Multidrug resistance-associated protein-1 (MRP1) genetic variants,MRP1 protein levels and severity of COPD

Background

Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD). We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV₁ in two independent population based cohorts. The aim of our study was to assess the associations of MRP1 SNPs with FEV₁ level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.

Methods

Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients. The effects of MRP1 SNPs were analyzed using linear regression models.

Results

One SNP, rs212093 was significantly associated with a higher FEV₁ level and less airway wall inflammation. Another SNP, rs4148382 was significantly associated with a lower FEV₁ level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.

Conclusions

This is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies.     

Interaction between invasive and potentially invasive shrub species does not influence relationships between their ecological success and distance from propagule sources

Although interactions between alien and native plant species are well studied, data on interactions between two co-existing alien species with respect to their invasibility are scarce. The aims of this study were (1) to evaluate three factors shaping abundance of the alien shrub species Cornus alternifolia: abundance of another alien (invasive) shrub species (Prunus serotina), type of tree stand (coniferous vs. broadleaved) and distance to propagule sources and (2) to assess the potential dispersal distance of the species studied. Densities of both species were assessed within 194 experimental plots (located in experimental plantations of trees) in Rogów Arboretum (Central Poland). P. serotina occurred on 79 and C. alternifolia on 33 of the 194 plots. The furthest distance of C. alternifolia from the propagule source was 338 m. C. alternifolia reached higher densities in coniferous than broadleaved tree stands. Density of C. alternifolia depended on tree stand type and distance from the propagule source, but did not depend on density of P. serotina. Density of C. alternifolia decreased with increasing distance from the propagule source; however, this relationship was modified by the type of tree stand: densities were lower in broadleaved than in coniferous stands. The presence of the invasive species seems to neither facilitate nor limit the dispersal distance of C. alternifolia, as these two species differ in shade tolerance. The study also provided the first information about C. alternifolia potential invasiveness, because earlier this species was noticed only as casually escaping from cultivation in Slovakia.     

A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke

The GTPase dynamin catalyzes membrane fission by forming a collar around the necks of clathrin-coated pits, but the specific structural interactions and conformational changes that drive this process remain a mystery. We present the GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2 ? and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 ?. The structures reveal the position and connectivity of dynamin fragments in the assembled structure, showing that G domain dimers only form between tetramers in sequential rungs of the dynamin helix. Using chemical crosslinking, we demonstrate that dynamin tetramers are made of two dimers, in which the G domain of one molecule interacts in trans with the GED of another. Structural comparison of GG(GMPPCP) to the GG transition-state complex identifies a hydrolysis-dependent powerstroke that may play a role in membrane-remodeling events necessary for fission.     

The trans-boundary importance of artificial bat hibernacula in managed European forests

Many European migratory bat species hibernate in large hollow trees, a decreasing resource in present day silviculture. Here, we report on the importance of man-made hibernacula to support trans-boundary populations of noctule bats (Nyctalus noctula), a species that performs seasonal long distance movements throughout Europe. In winter, we surveyed nine bat roosts (eight artificial and one natural) in Germany and collected small tufts of fur from a total of 608 individuals. We then measured the stable isotope ratios of the non-exchangeable hydrogen in fur keratin and estimated the origin of migrants using a refined isoscape origin model that included information on expected flight distances and migration directions. According to the stable isotope signature, 78 % of hibernating bats originated from local populations. The remaining 22 % of hibernacula occupants originated from distant populations, mostly from places in northern or eastern countries such as Sweden, Poland and Baltic countries. Our results confirm that many noctule bats cross one or several political borders during migration. Data on the breeding origin of hibernating noctule bats also suggest that artificial roosts may not only be important for local but also for distant populations. Protection of natural and artificial hibernacula in managed forests may support the trans-boundary populations of migratory bats when hollow trees are scarce in managed forests.     

