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Cardiomyopathy is commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD), even when they have normal renal function and arterial pressure. The role of cardiomyocyte polycystin-1 (PC1) in cardiovascular pathophysiology remains unknown. PC1 is a potential regulator of BIN1 that maintains T-tubule structure, and alterations in BIN1 expression induce cardiac pathologies. We used a cardiomyocyte-specific PC1-silenced (PC1-KO) mouse model to explore the relevance of cardiomyocyte PC1 in the development of heart failure (HF), considering reduced BIN1 expression induced T-tubule remodeling as a potential mechanism. PC1-KO mice exhibited an impairment of cardiac function, as measured by echocardiography, but no signs of HF until 7–9 months of age. Of the PC1-KO mice, 43% died suddenly at 7 months of age, and 100% died after 9 months with dilated cardiomyopathy. Total BIN1 mRNA, protein levels, and its localization in plasma membrane-enriched fractions decreased in PC1-KO mice. Moreover, the BIN1 + 13 isoform decreased while the BIN1 + 13 + 17 isoform was overexpressed in mice without signs of HF. However, BIN1 + 13 + 17 overexpression was not observed in mice with HF. T-tubule remodeling and BIN1 score measured in plasma samples were associated with decreased PC1-BIN1 expression and HF development. Our results show that decreased PC1 expression in cardiomyocytes induces dilated cardiomyopathy associated with diminished BIN1 expression and T-tubule remodeling. In conclusion, positive modulation of BIN1 expression by PC1 suggests a novel pathway that may be relevant to understanding the pathophysiological mechanisms leading to cardiomyopathy in ADPKD patients. [ABSTRACT FROM AUTHOR]

We studied the effect of [H.sub.2][O.sub.2] on the gating behavior of large-conductance [Ca.sup.2+]-sensitive voltage-dependent [K.sup.+] ([K.sub.V,Ca]) channels. We recorded potassium currents from single skeletal muscle channels incorporated into bilayers or using macropatches of Xenopus laevis oocytes membranes expressing the human Slowpoke (hSlo) [alpha]-subunit. Exposure of the intracellular side of [K.sub.V,Ca] channels to [H.sub.2][O.sub.2] (4-23 mM) leads to a time-dependent decrease of the open probability ([P.sub.o]) without affecting the unitary conductance. [H.sub.2][O.sub.2] did not affect channel activity when added to the extracellular side. These results provide evidence for an intracellular site(s) of [H.sub.2][O.sub.2] action. Desferrioxamine (60 [micro]M) and cysteine (1 mM) completely inhibited the effect of [H.sub.2][O.sub.2], indicating that the decrease in Po was mediated by hydroxyl radicals. The reducing agent dithiothreitol (DTT) could not fully reverse the effect of [H.sub.2][O.sub.2]. However, DTT did completely reverse the decrease in Po induced by the oxidizing agent 5,5'-dithio-bis-(2-nitrobenzoic acid). The incomplete recovery of [K.sub.V,Ca] channel activity promoted by DTT suggests that [H.sub.2][O.sub.2] treatment must be modifying other amino acid residues, e.g., as methionine or tryptophan, besides cysteine. Noise analysis of macroscopic currents in Xenopus oocytes expressing hSlo channels showed that [H.sub.2][O.sub.2] induced a decrease in current mediated by a decrease both in the number of active channels and [P.sub.o]. [K.sub.V,Ca] channels; [H.sub.2][O.sub.2]

Definitions of potassium and barium binding site functions are presented, along with supporting research. It is posited that the potassium lock-in site is the selectivity filter's external ion site, while the barium site is the internal ion site.

Cells possess a variety of organelles with characteristic structure and subcellular localization intimately linked to their specific function. While most are intracellular and found in virtually all eukaryotic cells, there is a small group of organelles of elongated cylindrical shapes in highly specialized cells that protrude into the extracellular space, such as cilia, flagella, and microvilli. The ATP required by intracellular organelles is amply available in the cytosol, largely generated by mitochondria. However, such is not the case for cilia and flagella, whose slender structures cannot accommodate mitochondria. These organelles consume massive amounts of ATP to carry out high energy‐demanding functions, such as sensory transduction or motility. ATP from the nearest mitochondria or other reactions within the cell body is severely limited by diffusion and generally insufficient to fuel the entire length of cilia and flagella. These organelles overcome this fuel restriction by local generation of ATP, using mechanisms that vary depending on the nutrients that are available in their particular external environment. Here, we review, with emphasis in mammals, the remarkable adaptations that cilia and flagella use to fuel their metabolic needs. Additionally, we discuss how a decrease in nutrients surrounding olfactory cilia might impair olfaction in COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Odor transduction in the cilia of olfactory sensory neurons involves several ATP‐requiring enzymes. ATP is generated by glycolysis in the ciliary lumen, using glucose incorporated from surrounding mucus, and by oxidative phosphorylation in the dendrite. During prolonged stimulation, the cilia maintain ATP levels along their length, by unknown means. We used immunochemistry, RT‐PCR, and immunoblotting to explore possible underlying mechanisms. We found the ATP‐shuttles, adenylate and creatine kinases, capable of equilibrating ATP. We also investigated how glucose delivered by blood vessels in the olfactory mucosa reaches the mucus. We detected, in sustentacular and Bowman's gland cells, the crucial enzyme in glucose secretion glucose‐6‐phosphatase, implicating both cell types as putative glucose pathways. We propose a model accounting for both processes. [ABSTRACT FROM AUTHOR]

