Semiquantitative promoter methylation of MLH1 and MSH2 genes and their impact on sperm DNA fragmentation and chromatin condensation in infertile men

To investigate the semiquantitative methylation alterations of MLH1 and MSH2 and the possible association among methylation of MLH1 and MSH2, sperm DNA fragmentation and sperm chromatin condensation in idiopathic oligoasthenoteratozoospermic men. Seventy-five idiopathic infertile men and 52 fertile and/or normozoospermic men were included in the study. SDF was analysed using the TUNEL assay in semen samples of 100 men. Promoter methylation of MLH1 and MSH2 genes was assessed by semiquantitative methylight analysis in semen samples of 39 and 40 men respectively. Sperm chromatin condensation was evaluated using aniline blue staining in 114 men. MLH1 promoter methylation was positively correlated with the percentage of aniline blue positive spermatozoa (r = 0.401, p = 0.0188). On the other hand, MSH2 promoter methylation was negatively correlated with sperm concentration and total sperm count (r = −0.421, p = 0.0068 and r = 0.4408, p = 0.009 respectively)

Mesoscale productivity fronts and local fishing opportunities in the European Seas

This study evaluates the relationship between both commercial and scientific spatial fisheries data and a new satellite-based estimate of potential fish production (Ocean Productivity available to Fish, OPFish) in the European Seas. To construct OPFish, we used productivity frontal features derived from chlorophyll-a horizontal gradients, which characterize 10%–20% of the global phytoplankton production that effectively fuels higher trophic levels. OPFish is relatively consistent with the spatial distribution of both pelagic and demersal fish landings and catches per unit of effort (LPUEs and CPUEs, respectively). An index of harvest relative to ocean productivity (HP index) is calculated by dividing these LPUEs or CPUEs with OPFish. The HP index reflects the intensity of fishing by gear type with regard to local fish production. Low HP levels indicate lower LPUEs or CPUEs than expected from oceanic production, suggesting over-exploitation, while high HP levels imply more sustainable fishing. HP allows comparing the production-dependent suitability of local fishing intensities. Our results from bottom trawl data highlight that over-exploitation of demersal species from the shelves is twice as high in the Mediterranean Sea than in the North-East Atlantic. The estimate of HP index by dominant pelagic and demersal gears suggests that midwater and bottom otter trawls are associated with the lowest and highest overfishing, respectively. The contrasts of fishing intensity at local scales captured by the HP index suggest that accounting for the local potential fish production can promote fisheries sustainability in the context of ecosystem-based fisheries management as required by international marine policies

Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL

As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology in more detail. We used multiplexed immunohistochemistry (mIHC) to study the immune contexture in adult precursor B cell ALL bone marrow (BM). In addition, we developed a multivariate risk prediction model that stratified a poor survival group based on clinical parameters and mIHC data. We analyzed BM biopsy samples of ALL patients (n = 52) and healthy controls (n = 14) using mIHC with 30 different immunophenotype markers and computerized image analysis. In ALL BM, the proportions of M1-like macrophages, granzyme B+CD57+CD8+ T cells, and CD27+ T cells were decreased, whereas the proportions of myeloid-derived suppressor cells and M2-like macrophages were increased. Also, the expression of checkpoint molecules PD1 and CTLA4 was elevated. In the multivariate model, age, platelet count, and the proportion of PD1+TIM3+ double-positive CD4+ T cells differentiated a poor survival group. These results were validated by flow cytometry in a separate cohort (n = 31). In conclusion, the immune cell contexture in ALL BM differs from healthy controls. CD4+PD1+TIM3+ T cells were independent predictors of poor outcome in our multivariate risk model, suggesting that PD1 might serve as an attractive immuno-oncological target in B-ALL.Peer reviewe

Immune cell contexture in the bone marrow tumor microenvironment impacts therapy response in CML

