Said the River: The Confluence of Ecotheology and Water

Environmental water issues are increasingly in the consciousness of environmental advocates, as well as scientists and engineers. Water experts have approached water issues from a scientific and engineering framework, which has led them to preference material and technical solutions. Yet those solutions have been insufficient. The interdisciplinary field of water studies has been critical of the scientific-engineering approach. Several water scholars have posited that water issues are social-human problems first, and material-technical problems second. They call for alternative approaches that emphasize reconstructing water as a necessary precursor to formulating effective, enduring solutions to environmental water issues. Likewise, ecotheological scholars and religious environmental movement organizations (REMOs) are developing responses to water issues but from a spiritual stance. A significant challenge for ecotheologians and REMOs is to instigate social change that may transform anti-ecological water practices. Water-focused ecotheologians and REMOs face particular problems because water is an unusually complex environmental entity, both categorically and physically. This dissertation investigates water as an environmental issue from the perspective of ecotheology, and also develops alternative approaches to water-focused advocacy from an ecotheological stance. It examines two categories of environmental water problems that are intertwined: shortages and water pollution. I identify, analyze, and evaluate discourses from three domains: the water sector, water studies, and ecotheology. From my research within the literature of the water sector and water studies, I conclude that the water sector has much to learn from water studies. I further concluded that water-focused REMOs not only have a distinctive contribution to make to both the water sector and to water studies, but that they may even be a “hydraulic force” for water conservation, protection, and restoration. As a result, to be effective instigators of change, they first need to recognize and challenge their incognizant social constructions of water. My research shows that several water-focused ecotheologians and REMOs have made modest gains in bringing attention to water issues and contributing insights based on their ecotheological doctrine and praxis. However, few of them demonstrated an awareness of water studies or of the significance of the social construction of water. For this reason, they are limited in their ability to instigate transformation of water practices. Nevertheless, while ecotheologians and REMOs may be hampered, they still have distinctive contributions to offer the larger discourses on water protection, conservation, and restoration. In this dissertation, I use the methods of constructive theology and ecological theology. Ecotheology offers an ecological critique of religious doctrine and a religious critique of cultural practices. In addition, I use two theoretical systems familiar to water studies and ecotheology. The first is social constructionism, which posits that knowledge of reality is organized, interpreted, and represented through human language and cognition. In turn, social constructs both enable and limit everyday practices. Second, as ecotheology aims to instigate transformation of ecologically harmful practices, I challenge conventional models of social change that have been assumed by the water sector and ecotheology. I contend that newer theories of social change better account for how culture is transformed and are therefore more useful models for water-focused advocacy. My central argument is that an ecotheological response to environmental water problems demands a more comprehensive and integrated approach to water. This approach would include: an understanding of how water is socially constructed; an ability to distinguish between water knowledge, water, and water-human relations; and knowledge of how circumscribed water constructs both enable and limit water practices. I further argue that before ecotheological doctrines of water can be reconstructed, water must be understood as material and non-material, as relational and transmutable, and that water and culture are mutually constitutive of one another. I integrate these insights with those of water-focused ecotheology and REMOs, which have both been critical of traditional constructions of humanity as separate from, superior to, and proper master of nature. In the second half of the dissertation, I explore social constructions of nature and human nature in Eurowestern culture. As constructs of water are grounded in those of nature and human nature, identifying and reconstructing the dominant constructs of each is a necessary precursor to reconstructing water. First, I discuss how nature and human nature have been constructed and the consequences of such constructions. Second, I examine reconstructions of each by ecotheologians. Third, I offer my own reconstructions. I content that nature is a unified whole that exists for its own sake and it is where all abiotic and biotic entities dwell. Further, God dwells in nature, participates with it, and makes it holy. In addition, human nature is neither ontologically distinct nor superior to other living beings in the world. Humans are embedded within nature, existing interdependently and interrelationally with other entitles. Additionally, while human beings are not ontologically distinct, by virtue of our ability to act collaboratively and to self-limit, humanity has a particular commission, given by God, to care and keep nature. Thus, I reconstruct the nature-human relationship as interdependent, and as entailing a moral obligation. In my last chapter, I conclude by offering three counternarratives of water, which I develop using my model of reimaging water through water awareness, literacy, and reconstruction as well as insights from water studies. I reconstruct water as a nexus, unfinishable, and part of holiness. It is in first understanding that water is relational, fluid, and in process that we may transform water-human engagements from being profligate and utilitarian to being sustainable and just

Is Cursive Handwriting a Needed Skill for the Twenty-First Century?

