Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells

We have previously shown that amifostine differentially modulated the DNA-damaging action of idarubicin in normal and cancer cells and that the presence of p53 protein and oncogenic tyrosine kinases might play a role in this diversity. Aim: To investigate further this effect we have studied the influence of amifostine on idarubicin-induced DNA double-strand breaks (DSBs) and apoptosis. Methods: We employed pulse-field gel electrophoresis () for the detection of DSBs and assessment of their repair in human normal lymphocytes and chronic myelogenous leukaemia K562 cells lacking p53 activity and expressing the BCR/ABL tyrosine kinase. Apoptosis was evaluated by caspase-3 activity assay assisted by the alkaline comet assay and DAPI staining. Results: Idarubicin induced DSBs in a dose-independent manner in normal and cancer cells. Both types of the cells did not repair these lesions in 120 min and amifostine differentially modulated their level — decreased it in the lymphocytes and increased in K562 cells. In contrast to control cells, amifostine potentated apoptotic DNA fragmentation, chromatin condensation and the activity of caspase-3 in leukaemia cells. Conclusion: Amifostine can differentially modulate DSBs and apoptosis induced by idarubicin in normal and cancer cells. It can protect normal cells against drug-induced DNA damage and it can potentate the action of the drug in leukaemic cells. Further studies on link between amifostine-induced modulation of DSBs and apoptosis of cancer cells will bring a deeper insight into molecular mechanism of amifostine action.Ранее нами было показано, что амифостин дифференциально модулирует ДНК-повреждающее действие идарубицина в нормальных и злокачественных клетках, и что наличие белка р53 и онкогенных тирозин киназ может иметь значение для этих различий. Цель: изучить влияние амифостина на идарубицин-опосредованные двухнитевые разрывы ДНК (DSBs) и апоптоз. Методы: мы применили гель-электрофорез в пульсирующем поле (PFGE) для выявления DSBs и изучения их репарации в нормальных лимфоцитах человека и клетках K562 хронической миелоидной лейкемии, у которых р53 неактивен и экспрессирована BCR/ABL-тирозин киназа. Апоптоз оценивали с помощью реактивов для выявления активности каспазы-3, проведения щелочного гель-электрофореза одиночных клеток и DAPI-окрашивания. Результаты: идарубицин вызывает образование DSBs в нормальных и злокачественных клетках независимо от дозы. Оба типа клеток не репарировали эти повреждения за 120 мин, при этом амифостин дифференциально молулировал уровень DSBs — уменьшал в лимфоцитах и увеличивал в K562-клетках. В отличие от контрольных клеток амифостин потенциировал апоптическую фрагментацию ДНК, конденсацию хроматина и активность каспазы-3 в лейкемических клетках. Выводы: амифостин может дифференциально модулировать DSBs и апоптоз, вызванные идарубицином в нормальных и злокачественных клетках. Он может защитить нормальные клетки от повреждения ДНК, вызванного химиопрепаратом, и в то же время потенциировать действие препарата на лейкемические клетки. Дальнейшие исследования связи между вызванной амифостином модуляцией DSBs и апоптоза опухолевых клеток позволит лучше понять молекулярные механизмы действия амифостина

Crystallographic orientation inhomogeneity and crystal splitting in biogenic calcite

The calcitic prismatic units forming the outer shell of the bivalve Pinctada margaritifera have been analysed using scanning electron microscopy–electron back-scatter diffraction, transmission electron microscopy and atomic force microscopy. In the initial stages of growth, the individual prismatic units are single crystals. Their crystalline orientation is not consistent but rather changes gradually during growth. The gradients in crystallographic orientation occur mainly in a direction parallel to the long axis of the prism, i.e. perpendicular to the shell surface and do not show preferential tilting along any of the calcite lattice axes. At a certain growth stage, gradients begin to spread and diverge, implying that the prismatic units split into several crystalline domains. In this way, a branched crystal, in which the ends of the branches are independent crystalline domains, is formed. At the nanometre scale, the material is composed of slightly misoriented domains, which are separated by planes approximately perpendicular to the c-axis. Orientational gradients and splitting processes are described in biocrystals for the first time and are undoubtedly related to the high content of intracrystalline organic molecules, although the way in which these act to induce the observed crystalline patterns is a matter of future research

