Differential Gene Expression of Cardiac Ion Channels in Human Dilated Cardiomyopathy

Background

Dilated cardiomyopathy (DCM) is characterized by idiopathic dilation and systolic contractile dysfunction of the cardiac chambers. The present work aimed to study the alterations in gene expression of ion channels involved in cardiomyocyte function.

Methods and Results

Microarray profiling using the Affymetrix Human Gene® 1.0 ST array was performed using 17 RNA samples, 12 from DCM patients undergoing cardiac transplantation and 5 control donors (CNT). The analysis focused on 7 cardiac ion channel genes, since this category has not been previously studied in human DCM. SCN2B was upregulated, while KCNJ5, KCNJ8, CLIC2, CLCN3, CACNB2, and CACNA1C were downregulated. The RT-qPCR (21 DCM and 8 CNT samples) validated the gene expression of SCN2B (p < 0.0001), KCNJ5 (p < 0.05), KCNJ8 (p < 0.05), CLIC2 (p < 0.05), and CACNB2 (p < 0.05). Furthermore, we performed an IPA analysis and we found a functional relationship between the different ion channels studied in this work.

Conclusion

This study shows a differential expression of ion channel genes involved in cardiac contraction in DCM that might partly underlie the changes in left ventricular function observed in these patients. These results could be the basis for new genetic therapeutic approaches.     

Mitochondrial dysfunction as a mediator of hippocampal apoptosis in a model of hepatic encephalopathy

In this study, we describe the presence of apoptosis, associated with a mitochondrial dysfunction in the hippocampus of animals in an experimental model defined as minimal hepatic encephalopathy (MHE). This experimental model was studied after 10 days of induced portal vein calibrated stricture, leading to portal hypertension and to a moderate hyperammonemia, without the presence of other evident central nervous system changes. The molecular mechanisms here proposed indicate the presence of apoptotic intrinsic pathways that point to hippocampal mitochondria as an important mediator of apoptosis in this experimental model. In this model of MHE, the presence of DNA fragmentation is documented by 2.3-times increased number of TUNEL-positive cells. These findings together with a higher ratio of the Bcl-2 family members Bax/Bcl-xL in the outer mitochondrial membrane of the MHE animals together with 11% of cytochrome c release indicate the presence of apoptosis in this experimental model. A detailed analysis of the hippocampal mitochondrial physiology was performed after mitochondrial isolation. The determination of the respiratory rate in the presence of malate plus glutamate and ADP showed a 45% decrease in respiratory control in MHE animals as compared with the sham group. A marked decrease of cytochrome oxidase (complex IV of the electron transport chain) was also observed, showing 46% less activity in hippocampal mitochondria from MHE animals. In addition, mitochondria from these animals showed less ability to maintain membrane potential (ΔΨ _m) which was 13% lower than the sham group. Light scattering experiments showed that mitochondria from MHE animals were more sensitive to swell in the presence of increased calcium concentrations as compared with the sham group. In addition, in vitro studies performed in mitochondria from sham animals showed that mitochondrial permeability transition (MPT) could be a mitochondrial mediator of the apoptotic signaling in the presence of NH₄ ⁺ and calcium.     

Treatment of volatile organic contaminants in a vertical flow filter: Relevance of different removal processes

Vertical flow filters and vertical flow constructed wetlands are established wastewater treatment systems and have also been proposed for the treatment of contaminated groundwater. This study investigates the removal processes of volatile organic compounds in a pilot-scale vertical flow filter. The filter is intermittently irrigated with contaminated groundwater containing benzene, MTBE and ammonium as the main contaminants. The system is characterized by unsaturated conditions and high contaminant removal efficiency. The aim of the present study is to evaluate the contribution of biodegradation and volatilization to the overall removal of benzene and MTBE. Tracer tests and flow rate measurements showed a highly transient flow and heterogeneous transport regime. Radon-222, naturally occurring in the treated groundwater, was used as a gas tracer and indicated a high volatilization potential. Radon-222 behavior was reproduced by numerical simulations and extrapolated for benzene and MTBE, and indicated these compounds also have a high volatilization potential. In contrast, passive sampler measurements on top of the filter detected only low benzene and MTBE concentrations. Biodegradation potential was evaluated by the analysis of catabolic genes involved in organic compound degradation and a quantitative estimation of biodegradation was derived from stable isotope fractionation analysis. Results suggest that despite the high volatilization potential, biodegradation is the predominant mass removal process in the filter system, which indicates that the volatilized fraction of the contaminants is still subject to subsequent biodegradation. In particular, the upper filter layer located between the injection tubes and the surface of the system might also contribute to biodegradation, and might play a crucial role in avoiding the emission of volatilized contaminants into the atmosphere.     

