Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Variations in the Difference between Mean Sea Level measured either side of Cape Hatteras and Their Relation to the North Atlantic Oscillation

We consider the extent to which the difference in mean sea level (MSL) measured on the North American Atlantic coast either side of Cape Hatteras varies as a consequence of dynamical changes in the ocean caused by fluctuations in the North Atlantic Oscillation (NAO). From analysis of tide gauge data, we know that changes in MSL-difference and NAO index are correlated on decadal to century timescales enabling a scale factor of MSL-difference change per unit change in NAO index to be estimated. Changes in trend in the NAO index have been small during the past few centuries (when measured using windows of order 60–120 years). Therefore, if the same scale factor applies through this period of time, the corresponding changes in trend in MSL-difference for the past few centuries should also have been small. It is suggested thereby that the sea level records for recent centuries obtained from salt marshes (adjusted for long-term vertical land movements) should have essentially the same NAO-driven trends south and north of Cape Hatteras, only differing due to contributions from other processes such as changes in the Meridional Overturning Circulation or ‘geophysical fingerprints’. The salt marsh data evidently support this interpretation within their uncertainties for the past few centuries, and perhaps even for the past millennium. Recommendations are made on how greater insight might be obtained by acquiring more measurements and by improved modelling of the sea level response to wind along the shelf

Selective breeding enhances coral heat tolerance to marine heatwaves

\ua9 The Author(s) 2024.Marine heatwaves are becoming more frequent, widespread and severe, causing mass coral bleaching and mortality. Natural adaptation may be insufficient to keep pace with climate warming, leading to calls for selective breeding interventions to enhance the ability of corals to survive such heatwaves, i.e., their heat tolerance. However, the heritability of this trait–a prerequisite for such approaches–remains unknown. We show that selecting parent colonies for high rather than low heat tolerance increased the tolerance of adult offspring (3–4-year-olds). This result held for the response to both 1-week +3.5 \ub0C and 1-month +2.5 \ub0C simulated marine heatwaves. In each case, narrow-sense heritability (h2) estimates are between 0.2 and 0.3, demonstrating a substantial genetic basis of heat tolerance. The phenotypic variability identified in this population could theoretically be leveraged to enhance heat tolerance by up to 1 \ub0C-week within one generation. Concerningly, selective breeding for short-stress tolerance did not improve the ability of offspring to survive the long heat stress exposure. With no genetic correlation detected, these traits may be subject to independent genetic controls. Our finding on the heritability of coral heat tolerance indicates that selective breeding could be a viable tool to improve population resilience. Yet, the moderate levels of enhancement we found suggest that the effectiveness of such interventions also demands urgent climate action

General beliefs about medicines among doctors and nurses in out-patient care: a cross-sectional study

Background: Doctors and nurses are two natural partners in the healthcare team, but they usually differ in their perspectives on how to work for increased health. These professions may also have different beliefs about medicines, a factor important for adherence to medicines. The aim was to explore general beliefs about medicines among doctors and nurses.Methods: Questionnaires were sent to 306 private practitioners (PPs), 298 general practitioners (GPs) and 303 nurses in the county of Västra Götaland, Sweden. The questionnaire included sociodemographic questions and the general part of the Beliefs about Medicines Questionnaire (BMQ), which measures the beliefs people have about medicines in general. General beliefs about medicines in relation to background variables were explored with independent t-tests and ANOVA analyses. Differences between occupations and influences of interaction variables were analysed with multiple linear regression models for general beliefs about medicines.  Results: The data collection resulted in 616 questionnaires (62.1% PPs; 61.6% GPs; 80.5% nurses). The majority of the PPs and 40% of the GPs were male but most of the nurses were female. The GPs' mean age was 47 years, PPs' 60 years and nurses' 52 years. Few nurses originated from non-Nordic countries while 15% of the PPs and 25% of the GPs did. Nurses saw medicines as more harmful and less beneficial than did PPs and GPs. These differences could not be explained by the included interaction variables. GPs with a Nordic background saw medicines as more beneficial and less harmful than did GPs with a non-Nordic background. Furthermore, GPs of non-Nordic origin were most likely to believe that medicines were  overprescribed by doctors.Conclusion: Doctors were more positive about medicines than nurses. The differences in beliefs about medicines found between doctors and nurses could not be explained by any of the included interaction variables. These differences in beliefs may be useful in discussions among future and practising doctors and nurses to enhance understanding of each other's profession and teamwork. </p

