Ozone-depleting substances (ODSs) and related chemicals

The amended and adjusted Montreal Protocol continues to be successful at reducing emissions and atmospheric abundances of most controlled ozone-depleting substances (ODSs).Global Ozone Research and Monitoring Projec

Vehicular Traffic–Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP)

BackgroundPolycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure.ObjectivesOur study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence.MethodsResidential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996–1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960–1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH–DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression.ResultsThe odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960–1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic–breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants].ConclusionsIn our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise.CitationMordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic–related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30–38; http://dx.doi.org/10.1289/ehp.130773

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Elevated risk of stillbirth in males: systematic review and meta-analysis of more than 30 million births

Background Stillbirth rates have changed little over the last decade, and a high proportion of cases are unexplained. This meta-analysis examined whether there are inequalities in stillbirth risks according to sex. Methods A systematic review of the literature was conducted, and data were obtained on more than 30 million birth outcomes reported in observational studies. The pooled relative risk of stillbirth was estimated using random-effects models. Results The crude mean rate (stillbirths/1,000 total births) was 6.23 for males and 5.74 for females. The pooled relative risk was 1.10 (95% confidence interval (CI): 1.07-1.13). The attributable fraction in the whole population was 4.2% (95% CI: 3.70-4.63), and the attributable fraction among male fetuses was 7.8% (95% CI: 7.0-8.66). Study populations from countries with known sex-biased sex selection issues had anomalous stillbirth sex ratios and higher overall stillbirth risks than other countries, reflecting increased mortality among females. Conclusions Risk of stillbirth in males is elevated by about 10%. The population-attributable risk is comparable to smoking and equates to approximately 100,000 stillbirths per year globally. The pattern is consistent across countries of varying incomes. Given current difficulties in reducing stillbirth rates, work to understand the causes of excess male risk is warranted. We recommend that stillbirths are routinely recorded by sex. This will also assist in exposing prenatal sex selection as elevated or equal risks of stillbirth in females would be readily apparent and could therefore be used to trigger investigation

Jeune syndrome: description of 13 cases and a proposal for follow-up protocol

Jeune syndrome (asphyxiating thoracic dystrophy, ATD) is a rare autosomal recessive skeletal dysplasia characterized by a small, narrow chest and variable limb shortness with a considerable neonatal mortality as a result of respiratory distress. Renal, hepatic, pancreatic and ocular complications may occur later in life. We describe 13 cases with ages ranging from 9 months to 22 years. Most patients experienced respiratory problems in the first years of their life, three died, one experienced renal complications, and one had hepatic problems. With age, the thoracic malformation tends to become less pronounced and the respiratory problems decrease. The prognosis of ATD seems better than described in literature and in our opinion this justifies long term intensive treatment in the first years. We also propose a follow-up protocol for patients with ATD

Prenatal Arsenic Exposure Alters Gene Expression in the Adult Liver to a Proinflammatory State Contributing to Accelerated Atherosclerosis

The mechanisms by which environmental toxicants alter developmental processes predisposing individuals to adult onset chronic disease are not well-understood. Transplacental arsenic exposure promotes atherogenesis in apolipoprotein E-knockout (ApoE−/−) mice. Because the liver plays a central role in atherosclerosis, diabetes and metabolic syndrome, we hypothesized that accelerated atherosclerosis may be linked to altered hepatic development. This hypothesis was tested in ApoE−/− mice exposed to 49 ppm arsenic in utero from gestational day (GD) 8 to term. GD18 hepatic arsenic was 1.2 µg/g in dams and 350 ng/g in fetuses. The hepatic transcriptome was evaluated by microarray analysis to assess mRNA and microRNA abundance in control and exposed pups at postnatal day (PND) 1 and PND70. Arsenic exposure altered postnatal developmental trajectory of mRNA and microRNA profiles. We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a). Gene ontology (GO) annotation analyses indicated that pathways for gluconeogenesis and glycolysis were suppressed in exposed pups at PND1, and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced by PND70. Promoter analysis of differentially-expressed transcripts identified enriched transcription factor binding sites and clustering to common regulatory sites. SREBP1 binding sites were identified in about 16% of PND70 differentially-expressed genes. Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8) and active SREBP1. Plasma AST and ALT levels were increased at PND70. These results suggest that transplacental arsenic exposure alters developmental programming in fetal liver, leading to an enduring stress and proinflammatory response postnatally that may contribute to early onset of atherosclerosis. Genes containing SREBP1 binding sites also suggest pathways for diabetes mellitus and rheumatoid arthritis, both diseases that contribute to increased cardiovascular disease in humans

Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides imidacloprid and clothianidin

Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR–neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH–π interactions in the Ls-AChBP–CTD complex than in the Ls-AChBP–IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs

Dedifferentiation and Proliferation of Mammalian Cardiomyocytes

It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1) cardiomyocyte purification from rat hearts, and 2) genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs), while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP) continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+).Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness, including the expression of c-kit and the capacity for multipotency

HIV infection and HERV expression: a review

The human genome contains multiple copies of retrovirus genomes known as endogenous retroviruses (ERVs) that have entered the germ-line at some point in evolution. Several of these proviruses have retained (partial) coding capacity, so that a number of viral proteins or even virus particles are expressed under various conditions. Human ERVs (HERVs) belong to the beta-, gamma-, or spuma- retrovirus groups. Endogenous delta- and lenti- viruses are notably absent in humans, although endogenous lentivirus genomes have been found in lower primates. Exogenous retroviruses that currently form a health threat to humans intriguingly belong to those absent groups. The best studied of the two infectious human retroviruses is the lentivirus human immunodeficiency virus (HIV) which has an overwhelming influence on its host by infecting cells of the immune system. One HIV-induced change is the induction of HERV transcription, often leading to induced HERV protein expression. This review will discuss the potential HIV-HERV interactions