Análise comparativa de revestimento de fachada: estudo de caso de substituição do revestimento cerâmico aderido por revestimento de acm em fachada ventilada em um edifício / Comparative analysis of facade coating: case study of replacement of ceramic coating adhered by acm coating on ventilated facade in a building

De modo geral, estamos vendo no Brasil uma evolução e busca por inovação nas técnicas construtivas. Buscando-se por materiais mais sustentáveis, eficientes e com maior durabilidade. Dada a importância da fachada de uma edificação, é fundamental que se dê bastante atenção a ela na hora de projetar uma construção nova, ou realizar uma reforma. O revestimento cerâmico aderido de fachada pode apresentar problemas muito precocemente, e com isso surge a necessidade da implementação de novas tecnologias construtivas que melhorem o desempenho e eleve a vida útil dos revestimentos de fachadas. A fachada ventilada é uma dessas novas tecnologias no Brasil. O princípio fundamental das fachadas ventiladas é seu sistema de juntas abertas, que permite que o espaço entre as placas não receba vedação completa nas aberturas inferiores e superiores, possibilitando, assim, a criação da lâmina de ar na cavidade entre as duas paredes. Dentre os materiais que podem ser aplicados em fachada ventilada, destaca-se o ACM, além de versátil e bonito, é um produto muito seguro. Nesse artigo objetivou-se comparar os custos da substituição de todo o revestimento cerâmico aderido mantendo-se o mesmo sistema, e comparando-o com a possibilidade de ter-se optado por fachada ventilada em ACM, em um edifício.  

KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor-Mediated Inhibition in Cholecystokinin-Containing Interneurons

Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABAB receptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK-INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole-cell recordings revealed slow GABABR-mediated inhibitory postsynaptic currents (IPSCs) in most CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising perisomatic-targeting basket cells (BCs), as well as dendrite-targeting (DT) interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs in CCK-INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR-mediated currents displayed strong desensitization, which was absent in KCTD12-deficient mice. This study highlights that GABABRs differentially control CCK-IN subtypes, and the kinetics and desensitization of GABABR-mediated currents are modulated by KCTD12 proteins

Differential surface density and modulatory effects of presynaptic GABAB receptors in hippocampal cholecystokinin and parvalbumin basket cells

The perisomatic domain of cortical neurons is under the control of two major GABAergic inhibitory interneuron types: regular-spiking cholecystokinin (CCK) basket cells (BCs) and fast-spiking parvalbumin (PV) BCs. CCK and PV BCs are different not only in their intrinsic physiological, anatomical and molecular characteristics, but also in their presynaptic modulation of their synaptic output. Most GABAergic terminals are known to contain GABAB receptors (GABABR), but their role in presynaptic inhibition and surface expression have not been comparatively characterized in the two BC types. To address this, we performed whole-cell recordings from CCK and PV BCs and postsynaptic pyramidal cells (PCs), as well as freeze-fracture replica-based quantitative immunogold electron microscopy of their synapses in the rat hippocampal CA1 area. Our results demonstrate that while both CCK and PV BCs contain functional presynaptic GABABRs, their modulatory effects and relative abundance are markedly different at these two synapses: GABA release is dramatically inhibited by the agonist baclofen at CCK BC synapses, whereas a moderate reduction in inhibitory transmission is observed at PV BC synapses. Furthermore, GABABR activation has divergent effects on synaptic dynamics: paired-pulse depression (PPD) is enhanced at CCK BC synapses, but abolished at PV BC synapses. Consistent with the quantitative differences in presynaptic inhibition, virtually all CCK BC terminals were found to contain GABABRs at high densities, but only 40% of PV BC axon terminals contain GABABRs at detectable levels. These findings add to an increasing list of differences between these two interneuron types, with implications for their network functions

Irritability in youth: A critical integrative review

Irritability, defined as proneness to anger that may reach an impairing extent, is common in youth. There has been a recent upsurge in relevant research. We combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions to address research gaps. Clinicians and researchers should assess irritability routinely; specific assessment tools are now available. Informant effects are prominent, stable, and vary by age and gender. The prevalence of irritability is particularly high in attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Irritability trajectories have been identified that are differentially associated with clinical outcomes; some begin early in life. Youth irritability is associated with increased risk later in life for anxiety, depression, behavioral problems, and suicidality. Irritability is moderately heritable and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for constructs related to irritability, but its efficacy in irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeted to frustration exposure). Associations between irritability and suicidality and the impact of cultural context are important, under-researched topics. Large, diverse, longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, thus affording important translational opportunities

