Getting the measure of eutrophication in the Baltic Sea: towards improved assessment principles and methods

The eutrophication status of the entire Baltic Sea is classified using a multi-metric indicator-based assessment tool. A total of 189 areas are assessed using indicators where information on reference conditions (RefCon), and acceptable deviation (AcDev) from reference condition could be combined with national monitoring data from the period 2001?C2006. Most areas (176) are classified as ??affected by eutrophication?? and only two open water areas and 11 coastal areas are classified as ??unaffected by eutrophication??. The classification is made by application of the recently developed HELCOM Eutrophication Assessment Tool (HEAT), which is described in this paper. The use of harmonized assessment principles and the HEAT tool allows for direct comparisons between different parts of the Baltic Sea despite variations in monitoring activities. The impaired status of 176 areas is directly related to nutrient enrichment and elevated loads from upstream catchments. Baltic Sea States have implemented nutrient management strategies since years which have reduced nutrient inputs. However, eutrophication is still a major problem for large parts of the Baltic Sea. The 2007 Baltic Sea Action Plan is projected to further reduce nutrient inputs aiming for a Baltic Sea unaffected by eutrophication by 2021.     

Epigenetic mechanisms in virus-induced tumorigenesis

About 15-20% of human cancers worldwide have viral etiology. Emerging data clearly indicate that several human DNA and RNA viruses, such as human papillomavirus, Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, hepatitis B virus, hepatitis C virus, and human T-cell lymphotropic virus, contribute to cancer development. Human tumor-associated viruses have evolved multiple molecular mechanisms to disrupt specific cellular pathways to facilitate aberrant replication. Although oncogenic viruses belong to different families, their strategies in human cancer development show many similarities and involve viral-encoded oncoproteins targeting the key cellular proteins that regulate cell growth. Recent studies show that virus and host interactions also occur at the epigenetic level. In this review, we summarize the published information related to the interactions between viral proteins and epigenetic machinery which lead to alterations in the epigenetic landscape of the cell contributing to carcinogenesis.     

Network-Based Data Integration for Selecting Candidate Virulence Associated Proteins in the Cereal Infecting Fungus Fusarium graminearum

The identification of virulence genes in plant pathogenic fungi is important for understanding the infection process, host range and for developing control strategies. The analysis of already verified virulence genes in phytopathogenic fungi in the context of integrated functional networks can give clues about the underlying mechanisms and pathways directly or indirectly linked to fungal pathogenicity and can suggest new candidates for further experimental investigation, using a ‘guilt by association’ approach. Here we study 133 genes in the globally important Ascomycete fungus Fusarium graminearum that have been experimentally tested for their involvement in virulence. An integrated network that combines information from gene co-expression, predicted protein-protein interactions and sequence similarity was employed and, using 100 genes known to be required for virulence, we found a total of 215 new proteins potentially associated with virulence of which 29 are annotated as hypothetical proteins. The majority of these potential virulence genes are located in chromosomal regions known to have a low recombination frequency. We have also explored the taxonomic diversity of these candidates and found 25 sequences, which are likely to be fungal specific. We discuss the biological relevance of a few of the potentially novel virulence associated genes in detail. The analysis of already verified virulence genes in phytopathogenic fungi in the context of integrated functional networks can give clues about the underlying mechanisms and pathways directly or indirectly linked to fungal pathogenicity and can suggest new candidates for further experimental investigation, using a ‘guilt by association’ approach.     

Genome-Wide Association Studies Identify Two Novel BMP15 Mutations Responsible for an Atypical Hyperprolificacy Phenotype in Sheep

Some sheep breeds are naturally prolific, and they are very informative for the studies of reproductive genetics and physiology. Major genes increasing litter size (LS) and ovulation rate (OR) were suspected in the French Grivette and the Polish Olkuska sheep populations, respectively. To identify genetic variants responsible for the highly prolific phenotype in these two breeds, genome-wide association studies (GWAS) followed by complementary genetic and functional analyses were performed. Highly prolific ewes (cases) and normal prolific ewes (controls) from each breed were genotyped using the Illumina OvineSNP50 Genotyping Beadchip. In both populations, an X chromosome region, close to the BMP15 gene, harbored clusters of markers with suggestive evidence of association at significance levels between 1E⁻⁰⁵ and 1E⁻⁰⁷. The BMP15 candidate gene was then sequenced, and two novel non-conservative mutations called FecX^Gr and FecX^O were identified in the Grivette and Olkuska breeds, respectively. The two mutations were associated with the highly prolific phenotype (p_FecX^Gr = 5.98E⁻⁰⁶ and p_FecX^O = 2.55E⁻⁰⁸). Homozygous ewes for the mutated allele showed a significantly increased prolificacy (FecX^Gr/FecX^Gr, LS = 2.50±0.65 versus FecX⁺/FecX^Gr, LS = 1.93±0.42, p<1E⁻⁰³ and FecX^O/FecX^O, OR = 3.28±0.85 versus FecX⁺/FecX^O, OR = 2.02±0.47, p<1E⁻⁰³). Both mutations are located in very well conserved motifs of the protein and altered the BMP15 signaling activity in vitro using a BMP-responsive luciferase test in COV434 granulosa cells. Thus, we have identified two novel mutations in the BMP15 gene associated with increased LS and OR. Notably, homozygous FecX^Gr/FecX^Gr Grivette and homozygous FecX^O/FecX^O Olkuska ewes are hyperprolific in striking contrast with the sterility exhibited by all other known homozygous BMP15 mutations. Our results bring new insights into the key role played by the BMP15 protein in ovarian function and could contribute to a better understanding of the pathogenesis of women′s fertility disorders.     

