Single nucleotide polymorphism -799C/T in matrix metalloproteinase-8 promoter region in arterial disease

Arterial disease is associated with elevated serum matrix metalloproteinase (MMP)-8 concentration. We studied the role of two promoter region single nucleotide polymorphisms (SNPs) of MMP-8 gene in the arterial disease. The population comprised patients with arterial disease (n?=?124) and healthy blood donors (n?=?100) as a reference group for MMP-8 SNPs (-799C/T and -381A/G) genotypes and serum concentrations. Genotype frequencies for MMP-8 -799C/T SNP in arterial disease were C/C (43.5%), C/T (32.3%) and T/T (24.2%), and in the reference group they were C/C (50.0%), C/T (40.0%) and T/T (10.0%; P?=?0.012). The -799C allele frequency was lower in the patients (59.7%) than in the reference group (70.0%; P?=?0.023). The -799C allele showed protective effects against the arterial disease with an odds ratio [95% confidence interval (CI)] of 0.372 (0.141-0.980, P?=?0.045) after adjustment for age, gender, and serum MMP-8 and TIMP-1 concentrations. Only in the reference group and whole study population (n?=?224), the -799TT genotype significantly associated with an increase in serum MMP-8 concentrations (P?=?0.047, 0.025). The -799C allele appeared protective against the arterial disease. The genotype may have an effect on systemic MMP-8 levels which could not, however, be seen in the arterial disease patients probably as a result of the strong inflammation involved in the disease pathogenesis.     

Frequency and density-dependent selection on life-history strategies--a field experiment

Negative frequency-dependence, which favors rare genotypes, promotes the maintenance of genetic variability and is of interest as a potential explanation for genetic differentiation. Density-dependent selection may also promote cyclic changes in frequencies of genotypes. Here we show evidence for both density-dependent and negative frequency-dependent selection on opposite life-history tactics (low or high reproductive effort, RE) in the bank vole (Myodes glareolus). Density-dependent selection was evident among the females with low RE, which were especially favored in low densities. Instead, both negative frequency-dependent and density-dependent selection were shown in females with high RE, which were most successful when they were rare in high densities. Furthermore, selection at the individual level affected the frequencies of tactics at the population level, so that the frequency of the rare high RE tactic increased significantly at high densities. We hypothesize that these two selection mechanisms (density- and negative frequency-dependent selection) may promote genetic variability in cyclic mammal populations. Nevertheless, it remains to be determined whether the origin of genetic variance in life-history traits is causally related to density variation (e.g. population cycles).     

Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes

The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.     

Generation of Metal-Binding Staphylococci through Surface Display of Combinatorially Engineered Cellulose-Binding Domains

Ni²⁺-binding staphylococci were generated through surface display of combinatorially engineered variants of a fungal cellulose-binding domain (CBD) from Trichoderma reesei cellulase Cel7A. Novel CBD variants were generated by combinatorial protein engineering through the randomization of 11 amino acid positions, and eight potentially Ni²⁺-binding CBDs were selected by phage display technology. These new variants were subsequently genetically introduced into chimeric surface proteins for surface display on Staphylococcus carnosus cells. The expressed chimeric proteins were shown to be properly targeted to the cell wall of S. carnosus cells, since full-length proteins could be extracted and affinity purified. Surface accessibility for the chimeric proteins was demonstrated, and furthermore, the engineered CBDs, now devoid of cellulose-binding capacity, were shown to be functional with regard to metal binding, since the recombinant staphylococci had gained Ni²⁺-binding capacity. Potential environmental applications for such tailor-made metal-binding bacteria as bioadsorbents in biofilters or biosensors are discussed.     

Tests for Trends in Incidence Rate Ratios

Breslow (1984) described an efficient score test for trend in incidence density rate ratios for cohort studies under a conditional Poisson or binomial model employing maximum likelihood estimation of the rate parameters. In this communication, an alternative derivation of this statistic that is based on an unconditional approach is provided, along with an examination of associated goodness-of-fit tests and methods of confidence interval estimation. The procedures are illustrated by a cohort study of ischemic heart disease mortality following industrial exposure to carbon disulfide.     

