Polymorphism of DNA mismatch repair genes in endometrial cancer

Endometrial cancer (EC) is the second most common malignancy associated with hereditary non-polyposis colorectal cancer (HNPCC) family. The development of HNPCC is associated with defects in DNA mismatch repair (MMR) pathway resulting in microsatellite instability (MSI). MSI is present in a greater number of EC than can be accounted for by inherited MMR mutations, therefore alternative mechanisms may underline defective MMR in EC, including polymorphic variation. Aim: We checked the association between EC occurrence and two polymorphisms of MMR genes: a 1032G>A (rs4987188) transition in the hMSH2 gene resulting in a Gly22Asp substitution and a –93G>A (rs1800734) transition in the promoter of the hMLH1 gene. Material and methods: These polymorphisms were genotyped in DNA from peripheral blood lymphocytes of 100 EC patients and 100 age-matched women by restriction fragment length polymorphism PCR. Results: A positive association (OR 4.18; 95% CI 2.23–7.84) was found for the G/A genotype of the –93G>A polymorphism of the hMLH1 gene and EC occurrence. On the ot­her hand, the A allele of this polymorphism was associated with decreased EC occurrence. The Gly/Gly genotype slightly increased the effect of the –93G>A-G/A genotype (OR 4.52; CI 2.41–8.49). Our results suggest that the –93G>A polymorphism of the hMLH1 gene singly and in combination with the Gly322Asp polymorphism of the hMSH2 gene may increase the risk of EC. Key Words: hMSH2, hMLH1, endometrial cancer, genetic polymorphism, MMR

Multifunctional platform based on electrospun nanofibers and plasmonic hydrogel. A smart nanostructured pillow for near-infrared light-driven biomedical applications

Multifunctional nanomaterials with the ability to respond to near-infrared (NIR) light stimulation are vital for the development of highly efficient biomedical nanoplatforms with a polytherapeutic approach. Inspired by the mesoglea structure of jellyfish bells, a biomimetic multifunctional nanostructured pillow with fast photothermal responsiveness for NIR light-controlled on-demand drug delivery is developed. We fabricate a nanoplatform with several hierarchical levels designed to generate a series of controlled, rapid, and reversible cascade-like structural changes upon NIR light irradiation. The mechanical contraction of the nanostructured platform, resulting from the increase of temperature to 42 °C due to plasmonic hydrogel-light interaction, causes a rapid expulsion of water from the inner structure, passing through an electrospun membrane anchored onto the hydrogel core. The mutual effects of the rise in temperature and water flow stimulate the release of molecules from the nanofibers. To expand the potential applications of the biomimetic platform, the photothermal responsiveness to reach the typical temperature level for performing photothermal therapy (PTT) is designed. The on-demand drug model penetration into pig tissue demonstrates the efficiency of the nanostructured platform in the rapid and controlled release of molecules, while the high biocompatibility confirms the pillow potential for biomedical applications based on the NIR light-driven multitherapy strategy

Antideuteron and deuteron production in mid-central Pb+Pb collisions at 158AA GeV

Production of deuterons and antideuterons was studied by the NA49 experiment in the 23.5% most central Pb+Pb collisions at the top SPS energy of $\sqrt{s_{NN}}$=17.3 GeV. Invariant yields for $\bar{d}$ and $d$ were measured as a function of centrality in the center-of-mass rapidity range $-1.2<y<-0.6$. Results for $\bar{d}(d)$ together with previously published $\bar{p}(p)$ measurements are discussed in the context of the coalescence model. The coalescence parameters $B_2$ were deduced as a function of transverse momentum $p_t$ and collision centrality.Comment: 9 figure

Measurement of event-by-event transverse momentum and multiplicity fluctuations using strongly intensive measures Δ[PT,N]\Delta[P_T, N] and Σ[PT,N]\Sigma[P_T, N] in nucleus-nucleus collisions at the CERN Super Proton Synchrotron

Results from the NA49 experiment at the CERN SPS are presented on event-by-event transverse momentum and multiplicity fluctuations of charged particles, produced at forward rapidities in central Pb+Pb interactions at beam momenta 20$A$, 30$A$, 40$A$, 80$A$, and 158$A$ GeV/c, as well as in systems of different size ($p+p$, C+C, Si+Si, and Pb+Pb) at 158$A$ GeV/c. This publication extends the previous NA49 measurements of the strongly intensive measure $\Phi_{p_T}$ by a study of the recently proposed strongly intensive measures of fluctuations $\Delta[P_T, N]$ and $\Sigma[P_T, N]$. In the explored kinematic region transverse momentum and multiplicity fluctuations show no significant energy dependence in the SPS energy range. However, a remarkable system size dependence is observed for both $\Delta[P_T, N]$ and $\Sigma[P_T, N]$, with the largest values measured in peripheral Pb+Pb interactions. The results are compared with NA61/SHINE measurements in $p+p$ collisions, as well as with predictions of the UrQMD and EPOS models.Comment: 12 pages, 14 figures, to be submitted to PR

