Guanosine modulates K+ membrane currents in SH-SY5Y cells: involvement of adenosine receptors.

Guanosine (GUO), widely considered a key signaling mediator, is implicated in the regulation of several cellular processes. While its interaction with neural membranes has been described, GUO still is an orphan neuromodulator. It has been postulated that GUO may eventually interact with potassium channels and adenosine (ADO) receptors (ARs), both particularly important for the control of cellular excitability. Accordingly, here, we investigated the effects of GUO on the bioelectric activity of human neuroblastoma SH-SY5Y cells by whole-cell patch-clamp recordings. We first explored the contribution of voltage-dependent K+ channels and, besides this, the role of ARs in the regulation of GUO-dependent cellular electrophysiology. Our data support that GUO is able to specifically modulate K+-dependent outward currents over cell membranes. Importantly, administering ADO along with GUO potentiates its effects. Overall, these results suggested that K+ outward membrane channels may be targeted by GUO with an implication of  ADO receptors in SH-SY5Y cells, but also support the hypothesis of a functional interaction of the two ligands. The present research runs through the leitmotif of the deorphanization of GUO, adding insight on the interplay with adenosinergic signaling and suggesting GUO as a powerful modulator of SH-SY5Y excitability.

TRPV1 channels in nitric oxide-mediated signalling: insight on excitatory transmission in rat CA1 pyramidal neurons.

Nitric oxide (NO) is a fascinating signalling molecule implicated in a plethora of biological functions, especially at the synaptic level. Exploring neurotransmission in the hippocampus could be instrumental in the individuation of putative targets for nitric-oxide mediated neuromodulation, especially in terms of the potential repercussions on fundamental processes i.e. synaptic plasticity and excitability-related phenomena. Among these targets, endovanilloid signalling constitutes an object of study since Transient Receptors Vanilloid type 1 (TRPV1) channels possess a NO-sensitive gate modulating its activation. Also, NO has been referred to as a mediator for numerous endocannabinoid effects. Notwithstanding, the linkage between TRPV1 and NO systems in neuromodulation still remains elusive. To this end, we aim at investigating the involvement of TRPV1 in nitric oxide-mediated influence on hippocampal processes. Electrophysiological whole-cell recordings in CA1 pyramidal neurons were applied to evaluate excitatory neurotransmission in rat brain slices. Indeed, miniature excitatory postsynaptic currents (mEPSCs) were analysed upon pharmacological manipulation of TRPV1 and NO signalling pathways. In detail, only the administration of the specific TRPV1 exogenous agonist - capsaicin - reduced the frequency and amplitude of mEPSC similarly to the inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitroindazole (7NI). In contrast, capsazepine, TRPV1 antagonist, does not influence excitatory transmission. The combined TRPV1 activation and nNOS blockade confirm the presence of a putative common mechanism. When we administered the endovanilloid-endocannabinoid ligand, i.e. anandamide, we unveiled a potentiation of neurotransmission that was selectively reverted by 7NI. Our data suggest that nitric oxide influences TRPV1 hippocampal signalling since these channels are not constitutively active, but can be "on-demand" activated to modulate excitation in CA1 pyramidal neurons, and that this effect is linked to nitric oxide production.

Correlation of Metabolic Syndrome with Redox Homeostasis Biomarkers: Evidence from High-Fat Diet Model in Wistar Rats.

Metabolic Syndrome (MetS) is an extremely complex disease. A non-balanced diet such as high-fat diet (HFD) induces metabolic dysfunction that could modify redox homeostasis. We here aimed at exploring redox homeostasis in male Wistar rats, following 8 weeks of HFD, correlating the eventual modification of selected biomarkers that could be associated with the clinical manifestations of MetS. Therefore, we selected parameters relative to both the glucose tolerance and lipid altered metabolism, but also oxidative pattern. We assessed some biomarkers of oxidative stress i.e., thiols balance, lipid peroxidation and antioxidant barriers, via the use of specific biochemical assays, individuating eventual cross correlation with parameters relative to MetS through a Principal Component Analysis (PCA). The present study shows that 8 weeks of HFD induce MetS in rats, altering glucose and lipid homeostasis and increasing visceral adipose tissue, but also impairing the physiological antioxidant responses that could not counteract the oxidative stress condition. Crucially, cross-correlation analysis suggested that the assessment of specific oxidative stress parameters reported here can provide information comparable to the more widely acquired biomarkers of Mets such as glucose tolerance. Lastly, hepatic steatosis in association with the oxidative stress condition was also highlighted by histological analysis. This research will elucidate the fundamental impact of these oxidative stress parameters on MetS induced in the HFD rat model, tracing paths for developing prevention approaches.

Methodology for the Accurate Measurement of the Power Dissipated by Braking Rheostats.

