Dysfunctional telomeres in primary cells from Fanconi anemia FANCD2 patients

© 2012 Joksic et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Fanconi anemia (FA) is characterized by sensitivity to DNA cross-linking agents, mild cellular, and marked clinical radio sensitivity. In this study we investigated telomeric abnormalities of non-immortalized primary cells (lymphocytes and fibroblasts) derived from FA patients of the FA-D2 complementation group, which provides a more accurate physiological assessment than is possible with transformed cells or animal models. Results: We analyzed telomere length, telomere dysfunction-induced foci (TIFs), sister chromatid exchanges (SCE), telomere sister chromatid exchanges (T-SCE), apoptosis and expression of shelterin components TRF1 and TRF2. FANCD2 lymphocytes exhibited multiple types of telomeric abnormalities, including premature telomere shortening, increase in telomeric recombination and aberrant telomeric structures ranging from fragile to long-string extended telomeres. The baseline incidence of SCE in FANCD2 lymphocytes was reduced when compared to control, but in response to diepoxybutane (DEB) the 2-fold higher rate of SCE was observed. In contrast, control lymphocytes showed decreased SCE incidence in response to DEB treatment. FANCD2 fibroblasts revealed a high percentage of TIFs, decreased expression of TRF1 and invariable expression of TRF2. The percentage of TIFs inversely correlated with telomere length, emphasizing that telomere shortening is the major reason for the loss of telomere capping function. Upon irradiation, a significant decrease of TIFs was observed at all recovery times. Surprisingly, a considerable percentage of TIF positive cells disappeared at the same time when incidence of γ-H2AX foci was maximal. Both FANCD2 leucocytes and fibroblasts appeared to die spontaneously at higher rate than control. This trend was more evident upon irradiation; the percentage of leucocytes underwent apoptosis was 2.59- fold higher than that in control, while fibroblasts exhibited a 2- h delay before entering apoptosis. Conclusion: The results of our study showed that primary cells originating from FA-D2 patients display shorten telomeres, elevated incidence of T-SCEs and high frequency of TIFs. Disappearance of TIFs in early response to irradiation represent distinctive feature of FANCD2 cells that should be examined further.This article is made available through the Brunel Open Access Publishing Fund. This work was supported by the Ministry of Education and Science of the Republic of Serbia (Project No.173046)

Neonatal outcome following exposure to organophosphorous pesticides

The aim of our study was to determine the neonatal outcome in mothers and children exposed to organophosphorous pesticides (OP). We found that 22.4% pregnant women were exposed to organophosphorous pesticides. OP pesticide concentration was higher in breast milk, newborn sera than maternal sera. Newborn parameters such as birth weight, birth length, head circumference, Apgar score and presence of meconium, as well as gestational age of delivery, showed no significant difference between the two groups. However, postpartum weight loss, hospitalization duration, levels of newborn bilirubin and glycaemia differed significantly between the two groups. Morbidity and presence of CNS disorders were six times and more than twelve times higher, respectively, in the OP-exposed than in the OP pesticide non-exposed group

Phytophagous hoverflies (Diptera Syrphidae) as indicators of changing landscapes

Spatial and temporal differences in landscape patterns are of considerable interest for understanding ecological processes. In this study, we assessed habitat quality by using the Syrph The Net database and data on decreasing species richness over a 25-year period for the two largest phytophagous hoverfly genera (Merodon and Cheilosia). Furthermore, within this time frame, we explored congruence between ecological responses (species richness and Biodiversity Maintenance Function for these two genera) and landscape structural changes through correlation analysis. Our results indicate that landscapes have experienced changes in aggregation, isolation/connectivity and landscape diversity, with these parameters being significantly correlated with Cheilosia species richness loss and habitat quality. We conclude that the genus Cheilosia is a good bioindicator that can highlight not only the current quality of an area but also temporal changes in landscape patterns.Peer reviewe

Simulations of lattice animals and trees

The scaling behaviour of randomly branched polymers in a good solvent is studied in two to nine dimensions, using as microscopic models lattice animals and lattice trees on simple hypercubic lattices. As a stochastic sampling method we use a biased sequential sampling algorithm with re-sampling, similar to the pruned-enriched Rosenbluth method (PERM) used extensively for linear polymers. Essentially we start simulating percolation clusters (either site or bond), re-weigh them according to the animal (tree) ensemble, and prune or branch the further growth according to a heuristic fitness function. In contrast to previous applications of PERM, this fitness function is {\it not} the weight with which the actual configuration would contribute to the partition sum, but is closely related to it. We obtain high statistics of animals with up to several thousand sites in all dimension 2 <= d <= 9. In addition to the partition sum (number of different animals) we estimate gyration radii and numbers of perimeter sites. In all dimensions we verify the Parisi-Sourlas prediction, and we verify all exactly known critical exponents in dimensions 2, 3, 4, and >= 8. In addition, we present the hitherto most precise estimates for growth constants in d >= 3. For clusters with one site attached to an attractive surface, we verify the superuniversality of the cross-over exponent at the adsorption transition predicted by Janssen and Lyssy. Finally, we discuss the collapse of animals and trees, arguing that our present version of the algorithm is also efficient for some of the models studied in this context, but showing that it is {\it not} very efficient for the `classical' model for collapsing animals.Comment: 17 pages RevTeX, 29 figures include

Experience with developing antibiotic stewardship programmes in Serbia : potential model for other Balkan countries?

Introduction: Antimicrobial resistance (AMR) and inappropriate use of antibiotics in children are important issues. Consequently, there is a need to develop comprehensive stewardship programmes even in hospitals with limited resources starting with children’s hospitals. Method: Retrospective observational analysis of antimicrobial utilization and resistance patterns over five years in a tertiary care children’s hospital in Serbia. Results: Cumulative AMR decreased but were still high, with high cumulative resistance rates among the most widely used antibiotics in the hospital. Total antibiotic use decreased from 2010 to 2014 although there was still high prescribing of reserved antibiotics. Conclusion: Concerns with inappropriate use, and high resistance rates, among some antibiotics used in the hospital are being used to develop guidance on future antibiotic use in this hospital, building on the recently introduced antibiotic stewardship programme, as well as encourage other hospitals in Serbia to review their policies

Plant-pollinator networks in semi-natural grasslands are resistant to the loss of pollinators during blooming of mass-flowering crops

Mass-flowering crops lead to spatial redistributions of pollinators and to transient shortages within nearby semi-natural grasslands, but the impacts on plant–pollinator interactions remain largely unexplored. Here, we characterised which pollinator species are attracted by oilseed rape and how this affected the structure of plant–pollinator networks in nearby grasslands. We surveyed 177 networks from three countries (Germany, Sweden and United Kingdom) in 24 landscapes with high crop cover, and compared them to 24 landscapes with low or no oilseed rape during and after crop blooming. On average 55% of grassland pollinator species were found on the crop, which attracted 8–35% of individuals away from grasslands. However, networks in the grasslands were resistant to these reductions, since mainly abundant and highly mobile species were attracted. Nonetheless, simulations indicated that network structural changes could be triggered if > 50% of individuals were attracted to the crop (a value well-above that found in our study system), which could affect community stability and resilience to further disturbance