Increasing evidence suggests that the immune system affects prognosis of chronic myeloid leukemia (CML), but the detailed immunological composition of the leukemia bone marrow (BM) microenvironment is unknown. We aimed to characterize the immune landscape of the CML BM and predict the current treatment goal of tyrosine kinase inhibitor (TKI) therapy, molecular remission 4.0 (MR4.0). Using multiplex immunohistochemistry (mIHC) and automated image analysis, we studied BM tissues of CML patients (n = 56) and controls (n = 14) with a total of 30 immunophenotype markers essential in cancer immunology. CML patients' CD4+ and CD8+ T-cells expressed higher levels of putative exhaustion markers PD1, TIM3, and CTLA4 when compared to control. PD1 expression was higher in BM compared to paired peripheral blood (PB) samples, and decreased during TKI therapy. By combining clinical parameters and immune profiles, low CD4+ T-cell proportion, high proportion of PD1+ TIM3-CD8+ T cells, and high PB neutrophil count were most predictive of lower MR4.0 likelihood. Low CD4+ T-cell proportion and high PB neutrophil counts predicted MR4.0 also in a validation cohort (n = 52) analyzed with flow cytometry. In summary, the CML BM is characterized by immune suppression and immune biomarkers predicted MR4.0, thus warranting further testing of immunomodulatory drugs in CML treatment.Peer reviewe

Hyperprolactinaemia does not always mean 'hyperprolactinaemia'!

The presence of macroprolactinaemia was investigated in the symptom-free hyperprolactinaemia cases to reveal its incidence. The serum prolactin (PRL) fractions in 21 female patients with hyperprolactinaemia without any clinical symptoms were analyzed with PEG (polyethylene glycol precipitation) procedure. In 14 of these 21 cases, hyperprolactinaemia was detected with a high fraction of macroprolactin. In cases with asymptomatic hyperprolactinaemia, it is more appropriate to employ the PEG precipitation test to detect the disorder. High levels of serum prolactin, do not essentially indicate the presence of a prolactinoma but may only indicate macroprolactinaemia. (C) 2004 Elsevier Ireland Ltd. All rights reserved

Multilevel Turbo Coded-Continuous Phase Frequency Shift Keying (MLTC-CPFSK) over satellite channels in space communication

In this paper, in order to improve bit error performance and bandwidth efficiency, we introduce a new type of Turbo coded modulation scheme, called Multilevel Turbo Coded-Continuous Phase Frequency Shift Keying (MLTC-CPFSK). The basic idea of multilevel coding is to partition a signal set into several levels and to encode separately each level by a proper component of the encoder. In MLTC-CPFSK, to provide phase continuity of the signals, Turbo encoder and Continuous Phase Encoder (CPE) are serially concatenated at the last level, while all other levels consist of only a turbo encoder. Therefore, the proposed system contains more than one turbo encoder/decoder blocks in its structure. The parallel input data sequences are encoded by our multilevel scheme and mapped to CPFSK signals. Then these modulated signals are passed through AWGN and fading channels. At the receiver side, input sequence of first level is estimated from the first turbo decoder. Then the other input sequences are computed using the estimated input bit streams of previous levels. Simulation results are drawn for 4CPFSK two-level turbo codes over AWGN, Rician, and Rayleigh channels for three iterations while frame sizes are chosen as 100 and 1024. Higher error performances are obtained from various type of MLTC-CPFSK systems compared to Trellis Coded CPFSK systems

Fluorescent probes in breast tumor

In our study, we developed a new method for fluorescence probes which is novel, inexpensive and renders useful information for prognosis on tumor tissues. It could be used in place of the receptors analysis. Comparative studies applying fluorescence probe techniques to the determination of Intracytoplasmic Immunoglobulin (Ic-IgG) have shown to generally provide more precise results and to be time saving as compared to receptors and DNA analysis. The use of fluorescence probe techniques for the measuring of Intra cytoplasmic Immunoglobulin (Ic-IgG) is well established for breast tumors. Ic-IgG has been determined in mammary turner cells with fluorescein isothiocynate (FTIC) labeled anti human IgG using the flow cytometer. Ic-IgG content provides additional prognostic information within both the estrogen receptor (ER) positive patient or estrogen receptor (ER) negative patient groups. There is a correlation between (ER) positive or (ER) negative patients and diploid or aneuploid patients