This study compared attitudes of elementary school teachers and secondary school teachers on cursive handwriting. The investigation included secondary and elementary teacher requirements of cursive handwriting and special education students’ requirement of cursive handwriting. The subjects were educators from a middle sized urban school district in Niagara County in upstate New York. The results of the study came from a researcher prepared questionnaire. The research found secondary and elementary school teachers to have similar attitudes regarding cursive handwriting being a necessity for the upcoming century. The discussion includes technology as well as opinions to support the teachers’ attitudes. The discrepancy between secondary and elementary teachers appeared with the requirement for special education students. Secondary teachers felt the requirement should be the same for all students regarding cursive handwriting. The elementary teachers, however, felt the need for making modifications in certain situations

Ethical issues in publishing in predatory journals

This is a correction for Biochemia Medica 2017;27(2):279-84. DOI: https://doi.org/10.11613/ BM.2017.030

Cytokine exposure mediates transcriptional activation of the orphan nuclear receptor Nur77 in hematopoietic cells

The orphan nuclear receptor Nur77 is an immediate-early response gene that based on tissue and cell context is implicated in a plethora of cellular processes, including proliferation, differentiation, apoptosis, metabolism, and inflammation. Nur77 has a ligand-binding pocket that is obstructed by hydrophobic side groups. Naturally occurring, cell-endogenous ligands have not been identified, and Nur77 transcriptional activity is thought to be regulated through posttranslational modification and modulation of protein levels. To determine whether Nur77 is transcriptionally active in hematopoietic cells in vivo, we used an upstream activating sequence (UAS)-GFP transgenic reporter. We found that Nur77 is transcriptionally inactive in vivo in hematopoietic cells under basal conditions, but that activation occurs following cytokine exposure by G-CSF or IL-3. We also identified a series of serine residues required for cytokine-dependent transactivation of Nur77. Moreover, a kinase inhibitor library screen and proximity labeling-based mass spectrometry identified overlapping kinase pathways that physically interacted with Nur77 and whose inhibition abrogated cytokine-induced activation of Nur77. We determined that transcriptional activation of Nur77 by G-CSF or IL-3 requires functional JAK and mTor signaling since their inhibition leads to Nur77 transcriptional inactivation. Thus, intracellular cytokine signaling networks appear to regulate Nur77 transcriptional activity in mouse hematopoietic cells

Women’s responses to changes in U.S. preventive task force’s mammography screening guidelines: results of focus groups with ethnically diverse women

Background: The 2009 U.S. Preventive Services Task Force (USPSTF) changed mammography guidelines to recommend routine biennial screening starting at age 50. This study describes women’s awareness of, attitudes toward, and intention to comply with these new guidelines. Methods: Women ages 40–50 years old were recruited from the Boston area to participate in focus groups (k = 8; n = 77). Groups were segmented by race/ethnicity (Caucasian = 39%; African American = 35%; Latina = 26%), audio-taped, and transcribed. Thematic content analysis was used. Results: Participants were largely unaware of the revised guidelines and suspicious that it was a cost-savings measure by insurers and/or providers. Most did not intend to comply with the change, viewing screening as obligatory. Few felt prepared to participate in shared decision-making or advocate for their preferences with respect to screening. Conclusions: Communication about the rationale for mammography guideline changes has left many women unconvinced about potential disadvantages or limitations of screening. Since further guideline changes are likely to occur with advances in technology and science, it is important to help women become informed consumers of health information and active participants in shared decision-making with providers. Additional research is needed to determine the impact of the USPSTF change on women’s screening behaviors and on breast cancer outcomes

RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells

RARA and RXRA contribute to myeloid maturation in both mice and humans, and deletion of Rxra and Rxrb augments leukemic growth in mice. While defining the domains of RXRA that are required for anti-leukemic effects in murine KMT2A-MLLT3 leukemia cells, we unexpectedly identified RXRA DT448/9PP as a constitutively active variant capable of inducing maturation and loss of their proliferative phenotype. RXRA DT448/9PP was associated with ligand-independent activity in reporter assays, with enhanced co-activator interactions, reduced engraftment in vivo, and activation of myeloid maturation transcriptional signatures that overlapped with those of cells treated with the potent RXRA agonist bexarotene, suggestive of constitutive activity that leads to leukemic maturation. Phenotypes of RXRA DT448/9PP appear to differ from those of two other RXRA mutations with forms of constitutive activity (F318A and S427F), in that DT448/9PP activity was resistant to mutations at critical ligand-interacting amino acids (R316A/L326A) and was resistant to pharmacological antagonists, suggesting it may be ligand-independent. These data provide further evidence that activated retinoid X receptors can regulate myeloid maturation and provide a novel constitutively active variant that may be germane for broader studies of retinoid X receptors in other settings

RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells.

RARA and RXRA contribute to myeloid maturation in both mice and humans, and deletion of Rxra and Rxrb augments leukemic growth in mice. While defining the domains of RXRA that are required for anti-leukemic effects in murine KMT2A-MLLT3 leukemia cells, we unexpectedly identified RXRA DT448/9PP as a constitutively active variant capable of inducing maturation and loss of their proliferative phenotype. RXRA DT448/9PP was associated with ligand-independent activity in reporter assays, with enhanced co-activator interactions, reduced engraftment in vivo, and activation of myeloid maturation transcriptional signatures that overlapped with those of cells treated with the potent RXRA agonist bexarotene, suggestive of constitutive activity that leads to leukemic maturation. Phenotypes of RXRA DT448/9PP appear to differ from those of two other RXRA mutations with forms of constitutive activity (F318A and S427F), in that DT448/9PP activity was resistant to mutations at critical ligand-interacting amino acids (R316A/L326A) and was resistant to pharmacological antagonists, suggesting it may be ligand-independent. These data provide further evidence that activated retinoid X receptors can regulate myeloid maturation and provide a novel constitutively active variant that may be germane for broader studies of retinoid X receptors in other settings.This work was supported by National Institutes of Health grant R01 HL128447 (JSW) , by the Siteman Investment Program (JSW) , the Washington University SPORE DRP (JSW and MAF) , the Children's Discovery Institute (JSW) , the Alex's Lemonade Stand Foundation Young Investigator Award (MAF) , the National Institutes of Health 5K12HD07622408 (MAF) , and grants from the Spanish Ministerio de Ciencia e Innovacion (MCI) (SAF2017-90604-REDT-NurCaMeIn, RTI2018-095928-BI00) (MR).S

Profiling the Stromal and Vascular Heterogeneity in Patient-derived Xenograft Models of Head and Neck Cancer: Impact on Therapeutic Response

Head and neck squamous cell carcinomas (HNSCC) represent a group of epithelial neoplasms that exhibit considerable heterogeneity in clinical behavior. Here, we examined the stromal and vascular heterogeneity in a panel of patient-derived xenograft (PDX) models of HNSCC and the impact on therapeutic response. Tumor sections from established tumors were stained for p16 (surrogate for human papillomavirus (HPV) infection), stromal (Masson’s trichrome) and vascular (CD31) markers. All PDX models retained the HPV/p16 status of the original patient tumor. Immunohistochemical evaluation revealed the presence of multiple vessel phenotypes (tumor, stromal or mixed) in the PDX panel. Vascular phenotypes identified in the PDX models were validated in a tissue microarray of human HNSCC. Treatment with a microtubule targeted vascular disrupting agent (VDA) resulted in a heterogeneous antivascular and antitumor response in PDX models. The PDX with the tumor vessel phenotype that exhibited higher CD31+ vessel counts and leaky vasculature on magnetic resonance imaging (MRI) was sensitive to VDA treatment while the PDX with the stromal vessel phenotype was resistant to therapy. Collectively, our results demonstrate the phenotypic and functional vascular heterogeneity in HNSCC and highlight the impact of this heterogeneity on response to antivascular therapy in PDX models of HNSC