1,721,063 research outputs found
Identification of measures predictive of age at first puberty
No full textGraves, Kody; Mordhorst, Bethany; Oldfather, Nicole; Wright, Elane; Hale, Benjamin; Boddicker, Rebecca; Keating, Aileen; Ross, Jason. (2012). Identification of measures predictive of age at first puberty. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/139386
Investigating mechanisms of ovotoxicity of Perfluorooctanoic acid and Zearalenone exposure and the influence of altered metabolic status on ovarian function
No full textExposure to xenobiotics termed ovotoxicants can alter the quality and maintenance of oocytes and synthesis and secretion of hormones, which are the major roles of the ovary, leading to premature ovarian failure and infertility. Obesity has several negative reproductive effects in women, and in female mice, mechanistic studies have discovered that obesity decreases the number of primordial follicles, alters steroidogenesis and folliculogenesis, altering the estrous cycle, and blunts the ovarian response to toxicant exposure. In this dissertation, the hypothesis that altered physiological status such as obesity or heat stress would enhance ovarian sensitivity to the ovotoxicants perfluorooctanoic acid (PFOA) and zearalenone (ZEN) was investigated. The rationale for this hypothesis was based upon similar metabolic alterations including hyperinsulinemia between obesity and heat stress in females.
A study to evaluate obesity-induced alterations to the ovarian proteome in obese rats was conducted and potential species differences in obesity-induced altered ovarian function related to ovotoxicant exposure were identified (Chapter 2). While no impacts of obesity on several markers of DNA damage were noted, LC-MS/MS analysis provided mechanistic insight into the impact of obesity in a rat model on ovarian endpoints related to genotoxicant response.
Per- and polyfluoroalkylated substances (PFAS) including PFOA are characterized by having strong bonds between carbon and fluorine groups and are persistent in the environment. They are extensively used in consumer goods including flame retardant coatings, non-stick cookware, food packaging, fire-fighting foam and cosmetics. In females, exposure to PFOA has been linked to delayed puberty, early menopause, endocrine disruption, reduced fertility, and premature ovarian insufficiency. Mechanisms of PFOA-induced ovarian toxicity including alterations to the levels of E2 and P4, changes to the ovarian abundance of proteins with documented involvement in reproduction, DNA damage sensing and repair, and chemical metabolism and changes in serum metabolome were investigated (Chapter 3). Additionally, hepatic abundance of genes involved in chemical metabolism were to understand mechanisms of action in which PFOA can cause non-alcoholic fatty liver disease and the potential subsequent ovarian effects (Chapter 4). Additionally, an obese group of mice were studied to ascertain if obesity would modulate the ovarian impacts of PFOA exposure (Chapters 3 and 4). We found alterations in ovarian abundance of proteins involved in DNA damage sensing and repair, chemical metabolism and reproduction. The alterations in the ovarian abundance of the proteins involved in DNA damage sensing and repair could suggest an increased risk for ovarian cancer. In addition, even though PFAS are not biotransformed in the body, the alterations in the ovarian abundance of proteins involved in chemical biotransformation could lead to changes in the capacity of the ovary to respond to other toxicants or can lead to alterations in how endogenous chemicals are biotransformed in the body. We also investigated if the metabolic status could impact how the ovary can respond to PFOA exposure and we found altered 17-estradiol levels, differences in the ovarian proteome, and in the serum metabolome. These differences might suggest that the livers of obese females exposed to PFOA function less efficiently than the liver of lean females.