Una tésis funadamental para el tratamiento de un área o territorio patrimonial se basa en gran medida en los aportes y registros de identidad cultural que puede desarrollar en el tiempo el medio físico construido, particularmente el espacio urbano en conjunción con su arquitectura. En este sentido la reinterpretación metodológica del concepto tipológico aplicado al patrimonio material resulta de gran valor al momento de investigar los elementos que estructuralmente y en distintas épocas han configurado una arquitectura profunda en vinculación con su medio, las condicionantes del entorno y el tiempo histórico. Valparaíso se constituye en un reservorio de arquitecturas diversas, originadas en un marco endógeno de condicionantes geotopográficas, climáticas, ambientales y sísmicas, reconocidas en conjunto como Paisaje Cultural. Así vista, la tipología se redefiniría como el trazado espacial que a través del tiempo ha sido capaz de incorporar, mutar y perfeccionar los factores vitruvianos de la arquitectura: proporción, forma, estructura, estética y construcción; llegando a plantear aportes de identidad que trascienden la mera función del inmueble o su figura aparente, contituyéndose en fragmentos que expresan la forma a manera borgheriana el global del Paisaje Cultural. La identidad arquitectónica en Valparaíso, respondería entonces a la definición de un proceso histórico decantado en el que las condicionantes del entorno determinan esquemas identificables y persistentes en los cuales se vinculan códigos y leyes en aspectos tales como la dimesión urbana, la espacialidad, la forma, la volumetría, la planimetría, el estilo, y sistemas constructivo-estructurales; a partir de los cuales es posible abordar la multiplicidad de arquitecturas, ordenándolas en familias tipológicas, cada una de las cuales manifiestan variaciones manteniendo unidad en el total. Las tipologías arquitectónicas en Valparaíso cumplen un rol documental como reflejo de la época en que fueron construidas, pero también dan cuenta sintética de procesos de configuración de la forma (sus durabilidades, persistencias y adjetividades), incubando las variables o "genomas" de ulteriores desarrollos arquitectónicos, abriendo interesantes vínculos con criterios de diseño e intervención contemporánea sobre un área histórico patrimonial. [ABSTRACT FROM AUTHOR]

Temperature and quality of the available food are important factors that influence the physiology of oysters; however, the combined effects have not been well studied. We evaluated the impacts of the temperature and diet on the growth, survival and biochemical composition in the Pacific oysterCrassostrea gigasspat, cultured in the laboratory for 8 weeks at 23, 26, 29 and 32°C and fedIsochrysissp.-Pavlova lutheri(IP) andDunaliella tertiolecta(Dt). The growth and biochemical composition showed a pattern, which changed in response to rising temperature. The shell length was significantly longer, in spat fed the IP diet, except at 32°C, where both diets produced poor growth results. The survival was<50% after 5 weeks at 32°C, whereas at all other temperatures it was>88%. High temperatures directly increased lipids and saturated fatty acids, while the proteins, carbohydrates and unsaturated fatty acids decreased. High temperatures achieved in the environment, as those reached on clear summer days during low tides, are an important stressor in oyster spat, especially when the quality of the available food is poor. [ABSTRACT FROM AUTHOR]

We studied the effect of H2O2 on the gating behavior of large-conductance Ca2+-sensitive voltage-dependent K+ (KV,Ca) channels. We recorded potassium currents from single skeletal muscle channels incorporated into bilayers or using macropatches of Xenopus laevis oocytes membranes expressing the human Slowpoke (hSlo) α-subunit. Exposure of the intracellular side of KV,Ca channels to H2O2 (4-23 mM) leads to a time-dependent decrease of the open probability (Po) without affecting the unitary conductance. H2O2 did not affect channel activity when added to the extracellular side. These results provide evidence for an intracellular site(s) of H2O2 action. Desferrioxamine (60 μM) and cysteine (1 mM) completely inhibited the effect of H2O2, indicating that the decrease in Po was mediated by hydroxyl radicals. The reducing agent dithiothreitol (DTT) could not fully reverse the effect of H2O2. However, DTT did completely reverse the decrease in Po induced by the oxidizing agent 5,5'-dithio-bis-(2-nitrobenzoic acid). The incomplete recovery of KV,Ca channel activity promoted by DTT suggests that H2O2 treatment must be modifying other amino acid residues, e.g., as methionine or tryptophan, besides cysteine. Noise analysis of macroscopic currents in Xenopus oocytes expressing hSlo channels showed that H2O2 induced a decrease in current mediated by a decrease both in the number of active channels and Po. [ABSTRACT FROM AUTHOR]