Mobile Phone Call Data as a Regional Socio-Economic Proxy Indicator

The advent of publishing anonymized call detail records opens the door for temporal and spatial human dynamics studies. Such studies, besides being useful for creating universal models for mobility patterns, could be also used for creating new socio-economic proxy indicators that will not rely only on the local or state institutions. In this paper, from the frequency of calls at different times of the day, in different small regional units (sub-prefectures) in Côte d''Ivoire, we infer users'' home and work sub-prefectures. This division of users enables us to analyze different mobility and calling patterns for the different regions. We then compare how those patterns correlate to the data from other sources, such as: news for particular events in the given period, census data, economic activity, poverty index, power plants and energy grid data. Our results show high correlation in many of the cases revealing the diversity of socio-economic insights that can be inferred using only mobile phone call data. The methods and the results may be particularly relevant to policy-makers engaged in poverty reduction initiatives as they can provide an affordable tool in the context of resource-constrained developing economies, such as Côte d''Ivoire''s.     

<Emphasis Type="Italic">Cortinarius</Emphasis> sect. <Emphasis Type="Italic">Riederi</Emphasis>: taxonomy and phylogeny of the new section with European and North American distribution

Cortinarius is one of the most species-rich genera of mushroom-forming fungi. Based on phylogenetic and morphological evidence, Cortinarius, sect. Riederi, is introduced at sectional level (= subsect. Riederi sensu Brandrud & Melot). The taxonomy, phylogeny, ecology and distribution of not only mainly European but also including some North American taxa of this section are treated, which includes nine species and two varieties. Of these, three taxa are described as new (C. burlinghamiae, C. pallidoriederi and C. argenteolilacinus var. dovrensis). The sect. Riederi species possess morphological features similar to Phlegmacium group(s) and forms a phylogenetically isolated lineage, with no supported affinity to other phlegmacioid groups. Three taxa are known from both Europe and North America, two species are known only from North America and five only from Europe. Altogether, eight of the ten taxa are associated with conifers or northern (boreal-subalpine) deciduous trees (Betula spp.). Only two species occur in more temperate forests (Fagus forests), and no species have so far been found in thermophilous Quercus forests     

Relationship between local perfusion and FFA uptake in human skeletal muscle-no effect of increased physical activity and aerobic fitness.

We investigated heredity-independent effects of increased physical activity and aerobic fitness on skeletal muscle free fatty acid (FFA) uptake, perfusion, and their heterogeneity at rest and during exercise. Also, the relationship between local skeletal muscle FFA uptake and perfusion was studied. Nine young adult male monozygotic twin pairs with significant difference in physical activity [229 min (SD 156) average time spent for conditioning exercise per week in more and 98 min (SD 71) in less active twins, P = 0.013] and aerobic fitness [18% (SD 10) difference in maximum O2 uptake] between brothers were studied using positron emission tomography. Submaximal knee-extension exercise increased perfusion, FFA uptake, and oxygen uptake in quadriceps femoris muscles 6-10 times compared with resting values (P < 0.001). More active twins tended to utilize more oxygen, while no differences were found in muscle perfusion or FFA uptake between groups. Mean perfusion and FFA uptake correlated strongly at a whole muscle level, both at rest (r = 0.97, P = 0.03 in more and r = 0.98, P = 0.02 in less active twins) and during exercise (r = 0.99, P = 0.01 and r = 0.94, P = 0.06), but at the voxel level (87 mm3) correlation was only moderate during exercise [r = 0.73 (SD 0.08) vs. r = 0.74 (SD 0.10), P = 0.92] and weak at rest [r = 0.28 (SD 0.13) vs. r = 0.33 (SD 0.21), P = 0.58]. Exercise decreased both perfusion and FFA uptake heterogeneity within the muscles (P < 0.001) similarly in both groups. In conclusion, long-term history of moderately increased physical activity tends to enhance muscle oxidative metabolism, but it does not have any significant influence on the FFA uptake or perfusion rates or their heterogeneity in skeletal muscle. Submaximal knee-extension exercise decreases heterogeneity of muscle FFA uptake and perfusion and improves matching between local muscle perfusion and FFA uptake. Thus it seems that the genetic influence is more important to determine the heterogeneity of perfusion and FFA uptake in skeletal muscle than exercise training.