Chloroacetamid Spray Drift and Leaf Tatters in Hackberry

During the last decade, leaf tatters has been reported in white oak and hackberry across several Midwestern states. Herbicide spray drift studies have shown that chloroacetamides can induce leaf tatters. The objectives of this research were to: 1) identify vulnerable bud developmental stages in hackberry and 2) determine if different commercial chloroacetamides affect severity of leaf tatters. In 2008, a preliminary spray drift experiment was conducted on mature trees from a former hackberry provenance test stand. Acetochlor (Harness), S-metolachlor (Dual II Magnum), and dimethenamid (Outlook) were applied at concentrations approximating 27%, 54%, 81%, or 108% of the recommended field rate. Three developmental stages before bud burst were present on the selected trees. Leaf tatters did not develop on the selected hackberry trees. However, symptoms were observed on neighboring, non-target hackberry trees, which had been in the leaf unfolding and expanding stages at the time of spraying. In 2009, three year old hackberry seedlings were treated with 1%, 10%, and 100% of the recommended field rate of acetochlor (Harness), S-metolachlor (Dual II Magnum), and dimethenamid (Outlook). Folded buds and two unfolding leaf developmental stages were present on seedlings. Another spray study was conducted on 32 mature hackberry trees from the provenance stand. A solution of 5608 mg a.i./L dimethenamid (Outlook) was applied to trees in the unfolding and/or expanding leaf stage. Treated trees represented four provenances. Image analysis was used to calculate seedling and mature tree leaf areas and estimate the seedling percentage of leaf tissue loss. Foliar damage was not significantly different between seedlings treated with water, 1%, or 10% of the field rate. Foliar damage was significantly different between seedlings treated with 1% or 100% of the field rate, and between seedlings treated with 10% or 100% of the field rate. Foliar damage in seedlings was not significantly different between the developmental stages. Additionally, symptoms of leaf tatters were observed on the treated mature hackberry. Future studies should focus on chloroacetamide concentrations above 10% of the recommended field rate.

XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through estrogen (E2)/ xenoestrogen inducedrapid ER signaling, which modifies the histone methyltransferase Enhancer of Zeste homolog 2 (EZH2) via activation of the PI3K/AKT pathway. We further hypothesized that there is a xenostrogen-specific effect on this pathway altering patterns of histone modification, DNA methylation and gene expression. In addition to our novel finding that E2/DES-induced phosphorylation of EZH2 by AKT reduces the levels of H3K27me3 in vitro and in vivo, this work demonstrates in vivo that a brief neonatal exposure to GEN, in contrast to BPA, activates the PI3K/AKT pathway to regulate EZH2 and decreases H3K27me3 levels in the neonatal uterus. Given that H3K27me3 is a repressive mark that has been shown to result in DNA methylation and gene silencing we investigated the methylation of developmentally reprogrammed genes. In support of this evidence, we show that neonatal DES exposure in comparison to VEH, leads to hypomethylation of the promoter of a developmentally reprogrammed gene, Gria2, that become hyper-responsive to estrogen in the adult myometrium indicating vi that DES exposure alter gene expression via chromatin remodeling and loss of DNA methylation. In the adult uterus, GEN and BPA exposure developmentally reprogrammed expression of estrogen-responsive genes in a manner opposite of one another, correlating with our previous data. Furthermore, the ability of GEN and BPA to developmental reprogram gene expression correlated with tumor incidence and multiplicity. These data show that xenoestrogens have unique effects on the activation of non-genomic signaling in the developing uterus that promotes epigenetic and genetic alterations, which are predictive of developmental reprogramming and correlate with their ability to modulate hormone-dependent tumor development.

Copper and human health: biochemistry, genetics, and strategies for modeling dose-response relationships

Copper (Cu) and its alloys are used extensively in domestic and industrial applications. Cu is also an essential element in mammalian nutrition. Since both copper deficiency and copper excess produce adverse health effects, the dose-response curve is U-shaped, although the precise form has not yet been well characterized. Many animal and human studies were conducted on copper to provide a rich database from which data suitable for modeling the dose-response relationship for copper may be extracted. Possible dose-response modeling strategies are considered in this review, including those based on the benchmark dose and categorical regression. The usefulness of biologically based dose-response modeling techniques in understanding copper toxicity was difficult to assess at this time since the mechanisms underlying copper-induced toxicity have yet to be fully elucidated. A dose-response modeling strategy for copper toxicity was proposed associated with both deficiency and excess. This modeling strategy was applied to multiple studies of copper-induced toxicity, standardized with respect to severity of adverse health outcomes and selected on the basis of criteria reflecting the quality and relevance of individual studies. The use of a comprehensive database on copper-induced toxicity is essential for dose-response modeling since there is insufficient information in any single study to adequately characterize copper dose-response relationships. The dose-response modeling strategy envisioned here is designed to determine whether the existing toxicity data for copper excess or deficiency may be effectively utilized in defining the limits of the homeostatic range in humans and other species. By considering alternative techniques for determining a point of departure and low-dose extrapolation (including categorical regression, the benchmark dose, and identification of observed no-effect levels) this strategy will identify which techniques are most suitable for this purpose. This analysis also serves to identify areas in which additional data are needed to better define the characteristics of dose-response relationships for copper-induced toxicity in relation to excess or deficiency.

