Five-year study assessing the clinical utility of anti-Müllerian hormone measurements in reproductive-age women with cancer

An important discussion point before chemotherapy is ovarian toxicity, a side-effect that profoundly affects young women with cancer. Their quality of life after successful treatment, including the ability to conceive, is a major concern. We asked whether serum anti-Müllerian hormone (AMH) measurements before chemotherapy for two most common malignancies are predictive of long-term changes in ovarian reserve? A prospective cohort study measured serum AMH in 66 young women with lymphoma and breast cancer, before and at 1 year and 5 years after chemotherapy, compared with 124 healthy volunteers of the same age range (18-43 years). Contemporaneously, patients reported their menses and live births during 5-year follow-up. After adjustment for age, serum AMH was 1.4 times higher (95% CI 1.1 to 1.9; P < 0.02) in healthy volunteers than in cancer patients before chemotherapy. A strong correlation was observed between baseline and 5-year AMH in the breast cancer group (P < 0.001, regression coefficient = 0.58, 95% CI 0.29 to 0.89). No significant association was found between presence of menses at 5 years and serum AMH at baseline (likelihood ratio test from logistics regression analysis). Reproductive-age women with malignancy have lower serum AMH than healthy controls even before starting chemotherapy. Pre-chemotherapy AMH was significantly associated with long-term ovarian function in women with breast cancer. At key time points, AMH measurements could be used as a reproductive health advisory tool for young women with cancer. Our results highlight the unsuitability of return of menstruation as a clinical indicator of ovarian reserve after chemotherapy. [Abstract copyright: Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.

Pion-Lambda-Sigma Coupling Extracted from Hyperonic Atoms

The latest measurements of the atomic level width in Sigma-hyperonic Pb atom offer the most accurate datum in the region of low-energy Sigma-hyperon physics. Atomic widths are due to the conversion of Sigma-nucleon into Lambda-nucleon. In high angular momentum states this conversion is dominated by the one-pion exchange. A joint analysis of the data of the scattering of negative-Sigma on proton converting into a Lambda and a neutron and of the atomic widths allows to extract a pseudovector pion-hyperon-Sigma coupling constant of 0.048 with a statistical error of +-0.005 and a systematic one of +-0.004. This corresponds to a pseudoscalar coupling constant of 13.3 with a statistical uncertainty of 1.4 and a systematic one of 1.1.Comment: 12 pages, 1 figure, Use of Revtex.st

Metal accumulation in tobacco expressing Arabidopsis halleri metal hyperaccumulation gene depends on external supply

Engineering enhanced transport of zinc to the aerial parts of plants is a major goal in bio-fortification. In Arabidopsis halleri, high constitutive expression of the AhHMA4 gene encoding a metal pump of the P1B-ATPase family is necessary for both Zn hyperaccumulation and the full extent of Zn and Cd hypertolerance that are characteristic of this species. In this study, an AhHMA4 cDNA was introduced into N. tabacum var. Xanthi for expression under the control of its endogenous A. halleri promoter known to confer high and cell-type specific expression levels in both A. halleri and the non-hyperaccumulator A. thaliana. The transgene was expressed at similar levels in both roots and shoots upon long-term exposure to low Zn, control, and increased Zn concentrations. A down-regulation of AhHMA4 transcript levels was detected with 10 μM Zn resupply to tobacco plants cultivated in low Zn concentrations. In general, a transcriptional regulation of AhHMA4 in tobacco contrasted with the constitutively high expression previously observed in A. halleri. Differences in root/shoot partitioning of Zn and Cd between transgenic lines and the wild type were strongly dependent on metal concentrations in the hydroponic medium. Under low Zn conditions, an increased Zn accumulation in the upper leaves in the AhHMA4-expressing lines was detected. Moreover, transgenic plants exposed to cadmium accumulated less metal than the wild type. Both modifications of zinc and cadmium accumulation are noteworthy outcomes from the biofortification perspective and healthy food production. Expression of AhHMA4 may be useful in crops grown on soils poor in Zn

Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization

Cancer cells are softer than the normal cells, and metastatic cells are even softer. These changes in biomechanical properties contribute to cancer progression by facilitating cell movement through physically constraining environments. To identify properties that enabled passage through physical constraints, cells that were more efficient at moving through narrow membrane micropores were selected from established cell lines. By examining micropore-selected human MDA MB 231 breast cancer and MDA MB 435 melanoma cancer cells, membrane fluidity and nuclear elasticity were excluded as primary contributors. Instead, reduced actin cytoskeleton anisotropy, focal adhesion density and cell stiffness were characteristics associated with efficient passage through constraints. By comparing transcriptomic profiles between the parental and selected populations, increased Ras/MAPK signalling was linked with cytoskeleton rearrangements and cell softening. MEK inhibitor treatment reversed the transcriptional, cytoskeleton, focal adhesion and elasticity changes. Conversely, expression of oncogenic KRas in parental MDA MB 231 cells, or oncogenic BRaf in parental MDA MB 435 cells, significantly reduced cell stiffness. These results reveal that MAPK signalling, in addition to tumour cell proliferation, has a significant role in regulating cell biomechanics