The second ovotoxicant investigated herein was ZEN, a non-steroidal mycotoxin with estrogenic activity that causes adverse effects on the female reproductive system, including altered folliculogenesis, decreased fertility, anovulation, vulvovaginitis, and altered follicle-stimulating hormone, progesterone, and 17-estradiol. Swine are the most sensitive species to ZEN exposure. Similar to obesity, heat stress (HS) causes hyperinsulinemia and impairs reproduction. It was hypothesized that HS would alter ovarian abundance of proteins involved in chemical metabolism, that ZEN exposure would alter abundance of ovarian chemical biotransformation proteins, and that an additive impact of HS and ZEN exposure would be observed. The levels of ovarian EPHX1, CYP2E1 and GSTP1 proteins were evaluated by western blots of protein isolated from prepubertal pigs held in a thermal-neutral environment with ad libitum access to a standard swine diet, a thermal-neutral environment with a restricted access to a standard swine diet, and a heat-stressed environment with the same plane of nutrition as thermal neutral feed restricted pigs. (Chapter 5). We found that HS itself alters the basal levels of EPHX1, CYP2E1 and GSTP1 in the ovary and identified that EPHX1 and GSTP1 are involved in the ovarian response to ZEN exposure. In addition, the ovarian abundance of EPHX1 was decreased in pigs who were feed restricted, probably indicating a response to reduced nutrient intake. These findings suggest that HS influences the ability of the ovary to respond to environmental stress possible leading to negative reproductive effects.
This dissertation supports the hypothesis that obesity in rats alters the ovarian proteome, that PFOA can induce DNA damage thereby activating DNA damage sensing and repair proteins and alters ovarian abundance of proteins involved in chemical metabolism and reproduction. Taken together this research supports the generation of the hypothesis by which PFOA may cause ovotoxicity and generates additional hypothesis-based questions for future research. Additionally, the work described in this dissertation demonstrates that PFOA exposure in females causes hepatic enlargement and alters hepatic abundance of genes involved in chemical biotransformation, observations that could be informative to ovarian function. It was also discovered that there are differences in the toxicity induced by PFOA in obese females as well as species difference between mice and rats in obesity-induced ovarian alterations. Finally, this work identifies ZEN-induced ovarian biotransformation in pigs and demonstrated an impact of hyperthermia on chemical biotransformation and a differential impact of ZEN exposure in HS females. In conclusion, this work provides evidence of a physiological influence of altered systemic metabolism on ovotoxicity outcomes
Impacts of Perfluorooctane Sulfonate and Perfluorooctanoic Acid on Ovarian Gap Junction Protein Expression
No full textPerfluorooctanoic acid (PFOA) is an environmentally-persistent manmade chemical known to bioaccumulate in the body of humans and animals. PFOA accumulates mostly in the blood serum, but also affects the kidney and liver. Studies have shown an increase in fetal resorption and neonatal mortality in animals, as well as longer time to pregnancy in humans. A high caloric diet may cause an amplification of the harmful effects of PFOA. In 2017-2018, the United States reported a 42.4% prevalence of obesity among adults. In the ovary, granulosa cell exchange is critical for cell differentiation and oocyte maturation to occur. The ovarian gap junction protein connexin 43 (CX43) facilitates communication between granulosa cells. This project aimed to determine the mechanism of action behind the reduced female fertility seen after exposure to PFOA, and if obesity would have an additive effect on the results
Investigating mechanisms of ovotoxicity of Perfluorooctanoic acid and Zearalenone exposure and the influence of altered metabolic status on ovarian function
No full textExposure to xenobiotics termed ovotoxicants can alter the quality and maintenance of oocytes and synthesis and secretion of hormones, which are the major roles of the ovary, leading to premature ovarian failure and infertility. Obesity has several negative reproductive effects in women, and in female mice, mechanistic studies have discovered that obesity decreases the number of primordial follicles, alters steroidogenesis and folliculogenesis, altering the estrous cycle, and blunts the ovarian response to toxicant exposure. In this dissertation, the hypothesis that altered physiological status such as obesity or heat stress would enhance ovarian sensitivity to the ovotoxicants perfluorooctanoic acid (PFOA) and zearalenone (ZEN) was investigated. The rationale for this hypothesis was based upon similar metabolic alterations including hyperinsulinemia between obesity and heat stress in females.
A study to evaluate obesity-induced alterations to the ovarian proteome in obese rats was conducted and potential species differences in obesity-induced altered ovarian function related to ovotoxicant exposure were identified (Chapter 2). While no impacts of obesity on several markers of DNA damage were noted, LC-MS/MS analysis provided mechanistic insight into the impact of obesity in a rat model on ovarian endpoints related to genotoxicant response.