The energy efficiency of transportation is a crucial point for the rail and metro system today. The optimized recovery of the energy provided by the electrical braking can lead to savings of about 10% to 30%. Such figures can be reached by infrastructure measures which allow the recovery of the breaking energy that is not directly consumed by the rail system and dissipated in rheostat resistors. A methodology for the accurate estimate of such energy is valuable for a reliable evaluation of the cost-benefit ratio associated with the infrastructural investment. The energy can be estimated by measuring a braking current flowing in the rheostats. The varying duty-cycle associated with the high dynamic variation, from zero to thousands of amperes, makes the current measurement very challenging. Moreover, the digitization of such waveforms introduces systematic errors that affect the energy estimation. To overcome these issues, this paper proposes a technique to measure the power and energy dissipated by the rheostat of a DC operated train with high accuracy. By means of an accurate model of the electrical braking circuit (chopper and rheostat) and the frequency characterization of the current transducer, a correction coefficient as a function of the duty-cycle is estimated. The method is then applied to data recorded during a measurement campaign performed on-board a 1.5 kV train of Metro de Madrid during normal operation. Using the proposed technique, the estimation of the dissipated braking energy is improved by 20%.

Dataset of measured and commented pantograph electric arcs in DC railways.

DC railways are characterized by particularly intense arcing caused by pantograph detachment, due to the large current intensity and the general implementation of onboard resonant filters, whose transient response is triggered by electric transients including electric arcs. Electric arc depends on the train speed (the relative speed between the sliding contact over the pantograph and the hot spot on the catenary system), the intensity of the collected pantograph current and the line voltage level. Electric arcs are broadband in nature and can trigger the system transient response dominated by the resonant filter, besides interfering with the operation of onboard equipment (such as for energy conversion and metering).

Low Power Contactless Voltage Sensor for Low Voltage Power Systems.

Contactless measurements represent the desirable solution in many contexts, where minimal cabling is required or, in general, cabling is not possible. This paper presents a new contactless voltage sensor for low voltage power systems. It is based on a contactless capacitive probe, which surrounds the power cable. It has two concentric electrodes insulated by a shield. A low power analog conditioning circuit evaluates the power line voltage by measuring the current in one of the capacitances of the probe. All the single stages of the circuit have been designed by using low-power rail-to-rail operational amplifiers, supplied at 3.3 V, in order to minimize the power absorption. The sensor has been characterized in various conditions, with sine waves and distorted signals, varying the frequency and the harmonic distortion. The influence of the current, flowing into the power cable, on the voltage measurement has been evaluated too. It shows a good accuracy (lower than 0.3%) from 100 V to 300 V, with a power consumption less than 5 mW.

Correction: Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation.

[This corrects the article DOI: 10.1371/journal.pgen.1005427.].

Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation.

Four related cows showed hairless streaks on various parts of the body with no correlation to the pigmentation pattern. The stripes occurred in a consistent pattern resembling the lines of Blaschko. The non-syndromic hairlessness phenotype observed occurred across three generations of a single family and was compatible with an X-linked mode of inheritance. Linkage analysis and subsequent whole genome sequencing of one affected female identified two perfectly associated non-synonymous sequence variants in the critical interval on bovine chromosome X. Both variants occurred in complete linkage disequilibrium and were absent in more than 3900 controls. An ERCC6L missense mutation was predicted to cause an amino acid substitution of a non-conserved residue. Analysis in mice showed no specific Ercc6l expression pattern related to hair follicle development and therefore ERCC6L was not considered as causative gene. A point mutation at the 5'-splice junction of exon 5 of the TSR2, 20S rRNA accumulation, homolog (S. cerevisiae), gene led to the production of two mutant transcripts, both of which contain a frameshift and generate a premature stop codon predicted to truncate approximately 25% of the protein. Interestingly, in addition to the presence of both physiological TSR2 transcripts, the two mutant transcripts were predominantly detected in the hairless skin of the affected cows. Immunohistochemistry, using an antibody against the N-terminal part of the bovine protein demonstrated the specific expression of the TSR2 protein in the skin and the hair of the affected and the control cows as well as in bovine fetal skin and hair. The RNA hybridization in situ showed that Tsr2 was expressed in pre- and post-natal phases of hair follicle development in mice. Mammalian TSR2 proteins are highly conserved and are known to be broadly expressed, but their precise in vivo functions are poorly understood. Thus, by dissecting a naturally occurring mutation in a domestic animal species, we identified TSR2 as a regulator of hair follicle development.

Environmental evaluation of municipal waste prevention.

Waste prevention has been addressed in the literature in terms of the social and behavioural aspects, but very little quantitative assessment exists of the environmental benefits. Our study evaluates the environmental consequences of waste prevention on waste management systems and on the wider society, using life-cycle thinking. The partial prevention of unsolicited mail, beverage packaging and food waste is tested for a "High-tech" waste management system relying on high energy and material recovery and for a "Low-tech" waste management system with less recycling and relying on landfilling. Prevention of 13% of the waste mass entering the waste management system generates a reduction of loads and savings in the waste management system for the different impacts categories; 45% net reduction for nutrient enrichment and 12% reduction for global warming potential. When expanding our system and including avoided production incurred by the prevention measures, large savings are observed (15-fold improvement for nutrient enrichment and 2-fold for global warming potential). Prevention of food waste has the highest environmental impact saving. Prevention generates relatively higher overall relative benefit for "Low-tech" systems depending on landfilling. The paper provides clear evidence of the environmental benefits of waste prevention and has specific relevance in climate change mitigation.