Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours

Ficolins are serum pattern recognition molecules. They have opsonic properties and are able to activate complement via the lectin pathway. This paper reports investigations concerning ficolin-2 and ficolin-3 in ovarian cancer (OC). Their serum levels, single nucleotide polymorphisms of the corresponding FCN2 and FCN3 genes and specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary OC and 197 controls operated on for reasons other than malignancies. The latter consisted of two reference groups: those with benign tumours (n = 123) and those with normal ovaries (NO) (n = 74). Serum ficolin-2 and ficolin-3 concentrations were higher among patients with malignant disease when compared with either of the reference groups. A significant correlation between ficolin-2 and ficolin-3 concentrations was found, while no correlations with CA125 antigen or CRP were observed. No differences in the frequency of single nucleotide polymorphisms at sites ?64, ?4 (promoter), +6359, or +6424 (exon 8) (FCN2 gene) nor in the frame-shift mutation 1637delC (FCN3 gene) were found between investigated groups. In contrast to serum concentrations, the expression of FCN2 gene (reported for the first time in ovarian sections) was significantly lower in women with OC in comparison with patients with NO but not with benign ovarian tumours. In case of FCN3 gene, its expression levels in OC group inversely correlated with serum ficolin-3 and were lower in comparison with controls.     

Immunotherapy: a way to improve the therapeutic outcome of photodynamic therapy?

Photodynamic therapy (PDT) is a treatment for cancer and non-cancerous lesions involving light and a sensitizing drug, a so-called photosensitizer. Photosensitizers for PDT usually accumulate in tumour tissues with some selectivity. Thus, malignant and abnormal cells can be destroyed by PDT which acts by producing singlet oxygen and possible other reactive oxygen species. However, the efficiency of PDT is often limited by shallow light penetration into tissue. In some cases one treatment modality cannot cure a patient because of treatment limitations and/or side effects. In recent years, many preclinical studies have indicated that the therapeutic outcome of PDT can be improved, doses and side effects lowered by combination with immunotherapy. Most experiments have been done with animals and cell lines. This review summarizes the current knowledge about different immunotherapeutic approaches which can be used to improve effectiveness and extend the applications of PDT in clinics.     

Influence of propofol concentration in human plasma on free fraction of the drug

Drugs exist in blood in two forms: free and bound to proteins and blood cells. It is generally assumed that only the unbound form of a drug exerts pharmacological activity as it is able to diffuse across the membranes and reach the site of action. Since for the majority of drugs their free fraction is usually constant, the therapeutic effect of the drug is most often correlated with its total concentration. However, in case of some disease states (e.g. renal or hepatic disorders) the protein concentration may change dramatically, resulting in clinically significant change of free drug fraction. The results presented in the paper prove that, in case of propofol, an increase of free fraction occurs with a decrease of total drug concentration. This dependence is observed both in vitro (in artificial and native human plasma) and in vivo. Free propofol fraction, which in clinical conditions ranges from 1 to 3%, at very low total propofol concentrations (below 0.01 microgml(-1)) tends to reach 100%. This increase of free drug percentage is discussed in terms of its possible reasons as well as its potential clinical relevance.     

Population and individual level of masting in a fleshy-fruited tree

Masting is usually considered as a population phenomenon but it results from individuals?? reproductive patterns. Studies of individual patterns of seed production and their synchrony are essential to an understanding of the mechanisms of masting. The aim of this study was to find the relationship between population and individual levels of masting. We examined individuals?? contribution to masting, considering their endogenous cycles, interannual variability and associated weather cues, as well as inter-individual synchrony of fruit production. We studied masting of Sorbus aucuparia L., which in Europe is one of the most common trees bearing fleshy fruits and is strongly affected by a specialized seed predator. The data are 11-year measurements of fruit production of 250 individuals distributed on a 27-ha area of subalpine forest in the Western Carpathians (Poland). Population- and individual-level interannual variability of fruit production was moderate. Synchrony among individuals was relatively high for all years, but the trees were much less synchronized in heavy crop years than in years of low fruit production. Weak synchrony among trees for heavy production years suggests that the predator satiation hypothesis does not explain the observed masting behavior. Fruit production, both at individual and at population level, was highly correlated with weather conditions. However, the presence of masting cannot be fully explained by the resource-matching hypothesis either. We suggest that adverse weather conditions effectively limit fruit production, causing high inter-individual synchrony in low crop years, whereas the unsynchronized heavy crop years seem to have been affected by individually available resources.     