Molecular and functional characterization of mouse S5D-SRCRB: a new group B member of the scavenger receptor cysteine-rich superfamily

The scavenger receptor cysteine-rich superfamily (SRCR-SF) members are transmembrane and/or secreted receptors exhibiting one or several repeats of a cysteine-rich protein module of ～100 aa, named scavenger receptor cysteine-rich (SRCR). Two types of SRCR domains (A or B) have been reported, which differ in the number of coding exons and intradomain cysteines. Although no unifying function has been reported for SRCR-SF members, recognition of pathogen-associated molecular patterns (PAMPs) was recently shown for some of them. In this article, we report the structural and functional characterization of mouse S5D-SRCRB, a new group B member of the SRCR-SF. The s5d-srcrb gene maps at mouse chromosome 7 and encompasses 14 exons extending over 15 kb. The longest cDNA sequence found is 4286 bp in length and encodes a mature protein of 1371 aa, with a predicted M(r) of 144.6 kDa. Using an episomal mammalian-expression system, a glycosylated soluble recombinant form >200 kDa was obtained and used as immunogen for the generation of specific rat mAbs. Subsequent immunohistochemical and real-time PCR analysis showed significant S5D-SRCRB expression in murine genitourinary and digestive tracts. S5D-SRCRB was shown to bind endogenous extracellular matrix proteins (laminin and galectin-1), as well as PAMPs present on Gram-positive and Gram-negative bacteria and fungi. PAMP binding by S5D-SRCRB induced microbial aggregation and subsequent inhibition of PAMP-induced cytokine release. These abilities suggest that S5D-SRCRB might play a role in the innate defense and homeostasis of certain specialized epithelial surfaces.     

Carcass transport decisions in Homo antecessor subsistence strategies

Pleistocene foragers used several prey acquisition and processing strategies. These strategies and their associated decisions are elucidated by taphonomic studies that cover animal transport, modifications by different agents and archaeological remains. Interpretative models of archaeological sites are by necessity based on natural and experimental observations. Ethno-archaeological data shows that several factors influenced decisions about carcass transport from the kill site to the home site. These factors often have little archaeological visibility. Díez et al. (1999) has previously interpreted the general characteristics of the macro-mammal remains from Gran Dolina Level TD6-2 (Sierra de Atapuerca, Burgos, Spain) as the result of anthropic accumulation, in which the anatomical profiles appeared to be the result of selective transport based on the animals’ weight. Recent taphonomic analysis has shown that carcasses with different weights may be subject to similar transport strategies, suggesting that other factors influenced these choices. The hominins that occupied TD6-2 (the TD6-2 hominin group), at least sometimes, transported large carcasses to the cave in their entirety, implying participation by groups of individuals in hunting parties. These individuals delayed their consumption of large amounts of food, instead moving it to Gran Dolina, where it was shared with other group members. These decisions are evidence of social cooperation and food sharing amongst early European hominins.     

Universal hydraulics of the flowering plants: vessel diameter scales with stem length across angiosperm lineages,habits and climates

Angiosperm hydraulic performance is crucially affected by the diameters of vessels, the water conducting conduits in the wood. Hydraulic optimality models suggest that vessels should widen predictably from stem tip to base, buffering hydrodynamic resistance accruing as stems, and therefore conductive path, increase in length. Data from 257 species (609 samples) show that vessels widen as predicted with distance from the stem apex across angiosperm orders, habits and habitats. Standardising for stem length, vessels are only slightly wider in warm/moist climates and in lianas, showing that, rather than climate or habit, plant size is by far the main driver of global variation in mean vessel diameter. Terminal twig vessels become wider as plant height increases, while vessel density decreases slightly less than expected tip to base. These patterns lead to testable predictions regarding evolutionary strategies allowing plants to minimise carbon costs per unit leaf area even as height increases.     

Two Different Epidemiological Scenarios of Border Disease in the Populations of Pyrenean chamois (Rupicapra p. pyrenaica) after the First Disease Outbreaks

Since 2001 several outbreaks of a new disease associated with Border disease virus (BDV) infection have caused important declines in Pyrenean chamois (Rupicapra pyrenaica) populations in the Pyrenees. The goal of this study was to analyze the post-outbreak BDV epidemiology in the first two areas affected by disease with the aim to establish if the infection has become endemic. We also investigated if BDV infected wild and domestic ruminants sharing habitat with chamois. Unexpectedly, we found different epidemiological scenarios in each population. Since the disease outbreaks, some chamois populations recuperated quickly, while others did not recover as expected. In chamois from the first areas, prevalence was high (73.47%) and constant throughout the whole study period and did not differ between chamois born before and after the BDV outbreak; in all, BDV was detected by RT-PCR in six chamois. In the other areas, prevalence was lower (52.79%) and decreased during the study period; as well, prevalence was significantly lower in chamois born after the disease outbreak. No BDV were detected in this population. A comparative virus neutralisation test performed with four BDV strains and one Bovine viral diarrhoea virus (BVDV) strain showed that all the chamois had BDV-specific antibodies. Pestivirus antibodies were detected in all the rest of analyzed species, with low prevalence values in wild ruminants and moderate values in domestic ruminants. No viruses were detected in these species. These results confirm the hypothesis that outbreaks of BDV infection only affect the Pyrenean chamois, although other wild ruminants can occasionally be infected. In conclusion, two different scenarios have appeared since the first border disease outbreaks in Pyrenean chamois: on the one hand frequent BDV circulation with possible negative impact on population dynamics in some areas and on the other, lack of virus circulation and quick recovery of the chamois population.