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)

Cheilosia cumanica (Dip.: Syrphidae), a new record of flower flies from Iran

Cheilosia (Convocheila) cumanica Szilady is recorded for the first time from Iran. This species is similar to C. laticornis Rondani morphologically; however, is distinguished from this close species in male by hairy eyes (bare in C. laticornis) and in female by longer third antennal segment that is three times longer than the second segment (less than 2.5 times in C. laticornis). This finding increase the number of Cheilosia species known from Iran to seven

Pancreatic pseudocyst eroding into the splenoportal venous confluence and mimicking an arterial aneurysm

We report the case of a 62-year-old man with chronic pancreatitis who presented with increasing abdominal pain. Sonography, magnetic resonance imaging, contrast-enhanced computed tomography, and ultimately catheter angiography demonstrated a pancreatic pseudocyst that had eroded into the splenoportal venous confluence, mimicking an arterial aneurysm. The diagnostic was confirmed at the time of surgical treatment. This case demonstrates the use of imaging to diagnose complications of pancreatitis, and the difficulty of distinguishing an eroding pseudocyst from an arterial aneurysm

Autologous Serum Eye Drops for Post-Chemical Injuries and Corneal Epithelial Defects

Aim: To evaluate success rate (efficacy, safety) in treatment of post-chemical injuries and corneal defects using autologous serum eye drops.Material and Methods: Authors reviewed 93 patients (116 eyes) hospitalized in Clinic of ophthalmology from 2010 to 2013, who had post-causoma corneal defects that were nonresponsive to conventional treatment and were treated with serum therapy. Authors correlated time of epithelialization of defects with rate of epithelial healing.Results: Authors investigated 93 patients (52 males, 41 females; aged 18 - 74) for treatment of corneal defects. Application of autologous serum therapy 56 (48.28%) of 116 eyes was healed in an average time of 4 weeks. Among 116 eyes, epithelial defects healed in 4 (3.45%) within 1 week, in additional 17 (14.65%) in 1-2 weeks, totalling 31 (26.72%) within 3 weeks. Five eyes (4.31%) completely healed at 5 week; three eyes (2.59%) had subsequent healing of epithelial defect at 6 week; 56 eyes completely healed within one month, and the remaining eight eyes healed within 1.5 month.Conclusion: Using serum therapy, it was managed to reduce time of healing from eleven weeks, which were necessary just couple years ago (before 2010) to four (maximum six) weeks to complete healing which are necessary today

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

Beam Interaction Measurements with a Retarding Field Analyzer in a High-Current High-Vacuum Positively-Charged Particle Accelerator

A Retarding Field Analyzer (RFA) was inserted in a drift region of a magnetic transport section of the high-current experiment (HCX) that is at high-vacuum to measure ions and electrons resulting from beam interaction with background gas and walls. The ions are expelled during the beam by the space-charge potential and the electrons are expelled mainly at the end of the beam, when the beam potential decays. The ion energy distribution shows the beam potential of {approx} 2100 V and the beam-background gas total cross-section of 1.6x10{sup -20} m{sup 2}. The electron energy distribution reveals that the expelled electrons are mainly desorbed from the walls and gain {approx} 22 eV from the beam potential decaying with time before entering the RFA. Details of the RFA design and of the measured energy distributions are presented and discussed

Apolipoprotein E is a pancreatic extracellular factor that maintains mature β-cell gene expression.

The in vivo microenvironment of tissues provides myriad unique signals to cells. Thus, following isolation, many cell types change in culture, often preserving some but not all of their in vivo characteristics in culture. At least some of the in vivo microenvironment may be mimicked by providing specific cues to cultured cells. Here, we show that after isolation and during maintenance in culture, adherent rat islets reduce expression of key β-cell transcription factors necessary for β-cell function and that soluble pancreatic decellularized matrix (DCM) can enhance β-cell gene expression. Following chromatographic fractionation of pancreatic DCM, we performed proteomics to identify soluble factors that can maintain β-cell stability and function. We identified Apolipoprotein E (ApoE) as an extracellular protein that significantly increased the expression of key β-cell genes. The ApoE effect on beta cells was mediated at least in part through the JAK/STAT signaling pathway. Together, these results reveal a role for ApoE as an extracellular factor that can maintain the mature β-cell gene expression profile