Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish

 This is the author accepted manuscript. The final version is available on open access from American Chemical Society via the DOI in this record The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10×) maximum foetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of micro-dissected heart tissues showed that both chemicals perturbed similar downstream molecular pathways and biological processes, including down-regulation of cartilage morphogenesis and filamentous protein synthesis. Collagen/keratin deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular- cardiovascular disease states.Biotechnology & Biological Sciences Research Council (BBSRC)Natural Environment Research Council (NERC

Roadmap for future research on plant pathogen effectors

Bacterial and eukaryotic plant pathogens deliver effector proteins into plant cells to promote pathogenesis. Bacterial pathogens containing type III protein secretion systems are known to inject many of these effectors into plant cells. More recently, oomycete pathogens have been shown to possess a large family of effectors containing the RXLR motif, and many effectors are also being discovered in fungal pathogens. Although effector activities are largely unknown, at least a subset suppress plant immunity. A plethora of new plant pathogen genomes that will soon be available thanks to next-generation sequencing technologies will allow the identification of many more effectors. This article summarizes the key approaches used to identify plant pathogen effectors, many of which will continue to be useful for future effector discovery. Thus, it can be viewed as a ‘roadmap’ for effector and effector target identification. Because effectors can be used as tools to elucidate components of innate immunity, advances in our understanding of effectors and their targets should lead to improvements in agriculture

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

Masculinity—Femininity

Six areas of research in developmental and personality psychology concerning sex-typed traits, attitudes, and interests are identified as elements of a common “masculinity-femininity” paradigm needing reexamination. The masculinity-femininity paradigm is defined in relationship to Money and Ehrhardt's model for gender identity differentiation and dimorphism. The six lines of research in the masculinity-femininity paradigm are then briefly critically examined: (1) the measurability of masculinity-femininity as a trait, (2) the identification model of masculinity-femininity development, (3) the effects of father absence on boys, (4) correlates of masculinity-femininity in life adjustment, (5) cross-sex identity in males, and (6) sex role identity problems in black males. The empirical and conceptual problems in each line of research are explored, and are substantial enough to suggest the need for alternate paradigms. Two alternate models for masculinity-femininity development are briefly sketched. First, masculinity-femininity development is analogized to moral development, as a phasic process ideally leading to sex role transcendence and androgyny. Second, the acquisition of masculinity-femininity is analogized to language acquisition, as a highly symbol-dependent learning process contingent upon the interaction between an innate acquisition apparatus and a corpus of observed sex role behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45567/1/11199_2004_Article_BF00288009.pd

Great Wall Starbucks

This is one of hundreds of 60-second radio spots created by the Center for East Asian Studies (CEAS) for Kansas Public Radio (KPR). The purpose of this outreach program is to introduce the people of Kansas to the culture and current issues of East Asia.Broadcast Transcript: For roughly 2,000 years, the Great Wall--or chang cheng in Chinese -- has snaked more than 4,000 miles through China's topography doing its duty: deterring invasions from the North. It has been somewhat less successful at deterring invasions from the West: neither its width of 5 meters nor its height of 10 has proven effective against consumerism in the form of designer coffee. That's right. Starbucks has opened a new store at badaling, 47 miles outside of Beijing and right along the Great Wall. When you think about it, it's not a bad marketing strategy: the Wall is high, the stairs relentless; what better than an espresso to energize you for the steep climb up? On second thought, make that a double. #ceas #china #tsutsui #gatewoo

Association of Short Interpregnancy Interval With Pregnancy Outcomes According to Maternal Age.

Importance: Interpregnancy intervals shorter than 18 months are associated with higher risks of adverse pregnancy outcomes. It is currently unknown whether short intervals are associated with increased risks among older women to the same extent as among younger women. Objective: To evaluate whether the association between short interpregnancy (delivery to conception) interval and adverse pregnancy outcomes is modified by maternal age. Design, Setting, and Participants: A population-based cohort study conducted in British Columbia, Canada, evaluated women with 2 or more singleton pregnancies from 2004 to 2014 with the first (index) pregnancy resulting in a live birth. Data analysis was performed from January 1 to July 20, 2018. Main Outcomes and Measures: Risks of maternal mortality or severe morbidity (eg, mechanical ventilation, blood transfusion >3 U, intensive care unit admission, organ failure, death), small-for-gestational age (<10th birthweight percentile for gestational age and sex), fetal and infant composite outcome (stillbirth, infant death, <third birthweight percentile for gestational age and sex, delivery <28 weeks), and spontaneous and indicated preterm delivery. Risks of each outcome for 3- to 24-month interpregnancy intervals were estimated, according to maternal age at index birth (20-34 and ≥35 years). Adjusted risk ratios (aRRs) comparing predicted risks at 3-, 6-, 9-, and 12-month intervals with risks at 18-month intervals for each age group were calculated. The potential role of other factors explaining any differences (unmeasured confounding) was examined in several sensitivity analyses. Results: Among 148 544 pregnancies, maternal mortality or severe morbidity risks were increased at 6-month compared with 18-month interpregnancy intervals for women aged 35 years or older (0.62% at 6 months vs 0.26% at 18 months; aRR, 2.39; 95% CI, 2.03-2.80), but not for women aged 20 to 34 years (0.23% at 6 months vs 0.25% at 18 months; aRR, 0.92; 95% CI, 0.83-1.02). Increased adverse fetal and infant outcome risks were more pronounced for women aged 20 to 34 years (2.0% at 6 months vs 1.4% at 18 months; aRR, 1.42; 95% CI, 1.36-1.47) than women 35 years or older (2.1% at 6 months vs 1.8% at 18 months; aRR, 1.15; 95% CI, 1.01-1.31). Risks of spontaneous preterm delivery at 6-month interpregnancy intervals were increased for women 20 to 34 years old (5.3% at 6 months vs 3.2% at 18 months; aRR, 1.65; 95% CI, 1.62-1.68) and to a lesser extent for women 35 years or older (5.0% at 6 months vs 3.6% at 18 months; aRR, 1.40; 95% CI, 1.31-1.49). Modest increases in risks of small-for-gestational age and indicated preterm delivery at short intervals did not vary meaningfully by maternal age. Sensitivity analyses suggested that observed associations were not fully explained by unmeasured confounding. Conclusions and Relevance: The findings of this study suggest that short interpregnancy intervals are associated with increased risks for adverse pregnancy outcomes for women of all ages