Multiplicity and transverse momentum fluctuations in inelastic proton-proton interactions at the CERN Super Proton Synchrotron

Measurements of multiplicity and transverse momentum fluctuations of charged particles were performed in inelastic p+p interactions at 20, 31, 40, 80 and 158 GeV/c beam momentum. Results for the scaled variance of the multiplicity distribution and for three strongly intensive measures of multiplicity and transverse momentum fluctuations \$\Delta[P_{T},N]\$, \$\Sigma[P_{T},N]\$ and \$\Phi_{p_T}\$ are presented. For the first time the results on fluctuations are fully corrected for experimental biases. The results on multiplicity and transverse momentum fluctuations significantly deviate from expectations for the independent particle production. They also depend on charges of selected hadrons. The string-resonance Monte Carlo models EPOS and UrQMD do not describe the data. The scaled variance of multiplicity fluctuations is significantly higher in inelastic p+p interactions than in central Pb+Pb collisions measured by NA49 at the same energy per nucleon. This is in qualitative disagreement with the predictions of the Wounded Nucleon Model. Within the statistical framework the enhanced multiplicity fluctuations in inelastic p+p interactions can be interpreted as due to event-by-event fluctuations of the fireball energy and/or volume.Comment: 18 pages, 12 figure

Measurement of Production Properties of Positively Charged Kaons in Proton-Carbon Interactions at 31 GeV/c

Spectra of positively charged kaons in p+C interactions at 31 GeV/c were measured with the NA61/SHINE spectrometer at the CERN SPS. The analysis is based on the full set of data collected in 2007 with a graphite target with a thickness of 4% of a nuclear interaction length. Interaction cross sections and charged pion spectra were already measured using the same set of data. These new measurements in combination with the published ones are required to improve predictions of the neutrino flux for the T2K long baseline neutrino oscillation experiment in Japan. In particular, the knowledge of kaon production is crucial for precisely predicting the intrinsic electron neutrino component and the high energy tail of the T2K beam. The results are presented as a function of laboratory momentum in 2 intervals of the laboratory polar angle covering the range from 20 up to 240 mrad. The kaon spectra are compared with predictions of several hadron production models. Using the published pion results and the new kaon data, the K+/\pi+ ratios are computed.Comment: 10 pages, 11 figure

Bisphenol A-glycidyl methacrylate induces a broad spectrum of DNA damage in human lymphocytes

Bisphenol A-glycidyl methacrylate (BisGMA) is monomer of dental filling composites, which can be released from these materials and cause adverse biologic effects in human cells. In the present work, we investigated genotoxic effect of BisGMA on human lymphocytes and human acute lymphoblastic leukemia cell line (CCRF-CEM) cells. Our results indicate that BisGMA is genotoxic for human lymphocytes. The compound induced DNA damage evaluated by the alkaline, neutral, and pH 12.1 version of the comet assay. This damage included oxidative modifications of the DNA bases, as checked by DNA repair enzymes EndoIII and Fpg, alkali-labile sites and DNA double-strand breaks. BisGMA induced DNA-strand breaks in the isolated plasmid. Lymphocytes incubated with BisGMA at 1 mM were able to remove about 50% of DNA damage during 120-min repair incubation. The monomer at 1 mM evoked a delay of the cell cycle in the S phase in CCRF-CEM cells. The experiment with spin trap—DMPO demonstrated that BisGMA induced reactive oxygen species, which were able to damage DNA. BisGMA is able to induce a broad spectrum of DNA damage including severe DNA double-strand breaks, which can be responsible for a delay of the cell cycle in the S phase

Epithelial-Mesenchymal Transition and Senescence in the Retinal Pigment Epithelium of NFE2L2/PGC-1 alpha Double Knock-Out Mice

Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. In our previous studies, we found that deficiencies in the nuclear factor, erythroid 2 like 2 (NFE2L2) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) genes caused AMD-like pathological phenotypes in mice. In the present work, we show hijacked epithelial-mesenchymal transition (EMT) due to the common loss of PGC-1 alpha and NFE2L2 (double knock-out, dKO) genes in aged animals. The implanted area was assessed by histology, immunohistochemistry and transmission electron microscopy. Confocal microscopy revealed altered regions in the filamentous actin ring. This contrasted with hexagonal RPE morphology in wild-type mice. The ultrastructural RPE features here illustrated loss of apical microvilli, alteration of cell-cell contact, loss of basal in-folding with deposits on Bruch's membrane, and excessive lipofuscin deposition in dKO samples. We also found the expression of epithelial-mesenchymal transition transcription factors, such as Snail, Slug, collagen 1, vimentin and OB-cadherin, to be significantly different in dKO RPEs. An increased immunoreactivity of senescence markers p16, DEC1 and HMGB1 was also noted. These findings suggest that EMT and senescence pathways may intersect in the retinas of dKO mice. Both processes can be activated by damage to the RPE, which may be caused by increased oxidative stress resulting from the absence of NFE2L2 and PGC-1 alpha genes, important for antioxidant defense. This dKO model may provide useful tools for studying AMD pathogenesis and evaluating novel therapies for this disease