Mutation or multiplication of the alpha-synuclein (Syn)-encoding gene is frequent cause of early onset Parkinson's disease (PD). Recent evidences point to the pathogenic role of excess Syn also in ...sporadic PD. Syn is a cytosolic protein, which has been shown to be released from neurons. Here we provide evidence that extracellular Syn induces an increase in surface-exposed glucose-related protein of 78 kDa (GRP78), which becomes clustered in microdomains of the neuronal plasma membrane. Upon interacting with Syn, GRP78 activates a signaling cascade leading to cofilin 1 inactivation and stabilization of microfilaments, thus affecting morphology and dynamics of actin cytoskeleton in cultured neurons. Downregulation of GRP78 abolishes the activity of exogenous Syn, indicating that it is the primary target of Syn. Inactivation of cofilin 1 and stabilization of actin cytoskeleton are present also in fibroblasts derived from genetic PD patients, which show a dramatic increase in stress fibers. Similar changes are displayed by control cells incubated with the medium of PD fibroblasts, only when Syn is present. The accumulation of Syn in the extracellular milieu, its interaction with the plasma membrane and Syn-driven clustering of GRP78 appear, therefore, responsible for the dysregulation of actin turnover, leading to early deficits in synaptic function that precede neurodegeneration.
Interfaces between conjugated polymers and aqueous electrolytes are gaining increasing interest for a number of different applications, including electrochemical cells, biosensors and functional ...organic devices for recording and stimulating the bioelectrical activity. In this field, devices sensitive to visible light are particularly interesting, both for inducing solar-driven photo-electrochemical reactions and for spatially selective, not-invasive optical control of living systems. We demonstrate that photoexcitation of the conjugated polymer leads to both capacitive and faradaic electrical signals at the interface with water. We introduce here a mesoporous, light sensitive polymer/electrolyte interface, we characterize its behavior and we reproduce the experimental data with an equivalent circuit model. Interestingly, we show that the use of polymer-based mesoporous devices offers a practical and simple handle for the modulation of the interface behavior. Device engineering allows to control the sign of charges at the polymer surface and to balance faradaic and capacitive currents established at the interface with water. This work opens up interesting opportunities towards applications in both photo-electrochemistry and biology.
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•Planar and mesoporous interfaces between rr-P3HT and aqueous electrolyte are characterized.•Mesoporous architecture enhances the occurrence of photo-electrochemical reactions at the interface.•Device engineering allows to control the sign of the surface potential difference.
Recently, water-gated organic field-effect transistors (WGOFET) have been intensively studied for their application in the biological field. Surprisingly, a very limited number of conjugated polymers ...have been reported so far. Here, we systematically explore a series of polythiophene derivatives, presenting different alkyl side chains lengths and orientation, and characterized by various morphologies: comparative evaluation of their performances allows highlighting the critical role played by alkyl side chains, which significantly affects the polymer/water interface capacitance. Reported results provide useful guidelines towards further development of WGOFETs and represent a step forward in the understanding of the polymer/water interface phenomena.
The Larderello geothermal field is located in the inner Northern Apennines (southern Tuscany), an area which has been affected by extensional tectonics since the Early–Middle Miocene. The structure ...of the Larderello field is characterised by NW-trending, NE-dipping Pliocene to Present normal faults. Their geometry down to depths of 4–5 km is constrained by field, borehole, and reflection seismic data. An association between extensional structures and heat flow maxima (up to 1000 mW/m
2) is recognisable from detailed surface heat flow mapping. In order to investigate the relationships among extensional structures and heat flow, subsurface isotherms were traced, subject to borehole control, along variously oriented geological cross-sections. The isotherms show vertical displacements associated with the recent normal faults and related deformation zones, which reach the brittle/ductile transition. Estimates of the relative importance of convective and conductive components of heat flow suggest that fluid circulation is particularly important in correspondence with the normal faults, accounting for the correlation between isotherm perturbations and extensional structures. In this view, extensional shear zones are interpreted as the main structural pathways for the flow of hot geothermal fluids.