Annual Report: Division of Acute Disease Prevention, Emergency Response, and Environmental Health 2015 April 25, 2016

This report is a result of the ADPER & EH division management team retreat that was held on July 30 and 31, 2015 where a gap was identified in our communication with customers, especially when it came to sharing information about planning efforts. The purpose of this report is to provide a comprehensive look at what ADPER & EH has accomplished in the past year as well as what we are working on for the future. It also serves as an annual informational resource for stakeholders, local partners, policy makers and the general public.

TERRITORIAL DISPUTES, LABOUR RELATIONS and ENVIRONMENTAL HEALTH IN AGROHIDRONEGOCIO sugarcane IN THE PONTAL PARANAPANEMA (SP)

This research aims to analyze the conflict over land in Postal do Paranapanema (state of São Paulo, Brazil), considering the competition for water resources and the degradation of environmental health in the area called the agrohidronegocio sugarcane. The survey results indicate that the expansion of sugarcane cultivation in this region is causing the worsening health of workers. Moreover, the research also seeks to identify alternative models to the hegemonic project of regional development based on matrix agrohidroenergetica. For this, the research has as interlocutors various types of social movements such as the Landless Workers Movement and the Movement of Dam Affected, and union leaders.

Perinatal Androgenic Exposure and Reproductive Health Effects Female Rat Offspring

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

ECOTOXICITY AND ENVIRONMENTAL RISK ASSESSMENT OF LARVICIDES USED IN THE CONTROL OF Aedes aegypti TO Daphnia magna ( CRUSTACEA, CLADOCERA)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Establishing occupational and environmental health design requirements for Lunar and Mars settlements

In a study of Lunar and Mars settlement concepts, an analysis was made of fundamental design assumptions in five technical areas against a model list of occupational and environmental health concerns. The technical areas included the proposed science projects to be supported, habitat and construction issues, closed ecosystem issues, the "MMM" issues--mining, material-processing, and manufacturing, and the human elements of physiology, behavior and mission approach. Four major lessons were learned. First it is possible to relate public health concerns to complex technological development in a proactive design mode, which has the potential for long-term cost savings. Second, it became very apparent that prior to committing any nation or international group to spending the billions to start and complete a lunar settlement, over the next century, that a significantly different approach must be taken from those previously proposed, to solve the closed ecosystem and "MMM" problems. Third, it also appears that the health concerns and technology issues to be addressed for human exploration into space are fundamentally those to be solved for human habitation of the earth (as a closed ecosystem) in the 21st century. Finally, it is proposed that ecosystem design modeling must develop new tools, based on probabilistic models as a step up from closed circuit models. ^

Increased geranylgeranylated K-Ras contributes to antineoplastic effects of farnesyltransferase inhibitors.

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are preferentially farnesylated. Small molecule inhibitors of farnesyltransferase (FTIs) have been developed as a means to alter Ras signaling. Our initial studies with FTIs in malignant and non-malignant cells revealed FTI-induced cell cycle arrest, reduced proliferation, and increased Ras signaling. These findings led us to the hypothesis that FTI induced increased GG’d Ras. We further hypothesized that the specific effects of FTI on cell cycle and growth result from increased signal strength of GG’d Ras. Our results did show that increase in GG’d K-Ras in particular results in reduced cell viability and cell cycle arrest. Genetically engineered constructs capable of only one type of prenylation confirmed that GG’d K-Ras recapitulated the effect of FTI in 293T cells. In tumor cell lines ERK and p38 MAPK pathways were both strongly activated in response to FTI, indicating the increased activity of GG’d K-Ras results in antiproliferative signals specifically through these pathways. These results collectively indicate FTI increases active GG’d K-Ras which activates ERK and p38 MAPKs to reduced cell viability and induce cell cycle arrest in malignant cells. This is the first report that identifies increased activity of GG’d K-Ras contributes to antineoplastic effects from FTI by increasing the activity of downstream MAPKs. Our observations suggest increased GG’d K-Ras activity, rather than inhibition of farnesylated Ras, is a major source of the cytostatic and cytotoxic effects of FTI. Our data may allow for determination of which patients would benefit from FTI by excluding tumors or diseases which have strong K-Ras signaling.