin labeling to monitor conformational changes through the insertion of MTSL [S-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1 H-pyrrol-3-yl)methyl methanesulfonothioate] on the dynamic activation loop and a stable site on the outer surface of the enzyme. The action of different ligands such as microtubule-associated protein (TPX2) and inhibitors could be discriminated as well as their ability to lock the activation loop in a fixed conformation. This study provides evidence for structural adaptations that could be used for drug design and a methodological approach that has potential to characterize inhibitors in development

Response of a mixed grass prairie to an extreme precipitation event

Citation: Concilio, A. L., Prevey, J. S., Omasta, P., O'Connor, J., Nippert, J. B., & Seastedt, T. R. (2015). Response of a mixed grass prairie to an extreme precipitation event. Ecosphere, 6(10), 12. doi:10.1890/es15-00073.1Although much research has been conducted to measure vegetation response to directional shifts in climate change drivers, we know less about how plant communities will respond to extreme events. Here, we evaluate the response of a grassland community to an unprecedented 43 cm rainfall event that occurred in the Front Range of Colorado in September, 2013 using vegetation plots that had been monitored for response to simulated precipitation changes since 2011. This rain caused soils to stay at or above field capacity for multiple days, and much of the seed bank germinated following the early autumn event. Annual introduced grasses, especially cheatgrass (Bromus tectorum), and several introduced forbs demonstrated strong positive increases in cover the following growing season. Native cool season grasses and native forbs showed limited changes in absolute cover despite continued high soil water availability, while native warm season grasses increased in cover the following summer. Treatments that previously altered the amounts and seasonality of rainfall during the 2011-2013 interval showed legacy effects impacting cover responses of introduced species and warm-season native grasses. Resin bag estimates of inorganic nitrogen flux resulting from the event indicated twice as much nitrogen movement compared to any previous collections during the 2011-2013 interval. Nitrogen additions to a subset of plots made in spring of 2014 demonstrated that the relative cover of introduced species could be further increased with additional soil nitrogen. Collectively, these results support the contention that extreme precipitation events can favor species already benefiting from other environmental change drivers

Anterior Segment-Optical Coherence Tomography features in Blau syndrome.

Blau syndrome (BS) is a rare granulomatous auto-inflammatory disease, characterized by the classic clinical triad of joints, skin and ocular involvements. Ocular manifestation usually consists in a bilateral insidious chronic anterior uveitis with a potential evolution to panuveitis. We describe the case of two siblings, an 8-years old female and a 5-years old male, with a diagnosis of BS, evaluated by Anterior Segment-Optical Coherence Tomography (AS-OCT). In the female patient, slit-lamp examination revealed bilateral anterior granulomatous uveitis and inflammatory sequelae. AS-OCT revealed high intensity reflective layers in the anterior cornea, hyperreflective dots both in the aqueous humor and in the posterior corneal surface. In the male, no signs of inflammation were detected both on slit-lamp examination and AS-OCT scans. AS-OCT is a valuable, non-invasive tool that could improve the diagnosis of ocular involvement, better characterize and follow-up corneal alterations and anterior segment features in pediatric patients with BS

Electrical Hole Transport Properties of an Ambipolar Organic Compound With Zn-Atoms on a Crystalline Silicon Heterostructure

In this paper, we investigate the electrical hole transport properties of an organic/inorganic heterostructure consisting of a thin organic film, that combines hole and electron conducting molecules around a bridging Zn-atom, deposited on top of an n-type crystalline silicon substrate. Current-voltage characteristics and capacitance voltage measurements have been used for the determination of the organic layer dielectric and hole conduction parameters

Numerical and experimental transition results evaluation for a morphing wing and aileron system

A new wing-tip concept with morphing upper surface and interchangeable conventional and morphing ailerons was designed, manufactured, bench and wind tunnel tested. The development of this wing tip model was performed in the frame of an international CRIAQ project, and the purpose was to demonstrate the wing upper surface and aileron morphing capabilities in improving the wing tip aerodynamic performances. During numerical optimization with ‘in-house’ genetic algorithm software, and during wind tunnel experimental tests, it was demonstrated that the air flow laminarity over the wing skin was promoted, and the laminar flow was extended with up to 9% of the chord. Drag coefficient reduction of up to 9% was obtained when the morphing aileron was introduced

