Effect of pre-exposure to beta rays of tritium on some biochemical parameters measured in organs of rats subsequently irradiated with fast neutrons

The experiment examined biological responses produced by combined sequential exposure to low-level tritium contamination, followed by challenging irradiation with fast neutrons. Modifications of endogenous antioxidant potential of different organs in rats were discussed in relation to tissue radiosensitivity. Rats pre-contaminated to 7 cGy and 35 cGy have been additionally irradiated to 1 Gy with fast neutrons. Lipid peroxide level was determined in liver, kidney, small intestine, spleen, bone marrow, and plasma. Reduced glutathione (GSH) level and glucose-6-phosphate dehydrogenase (G6PDH) activity were determined in erythrocytes. An in vitro thymidine uptake assay was performed in isolated bone marrow cells. The lipid peroxide level decreased significantly only in liver and kidney from rats pre-exposed to 35 cGy. For small intestine and spleen, tissues of comparatively higher radiosensitivity, no induced radioprotection was observed, as reflected in the homeostasis of the lipid peroxides. The same behavior was observed in bone marrow, the most radiosensitive tissue studied. However, the bone marrow thymidine-incorporation assay revealed a possible adaptive-type reaction in rats pre-exposed to 35 cGy. We conclude that for radiosensitive tissues pre-exposure to chronic low doses of low linear energy transfer (LET) irradiation has no protective effect on their antioxidant status, whereas a protective effect is observed in radioresistent tissues.     

Why conserve biodiversity? A multi-national exploration of stakeholders’ views on the arguments for biodiversity conservation

Given the concern about biodiversity loss, there are a number of arguments used for biodiversity conservation ranging from those emphasising the intrinsic value of biodiversity to those on the direct use value of ecosystems. Yet arguing the case for biodiversity conservation effectively requires an understanding of why people value biodiversity. We used Q methodology to explore and understand how different conservation practitioners (social and natural science researchers, environmental non-Governmental organisations and decision-makers) in nine European countries argue for conservation. We found that there was a plurality of views about biodiversity and its conservation. A moral argument and some arguments around the intrinsic and ecological value of biodiversity were held by all stakeholder groups. They also shared the view that species valuation does not justify the destruction of nature. However, there were also some differences within and between the groups, which primarily reflected the espousal of either ecocentric or anthropocentric viewpoints. Our findings suggest that moral arguments and those around biodiversity’s intrinsic and ecological value could potentially serve as a starting point for building consensus among conservation practitioners.     

Can Environment Predict Cryptic Diversity? The Case of Niphargus Inhabiting Western Carpathian Groundwater

In the last decade, several studies have shown that subterranean aquatic habitats harbor cryptic species with restricted geographic ranges, frequently occurring as isolated populations. Previous studies on aquatic subterranean species have implied that habitat heterogeneity can promote speciation and that speciation events can be predicted from species’ distributions. We tested the prediction that species distributed across different drainage systems and karst sectors comprise sets of distinct species. Amphipods from the genus Niphargus from 11 caves distributed along the Western Carpathians (Romania) were investigated using three independent molecular markers (COI, H3 and 28S). The results showed that: 1) the studied populations belong to eight different species that derive from two phylogenetically unrelated Niphargus clades; 2) narrow endemic species in fact comprise complexes of morphologically similar species that are indistinguishable without using a molecular approach. The concept of monophyly, concordance between mitochondrial and nuclear DNA, and the value of patristic distances were used as species delimitation criteria. The concept of cryptic species is discussed within the framework of the present work and the contribution of these species to regional biodiversity is also addressed.     

Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice

Heterozygous loss-of-function mutation of the human gene for the mitochondrial protease HtrA2 has been associated with increased risk to develop mitochondrial dysfunction, a process known to contribute to neurodegenerative disorders such as Huntington's disease (HD) and Parkinson's disease (PD). Knockout of HtrA2 in mice also leads to mitochondrial dysfunction and to phenotypes that resemble those found in neurodegenerative disorders and, ultimately, lead to death of animals around postnatal day 30. Here, we show that Idebenone, a synthetic antioxidant of the coenzyme Q family, and Resveratrol, a bioactive compound extracted from grapes, are both able to ameliorate this phenotype. Feeding HtrA2 knockout mice with either compound extends lifespan and delays worsening of the motor phenotype. Experiments conducted in cell culture and on brain tissue of mice revealed that each compound has a different mechanism of action. While Idebenone acts by downregulating the integrated stress response, Resveratrol acts by attenuating apoptosis at the level of Bax. These activities can account for the delay in neuronal degeneration in the striata of these mice and illustrate the potential of these compounds as effective therapeutic approaches against neurodegenerative disorders such as HD or PD.     