A triple-isotope approach to predict the breeding origins of European bats

Despite a commitment by the European Union to protect its migratory bat populations, conservation efforts are hindered by a poor understanding of bat migratory strategies and connectivity between breeding and wintering grounds. Traditional methods like mark-recapture are ineffective to study broad-scale bat migratory patterns. Stable hydrogen isotopes (δD) have been proven useful in establishing spatial migratory connectivity of animal populations. Before applying this tool, the method was calibrated using bat samples of known origin. Here we established the potential of δD as a robust geographical tracer of breeding origins of European bats by measuring δD in hair of five sedentary bat species from 45 locations throughout Europe. The δD of bat hair strongly correlated with well-established spatial isotopic patterns in mean annual precipitation in Europe, and therefore was highly correlated with latitude. We calculated a linear mixed-effects model, with species as random effect, linking δD of bat hair to precipitation δD of the areas of hair growth. This model can be used to predict breeding origins of European migrating bats. We used δ(13)C and δ(15)N to discriminate among potential origins of bats, and found that these isotopes can be used as variables to further refine origin predictions. A triple-isotope approach could thereby pinpoint populations or subpopulations that have distinct origins. Our results further corroborated stable isotope analysis as a powerful method to delineate animal migrations in Europe.     

Multiproxy study of anthropogenic and climatic changes in the last two millennia from a small mire in central Poland

The Żabieniec kettle hole is the first peatland in central Poland analyzed quantitatively with four biotic proxies (plant macrofossils, pollen, testate amoebae and chironomids) to reconstruct the past environmental change. Palaeoecological data were supported by historical and archaeological records. We focused on autogenic vegetation change and human impact in relation to climatic effects. The aims of our study were (a) to describe the development history of the mire during the last 2,000 years, (b) to date and reconstruct the anthropogenic land-use changes and (c) to discuss a possible climatic signal in the peat archive. The combination of proxies revealed dramatic shifts that took place in the peatland since the Roman Period. Żabieniec was a very wet telmatic habitat until ca. AD 600. Then, the water table declined, and the site transformed into a Sphagnum-dominated mire. This dry shift took place mainly during the Early Medieval Period. Human impact was gradually increasing, and it was particularly emphasized by deforestation since AD 1250 (beginning of the Late Medieval Period). Consequently, surface run-off and aeolian transport from the exposed soils caused the eutrophication of the mire. Furthermore, chironomids and testate amoebae reveal the beginning of a wet shift ca. AD 1350. Openness considerably increased in the Late Medieval and the Modern Periods. The highest water table during the last 1,000 years was recorded between AD 1500 and 1800. This wet event is connected with deforestation, but it could be also associated with the Little Ice Age. Our study shows plant succession in the Żabieniec peatland, which can be explained with the recent landscape transformation. However, such changes are also possibly linked with the major climatic episodes during the last two millennia, such as the Medieval Warm Period and the Little Ice Age. Guest editors: K. Buczkó, J. Korponai, J. Padisák & S. W. Starratt Palaeolimnological Proxies as Tools of Environmental Reconstruction in Fresh Water     

BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells

The oncogenic BCR/ABL tyrosine kinase facilitates the repair of DNA double-strand breaks (DSBs). We find that after gamma-irradiation BCR/ABL-positive leukemia cells accumulate more DSBs in comparison to normal cells. These lesions are efficiently repaired in a time-dependent fashion by BCR/ABL-stimulated non-homologous end-joining (NHEJ) followed by homologous recombination repair (HRR) mechanisms. However, mutations and large deletions were detected in HRR and NHEJ products, respectively, in BCR/ABL-positive leukemia cells. We propose that unfaithful repair of DSBs may contribute to genomic instability in the Philadelphia chromosome-positive leukemias.