DIGISER. Digital Innovation in Governance and Public Service Provision

Digital Innovation Challenges In view of the increasingly intense pressures on the public sector to address the challenges of our time, governments and other public entities are gradually adopting digital innovation, seeking to promote quality public services. Digital technologies and capabilities create opportunities to re-organise public service inno- vation and delivery in ways that reduce cost and increase quality, proactiveness and citizen-centricity. Multilevel governance, networks and other collaboration systems (at local, regional, national and interna- tional level) are gaining importance as key drivers of this process of digital innovation and transformation. The link to the innovation ecosystem, including all sectors of activity, both private and public (e.g., academia, industry, business, citizens and governments) appears as fundamental in all phases of the creation, devel- opment, implementation and maintenance of public services and policy making. Information and communi- cation technologies are conceived as essential elements to support the creation and sustainability of these collaboration processes. In an era in which information gains relevance in the management of the territory and allows new power relations, the expectations of citizens are increasingly demanding and specific. Considering the develop- ments of recent years, such as the economic, social and health crises, the pressure placed on the resolution of global challenges is progressively transferred to the scope of cities. There are several elements that con- tribute to the importance of cities in the digital innovation transformation process namely buying- power, being closer to citizens and being able to work across different sectors. In fact, urban territories increasingly represent a greater number of citizens - in Europe, for example, they correspond to 75% of the population - have greater autonomy in management, worldwide they contribute to 80% of the global GDP and have the potential to provide a major contribution to the resolution of global challenges. The balance between change (promoted by the digital innovation strategies) and stability (driven by organi- sational inertia) needs to be handled carefully. The transformation process has to be based on a long-term strategy and to occur in a sustainable way, by focusing on learning experiences and knowledge and tech- nology transfer, while being sensitive to the local context to ensure improvement. At the European level, the Digital Transition has been considered a main goal for the next decade. The EU launched the European Green Deal and Europe Fit for the Digital Age, a twin initiative, which links green and digital transition. The vision for the EU ́s digital decade is reflected in the Digital Compass 2030 and includes 4 cardinal points: skills, government, infrastructure and Business. With the aim of having 100% of the key public services online by 2030, the digital compass ensures that digital will contribute in a positive way to improve citizens quality of life while reducing the resources spent. To support this vision, and by understanding the importance of community-led data-driven solutions and the potential of collaborative ap- proaches, several initiatives are being implemented. The Living-in.EU movement, for example, points out the European Way’ where multi-level governance and co-creation processes support the development of a cohesive digital Europe in the path towards digital transition. Another initiative contributing to this strategy is promoted by Open & Agile Smart Cities which is connecting cities through Minimal Interoperability Mech- anisms (MIMs) - “a set of practical capabilities based on open technical specifications that allow cities and communities to replicate and scale solutions globally”. The MIMs contribute to the creation of the European Single Market by providing a common technical ground for the procurement and deployment of urban data platforms and end-to-end solutions in cities

Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multicentre nation-wide cohort

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3-13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1-1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1-1.4, P

Density functional theory studies of MTSL nitroxide side chain conformations attached to an activation loop

A quantum-mechanical (QM) method rooted on density functional theory (DFT) linked to the Stochastic Liouville equation (SLE) in the Fokker Planck (FP) form has been employed for the first time to sample the methane-thiosulfonate spin label (MTSL) conformational space attached to the Aurora-A kinase activation loop and to calculate the EPR spectrum. The features of the calculated energy surface allowed us to describe the system in a limited number of rotamers stabilized by interactions of the MTSL side chain and neighbouring residues. The relevant magnetic parameters and the electron paramagnetic resonance (EPR) spectrum were subsequently calculated from the trajectories of the spin probe in the protein environment. The comparison between theoretical and experimental continuous wave (CW) EPR spectra revealed some small differences in the EPR line shape which arises from the combinations of g- and A-values obtained from the conformations selected. The theoretical approach adopted in this work can be used to recognise the contribution of MTSL rotamers to the EPR spectrum in order to help extract structural/dynamics properties of protein from the experimental data