Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression: The NewGeneris cohort

Background: Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research

Psychometric Properties and Correlates of Precarious Manhood Beliefs in 62 Nations

Precarious manhood beliefs portray manhood, relative to womanhood, as a social status that is hard to earn, easy to lose, and proven via public action. Here, we present cross-cultural data on a brief measure of precarious manhood beliefs (the Precarious Manhood Beliefs scale [PMB]) that covaries meaningfully with other cross-culturally validated gender ideologies and with country-level indices of gender equality and human development. Using data from university samples in 62 countries across 13 world regions (N = 33,417), we demonstrate: (1) the psychometric isomorphism of the PMB (i.e., its comparability in meaning and statistical properties across the individual and country levels); (2) the PMB’s distinctness from, and associations with, ambivalent sexism and ambivalence toward men; and (3) associations of the PMB with nation-level gender equality and human development. Findings are discussed in terms of their statistical and theoretical implications for understanding widely-held beliefs about the precariousness of the male gender role

Freehand interaction with large-scale 3D map data

In this paper, we present our method and apparatus to visualize and interact with large-scale 3D map data on a 3D light-field display in real time. 3D map data are streamed over Internet to the display in real-time based on request sent by the application. On the user side, data is processed and visualized on a large-scale 3D light field display. We present a method to efficiently interact with the visualized 3D map using freehand gestures. We use a Leap Motion sensor that supports sufficient refresh rate for our current application and is able to accurately track and acquire information on the user hand position. This information is further processed to support natural and fast interaction. We have also developed a method to automatically adjust the map\u27s plane to the screen plane of the display. The visualization and interaction method is scalable and allows the exploration of large-scale 3D maps down to the street level

Quasar Candidates behind the Milky Way Disk and M31

Quasars behind the Milky Way, M31 and other nearby galaxies are useful for absorption line studies. Here we report spectroscopic follow-up of four quasar candidates behind the Galactic plane and two behind the Andromeda galaxy

Selective sweep at the Rpv3 locus in mildew resistant grapevines

The Rpv3 locus is a major determinant of downy mildew resistance in grapevine (Vitis spp.). A selective sweep at this locus was revealed by the DNA genotyping of 580 grapevines, which include a highly diverse set of 265 European varieties that predated the spread of North American mildews, 82 accessions of wild species, and 233 registered breeding lines with North American ancestry produced in the past 150 years. ArtiWcial hybridisation and subsequent phenotypic selection favoured a few Rpv3 haplotypes that were introgressed from wild vines and retained in released varieties. Seven conserved haplotypes in five descent groups of resistant varieties were traced back to their founders: (1) \u2018Munson\u2019, a cross between two of Hermann Jaeger\u2019s selections of V. rupestris and V. lincecumii made in the early 1880s in Missouri, (2) V. rupestris \u2018Ganzin\u2019, Wrst utilised for breeding in 1879 by Victor Ganzin in France, (3) \u2018Noah\u2019, selected in 1869 from intermingled accessions of V. riparia and V. labrusca by Otto Wasserzieher in Illinois, (4) \u2018Bayard\u2019, a V. rupestris \ua3 V. labrusca oVspring generated in 1882 by George Couderc in France, and (5) a wild form closely related to V. rupestris accessions in the Midwestern United States and introgressed into \u2018Seibel 4614\u2019 in the 1880s by Albert Seibel in France. Persistence of these Rpv3 haplotypes across many of the varieties generated by human intervention indicates that a handful of vines with prominent resistance have laid the foundation for modern grape breeding. A rampant hot spot of NB-LRR genes at the Rpv3 locus has provided a distinctive advantage for the adaptation of native North American grapevines to withstand downy mildew. The coexistence of multiple resistance alleles or paralogues in the same chromosomal region but in diVerent haplotypes counteracts efforts to pyramidise them in a diploid individual via conventional breeding

New lexicon and criteria for the diagnosis of Alzheimer's disease.

No

Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: Predictive value of centrally reviewed expression of estrogen and progesterone receptors - International Breast Cancer Study Group

Purpose To centrally assess estrogen receptor (ER) and progesterone receptor (PgR) levels by immunohistochemistry and investigate their predictive value for benefit of chemo-endocrine compared with endocrine adjuvant therapy alone in two randomized clinical trials for node-negative breast cancer. Patients and Methods International Breast Cancer Study Group Trial VIII compared cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for 6 cycles followed by endocrine therapy with goserelin with either modality alone in pre- and perimenopausal patients. Trial IX compared three cycles of CMF followed by tamoxifen for 5 years versus tamoxifen alone in postmenopausal patients. Central Pathology Office reviewed 883 (83%) of 1,063 patients on Trial VIII and 1,365 (82%) of 1,669 on Trial IX and determined ER and PgR by immunohistochemistry. Disease-free survival (DFS) was compared across the spectrum of expression of each receptor using the Subpopulation Treatment Effect Pattern Plot methodology. Results Both receptors displayed a bimodal distribution, with substantial proportions showing no staining (receptor absent) and most of the remainder showing a high percentage of stained cells. Chemo-endocrine therapy yielded DFS superior to endocrine therapy alone for patients with receptor-absent tumors, and in some cases also for those with low levels of receptor expression. Among patients with ER-expressing tumors, additional prediction of benefit was suggested in absent or low PgR in Trial VIII but not in Trial IX. Conclusion Low levels of ER and PgR are predictive of the benefit of adding chemotherapy to endocrine therapy. Low PgR may add further prediction among pre- and perimenopausal but not postmenopausal patients whose tumors express ER

Photometric and radial-velocity time series of RR Lyrae stars in M3 : analysis of single-mode variables

We present the first simultaneous photometric and spectroscopic investigation of a large set of RR Lyrae variables in a globular cluster. The radial-velocity data presented comprise the largest sample of RVs of RR Lyrae stars ever obtained. The target is M3; $BVI_{\mathrm{C}}$ time-series of 111 and $b$ flux data of further 64 RRab stars, and RV data of 79 RR Lyrae stars are published. Blazhko modulation of the light curves of 47 percent of the RRab stars are detected. The mean value of the center-of-mass velocities of RR Lyrae stars is $-146.8$ km s$^{-1}$ with 4.52 km s$^{-1}$ standard deviation, which is in good agreement with the results obtained for the red giants of the cluster. The ${\Phi_{21}}^{\mathrm RV}$ phase difference of the RV curves of RRab stars is found to be uniformly constant both for the M3 and for Galactic field RRab stars; no period or metallicity dependence of the ${\Phi_{21}}^{\mathrm RV}$ is detected. The Baade-Wesselink distances of 26 non-Blazhko variables with the best phase-coverage radial-velocity curves are determined; the corresponding distance of the cluster, $10480\pm210$ pc, agrees with the previous literature information. A quadratic formula for the $A_{\mathrm{puls}}-A_V$ relation of RRab stars is given, which is valid for both OoI and OoII variables. We also show that the $(V-I)_0$ of RRab stars measured at light minimum is period dependent, there is at least 0.1 mag difference between the colours at minimum light of the shortest- and longest-period variables.Comment: 22 pages, 14 figures, accepted for publication in the Monthly Notices of the Royal Astronomical Societ