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Abstract: In Leydig cells, hormonal stimulation by LH/hCG entails increased intracellular Ca2+ levels and steroid production, as well as hyperpolarization of the cell membrane. The large-conductance Ca2+-activated K+-channel (BKCa) is activated by raised intracellular Ca2+ and voltage and typically hyperpolarizes the cell membrane. Whether BKCa is functionally involved in steroid production of Leydig cells is not known. In order to explore this point we first investigated the localization of BKCa in human and hamster testes and then used a highly specific toxin, the BKCa blocker iberiotoxin (IbTx), to experimentally dissect a role of BKCa. Immunohistochemistry and RT-PCR revealed that adult Leydig cells of both species are endowed with these channels. Ontogeny studies in hamsters indicated that BKCa becomes strongly detectable in Leydig cells only after they acquire the ability to produce androgens. Using purified Leydig cells from adult hamsters, membrane potential changes in response to hCG were monitored. HCG hyperpolarized the cell membrane, which was prevented by the selective BKCa blocker IbTx. Steroidogenic acute regulatory (StAR) mRNA expression and testosterone production were not affected by IbTx under basal conditions but markedly increased when hCG, in submaximal and maximal concentration or when db-cAMP was added to the incubation media. A blocker of KV4-channels, expressed by Leydig cells, namely phrixotoxin-2 (PhTx-2) was not effective. In summary, the data reveal BKCa as a crucial part of the signaling cascade of LH/hCG in Leydig cells. The hyperpolarizing effect of BKCa in the Leydig cell membrane appears to set in motion events limiting the production of testosterone evoked by stimulatory endocrine mechanisms. [Copyright &y& Elsevier]

Abstract: Multilayered zirconia toughened alumina (ZTA) and c-zirconia coatings were prepared using electron beam physical vapour deposition (EB-PVD). Characterizations of the morphology and chemical composition of the deposited coatings were performed using scanning electron microscopy (SEM) and X-ray diffraction analysis (XRD). Scratch resistance, nano-indentation and bending strength were used for the evaluation of the mechanical properties. X-ray diffraction of the top ceramic TBC surface showed that it consists entirely of cubic ZrO2 phase. The energy-dispersive X-ray spectroscopy analysis (EDS) showed that α-Al2O3 is the only oxide phase present at the interface, while SEM indicated the presence of columnar c-ZrO2 as the only phase of the top coat. Delamination over a large region was observed in the case of double layer (ZTA) coating. In contrast, the multilayered (ZTA1+ZTA2+c-Z) coating showed neither delamination nor cracking. The hardness and scratch measurements showed that the top coat c-ZrO2 layer is harder than the ZTA layers. The thermal conductivity of the multilayer coatings was estimated using the theoretical density and thermal conductivity values of zirconia toughened alumina (ZTA) and cubic-zirconia (c-ZrO2) together with their experimentally measured data. [Copyright &y& Elsevier]

Electrical synapses are neuronal gap junction (GJ) channels associated with a macromolecular complex called the electrical synapse density (ESD), which regulates development and dynamically modifies electrical transmission. However, the proteomic makeup and molecular mechanisms utilized by the ESD that direct electrical synapse formation are not well understood. Using the Mauthner cell of zebrafish as a model, we previously found that the intracellular scaffolding protein ZO1b is a member of the ESD, localizing postsynaptically, where it is required for GJ channel localization, electrical communication, neural network function, and behavior. Here, we show that the complexity of the ESD is further diversified by the genomic structure of the ZO1b gene locus. The ZO1b gene is alternatively initiated at three transcriptional start sites resulting in isoforms with unique N-termini that we call ZO1b-Alpha, -Beta, and -Gamma. We demonstrate that ZO1b-Beta and ZO1b-Gamma are broadly expressed throughout the nervous system and localize to electrical synapses. By contrast, ZO1b-Alpha is expressed mainly non-neuronally and is not found at synapses. We generate mutants in all individual isoforms, as well as double mutant combinations in cis on individual chromosomes, and find that ZO1b-Beta is necessary and sufficient for robust GJ channel localization. ZO1b-Gamma, despite its localization to the synapse, plays an auxiliary role in channel localization. This study expands the notion of molecular complexity at the ESD, revealing that an individual genomic locus can contribute distinct isoforms to the macromolecular complex at electrical synapses. Further, independent scaffold isoforms have differential contributions to developmental assembly of the interneuronal GJ channels. We propose that ESD molecular complexity arises both from the diversity of unique genes and from distinct isoforms encoded by single genes. Overall, ESD proteomic diversity is expected to have critical impacts on the development, structure, function, and plasticity of electrical transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Michel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: There is a need to elucidate the underlying neural mechanisms subserving working memory and divided attention functioning. Recent neuroimaging studies provide evidence for anatomical co-localization of both functions. In the present study we used a functional intervention, whereby we applied a novel type of focalised, non-invasive brain stimulation, High-Definition transcranial Direct Current Stimulation (HD-tDCS), to the regions subserving these processes, the left intraparietal sulcus (IPS) and left dorsolateral prefrontal cortex (LDLPFC). Our aim was therefore to modulate activity in these regions using HD-tDCS and thereby assess their relevance for working memory, divided attention and their shared sub-processes. Method: 78 participants were evenly randomized to one of three conditions in a single blind, parallel group study design. Anodal or sham HD-tDCS was applied to either the left IPS or LDLPFC while participants completed a verbal working memory task, a divided attention task, and two tasks measuring subcomponents of working memory (updating and maintenance). Results: Focalised stimulation of the IPS and LDLPFC did not significantly modulate performance compared to sham stimulation. However, moderate effect sizes were obtained for at least one HD-tDCS condition relative to sham for all tasks, warranting further research into the functional importance of the IPS in subserving these abilities. Conclusions: The current results may be useful for informing future tDCS studies for modulating working memory and divided attention functioning.