Plasmonic nanostructures for light trapping in thin-film solar cells

The optical properties of localized surface plasmon resonances (LSPR) sustained by self-assembled silver nanoparticles are of great interest for enhancing light trapping in thin film photovoltaics. First, we report on a systematic investigation of the structural and the optical properties of silver nanostructures fabricated by a solid-state dewetting process on various substrates. Our study allows to identify fabrication conditions in which circular, uniformly spaced nanoparticles are obtainable. The optimized NPs are then integrated into plasmonic back reflector (PBR) structures. Second, we demonstrate a novel procedure, involving a combination of opto-electronic spectroscopic techniques, allowing for the quantification of useful and parasitic absorption in thin photovoltaic absorber deposited on top of the PBR. We achieve a significant broadband useful absorption enhancement of 90% for 0.9 um thick uc-Si:H film and demonstrate that optical losses due to plasmonic scattering are insignificant below 730 nm. Finally, we present a successful implementation of a plasmonic light trapping scheme in a thin film a-Si:H solar cell. The quantum efficiency spectra of the devices show a pronounced broadband enhancement resulting in remarkably high short circuit current densities (Jsc)

Promoter methylation of cancer-related genes in gastric carcinoma

Genetic changes associated with gastric cancer are not completely known, but epigenetic mechanisms involved in this disease seem to play an important role in its pathophysiology. One of these mechanisms, an aberrant methylation in the promoter regions of genes involved in cancer induction and promotion, may be of particular importance in gastric cancer. Aim: To analyze the methylation status of eight genes: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1, hMLH1, Fas in gastric cancer patients. Methods: The methylation pattern of the genes was assessed by methylation specific restriction enzyme PCR (MSRE-PCR) in gastric tumors taken during surgery of 27 patients and compared with the methylation pattern in material obtained from biopsy in 25 individuals without cancer and pre-cancerous lesions. Results: We observed a promoter hypermethylation in the Casp8, hMLH1, CDH1 and MDR1 in gastric cancer patients as compared with the controls. Additionally, we investigated the relationship between promoter hypermethylation and age, gender, smoking and gastric cancer family history. The hypermethylation of the hMLH1 gene occurred more frequently in female than in men, and the hypermethylation of the CDH1 gene was observed preferentially in smoking than in non-smoking individuals. Conclusion: The data obtained indicate that changes in DNA methylation may contribute to gastric carcinogenesis.Генетические изменения, ассоциированные с опухолью желудка, изучены не в полной мере. В то же время эпигенетические механизмы скорее всего играют ключевую роль и лежат в основе возникновения этого заболевания. Один из таких механизмов– нарушенияметилирования промоторов генов, которые регулируют злокачественнуютрансформациюи прогрессирование опухолевого процесса, может быть особенно важным в развитии рака желудка. Цель: проанализировать статус метилирования промоторов восьми генов: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1, hMLH1, Fas у больных раком желудка. Методы: метилирование промоторов генов изучали с помощьюспецифической к сайтамметилирования рестрикцией с ПЦР (MSRE-PCR) на хирургическомматериале (опухоли желудка) 27 пациентов. Вкачестве контроля использовали иопсийныйматериал, полученный от 25 больных, у которых не было выявлено рака или предраковых состояний. Результаты: отмечали гиперметилирование промоторов генов Casp8, hMLH1, CDH1 и MDR1 в опухолевой ткани желудка по сравнению с контрольными образцами. Кроме того, нами была прослежена взаимосвязь между гиперметилированием промоторов генов и возрастом, полом пациентов, курением и семейной историей заболевания раком желудка. Гиперметилирование гена hMLH1 выявляли чаще у женщин, чем у мужчин, а гиперметилирование гена CDH1 — в основном у курильщиков. Выводы: полученные данные свидетельствуют о том, что метилирование ДНК может играть важную роль при развитии рака желудка

Colloidal plasmonic back reflectors for light trapping in solar cells

Novel plasmonic scattering structures are presented, composed of self-assembled arrays of monosized colloidal gold nanospheres, for light trapping in photovoltaics

On a functional equation involving iterates and powers

We present a complete list of all continuous solutions f : (0,+∞)→(0,+∞) of the equation f 2(x) = γ [f (x)]αxβ, where α, β and γ > 0 are given real numbers

Serum levels of IL-6 type cytokines and soluble IL-6 receptors in active B-cell chronic lymphocytic leukemia and in cladribine induced remission.