Per- and polyfluoroalkylated substances (PFAS) including PFOA are characterized by having strong bonds between carbon and fluorine groups and are persistent in the environment. They are extensively used in consumer goods including flame retardant coatings, non-stick cookware, food packaging, fire-fighting foam and cosmetics. In females, exposure to PFOA has been linked to delayed puberty, early menopause, endocrine disruption, reduced fertility, and premature ovarian insufficiency. Mechanisms of PFOA-induced ovarian toxicity including alterations to the levels of E2 and P4, changes to the ovarian abundance of proteins with documented involvement in reproduction, DNA damage sensing and repair, and chemical metabolism and changes in serum metabolome were investigated (Chapter 3). Additionally, hepatic abundance of genes involved in chemical metabolism were to understand mechanisms of action in which PFOA can cause non-alcoholic fatty liver disease and the potential subsequent ovarian effects (Chapter 4). Additionally, an obese group of mice were studied to ascertain if obesity would modulate the ovarian impacts of PFOA exposure (Chapters 3 and 4). We found alterations in ovarian abundance of proteins involved in DNA damage sensing and repair, chemical metabolism and reproduction. The alterations in the ovarian abundance of the proteins involved in DNA damage sensing and repair could suggest an increased risk for ovarian cancer. In addition, even though PFAS are not biotransformed in the body, the alterations in the ovarian abundance of proteins involved in chemical biotransformation could lead to changes in the capacity of the ovary to respond to other toxicants or can lead to alterations in how endogenous chemicals are biotransformed in the body. We also investigated if the metabolic status could impact how the ovary can respond to PFOA exposure and we found altered 17-estradiol levels, differences in the ovarian proteome, and in the serum metabolome. These differences might suggest that the livers of obese females exposed to PFOA function less efficiently than the liver of lean females.
The second ovotoxicant investigated herein was ZEN, a non-steroidal mycotoxin with estrogenic activity that causes adverse effects on the female reproductive system, including altered folliculogenesis, decreased fertility, anovulation, vulvovaginitis, and altered follicle-stimulating hormone, progesterone, and 17-estradiol. Swine are the most sensitive species to ZEN exposure. Similar to obesity, heat stress (HS) causes hyperinsulinemia and impairs reproduction. It was hypothesized that HS would alter ovarian abundance of proteins involved in chemical metabolism, that ZEN exposure would alter abundance of ovarian chemical biotransformation proteins, and that an additive impact of HS and ZEN exposure would be observed. The levels of ovarian EPHX1, CYP2E1 and GSTP1 proteins were evaluated by western blots of protein isolated from prepubertal pigs held in a thermal-neutral environment with ad libitum access to a standard swine diet, a thermal-neutral environment with a restricted access to a standard swine diet, and a heat-stressed environment with the same plane of nutrition as thermal neutral feed restricted pigs. (Chapter 5). We found that HS itself alters the basal levels of EPHX1, CYP2E1 and GSTP1 in the ovary and identified that EPHX1 and GSTP1 are involved in the ovarian response to ZEN exposure. In addition, the ovarian abundance of EPHX1 was decreased in pigs who were feed restricted, probably indicating a response to reduced nutrient intake. These findings suggest that HS influences the ability of the ovary to respond to environmental stress possible leading to negative reproductive effects.
This dissertation supports the hypothesis that obesity in rats alters the ovarian proteome, that PFOA can induce DNA damage thereby activating DNA damage sensing and repair proteins and alters ovarian abundance of proteins involved in chemical metabolism and reproduction. Taken together this research supports the generation of the hypothesis by which PFOA may cause ovotoxicity and generates additional hypothesis-based questions for future research. Additionally, the work described in this dissertation demonstrates that PFOA exposure in females causes hepatic enlargement and alters hepatic abundance of genes involved in chemical biotransformation, observations that could be informative to ovarian function. It was also discovered that there are differences in the toxicity induced by PFOA in obese females as well as species difference between mice and rats in obesity-induced ovarian alterations. Finally, this work identifies ZEN-induced ovarian biotransformation in pigs and demonstrated an impact of hyperthermia on chemical biotransformation and a differential impact of ZEN exposure in HS females. In conclusion, this work provides evidence of a physiological influence of altered systemic metabolism on ovotoxicity outcomes
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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