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Silent Offspring: Single-cell Sequencing Reveals How DDT May Harm Ovarian Health in the Japanese Medaka Fish Model
Epidemiological studies continue to reveal associations between the organochlorine pesticide, dichlorodiphenyltrichloroethane (DDT) and reproductive diseases across species including urogenital carcinoma in sea lions, eggshell thinning in birds, and premature ovarian failure and cancer in humans. Advancing understanding of endocrine disruption at the molecular and cellular level is essential for determining possible developmental origins of adult-onset reproductive diseases. However, identifying mechanisms by which DDT affects developing gonads is a logistical and ethical challenge in long-lived, free-ranging species. The Japanese medaka (Oryzias latipes) is a valuable model for sex-specific toxicological studies due to its chromosomal sex determination, short generation time, and highly mapped genome. Medaka exposed to the estrogenic isomer, o,p’-DDT, at the part per billion (ppb) level experience ovarian abnormalities, reduced fertility, and reduced offspring survival. Yet, molecular mechanisms remain unclear despite decades of research and ongoing public health concerns surrounding DDT’s environmental persistence. This dissertation research investigated how early developmental exposures to o,p’-DDT alter gene regulation networks in the ovary using both traditional and innovative sequencing and molecular technologies. Because o,p’-DDT is a potent estrogen receptor agonist, the central hypothesis was that cell types involved in estrogen signaling would have significantly altered expression of steroidogenesis-related genes following DDT exposure. Chapter 1 discussed the reproductive toxicity of DDT and its impacts on ovarian development and health in the Japanese medaka. Chapter 2 defined long-term reproductive consequences of environmentally relevant, low dose o,p’-DDT exposure during an early window of ovarian differentiation using targeted quantification of estrogen- and steroidogenesis-related genes, hormone quantification, and histopathology. Chapter 3 used cutting-edge single cell transcriptomics (scRNA-seq) to gain a comprehensive view of which ovarian somatic cell types and gene regulatory networks (both steroid hormone- dependent and hormone-independent) are permanently altered by early-life exposure to o,p’-DDT. Contrary to the original hypothesis, the most significantly altered genes and signaling pathways were not steroidogenesis-related, but rather corresponded to upregulation of pro-inflammatory signaling and oxidative stress. This finding revealed an unexpected plausible mechanism of DDT-induced decreases in fertility in the medaka, prioritizing gene targets for further mechanistic studies in aquatic species impacted by persistent DDT exposure. Furthermore, it paired medaka with scRNA-seq to explore a potential high-throughput comprehensive pipeline for suspect endocrine disruptor screening, enhancing predictive toxicology to meet public and environmental health needs
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Studies on The Olfactory Biology and Behavioral Responses to Copper Exposure of The Native Indicator Species Delta Smelt (Hypomesus transpacificus)
The Delta Smelt (Hypomesus transpacificus) is a small Osmerid native to the San Francisco Bay Delta (Bay-Delta) in California. Delta Smelt population has declined dramatically since the species was declared as endangered in 1993, and now has been listed as critically endangered by the International Union for Conservation of Nature (IUCN). The Bay Delta is a highly modified ecosystem, and the Delta Smelt has been used as an indicator species to assess the overall health of this ecosystem. Recently, a wealth of evidence exists showing that anthropogenic intervention and change in ecosystems leads to alteration in the sensory perception of the environment by aquatic animals compromising survival in highly modified environments. One of the main modalities used by aquatic organisms to assess and survive in the wild is the olfactory system. The olfactory system is involved in pivotal functions such as recognition of predators, kin recognition, mating, foraging and migration. The olfactory system is highly susceptible to contaminants including copper, which is a common contaminant and a well-studied and measurable olfactory toxicant of fish. A link between the olfactory biology and the effects of common contaminants (i.e., copper) found in the Bay Delta on Delta Smelt is lacking. I studied the basic morphological characteristics of the olfactory organ (olfactory rosette) of Delta Smelt using histological, immunohistochemical and ultrastructural techniques; the olfactory mediated behavioral responses to predation related odorants using a behavioral standardized assay and tracking software; and finally, I evaluated morphological changes of the olfactory epithelium and