Objective: There is currently substantial heterogeneity in electroconvulsive therapy (ECT) treatment methods between clinical settings. Understanding how this variation in clinical practice is related to treatment outcomes is essential for optimizing service delivery. The Clinical Alliance and Research in ECT Network is a clinical and research framework with the aims of improving clinical practice, enabling auditing and benchmarking, and facilitating the collection of naturalistic clinical data., Methods: The network framework and clinical and treatment variables collected and rationale for the use of particular outcome measures are described. Survey results detailing the use of ECT across initial participating clinical centers were examined., Results: The data are reported from 18 of 22 participating centers, the majority based in Australia. Melancholic unipolar depression was the most common clinical indication (78%). Right unilateral (44%) and bifrontal (39%) were the most commonly used electrode placements. Eighty one percent of the centers used individual seizure titration for initial dosing., Conclusions: There was substantial heterogeneity in the use of ECT between participating centers, indicating that the Network is representative of modern ECT practice. The Clinical Alliance and Research in ECT Network may therefore offer the opportunity to improve service delivery and facilitate the investigation of unresolved research questions pertaining to modern ECT practice.

The climate change and the proceeding urbanization create future health challenges. Consequently, more people around the globe will be impaired by extreme weather events, such as heat waves. This study investigates the causes for the emergence of surface urban heat islands and its change during heat waves in 70 European cities. A newly created climate class indicator, a set of meaningful landscape metrics, and two population-related parameters were applied to describe the Surface Urban Heat Island Magnitude (SUHIM) - the mean temperature increase within the urban heat island compared to its surrounding, as well as the Heat Magnitude (HM) - the extra heat load added to the average summer SUHIM during heat waves. We evaluated the relevance of varying urban parameters within linear models. The exemplary European-wide heat wave in July 2006 was chosen and compared to the average summer conditions using MODIS land surface temperature with an improved spatial resolution of 250m. The results revealed that the initial size of the urban heat island had significant influence on SUHIM. For the explanation of HM the size of the heat island, the regional climate and the share of central urban green spaces showed to be critical. Interestingly, cities of cooler climates and cities with higher shares of urban green spaces were more affected by additional heat during heat waves. Accordingly, cooler northern European cities seem to be more vulnerable to heat waves, whereas southern European cities appear to be better adapted. Within the ascertained population and climate clusters more detailed explanations were found. Our findings improve the understanding of the urban heat island effect across European cities and its behavior under heat waves. Also, they provide some indications for urban planners on case-specific adaptation strategies to adverse urban heat caused by heat waves., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Substantive and concerted action is needed to mitigate climate change. However, international negotiations struggle to adopt ambitious legislation and to anticipate more climate-friendly developments. Thus, stronger actions are needed from other players. Cities, being greenhouse gas emission centers, play a key role in promoting the climate change mitigation movement by becoming hubs for smart and low-carbon lifestyles. In this context, a stronger linkage between greenhouse gas emissions and urban development and policy-making seems promising. Therefore, simple approaches are needed to objectively identify crucial emission drivers for deriving appropriate emission reduction strategies. In analyzing 44 European cities, the authors investigate possible socioeconomic and spatial determinants of urban greenhouse gas emissions. Multiple statistical analyses reveal that the average household size and the edge density of discontinuous dense urban fabric explain up to 86% of the total variance of greenhouse gas emissions of EU cities (when controlled for varying electricity carbon intensities). Finally, based on these findings, a multiple regression model is presented to determine greenhouse gas emissions. It is independently evaluated with ten further EU cities. The reliance on only two indicators shows that the model can be easily applied in addressing important greenhouse gas emission sources of European urbanites, when varying power generations are considered. This knowledge can help cities develop adequate climate change mitigation strategies and promote respective policies on the EU or the regional level. The results can further be used to derive first estimates of urban greenhouse gas emissions, if no other analyses are available., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In early July 2013, the City of Milwaukee Health Department (MHD) was notified by the Wisconsin Division of Public Health of an increase in reported cases of legionellosis in southeastern Wisconsin. Legionellosis is a reportable disease to state and local public health authorities in Wisconsin. During June 1-September 30, 2013, a total of 58 clinically diagnosed cases of Legionnaires' disease, confirmed by laboratory testing, were reported in Milwaukee County, more than twice the number of total annual case reports in each of the previous 5 years. Forty-five (78%) of these cases were reported in the city of Milwaukee. The median age of county patients was 53 years (range = 29-77 years); all but one was hospitalized, and no deaths were reported. MHD received one report of a death attributed to legionellosis in the county during this period.