Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization,In Vitro and In Vivo Studies

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.     

In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model

There is a need to develop identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity. Here we used the human EndoC-βH1 β-cell line, the rat β-cell line INS-1E and dispersed mouse islet cells to assess the effects of endocrine disruptors on cell viability and glucose-stimulated insulin secretion (GSIS). We tested six chemicals at concentrations within human exposure (from 0.1 pM to 1 µM). Bisphenol-A (BPA) and tributyltin (TBT) were used as controls while four other chemicals, namely perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS) and dichlorodiphenyldichloroethylene (DDE), were used as “unknowns”. Regarding cell viability, BPA and TBT increased cell death as previously observed. Their mode of action involved the activation of estrogen receptors and PPARγ, respectively. ROS production was a consistent key event in BPA-and TBT-treated cells. None of the other MDCs tested modified viability or ROS production. Concerning GSIS, TBT increased insulin secretion while BPA produced no effects. PFOA decreased GSIS, suggesting that this chemical could be a “new” diabetogenic agent. Our results indicate that the EndoC-βH1 cell line is a suitable human β-cell model for testing diabetogenic MDCs. Optimization of the test methods proposed here could be incorporated into a set of protocols for the identification of MDCs.     

Polymerizable Skin Hydrogel for Full Thickness Wound Healing

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically. In this study, we describe the development of a polymerizable skin hydrogel consisting of keratinocytes and fibroblast entrapped within a fibrin scaffold. We histologically characterized the construct and evaluated its use on an in vivo wound healing model of skin damage. Our results indicate that the proposed methodology can be used to effectively regenerate skin wounds, avoiding the secondary in vitro culture steps and thus, shortening the time needed until transplantation in comparison with other bilayer skin models. This is achievable due to the instant polymerization of the keratinocytes and fibroblast combination that allows a direct application on the wound. We suggest that the polymerizable skin hydrogel is an inexpensive, easy and rapid treatment that could be transferred into clinical practice in order to improve the treatment of skin wounds.     

A guiding framework and approach for implementation research in substance use disorders treatment.

This paper introduces readers to the concepts of implementation science, implementation theory, and implementation frameworks and models. A wide range of models has been published in the literature related to implementation. The paper will present an overview of the Consolidated Framework for Implementation Research (CFIR), which is a comprehensive typology that unifies and consolidates the array of constructs that influence implementation from the perspective of these models. The CFIR is then used to evaluate implementation models used in studies of substance use disorder (SUD) treatments. Implementation research is scarce, with few prospective studies of theory-driven implementation. We assert that future research in SUD needs to meet three overarching objectives to promote wider implementation of evidence-based practices: (a) differentiation of core versus adaptable components of evidence-based interventions need; (b) development of methods to design implementation strategies, effectively adapted to the broad context; and (c) design and testing of predictive models to assess likelihood of effective implementation and prospects for sustainability while taking into account salient contextual factors. A recommended strategy for accomplishing these objectives is described. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Error‐resistant RFID‐assisted wireless sensor networks for cardiac telehealthcare

Wireless transmission of a patient's electrocardiogram (ECG) signals can be used to reduce cardiac healthcare cost. However, wireless transmissions have high error rates due to radio interference. The ECG signal, where every second of data could mean abnormal patterns, cannot tolerate such losses. Due to this healthcare crisis, the ability for a device to remotely monitor a patient's medication intake and transmit accurate ECG readings, while being cost efficient, is a major innovation. In this research, we integrate a multi‐hop wireless sensor network (WSN) with radio frequency identification (RFID) readers. Our system has two distinct features: (1) remotely supervise patient medication intake via RFID technology, and (2) accurately and remotely transmitting a patient's ECG by adopting extended Kalman filter (EKF) for wireless error recovery. Copyright © 2008 John Wiley & Sons, Ltd.     

Exciton Formation Dynamics and Band-Like Free Charge-Carrier Transport in 2D Metal Halide Perovskite Semiconductors

Metal halide perovskite (MHP) semiconductors have driven a revolution in optoelectronic technologies over the last decade, in particular for high-efficiency photovoltaic applications. Low-dimensional MHPs presenting electronic confinement have promising additional prospects in light emission and quantum technologies. However, the optimisation of such applications requires a comprehensive understanding of the nature of charge carriers and their transport mechanisms. This study employs a combination of ultrafast optical and terahertz spectroscopy to investigate phonon energies, charge-carrier mobilities, and exciton formation in 2D (PEA)₂PbI₄ and (BA)₂PbI₄ (where PEA is phenylethylammonium and BA is butylammonium). Temperature-dependent measurements of free charge-carrier mobilities reveal band transport in these strongly confined semiconductors, with surprisingly high in-plane mobilities. Enhanced charge-phonon coupling is shown to reduce charge-carrier mobilities in (BA)₂PbI₄ with respect to (PEA)₂PbI₄. Exciton and free charge-carrier dynamics are disentangled by simultaneous monitoring of transient absorption and THz photoconductivity. A sustained free charge-carrier population is observed, surpassing the Saha equation predictions even at low temperature. These findings provide new insights into the temperature-dependent interplay of exciton and free-carrier populations in 2D MHPs. Furthermore, such sustained free charge-carrier population and high mobilities demonstrate the potential of these semiconductors for applications such as solar cells, transistors, and electrically driven light sources.     

Proactive defragmentation in elastic optical networks under dynamic load conditions

The main weakness of elastic optical networks (EON), under dynamic traffic conditions, stems from spectrum fragmentation. A lot of research efforts have been dedicated during recent years to spectrum defragmentation. In this work, a thorough study about proactive defragmentation is carried out. Effects of the different defragmentation parameters on the EON performance are analyzed, and appropriate values of the defragmentation period, which guarantee suitable network performance while keeping the network control complexity at reasonable values, are obtained by means of extensive simulations. Benefit obtained by applying different defragmentation strategies, in terms of increase in the supported load at a given bandwidth blocking probability, is also reported. Different traffic conditions and network topologies are simulated to assess the validity of the obtained results.     

The use of visual search for knowledge gathering in image decision support

This paper presents a new method of knowledge gathering for decision support in image understanding based on information extracted from the dynamics of saccadic eye movements. The framework involves the construction of a generic image feature extraction library, from which the feature extractors that are most relevant to the visual assessment by domain experts are determined automatically through factor analysis. The dynamics of the visual search are analyzed by using the Markov model for providing training information to novices on how and where to look for image features. The validity of the framework has been evaluated in a clinical scenario whereby the pulmonary vascular distribution on Computed Tomography images was assessed by experienced radiologists as a potential indicator of heart failure. The performance of the system has been demonstrated by training four novices to follow the visual assessment behavior of two experienced observers. In all cases, the accuracy of the students improved from near random decision making (33%) to accuracies ranging from 50% to 68%.