Differenzielle Verteilung von GABAB Rezeptoren, Kir3 und Cav2 Ionenkanälen in Parvalbumin und Cholecystokinin exprimierenden Interneuronen des Hippocampus

Kortikale neuronale Aktivität unterliegt der präzisen Kontrolle eines heterogenen Netzwerkes inhibitorischer GABAerger Interneurone. Parvalbumin- (PV) und Cholecystokinin- (CCK) exprimierende (+) Neurone übernehmen eine Schlüsselfunktion bei der Synchronisation der rhythmischen Aktivität im Hippocampus. Während die GABAA-Rezeptor vermittelte Inhibition bereits gut beschrieben wurde, weiß man nur wenig über die Rolle der metabotropen GABAB Rezeptoren (GABABR), einem Heterodimer bestehend aus GABAB1 und GABAB2. Postsynaptische GABABR aktivieren G Protein-gekoppelte einwärtsgleichgerichtete Kaliumkanäle (Kir3) und induzieren langsame postsynaptische Potentiale, während präsynaptische GABABR die Ausschüttung von Neurotransmittern modulieren, indem sie spannungsgesteuerte Calciumkanäle vom Cav2-Typ hemmen. In der vorliegenden Arbeit wurde die Verteilung der GABAB1 Untereinheit und ihrer beiden Isoformen GABAB1a und GABAB1b, sowie deren Effektorionenkanäle Kir3 und Cav2 mit Hilfe von Immunfluoreszenz- und hochauflösender Elektronenmikroskopie und mittels eines Computermodells untersucht. Auf lichtmikroskopischer Ebene konnte in PV+ Interneuronen eine schwache Immunreaktivität für GABAB1 detektiert werden. Im Gegensatz dazu waren PV-negative Zellkörper, deren Lage auf CCK+ Interneurone hindeutete, sehr stark für die Rezeptoruntereinheit gefärbt. Auf ultrastruktureller Ebene konnte hier gezeigt werden, dass die Dendriten beider Interneuronpopulationen immunpositiv für GABAB1 waren und die GABAB1b Isoform den Hauptanteil der GABAB1 Rezeptoruntereinheit repräsentiert. Ein Computermodell wurde erstellt um eine uniforme Rezeptorverteilung zu simulieren. Es konnte dadurch gezeigt werden, dass die dendritische GABAB1 Verteilung in CCK+ Interneuronen mit einem uniformen Modell beschrieben werden kann, während GABABR auf PV+ Dendriten mit exzitatorischen Synapsen räumlich assoziiert sind und daher möglicherweise die glutamaterge synaptische Übertragung modulieren. Mit Immunfluoreszenzmikroskopie konnte hier gezeigt werden, dass beide Interneurontypen immunreaktiv für die im Gehirn am meisten verbreiteten Kir3 Untereinheiten Kir3.1, Kir3.2 und Kir3.3 waren. Mit quantitativer Immunelektronenmikroskopie wurde außerdem festgestellt, dass es Unterschiede in der Dichte der einzelnen Untereinheiten zwischen PV+ und CCK+ Neuronen gab. Mögliche Unterschiede in der Zusammensetzung der tetrameren Kir3 Kanäle könnten somit eine Erklärung für Unterschiede in den postsynaptischen GABAB-vermittelten Kaliumströmen zwischen den beiden Zelltypen sein. Präsynaptische GABAB Rezeptoren reduzieren die Ausschüttung von Neurotransmitter, indem sie Cav2 Calciumkanäle modulieren. Mittels immunogoldmarkierter Gefrierbruchreplika (SDS-FRL) konnte gezeigt werden, dass sowohl Axonterminale von PV+ als auch CCK+ Korbzellen, die jeweils durch Antikörper gegen den muscarinischen Rezeptor-2 (M2) und den Cannabinoid-Rezeptor-1 (CB1) identifiziert wurden, beide immunreaktiv für GABAB1 waren. Annähernd alle CB1+ Boutons waren für GABAB1 markiert, jedoch nur 50 % der M2+ Axonterminale. Effektive und zuverlässige Transmitterexocytose setzt eine effektive Kopplung von Calciumquelle und –sensor voraus. Dementsprechend konnten Cav2.1 (P/Q-Typ) Calciumkanäle in der aktiven Zone der präsynaptischen Membran von M2+ Boutons detektiert werden. Außerdem waren Immunogoldpartikel für Cav2.1 in Clustern angeordnet, deren Größenordnung zwischen 2-5 Immunogoldpartikeln lag. Zusammengefasst ergeben die Resultate dieser Studie einen umfassenden Überblick über die präzise subzelluläre Verteilung von GABABR sowie deren Effektorionenkanäle in PV+ und CCK+ Interneuronen und erweitert Eigenschaften der beiden Zelltypen um eine inhibitorische Komponente, die sowohl die Eingänge als auch die Ausgänge der Neurone moduliert. Unterschiede in der subzellulären Lokalisation der Proteine tragen außerdem zur Erweiterung der funktionellen Dichotomie der PV+ und CCK+ Interneuronpopulationen