Exploring the dating of “dirty” speleothems and cave sinters using radiocarbon dating of preserved organic matter

Speleothems and other carbonate deposits such as tufa containing high proportions of detrital material can be difficult to chemically date due to detrital thorium levels causing a high level of error in conventional U-Th disequilibrium dating. Here we investigate the use of an alternative technique centring on radiocarbon dating of organic matter preserved within the detrital fraction. Non-acid soluble humic, particulate and detritally absorbed organic matter was recovered from eight samples from a flowstone sinter formed within a roman aqueduct at Trento in Italy with a maximum age of 100 CE (1850 cal yr BP), and two repeat samples from a dripstone formed within the 20th Century on a wire fence at Lilly-Pilly Cave, Buchan Caves Reserve in Victoria, Australia. In the aqueduct samples the median calibrated 14C ages ranged from 2232 to 2889 cal yr BP, with 95.4% probability age range in the youngest and oldest samples of 2153–2337 and 2342–3449 cal yr BP respectively. The median age of the more modern dripstone was 336 cal yr BP, with a 95.4% probability age range of 148–486 cal yr BP. These results provide very approximate ball-park estimates of the age of the sample, but are consistently too old when compared to the known maximum ages of formation. It is hypothesised that this offset is due to a combination of the nature of the organic carbon transported from the source organic matter pools, and reworking of both modern and old organic carbon by in situ microbial communities

Study of the Sigma-nucleus potential by the (pi^-,K^+) reaction on medium-to-heavy nuclear targets

In order to study the Sigma-nucleus optical potential, we measured inclusive (pi^-,K^+) spectra on medium-to-heavy nuclear targets: CH_2, Si, Ni, In and Bi. The CH_2 target was used to calibrate the excitation energy scale by using the elementary process p + pi^- -> K^+ + Sigma^-, where the C spectrum was also extracted. The calibration was done with +-0.1 MeV precision. The angular distribution of the elementary cross section was measured, and agreed well with the previous bubble chamber data, but with better statistics, and the magnitudes of the cross sections of the measured inclusive (pi^-,K^+) spectra were also well calibrated. All of the inclusive spectra were found to be similar in shape at a region near to the Sigma^- binding energy threshold, showing a weak mass-number dependence on the magnitude of the cross section. The measured spectra were compared with a theoretical calculation performed within the framework of the Distorted Wave Impulse Approximation (DWIA). It has been demonstrated that a strongly repulsive \sig-nucleus potential with a non-zero size of the imaginary part is required to reproduce the shape of the measured spectra.Comment: 21 pages, 24 figures, submitted to PR

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold

Analyser of images assisted by neural network, searching for diagnostically important fetures in radionuclide cardiac and renal dynamic studies

Przedstawiono zastosowanie sztucznych sieci neuronowych do automatycznej analizy dynamicznych badań scyntygraficznych serca i nerek. Zmiany radioaktywne w czasie, dla każdego piksela pola obrazowego, były oceniane przez odpowiednio wytrenowane sieci. Proponowana metoda umożliwia łatwą i szybką analize serii scyntygramów poprzez wyswietlanie pojedynczych obrazów ukazujacych regiony o róznym stopniu patologicznego przepływu krwi w wyniku istnienia przecieku lewo-prawego lub miejsca prawidłowej i upośledzonej funkcji nerek.The ability of the artificial neural network (ANNs) to automatic analysing either the cardiac or renal sequential scintigrams was presented. The time/activity curves, for each pixel were evaluated by appropriate trained ANNs. The proposed method permits an easy and fast analysis of series of scintigrams, by mapping results either as the regions of different degrees of pathological blood flow because of left-to-right shunt or as the places in kindey of normal and abnormal renal function

Mutations in the Non-Catalytic Subunit Dpb2 of DNA Polymerase Epsilon Affect the Nrm1 Branch of the DNA Replication Checkpoint

To preserve genome integrity, the S-phase checkpoint senses damaged DNA or nucleotide depletion and when necessary, arrests replication progression and delays cell division. Previous studies, based on two pol2 mutants have suggested the involvement of DNA polymerase epsilon (Pol ε) in sensing DNA replication accuracy in Saccharomyces cerevisiae. Here we have studied the involvement of Pol ε in sensing proper progression of DNA replication, using a mutant in DPB2, the gene coding for a non-catalytic subunit of Pol ε. Under genotoxic conditions, the dpb2-103 cells progress through S phase faster than wild-type cells. Moreover, the Nrm1-dependent branch of the checkpoint, which regulates the expression of many replication checkpoint genes, is impaired in dpb2-103 cells. Finally, deletion of DDC1 in the dpb2-103 mutant is lethal supporting a model of strand-specific activation of the replication checkpoint. This lethality is suppressed by NRM1 deletion. We postulate that improper activation of the Nrm1-branch may explain inefficient replication checkpoint activation in Pol ε mutants