behavioral responses to alarm cues after copper exposures using concentrations of 2, 8 and 32 µg/L and two exposure times (24 and 96 hours). The Delta Smelt can be classified as a macrosmatic fish, based on the morphological features of the olfactory rosette. This fish has multilamellar, paired olfactory rosettes containing a highly specialized olfactory epithelium. The olfactory epithelium was composed by several populations of cells including sensory neurons with distinct morphology and immunocytochemical features. Delta Smelt have a highly sophisticated and sensitive response to predation related odorants. They detect alarm cues in a concentration dependent fashion using olfaction and display specific behaviors (escape responses and freezing) upon detection that all together are considered as olfactory mediated antipredator behaviors. Finally, I demonstrated using histopathological and immunohistochemical techniques that Delta Smelt olfactory epithelium is highly susceptible to copper exposure at concentrations commonly found in the Bay Delta and considered as sublethal. Moreover, there were differential effects on antipredator behaviors after exposure to copper for 24 and 96 hours. Fish exposed to 8 µg/L of copper for 24 hours showed severe damage to the olfactory epithelium and hyperexcitability when presented to alarm cues. At higher concentrations, the epithelium was severely damaged, the antipredator response was absent and there were signs of histological and behavioral toxicity. The results of these experiments demonstrate that Delta Smelt is a highly olfactory species and establishes that copper contamination can impair olfactory responses at environmentally relevant concentrations in this endangered fish
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Plastics and priority pollutants : a multiple stressor in aquatic habitats
Includes bibliographical references.Plastic debris litters our planet and can harm wildlife physically and chemically. Large debris entangles organisms and small fragments bioaccumulate. Several ingredients of plastic are hazardous and in aquatic habitats plastic debris sorbs priority pollutants from water. Thus, plastic debris is associated with a complex chemical mixture, including the material itself, ingredients and ambient contaminants. Here, we assessed how plastic debris acts as a multiple stressor in aquatic habitats. First, we quantified the relationship between different polymers and chemical contaminants in an urban bay. For organics, HDPE, LDPE and PP sorbed consistently greater concentrations of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) than PET and PVC. In contrast, for metals, all types of plastic tended to sorb similar concentrations of aluminum, chromium, manganese, iron, cobalt, nickel, zinc, cadmium and lead. Over a 12-month period, concentrations of all contaminants increased over time. Thus, hazards are not equal among plastic debris, varying by polymer, location and the length of time since becoming debris. Next, we exposed fish to low-density polyethylene (which sorbed relatively large concentrations of chemical contaminants) to assess the hazards of this complex mixture. After a laboratory dietary exposure, Japanese medaka (Oryzias latipes) exposed to the mixture of plastic + pollutants had greater concentrations of polybrominated diphenyl ethers (PBDEs) in their tissues (P < 0.05) and suffered liver toxicity and pathology. Furthermore, our results suggest that plastic debris may cause endocrine disruption???we observed reduced expression of vitellogenin and choriogenin genes and intersex. Moreover, fish fed virgin polyethylene material showed signs of stress, confirming that future assessments should consider the complex mixture of plastic and pollutants. Next, we examined the relationship between bioaccumulation and plastic contamination in the South Atlantic and found a positive relationship between plastic density and concentrations of PBDEs in the tissue of mesopelagic fish. This suggests that the bioaccumulation observed in the laboratory occurs in nature, and that plastic debris is another vector for pollutants to contaminate aquatic foodwebs. Finally, we evaluated the existing chemical, toxicological and ecological evidence about hazards of plastic debris and priority pollutants and found that at least 78% of the priority pollutants listed by the US EPA are associated with plastic debris as an ingredient or sorbed from the environment. The culmination of this and our own findings led us to conclude that current consumer practices and policy for managing plastic is scientifically outdated. We recommend reclassifying classes of plastic debris as ???hazardous???, providing a relatively simple mechanism, using existing legislation, to rehabilitate affected habitats and prevent further accumulations of hazardous debris
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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