5-Ethynyl-1-β-D-ribofuranosyl-1H-[1,2,3]triazole-4-carboxylic acid amide (ETCAR) and its analogues: synthesis and cytotoxic properties

Efficient Pd(0)-catalysed synthesis of 5-alkynyl-1-β-D-ribofuranosyl-1H-[1,2,3]triazole-4-carboxylic acid amide depends on the presence of different protecting groups of the ribose moiety. Peracetylated 5-iodo substrate (15) couples with terminal alkynes or trimethyl-[(tributylstannyl)ethynyl]silane in 50-71% and 72% yield (ETCAR), respectively, although its hydrodehalogenation to 19 is noticeable. On the other hand, hydrodehalogenation of acetonide (16) predominates over coupling with terminal alkyne and slightly decreases a yield of cross-coupling reaction with trimethyl[(tributylstannyl)ethynyl]silane. Alternative conditions of reaction with terminal alkynes, to exclude so far identified hydride sources to produce hydridopalladium species, have been established for acetonide 16 and allowed to achieve 72% of coupling. Fluoromethyl derivative (42) was prepared from its 5-hydroxymethyl precursor by fluorination with DAST. Additionally, X-ray structural analysis of 42 was performed. All 1,2,3-triazolonucleosides and two synthesized cycloSal-pronucleotides were evaluated for cytotoxic activity against K562, HeLa and HUVEC cells.     

Irrelevance of CHEK2 variants to diagnosis of breast/ovarian cancer predisposition in Polish cohort

CHEK2 gen encodes cell cycle checkpoint kinase 2 that participates in the DNA repair pathway, cell cycle regulation and apoptosis. Mutations in CHEK2 gene may result in kinase inactivation or reduce both catalytic activity and capability of binding other proteins. Some studies indicate that alterations in CHEK2 gene confers increase the risk of breast cancer and some other malignancies, while the results of other studies are inconclusive. Thus the significance of CHEK2 mutations in aetiology of breast cancer is still debatable. The aim of our study was to evaluate the relationship between the breast/ovarian cancer and CHEK2 variants by: i) the analysis of the frequency of selected CHEK2 variants in breast and ovarian cancer patients compared to the controls; ii) evaluation of relationships between the certain CHEK2 variants and clinico-histopathological and pedigree data. The study was performed on 284 breast cancer patients, 113 ovarian cancer patients and 287 healthy women. We revealed the presence of 430T > C, del5395 and IVS2 + 1G > A variants but not 1100delC in individuals from both study and control groups. We did not observe significant differences between cancer patients and controls neither in regard to the frequency nor to the type of CHEK2 variants. We discussed the potential application of CHEK2 variants in the evaluation of breast and ovarian cancer predisposition.     

The Concentration of Manganese, Iron and Strontium in Bone of Red Fox Vulpes vulpes (L. 1758)

The aims of the study were to determine manganese (Mn), iron (Fe) and strontium (Sr) concentrations in fox bone samples from north-western Poland and to examine the relationships between the bone Mn, Fe and Sr concentrations and the sex and age of the foxes. In the studied samples of fox cartilage, cartilage with adjacent compact bone, compact bone and spongy bone, the concentrations of the analysed metals had the following descending order: Fe > Sr > Mn. The only exception was in compact bone, in which the concentrations were arranged in the order Sr > Fe > Mn. Manganese concentrations were significantly higher in cartilage, compact bone and cartilage with compact bone than in spongy bone. Iron concentrations were higher in cartilage and spongy bone compared with compact bone. Strontium concentrations were greater in compact bone than in cartilage and spongy bone. The manganese, iron and strontium concentrations in the same type of bone material in many cases correlated with each other, with the strongest correlation (r?>?0.70) between Mn and Fe in almost all types of samples. In addition, concentrations of the same metals in different bone materials were closely correlated for Mn and Fe in cartilage and cartilage with adjacent compact bone, and for Sr in compact bone and cartilage with compact bone. In the fox from NW Poland, there were no statistically significant differences in Mn, Fe and Sr in any of the types of bone material between the sexes and immature and adult foxes.     

Motor unit potentials with satellites in dystrophinopathies

IntroductionThe objective of this study was to analyze the motor unit potentials (MUPs) with satellite components i.e., delayed by at least 2 ms baseline from the main component, in the dystrophinopathies.MethodsThe parameters of the MUPs recorded from the biceps brachii muscle in the Duchenne and Becker Muscle Dystrophy (DMD, BMD) were analyzed. The origin of the MUP satellite components was studied using a computer simulation.ResultsAs compared with normal potentials, both the main and the satellite MUP components are smaller in size, while the main components are more irregular. The computer simulation allows the range of muscle fiber diameters to be determined, and suggests that the variability characterizing diameters within the motor unit is responsible for generating the delayed, satellite components, via the linear relationship between the fiber diameter and the conduction velocity of the action potential.DiscussionThe enhanced understanding of the origin of the MUP satellite components augments the knowledge about the relationship between muscle morphology and bioelectrical activity. The indirect evaluation of the range of muscle fiber diameters by means of a computer simulation may provide a new quantitative morphological data available from the EMG.