Multilevel functional clustering analysis

Summary In this article, we investigate clustering methods for multilevel functional data, which consist of repeated random functions observed for a large number of units (e.g., genes) at multiple subunits (e.g., bacteria types). To describe the within- and between variability induced by the hierarchical structure in the data, we take a multilevel functional principal component analysis (MFPCA) approach. We develop and compare a hard clustering method applied to the scores derived from the MFPCA and a soft clustering method using an MFPCA decomposition. In a simulation study, we assess the estimation accuracy of the clustering membership and the cluster patterns under a series of settings: small versus moderate number of time points; various noise levels; and varying number of subunits per unit. We demonstrate the applicability of the clustering analysis to a real data set consisting of expression profiles from genes activated by immunity system cells. Prevalent response patterns are identified by clustering the expression profiles using our multilevel clustering analysis.     

Profile of common prostate cancer risk variants in an unscreened Romanian population

To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome‐wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P‐value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10^?4), rs7929962 at 11q13.3 (P = 2.7 × 10^?4) and rs9364554 at 6q25.2 (P = 4.7 × 10^?4). None of the variants tested in the Romanian GWAS reached genome‐wide significance (P‐value <5 × 10^?8) but 807 markers had P‐values <1 × 10^?4. Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population.     

Atmospheric concentrations of selected allergenic fungal spores in relation to some meteorological factors,in Timişoara (Romania)

Present investigation was undertaken to study the dynamics of relationships between atmospheric fungal spores and meteorological factors in western Romania. The airborne spore sampling was carried out by employing volumetric sampling. A total of nine meteorological parameters were selected for this investigation. During 2008–2010, it was found the same pattern of behaviour in the atmosphere for selected spore types (Alternaria, Cladosporium, Pithomyces, Epicoccum and Torula). The spores occurred in the air throughout the whole year, but maximum concentrations were reached in summer. Cladosporium and Alternaria peak levels were observed in June. Epicoccum peak value was found in September. The relationships between airborne spore concentrations and environmental factors were assessed using the analysis of Spearman’s rank correlations and multiple linear regressions. Spearman’s rank correlation analysis revealed that maximum, minimum and mean temperature, and number of sunshine hours were strongly (p < 0.01) and directly proportional to the concentration of all analysed fungal spores. Negative and significant correlations were with daily mean relative humidity. The variance explained percentage by regression analyses varied between 30.6 and 39.6 % for Alternaria and Cladosporium airborne spores. Statistical methods used in this study are complementary and confirmed stable dependence of Alternaria and Cladosporium spore concentrations on meteorological factors. The climate change parameters either increased temperatures, changed precipitation regimes or a combination of both affected allergenic fungal spore concentrations in western Romania. This study demonstrates the need for investigations throughout the year, from month to month, regarding the correct interpretation of airborne spore relationships with meteorological parameters.     

Insights into the binding of ferulic acid to the thermally treated xanthine oxidase

Ferulic acid (FA) is a biologically active compound used as an additive in the food industry, and possesses a wide range of therapeutic effects for treating different health problems. The interaction between FA and bovine xanthine oxidase (XOD) has been investigated by means of fluorescence spectroscopy methods. The numbers of binding sites and the binding constants were estimated at various temperatures and the results indicated the existence of one specific FA binding site of XOD. Detailed information on the interaction between molecules gathered after performing in silico molecular docking indicated the accommodation of the FA molecule in a XOD binding pocket, in close vicinity to the active site residues. The formation of the XOD–FA complex causes the quenching of protein fluorescence. The process followed a static mechanism at lower temperatures, and a dynamic mechanism at higher temperatures. The thermodynamic parameters calculated on the basis of different temperatures revealed that the association between FA and XOD is a spontaneous process driven by enthalpy and dominated by hydrogen bonding and van der Waals interaction. The results of synchronous fluorescence and 3D fluorescence spectra showed that the conformation of protein was altered in the presence of FA. Copyright © 2016 John Wiley & Sons, Ltd.     

The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1

In mice, targeted deletion of the serine protease HtrA2 (also known as Omi) causes mitochondrial dysfunction leading to a neurodegenerative disorder with parkinsonian features. In humans, point mutations in HtrA2 are a susceptibility factor for Parkinson's disease (PARK13 locus). Mutations in PINK1, a putative mitochondrial protein kinase, are associated with the PARK6 autosomal recessive locus for susceptibility to early-onset Parkinson's disease. Here we determine that HtrA2 interacts with PINK1 and that both are components of the same stress-sensing pathway. HtrA2 is phosphorylated on activation of the p38 pathway, occurring in a PINK1-dependent manner at a residue adjacent to a position found mutated in patients with Parkinson's disease. HtrA2 phosphorylation is decreased in brains of patients with Parkinson's disease carrying mutations in PINK1. We suggest that PINK1-dependent phosphorylation of HtrA2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress.