Differential expression of genes participating in cardiomyocyte electrophysiological remodeling via membrane ionic mechanisms and Ca2+-handling in human heart failure

Molecular and Cellular Biochemistry - Excitation–contraction coupling in normal cardiac function is performed with well balanced and coordinated functioning but with complex dynamic...     

Linkage between energy status of perivascular cells and mineralization of the chick growth cartilage

The objective of this investigation was to investigate the relationship between the energy status of epiphyseal chondrocytes of the chick growth cartilage and the development of mineralization. A microfluorimetric scanning technique was used to measure the reduced pyridine nucleotide content of transverse sections of freeze-trapped cartilage; these measurements were related to tissue structure by scanning electron microscopy. The results of this study show that the energy status of cells in the hypertrophic region of the growth cartilage is more complex than was previously believed. In hypertrophic cartilage, most chondrocytes are in a reduced state. However, in the early hypertrophic region, the vascular channels that penetrate the cartilage from the metaphysis exert a profound local effect on the energy metabolism of perivascular chondrocytes. Thus, around each of the channels, there exists a zone of chondrocytes about 40-60 micron wide which exhibits a low fluorescence yield. The fluorescence level suggests that these perivascular cells have a higher level of oxidative metabolism than hypertrophic chondrocytes that are a distance (greater than 150 micron) from the vascular channels. This finding, in conjunction with our earlier observation that mineralization is first seen in the perivascular region, leads us to the conclusion that mineralization is associated with cellular oxidative activity. We now reject the long-held concept that in cartilage the development of mineralization is entirely due to tissue hypoxia.     

Field measurements and modeling of groundwater flow and biogeochemistry at Moses Hammock, a backbarrier island on the Georgia coast

A combination of field measurements, laboratory experiments and model simulations were used to characterize the groundwater biogeochemical dynamics along a shallow monitoring well transect on a coastal hammock. A switch in the redox status of the dissolved inorganic nitrogen (DIN) pool in the well at the upland/saltmarsh interface occurred over the spring-neap tidal transition: the DIN pool was dominated by nitrate during spring tide and by ammonium during neap tide. A density-dependent reaction-transport model was used to investigate the relative importance of individual processes to the observed N redox-switch. The observed N redox-switch was evaluated with regard to the roles of nitrification, denitrification, dissimilatory nitrate reduction to ammonium (DNRA), ammonium adsorption, and variations in inflowing water geochemistry between spring and neap tides. Transport was driven by measured pressure heads and process parameterizations were derived from field observations, targeted laboratory experiments, and the literature. Modeling results suggest that the variation in inflow water chemistry was the dominant driver of DIN dynamics and highlight the importance of spring-neap tide variations in the high marsh, which influences groundwater biogeochemistry at the marsh-upland transition.     

An improved reconstruction of May–June precipitation using tree-ring data from western Turkey and its links to volcanic eruptions

We developed a high quality reconstruction of May–June precipitation for the interior region of southwestern Turkey using regional tree-ring data calibrated with meteorological data from Burdur. In this study, three new climate sensitive black pine chronologies were built. In addition to new chronologies, four previously published black pine chronologies were used for the reconstruction. Two separate reconstructions were developed. The first reconstruction used all site chronologies over the common interval AD 1813–2004. The second reconstruction used four of the chronologies with a common interval AD 1692–2004. R ² values of the reconstructions were 0.64 and 0.51 with RE values of 0.63 and 0.51, respectively. During the period AD 1692–1938, 41 dry and 48 wet events were found. Very dry years occurred in AD 1725, 1814, 1851, 1887, 1916, and 1923, while very wet years occurred in AD 1736, 1780, 1788, 1803, and 1892. The longest dry period was 16 years long between 1860 and 1875. We then explored relationships between the reconstructed rainfall patterns and major volcanic eruptions, and discovered that wetter than normal years occurred during or immediately after the years with the largest volcanic eruptions.     

?-Blocker Timolol Prevents Arrhythmogenic Ca2+ Release and Normalizes Ca2+ and Zn2+ Dyshomeostasis in Hyperglycemic Rat Heart

