Myelin pathology: Involvement of molecular chaperones and the promise of chaperonotherapy

The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal chaperoning system, which is unable to assist the defective myelin protein in its folding and migration, or due to mutations in chaperone genes, leading to functional defects in assisting myelin maturation/migration. The latter are a subgroup of genetic chaperonopathies causing demyelination. In this brief review, we describe some paradigmatic examples pertaining to the chaperonins Hsp60 (HSPD1, or HSP60, or Cpn60) and CCT (chaperonin-containing TCP-1). Our aim is to make scientists and physicians aware of the possibility and advantages of classifying patients depending on the presence or absence of a chaperonopathy. In turn, this subclassification will allow the development of novel therapeutic strategies (chaperonotherapy) by using molecular chaperones as agents or targets for treatment

High-contrast imaging of 180{\deg} ferroelectric domains by optical microscopy using ferroelectric liquid crystals

Ferroelectric liquid crystals (FLCs) couple the direction of their spontaneous electric polarization to the direction of tilt of their optic axis. Consequently, reversal of the electric polarization by an electric field gives rise to an immediate and lasting optical response when an appropriately aligned FLC is observed between crossed polarizers, with one field direction yielding a dark image, and the opposite direction yielding a bright image. Here this peculiar electro-optic response is used to image, with high optical contrast, 180{\deg} ferroelectric domains in a crystalline substrate of magnesium-doped lithium niobate. The lithium niobate substrate contains a few domains with upwards electric polarization surrounded by regions with downward electric polarization. In contrast to a reference non-chiral liquid crystal that is unable to show ferroelectric behavior due to its high symmetry, the FLC, which is used as a thin film confined between the lithium niobate substrate and an inert aligning substrate, reveals ferroelectric domains as well as their boundaries, with strong black and white contrast. The results show that FLCs can be used for non-destructive read-out of domains in underlying ferroelectrics, with potential applications in e.g. photonic devices and non-volatile ferroelectric memories.Comment: 12 pages, 3 figure

Advanced Echocardiography for the Diagnosis and Management of Infective Endocarditis

Echocardiography is fundamental for the management of infective endocarditis (IE) across all stages of the illness including diagnosis, surveillance during medical therapy, identification of prognostic markers, planning perioperative intervention, postoperative assessment, and follow-up after completion of definitive therapy. Modern era echocardiography (echo) offers outstanding temporal and spatial image resolution, providing the opportunity for early diagnosis of this life-threatening infection. Emerging imaging modalities, such as real-time three-dimensional (3D) echocardiography, offer a novel way of readily visualizing the extent of intracardiac infection and the relationship of pathology to adjacent cardiac structures, well before surgical intervention, without radiation exposure or significant risk to the patient. Echocardiography can have a positive impact on the management of every stage of this disease, with the opportunity to improve outcomes

The Role of Modern-Era Echocardiography in Identification of Cardiac Risk Factors for Infective Endocarditis

This chapter provides an updated overview of the scientific literature on cardiac pathology predisposing to infective endocarditis and the estimated risk associated with selected lesion-specific abnormalities, in an era of changing epidemiology and advanced echocardiographic imaging. Importantly, with the evolution of modern-era echo, subtle changes in valve structure and function are now easily detectable and a proportion of cases of apparently ‘normal’ valves involved with IE, may in fact have subtle pre-existing pathological and/or haemodynamic abnormalities. The chapter will have a clinical focus with an aim to provide the Physician with up-to-date and practical information on cardiac risk factor identification for infective endocarditis

A DECISION SUPPORT SYSTEM FOR SUSTAINABLE OPERATIONS MANAGEMENT IN SMALL POWER PLANTS

The importance of environmentally-friendly electricity production is recognized as one of the most important challenges of our future, covering a broad context of research topics and promoting future scenarios based on renewable energies and new technologies. In the short term, however, energy generation will still be largely relying on power plants fired with fossil fuels whose emissions of pollutants are regulated by the industrial emissions directive in the EU legislation. Such directive does not apply to small and medium combustion plants, which until now, have only been subject to national regulations. As part of its air quality package from December 2013, the EU Commission has proposed a new directive which forces such plants to provide periodic measurements of pollutants, keep records of their environmental impact and provide information to the competent authorities. This situation has renewed the attention towards the systems for continuous emission monitoring in SMC. Such systems are in fact very expensive, therefore they require an optimized design in order be affordable for a SMC. This research, in particular, refers to the context of micro-grids and isolated power generation plants based on a set of diesel engine generators (GenSet) and addresses the topic of the development decision support systems (DSS) for environmentally-friendly power genset management. The system is based on a Selective Catalytic Reduction (SCR) reactor coupled with continuous emission monitoring system (CEMS) to reduce the environmental impact and generate information to support the management processes. The paper also reports the preliminary experimental results obtained in the power plant located in the small island of Favignana in the Mediterranean sea. These results demonstrate how the system developed and the approach proposed reduces the emission of pollutants with a substantial benefit for the local community, in a context where more environmentally efficient production technologies can hardly be employed

The neurochaperonopathies: Anomalies of the chaperone system with pathogenic effects in neurodegenerative and neuromuscular disorders

The chaperone (or chaperoning) system (CS) constitutes molecular chaperones, co-chaperones, and chaperone co-factors, interactors and receptors, and its canonical role is protein quality control. A malfunction of the CS may cause diseases, known as the chaperonopathies. These are caused by qualitatively and/or quantitatively abnormal molecular chaperones. Since the CS is ubiquitous, chaperonopathies are systemic, affecting various tissues and organs, playing an etiologic-pathogenic role in diverse conditions. In this review, we focus on chaperonopathies involved in the pathogenic mechanisms of diseases of the central and peripheral nervous systems: the neurochaperonopathies (NCPs). Genetic NCPs are linked to pathogenic variants of chaperone genes encoding, for example, the small Hsp, Hsp10, Hsp40, Hsp60, and CCT-BBS (chaperonin-containing TCP-1-Bardet\u2013Biedl syndrome) chaperones. Instead, the acquired NCPs are associated with malfunctional chaperones, such as Hsp70, Hsp90, and VCP/p97 with aberrant post-translational modifications. Awareness of the chaperonopathies as the underlying primary or secondary causes of disease will improve diagnosis and patient management and open the possibility of investigating and developing chaperonotherapy, namely treatment with the abnormal chaperone as the main target. Positive chaperonotherapy would apply in chaperonopathies by defect, i.e., chaperone insufficiency, and consist of chaperone replacement or boosting, whereas negative chaperonotherapy would be pertinent when a chaperone actively participates in the initiation and progression of the disease and must be blocked and eliminated

Un diálogo sobre la interpretación legal y constitucional

En estos últimos años, la Corte Suprema se ha concentrado en enfatizar el significado de las normas promulgadas no solo en casos que involucran la interpretación de leyes,1 sino también en casos que involucran la involucran la interpretación de la Constitcuón. Mientras esta tendencia en general ha ganado aprobación entre los jueces, ha sido cuestionada entre los académicos. Los críticos sostienen que el textualismo le da demasiada importancia al texto y subestima otras pruebas para interpretar las normas que surgen del proceso de creación de leyes. Los críticos argumentan que los textualistas se comportan de forma selectiva, apegándose al texto cuando no tienen la voluntad de basarse en evidencia extrínseca.5 Sostienen que, aunque el textualismo trabaje en casos de interpretación de leyes, simplemente no puede funcionar para una Constitución vieja, que usa vocabulario amplio y que es difícil de modificar;6 y por eso es que los textualistas necesitan actuar inconsistentemente cuando tratan casos de interpretación de leyes y constitucionales. Este dialogo examinará y pretenderá dar una respuesta a algunas de las preguntas más comunes que plantea este debate

A flexible and portable harvesting-storage device by quasi-solid-state supercapacitor and dye-sensitized solar cell integration

In recent years the utilization of power in off grid conditions is dramatically increasing. For this reason research is putting much effort in obtaining improvements in energy storage devices efficiencies and in discovering alternatives concerning easiness of fabrication that can be industrially implemented. In this framework, integration of energy storage devices with energy harvesting systems is obtaining more and more significance since the amount of energy that can be stored especially in Electrochemical Double Layer Capacitors (EDLCs) is limited. To this purpose, herein we present an innovative flexible integrated device composed by a symmetrical aqueous EDLC and a TiO2 nanotubes-based Dye Sensitized Solar cell (DSSC). A UV photo-polymerized quasi-solid electrolyte was used in both sections. At first a self-standing flexible polymer matrix was fabricated starting from Bisphenol A ethoxylate dimethacrylate (BEMA) and poly (ethylene glycol) methyl ether methacrylate (PEGMA), adding a 3% by weight of 2hydroxy-2-methyl-1-phenyl-1-propanone (Darocur 1173) as photoinitiator. Then, the matrix was soaked in two different liquid electrolytes, a 2 M NaCl aqueous solution for the energy storage section and an Iodine-based liquid electrolyte for the DSSC unit. This is the first work in which this type of polymer electrolyte membrane is used for an EDLC. The electrodes were fabricated onto Stainless-steel and Titanium grids, for EDLC and DSSC respectively. TiO2 nanotubes were grown by means of anodic oxidation as photoanode semiconductor material, while EDLC active material was composed by 85% of graphene nanoplatelets and 15% of Acetylene Black. The harvesting-storage device (HSD) was sealed by a light-cured photo-polymerization method. The measured overall photon-to-electrical conversion and storage efficiency for the HSD was 1.02% under standard test conditions. This value increases for lower illumination conditions reaching 1.46% at 0.3 Sun