Gene Expression Analysis Implicates a Death Receptor Pathway in Schizophrenia Pathology

An increase in apoptotic events may underlie neuropathology in schizophrenia. By data-mining approaches, we identified significant expression changes in death receptor signaling pathways in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia, particularly implicating the Tumor Necrosis Factor Superfamily member 6 (FAS) receptor and the Tumor Necrosis Factor [ligand] Superfamily member 13 (TNFSF13) in schizophrenia. We sought to confirm and replicate in an independent tissue collection the noted mRNA changes with quantitative real-time RT-PCR. To test for regional and diagnostic specificity, tissue from orbital frontal cortex (OFC) was examined and a bipolar disorder group included. In schizophrenia, we confirmed and replicated significantly increased expression of TNFSF13 mRNA in the DLPFC. Also, a significantly larger proportion of subjects in the schizophrenia group had elevated FAS receptor expression in the DLPFC relative to unaffected controls. These changes were not observed in the bipolar disorder group. In the OFC, there were no significant differences in TNFSF13 or FAS receptor mRNA expression. Decreases in BH3 interacting domain death agonist (BID) mRNA transcript levels were found in the schizophrenia and bipolar disorder groups affecting both the DLPFC and the OFC. We tested if TNFSF13 mRNA expression correlated with neuronal mRNAs in the DLPFC, and found significant negative correlations with interneuron markers, parvalbumin and somatostatin, and a positive correlation with PPP1R9B (spinophilin), but not DLG4 (PSD-95). The expression of TNFSF13 mRNA in DLPFC correlated negatively with tissue pH, but decreasing pH in cultured cells did not cause increased TNFSF13 mRNA nor did exogenous TNFSF13 decrease pH. We concluded that increased TNFSF13 expression may be one of several cell-death cytokine abnormalities that contribute to the observed brain pathology in schizophrenia, and while increased TNFSF13 may be associated with lower brain pH, the change is not necessarily causally related to brain pH

β-Catenin is involved in alterations in mitochondrial activity in non-transformed intestinal epithelial and colon cancer cells

BACKGROUND: Alteration in respiratory activity and mitochondrial DNA (mtDNA) transcription seems to be an important feature of cancer cells. Leukotriene D(4) (LTD(4)) is a proinflammatory mediator implicated in the pathology of chronic inflammation and cancer. We have shown earlier that LTD(4) causes translocation of beta-catenin both to the mitochondria, in which it associates with the survival protein Bcl-2 identifying a novel role for beta-catenin in cell survival, and to the nucleus in which it activates the TCF/LEF transcription machinery. METHODS: Here we have used non-transformed intestinal epithelial Int 407 cells and Caco-2 colon cancer cells, transfected or not with wild type and mutated (S33Y) beta-catenin to analyse its effect on mitochondria activity. We have measured the ATP/ADP ratio, and transcription of the mtDNA genes ND2, ND6 and 16 s in these cells stimulated or not with LTD(4). RESULTS: We have shown for the first time that LTD(4) triggers a cellular increase in NADPH dehydrogenase activity and ATP/ADP ratio. In addition, LTD(4) significantly increased the transcription of mtDNA genes. Overexpression of wild-type beta-catenin or a constitutively active beta-catenin mutant mimicked the effect of LTD(4) on ATP/ADP ratio and mtDNA transcription. These elevations in mitochondrial activity resulted in increased reactive oxygen species levels and subsequent activations of the p65 subunit of NF-kappaB. CONCLUSIONS: The present novel data show that LTD(4), presumably through beta-catenin accumulation in the mitochondria, affects mitochondrial activity, lending further credence to the idea that inflammatory signalling pathways are intrinsically linked with potential oncogenic signals

Chlamydia trachomatis infection during pregnancy associated with preterm delivery: a population-based prospective cohort study

Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and may influence pregnancy outcome. This study was conducted to assess the effect of chlamydial infection during pregnancy on premature delivery and birthweight. Pregnant women attending a participating midwifery practice or antenatal clinic between February 2003 and January 2005 were eligible for the study. From 4,055 women self-administered questionnaires and urine samples, tested by PCR, were analysed for C. trachomatis infection. Pregnancy outcomes were obtained from midwives and hospital registries. Gestational ages and birthweights were analysed for 3,913 newborns. The C. trachomatis prevalence was 3.9%, but varied by age and socio-economic background. Chlamydial infection was, after adjustment for potential confounders, associated with preterm delivery before 32 weeks (OR 4.35 [95% CI 1.3, 15.2]) and 35 weeks gestation (OR 2.66 [95% CI 1.1, 6.5]), but not with low birthweight. Of all deliveries before 32 weeks and 35 weeks gestation 14.9% [95% CI 4.5, 39.5] and 7.4% [95% CI 2.5, 20.1] was attributable to C. trachomatis infection. Chlamydia trachomatis infection contributes significantly to early premature delivery and should be considered a public health problem, especially in young women and others at increased risk of C. trachomatis infection

Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes

Background Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix® GeneChip® Bovine Genome Array with 24,072 gene probe sets representing more than 23,000 gene transcripts. Results Control and infected animals had similar mean white blood cell counts. However, the mean number of lymphocytes was significantly increased in the infected group relative to the control group (P = 0.001), while the mean number of monocytes was significantly decreased in the BTB group (P = 0.002). Hierarchical clustering analysis using gene expression data from all 5,388 detectable mRNA transcripts unambiguously partitioned the animals according to their disease status. In total, 2,960 gene transcripts were differentially expressed (DE) between the infected and control animal groups (adjusted P-value threshold ≤ 0.05); with the number of gene transcripts showing decreased relative expression (1,563) exceeding those displaying increased relative expression (1,397). Systems analysis using the Ingenuity® Systems Pathway Analysis (IPA) Knowledge Base revealed an over-representation of DE genes involved in the immune response functional category. More specifically, 64.5% of genes in the affects immune response subcategory displayed decreased relative expression levels in the infected animals compared to the control group. Conclusions This study demonstrates that genome-wide transcriptional profiling of PBL can distinguish active M. bovis-infected animals from control non-infected animals. Furthermore, the results obtained support previous investigations demonstrating that mycobacterial infection is associated with host transcriptional suppression. These data support the use of transcriptomic technologies to enable the identification of robust, reliable transcriptional markers of active M. bovis infection.This work was supported by Investigator Grants from Science Foundation Ireland (Nos: SFI/01/F.1/B028 and SFI/08/IN.1/B2038), a Research Stimulus Grant from the Department of Agriculture, Fisheries and Food (No: RSF 06 405) and a European Union Framework 7 Project Grant (No: KBBE-211602-MACROSYS). KEK is supported by the Irish Research Council for Science, Engineering and Technology (IRCSET) funded Bioinformatics and Systems Biology PhD Programme http://bioinfo-casl.ucd.ie/PhD

L1pred: A Sequence-Based Prediction Tool for Catalytic Residues in Enzymes with the L1-logreg Classifier

To understand enzyme functions, identifying the catalytic residues is a usual first step. Moreover, knowledge about catalytic residues is also useful for protein engineering and drug-design. However, to experimentally identify catalytic residues remains challenging for reasons of time and cost. Therefore, computational methods have been explored to predict catalytic residues. Here, we developed a new algorithm, L1pred, for catalytic residue prediction, by using the L1-logreg classifier to integrate eight sequence-based scoring functions. We tested L1pred and compared it against several existing sequence-based methods on carefully designed datasets Data604 and Data63. With ten-fold cross-validation, L1pred showed the area under precision-recall curve (AUPR) and the area under ROC curve (AUC) of 0.2198 and 0.9494 on the training dataset, Data604, respectively. In addition, on the independent test dataset, Data63, it showed the AUPR and AUC values of 0.2636 and 0.9375, respectively. Compared with other sequence-based methods, L1pred showed the best performance on both datasets. We also analyzed the importance of each attribute in the algorithm, and found that all the scores contributed more or less equally to the L1pred performance