We have investigated the serum concentrations of interleukin-6 (IL-6) and two IL-6 family cytokines-oncostatin M (OSM) and leukemia inhibitory factor (LIF)-in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 17 healthy controls using the enzyme-linked immunosorbent assay (ELISA) method. Simultaneously, we measured the serum levels of the soluble forms of two subunits of the IL-6 receptor complex-ligand binding glycoprotein 80 (sIL-6R) and glycoprotein 130 (sgp130). The cytokines and receptors were evaluated in 25 untreated patients and 38 patients treated with cladribine (2-CdA), as well as in 17 healthy controls. We have correlated the serum levels of these proteins with Rai's clinical stage of the disease, the response to 2-CdA treatment and some hematological parameters. We have also evaluated the correlation of the IL-6 serum level with the concentration of OSM and IL-6 soluble receptors. IL-6 was measurable in 62/63 (98.4%), OSM in 20/25 (80%) of untreated and 14/38 (37.8%) of the treated patients. sIL-6R and sgp130 were detectable in all 63 patients and LIF in none of the CLL patients. IL-6 serum level in untreated patients was not significantly different as compared to its concentration in the control group (P>0.05). However, in the patients treated with 2-CdA the IL-6 level was significantly lower (P<0.02), and the lowest concentration was found in the patients with complete remission (CR; median 1.4pg/ml; P<0.02). The concentration of sIL-6R was significantly higher in untreated (median 61.8 ng/ml) and treated (median 50.1 ng/ml) CLL patients when compared to normal persons (median 41.2 ng/ml; P=0.04; P<0.001, respectively). There was no difference between the sIL-6R levels in the patients with CR and the healthy controls. In non-responders sIL-6R concentration was the highest and similar to its level in the untreated patients. OSM level was higher in the untreated patients (median 1.8pg/ml) than in the normal controls (median 0.0pg/ml; P<0.001) and in the CR patients (median 0.0pg/ml; P<0.03). The serum concentration of sgp130 was similar in the untreated (median 480 pg/ml) and treated (median 470 pg/ml) patients, as well as in the healthy persons (median 420 pg/ml; P>0.05). We have found significant positive correlation between the levels of sIL-6R and the lymphocytes count in CLL patients (p=0.423; P<0.001). In addition, sIL-6R and OSM serum concentrations correlated also with CLL Rai stage. In conclusion, the serum level of IL-6, OSM and sIL-6R, but not LIF and sgp130, are useful indicators of CLL activity

Off-axis electron holography of magnetic nanostructures: magnetic behavior of Mn rich nanoprecipitates in (Mn,Ga)As system

The Lorentz off-axis electron holography technique is applied to study the magnetic nature of Mn rich nanoprecipitates in (Mn,Ga)As system. The effectiveness of this technique is demonstrated in detection of the magnetic field even for small nanocrystals having an average size down to 20 nm.Comment: 11 pages, 3 figure

Reducing the polynomial-like iterative equations order and a generalized Zoltan Boros' problem

We present a technique for reducing the order of polynomial-like iterative equations; in particular, we answer a question asked by Wenmeng Zhang and Weinian Zhang. Our method involves the asymptotic behaviour of the sequence of consecutive iterates of the unknown function at a given point. As an application we solve a generalized problem of Zoltán Boros posed during the 50th ISFE

Diffractive triangulation of radiative point sources

We describe a general method to determine the location of a point source of waves relative to a twodimensional single-crystalline active pixel detector. Based on the inherent structural sensitivity of crystalline sensor materials, characteristic detector diffraction patterns can be used to triangulate the location of a wave emitter. The principle described here can be applied to various types of waves, provided that the detector elements are suitably structured. As a prototypical practical application of the general detection principle, a digital hybrid pixel detector is used to localize a source of electrons for Kikuchi diffraction pattern measurements in the scanning electron microscope. This approach provides a promising alternative method to calibrate Kikuchi patterns for accurate measurements of microstructural crystal orientations, strains, and phase distributions