The diversity of endophytic fungi in the above-ground tissue of two Lycopodium species in Poland

Endophytes are a large and diverse group of fungi that colonize healthy plant tissues without causing any symptoms. The majority of studies have focused on angiosperm and conifer hosts and few have examined the endophytes of lycophytes. In the present study, we characterized culturable endophytic fungi in two closely related Lycopodium species (L. annotinum and L. clavatum) from pine, beech, oak and spruce forests across Poland. More than 400 strains were isolated but only 18 Ascomycete species were identified. Members of the Dothideomycetes dominated the fungal endophyte communities in Lycopodium. The most abundant taxa cultured were Phoma brasiliensis (from L. clavatum) and Paraconiothyrium lycopodinum (from L. annotinum). Five taxa were isolated exclusively from L. annotinum, but only two of them (Paraconiothyrium lycopodinum and Mycosphaerella sp.) were relatively abundant. Two taxa were only found in L. clavatum, namely: Stagonospora pseudovitensis and an unidentified Dothideomycete. The taxon assigned as Ascomycota 2 (SH219457.06FU) was isolated only from strobili of both host species. Direct PCR and cloning from L. annotinum shoots revealed a substantially greater endophyte richness compared with the results from culturing.     

Haemolysis and Perturbations in the Systemic Iron Metabolism of Suckling,Copper-Deficient Mosaic Mutant Mice – An Animal Model of Menkes Disease

The biological interaction between copper and iron is best exemplified by the decreased activity of multicopper ferroxidases under conditions of copper deficiency that limits the availability of iron for erythropoiesis. However, little is known about how copper deficiency affects iron homeostasis through alteration of the activity of other copper-containing proteins, not directly connected with iron metabolism, such as superoxide dismutase 1 (SOD1). This antioxidant enzyme scavenges the superoxide anion, a reactive oxygen species contributing to the toxicity of iron via the Fenton reaction. Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter. We found that the erythrocytes of these mutants are copper-deficient, display decreased SOD1 activity/expression and have cell membrane abnormalities. In consequence, the mosaic mice show evidence of haemolysis accompanied by haptoglobin-dependent elimination of haemoglobin (Hb) from the circulation, as well as the induction of haem oxygenase 1 (HO1) in the liver and kidney. Moreover, the hepcidin-ferroportin regulatory axis is strongly affected in mosaic mice. These findings indicate that haemolysis is an additional pathogenic factor in a mouse model of Menkes diseases and provides evidence of a new indirect connection between copper deficiency and iron metabolism.     

Anthropometry and Body Composition of Adolescents in Cracow,Poland

Background and Objective

The aim of the present study was to determine the level of adiposity and obesity in Polish adolescents and compare the results with earlier studies conducted in this population as well as those carried out in other populations.

Methods

The study group consisted of 456 boys and 514 girls aged 14-18 years living in Cracow chosen from randomly selected secondary schools. Weight, height, waist, and hip circumference (WC, HC) as well as triceps, biceps, subscapular, and suprailiac skinfold thickness (SFT) were measured. Body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), subscapular/triceps skinfold ratio (STR), and percentage body fat were computed. The prevalence of overweight and obesity based on Polish children growth reference were calculated and age-dependent and gender-specific smoothed percentile curves for BMI and ROC curves were generated.

Results

Weight, height, WC, HC (up 16yr), WHtR (up 15yr), and WHR were considerably higher in males than females. Weight, height, and HC increased with age; WHtR remained the same. The prevalence of overweight and obesity were 10.2% (boys 10.3%; girls 10.1%) and 4.2% (boys 5.3%; girls 3.3%). ROC analysis revealed that WHtR was the best tool for detection of obesity (AUC of 0.982±0.007) in males, whereas the sum of four SFTs (AUC: 0.968±0.011) and WHtR (AUC: 0.963±0.012) were the best predictors of obesity in females.

Conclusions

The level of adiposity in Cracow adolescents increased during the last decade. However, it is still lower than in other well-developed societies struggling with obesity epidemics.     

PBX1 is dispensable for neural commitment of RA-treated murine ES cells

Experimentation with PBX1 knockout mice has shown that PBX1 is necessary for early embryogenesis. Despite broad insight into PBX1 function, little is known about the underlying target gene regulation. Utilizing the Cre–loxP system, we targeted a functionally important part of the homeodomain of PBX1 through homozygous deletion of exon-6 and flanking intronic regions leading to exon 7 skipping in embryonic stem (ES) cells. We induced in vitro differentiation of wild-type and PBX1 mutant ES cells by aggregation and retinoic acid (RA) treatment and compared their profiles of gene expression at the ninth day post-reattachment to adhesive media. Our results indicate that PBX1 interactions with HOX proteins and DNA are dispensable for RA-induced ability of ES to express neural genes and point to a possible involvement of PBX1 in the regulation of imprinted genes.