Underground temperature data from height boreholes logged between 1981 and 2000 were studied to infer the climate change in central-northern Italy during the last 250 years. The ground surface ...temperature history was reconstructed by using the functional space inversion method. A different inverse approach was also used for two temperature sets to obtain the fine details of the most recent surface temperature change. The results were compared with the air temperature recorded since the beginning of the 19th century at meteorological observatories. The analysis puts into evidence that the trend of the temperature change in the western side of the Apennines chain differs from that of the eastern side. Since 1750 the western side shows temperature lower than that of the 1990s, with minimum values in the period 1930–1960, followed by an almost linear increase in the ground surface temperature. Along the eastern side the temperature is always larger than that inferred for the 1970s, with maximum values in the period 1920–1940, which is followed by a sharp temperature decrease. Only since 1970–1980 a local warming phase has started. By combining borehole temperature logs with meteorological surface air temperature records, the pre-observational mean temperature was calculated. The results corroborate the difference of the climatic histories in both sides of the Apennines concerning the ground surface temperatures. It also appears that the recent climatic changes have partly a local origin and can obscure the changes forced by the regional surface air temperature influence.
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•Charge transport in a squaraine-based blend is studied using admittance spectroscopy.•At low voltage a hole-dominated space-charge limited regime is identified.•Hole transport is ...dispersive and electric-field dependent.•At high voltage a bipolar regime is attained.•Trap-mediated recombination takes place in bipolar regime.
Thanks to their strong absorption in the near infrared, squaraine dyes have raised interest in the field of organic photovoltaics and photodetection. We develop photodetectors based on the bulk heterojunction of an indolic squaraine and of a fullerene derivative, obtaining an external quantum efficiency as high as 12% at 590nm. To gain insight into carrier transport and recombination phenomena, devices are characterized in the dark by means of admittance spectroscopy. At low applied voltages carrier transport is dominated by holes, which show dispersive transport and an electric field dependent mobility of about 10−5–10−4cm2V−1s−1. At higher voltages electron injection occurs as well and a bipolar, recombination-limited regime sets in. The modeling of the low-frequency negative capacitance contribution suggests a trap-mediated carrier recombination mechanism.
The He isotope composition of paleofluids entrapped in fluid inclusions of hydrothermal minerals is compared with the present‐day fluid composition of the Larderello geothermal field. Almost constant ...values of (3He/4He)m/(3He/4He)air (=R/Ra) over time indicate that no important changes have occurred in the deep source of gases, at least during the last 3.8 million years. On a regional scale, a correlation has been found between the R/Ra spatial distribution, heat flow, and Bouguer gravity anomaly. High values of R/Ra and heat flow, and low Bouguer anomaly values indicate that the Larderello field is an area of preferential escape for mantle‐derived fluids. A positive correlation has also been found between the R/Ra spatial distribution and a major seismic reflector named the “K horizon.” A deep magma source, refilled by periodic gas input from the mantle, is the most likely source of 3He‐enriched fluids and the anomalously high heat flow. The nearly constant value of R/Ra clearly indicates that input of fresh mantle material has occurred up to recent times. Clear evidence of mixing between mantle and crustal fluids indicates that the high R/Ra is the lower limit of the actual mantle value, which is suggested to be similar to the subcontinental European mantle. The decrease of R/Ra over time in the peripheral part of the Larderello field indicates that important changes in the feeding fracture system and/or cooling rate have occurred in these areas.
Ventilator associated pneumonia Bellani, S; Nesci, M; Celotto, S ...
Minerva anestesiologica
69, Številka:
4
Journal Article
Ventilator associated pneumonia (VAP) is a nosocomial lower respiratory tract infection that ensues in critically ill patients undergoing mechanical ventilation. The reported incidence of VAP varies ...between 9% and 68% with a mortality ranging between 33% and 71%. Two key factors are implicated in the pathogenesis of VAP: bacterial colonization of the upper digestive-respiratory tract and aspiration of oral secretions into the trachea. Preventive measurements are advocated to reduce the incidence of VAP, such as selective decontamination of the digestive tract (SDD), supraglottic aspiration and positioning. Prompt recognition and treatment of established VAP has also been demostrated to affect outcome. Therefore, the knowledge of risk factors associated with the development of VAP and the implementation of strategies to prevent, diagnose and treat VAP are mainstems in the nursing of mechanically ventilated patients.
The aim of hemodynamic monitoring in intensive care is to recognize derangements in physiologic variables, which herald the progression toward organ failure. Traditionally the term "vital signs" ...refers to heart rate, arterial pressure, respiratory rate and body temperature monitoring. Continuous monitoring of vital signs, is advocated, since trends are more significant than single measurements, and is still a cornerstone, in the hemodynamic evaluation of a critically ill patient. Nevertheless, the spectrum of hemodynamic derangements that can arise during intensive care unit stay is very large and often additional information, beside the vital signs, are needed to evaluate correctly the individual patient.
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