Defective cardiac mechanical activity in diabetes results from alterations in intracellular Ca²⁺ handling, in part, due to increased oxidative stress. Beta-blockers demonstrate marked beneficial effects in heart dysfunction with scavenging free radicals and/or acting as an antioxidant. The aim of this study was to address how β-blocker timolol-treatment of diabetic rats exerts cardioprotection. Timolol-treatment (12-week), one-week following diabetes induction, prevented diabetes-induced depressed left ventricular basal contractile activity, prolonged cellular electrical activity, and attenuated the increase in isolated-cardiomyocyte size without hyperglycemic effect. Both in vivo and in vitro timolol-treatment of diabetic cardiomyocytes prevented the altered kinetic parameters of Ca²⁺ transients and reduced Ca²⁺ loading of sarcoplasmic reticulum (SR), basal intracellular free Ca²⁺ and Zn²⁺ ([Ca²⁺]_i and [Zn²⁺]_i), and spatio-temporal properties of the Ca²⁺ sparks, significantly. Timolol also antagonized hyperphosphorylation of cardiac ryanodine receptor (RyR2), and significantly restored depleted protein levels of both RyR2 and calstabin2. Western blot analysis demonstrated that timolol-treatment also significantly normalized depressed levels of some [Ca²⁺]_i-handling regulators, such as Na⁺/Ca²⁺ exchanger (NCX) and phospho-phospholamban (pPLN) to PLN ratio. Incubation of diabetic cardiomyocytes with 4-mM glutathione exerted similar beneficial effects on RyR2-macromolecular complex and basal levels of both [Ca²⁺]_i and [Zn²⁺]_i, increased intracellular Zn²⁺ hyperphosphorylated RyR2 in a concentration-dependent manner. Timolol also led to a balanced oxidant/antioxidant level in both heart and circulation and prevented altered cellular redox state of the heart. We thus report, for the first time, that the preventing effect of timolol, directly targeting heart, seems to be associated with a normalization of macromolecular complex of RyR2 and some Ca²⁺ handling regulators, and prevention of Ca²⁺ leak, and thereby normalization of both [Ca²⁺]_i and [Zn²⁺]_i homeostasis in diabetic rat heart, at least in part by controlling the cellular redox status of hyperglycemic cardiomyocytes.     

Efficient Pre-mRNA Cleavage Prevents Replication-Stress-Associated Genome Instability

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β3-adrenergic receptor activation plays an important role in the depressed myocardial contractility via both elevated levels of cellular free Zn2+ and reactive nitrogen species

Role of β₃-AR dysregulation, as either cardio-conserving or cardio-disrupting mediator, remains unknown yet. Therefore, we examined the molecular mechanism of β₃-AR activation in depressed myocardial contractility using a specific agonist CL316243 or using β₃-AR overexpressed cardiomyocytes. Since it has been previously shown a possible correlation between increased cellular free Zn²⁺ ([Zn²⁺]_i) and depressed cardiac contractility, we first demonstrated a relation between β₃-AR activation and increased [Zn²⁺]_i, parallel to the significant depolarization in mitochondrial membrane potential in rat ventricular cardiomyocytes. Furthermore, the increased [Zn²⁺]_i induced a significant increase in messenger RNA (mRNA) level of β₃-AR in cardiomyocytes. Either β₃-AR activation or its overexpression could increase cellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels, in line with significant changes in nitric oxide (NO)-pathway, including increases in the ratios of pNOS3/NOS3 and pGSK-3β/GSK-3β, and PKG expression level in cardiomyocytes. Although β₃-AR activation induced depression in both Na⁺- and Ca²⁺-currents, the prolonged action potential (AP) seems to be associated with a marked depression in K⁺-currents. The β₃-AR activation caused a negative inotropic effect on the mechanical activity of the heart, through affecting the cellular Ca²⁺-handling, including its effect on Ca²⁺-leakage from sarcoplasmic reticulum (SR). Our cellular level data with β₃-AR agonism were supported with the data on high [Zn²⁺]_i and β₃-AR protein-level in metabolic syndrome (MetS)-rat heart. Overall, our present data can emphasize the important deleterious effect of β₃-AR activation in cardiac remodeling under pathological condition, at least, through a cross-link between β₃-AR activation, NO-signaling, and [Zn²⁺]_i pathways. Moreover, it is interesting to note that the recovery in ER-stress markers with β₃-AR agonism in hyperglycemic cardiomyocytes is favored. Therefore, how long and to which level the β₃-AR agonism would be friend or become foe remains to be mystery, yet.     

<Emphasis Type="Italic">Walckenaeria aksoyi</Emphasis> sp. n. (Araneae: Linyphiidae) from Turkey

Walckenaeria aksoyi sp. n. (Araneae: Linyphiidae) is described based on males from Marmaris Province in Turkey.     

In Silico Geobacter sulfurreducens Metabolism and Its Representation in Reactive Transport Models

Microbial activity governs elemental cycling and the transformation of many anthropogenic substances in aqueous environments. Through the development of a dynamic cell model of the well-characterized, versatile, and abundant Geobacter sulfurreducens, we showed that a kinetic representation of key components of cell metabolism matched microbial growth dynamics observed in chemostat experiments under various environmental conditions and led to results similar to those from a comprehensive flux balance model. Coupling the kinetic cell model to its environment by expressing substrate uptake rates depending on intra- and extracellular substrate concentrations, two-dimensional reactive transport simulations of an aquifer were performed. They illustrated that a proper representation of growth efficiency as a function of substrate availability is a determining factor for the spatial distribution of microbial populations in a porous medium. It was shown that simplified model representations of microbial dynamics in the subsurface that only depended on extracellular conditions could be derived by properly parameterizing emerging properties of the kinetic cell model.