bei. Neuronal activity in mammalian cortical networks is controlled by GABAergic inhibitory interneurons. Important key players in the synchronization of hippocampal activity are the parvalbumin - (PV) and cholecystokinin- (CCK) positive (+) cells. Whereas inhibition mediated by fast-conducting GABAA receptors is well characterized, only little is known about the contribution of metabotropic GABAB receptors (GABABRs). Postsynaptic GABABRs activate G protein-coupled inwardly-rectifying K+ (Kir3) channels resulting in slow inhibitory postsynaptic potentials, while presynaptic GABABRs modulate transmitter release by inhibiting high voltage-activated Ca2+ channels. In the present thesis, the distribution of the GABABR subunit GABAB1 and its isoforms GABAB1a and GABAB1b, as well as effector Kir3 and Cav2 channels were examined using a combination of immunofluorescence and high-resolution immunoelectron microscopy together with computational modelling. At light microscopic level, PV+ interneurons showed weak immunoreactivity for GABAB1, whereas putative CCK+ cells were strongly stained for the receptor subunit. However, both cell types were consistently immunolabeled for GABAB1 localized to the plasma membrane of dendritic shafts. Qualitative analysis revealed that GABAB1b was the predominant isoform in this compartment. Recent results have demonstrated that on PV+ dendritic shafts, GABAB1 proteins are enriched in the vicinity of glutamatergic synapses whereas, the receptor subunit was evenly distributed over the plasma membrane of CCK+ dendritic shafts. By establishing a computational model simulating a uniform receptor distribution, it could be confirmed that the underlying distribution of GABABRs in CCK+ cells was indeed uniform. In contrast, GABAB1 proteins on PV+ dendritic shafts show a spatial association with glutamatergic synapses suggesting that the GABABR in this cell type potentially modulates excitatory neurotransmission. Consistent with the presence of GABABRs, the two interneuron types were immunoreactive for the most abundant Kir3 subunits in the brain, Kir3.1, Kir3.2 and Kir3.3. While immunofluorescence microscopy clearly demonstrated the presence of all three Kir3 proteins, a detailed quantitative immunoelectron analysis revealed differences between Kir3 subunit densities on dendritic shafts of both PV+ and CCK+ interneurons. As the subunit composition determines characteristics like open probability and conductance of the Kir3 channels, their differential distribution on PV+ and CCK+ dendrites might explain differences in the GABAB-mediated Kir3 response between the two cell types. Presynaptically, GABABRs reduce the release of neurotransmitter by modulating Cav2 channels. By using the highly-sensitive sodium dodecyl sulphate-digested freeze fracture replica labeling (SDS-FRL), it could be shown that GABABRs were abundant in M2- and CB1- expressing axon terminals of putative PV+ and CCK+ basket cells, respectively. However, only approximately half of the M2+, but virtually all CB1+ boutons contained the GABAB1 protein. The efficacy and reliability of neurotransmitter release was proposed to depend on the efficient coupling of calcium source and calcium sensor. Using SDS-FRL, it could be demonstrated that in M2+ axon terminals, immunogold particles for Cav2.1 were concentrated over the presynaptic grid, in good agreement with the tight coupling of calcium channels and the release site proposed for PV+ basket cell terminals. Interestingly, Cav2.1 proteins appeared in clusters and their size corresponded well to the number of calcium channels that was proposed to be present in the vicinity of a single priming vesicle. Taken together, results presented in this study give an extensive image about the presence and precise subcellular localization of GABABRs and effector ion channels in PV+ and CCK+ interneurons which adds a completely new facet of modulatory influence to PV+ cells. Furthermore differences in the subcellular localization and densities of the proteins will further extend the functional dichotomy of the two cell types. <br