Biological role of conceptus derived factors during early pregnancy in ruminants

Dissertation supervisor: Dr. Thomas Spencer.Includes vita.In cycling domestic animals, pregnancy loss during early gestation is a major cause of infertility. The majority of pregnancy loss during this time is due to errors in mitotic division early in development, or occurs later in gestation and is characterized by endometrial dysfunction, or asynchrony between the conceptus (embryo and trophectoderm) and uterus. During early pregnancy in sheep, endometrial functions are primarily regulated by ovarian progesterone (P4) and interferon tau (IFNT) from the conceptus trophectoderm. In addition to IFNT, the conceptus as well as the endometrium synthesize prostaglandins (PGs) via prostaglandin synthase two (PTGS2) and cortisol via hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1). The central hypothesis is that factors from the ovary (progesterone), the conceptus (interferon tau, prostaglandins, and cortisol) and endometrium (prostaglandins and cortisol) regulate endometrial function and conceptus survival and development in ruminants. This work tested that hypothesis that conceptus derived factors regulate gene expression changes in the trophectoderm which are essential for trophectoderm development and conceptus elongation in sheep. The hypothesis was addressed by determining the physiological roles of: (1) IFNT and interferon receptors 1 and 2 (IFNAR1 and IFNAR2) in conceptus development; (2) PG signaling through peroxisome proliferator activator receptors delta (PPARD) and gamma (PPARG) in the elongating conceptus; (3) the cortisol converting enzymes HSD11B1 and HSD11B2 in conceptus development; (4) the role of the glucocorticoid receptor (GR) in cortisol signaling during conceptus elongation. Gene knockout studies utilizing osmotic pumps to deliver morpholino antisense oligonucleotides, lentiviral transduction of shRNAs, and CRISPR/Cas9 based genome editing were used to target the conceptus during elongation. Results of the studies established that: (1) IFNT is not only the maternal recognition of pregnancy signal, but is also required for conceptus elongation; (2) the IFN receptors IFNAR1 and IFNAR2 are not important for autocrine based signaling to the conceptus trophectoderm during development; (3) PPARG, but not PPARD is essential for conceptus elongation; (4) PPARG regulated pathways are involved in lipid uptake and metabolism in the day 14 conceptus; (5) Regulation of intracellular cortisol levels by HSD11B1 is important for conceptus development; (6) inactivation of bioactive cortisol by the enzyme HSD11B2 is not essential for conceptus elongation, but is important for proper conceptus development; and (7) signaling through GR is not essential for conceptus development up to day 14 of pregnancy. Collectively, results of these studies support the idea that IFNT, PGs and cortisol are all important regulators of conceptus elongation during early pregnancy in ruminants. Knowledge gained from these studies provides new insight into the physiological pathways governing conceptus development and elongation. Information from these studies provides a foundation for future translational research that is necessary to increase fertility of domestic ruminants.Includes bibliographical references (pages 259-295)

Naturopathic Physician Attitudes and Practices for Vaccination and Primary Care in the State of Vermont

Introduction: Recent increase in measles cases has sparked vaccination controversy. Naturopathic physicians (NDs) have been recognized as primary care providers by VT since 2012. It is not well understood how NDs address vaccination with patients. Our goal was to determine how Vermont NDs address vaccines and preventative care with their patients.https://scholarworks.uvm.edu/comphp_gallery/1234/thumbnail.jp

Redesigning the Frederick Meijer Honors College Curriculum

Welcome reader, We appreciate your interest in our design challenge of reimaging the Frederik Meijer Honors College curriculum. Over the course of several months, we have worked diligently through the design thinking process to arrive at a solution that meets the needs of FMHC stakeholders. We have conducted interviews with these stakeholders in order to gain empathy and conducted secondary research which allowed us to broaden the scope of our insights and search for potential solutions. Many hours were spent ideating our own solutions and prototyping them through a collaborator debrief process. This portfolio contains the details of our process start to finish, showing how we used design thinking to redesign the FMHC curriculum. We are proud to be a part of the process of reinventing the Honors College curriculum.The effect of our efforts will create a more enriching college experience for future generations. Thank you for taking the time to explore and innovate with us. Sincerely, Team Vitality Kathryn Malia Brooks Bradley Williams Kelsey Rutkowski Andrew Dzierwa Bethany Chambe

Climatology, storm morphologies, and environments of tornadoes in the British Isles: 1980–2012

A climatology is developed for tornadoes during 1980–2012 in the British Isles, defined in this article as England, Scotland, Wales, Northern Ireland, Republic of Ireland, Channel Islands, and the Isle of Man. The climatology includes parent storm type, interannual variability, annual and diurnal cycles, intensities, oc- currence of outbreaks (defined as three or more tornadoes in the same day), geographic distribution, and environmental conditions derived from proximity soundings of tornadoes. Tornado reports are from the Tornado and Storm Research Organization (TORRO). Over the 33 years, there were a mean of 34.3 tor- nadoes and 19.5 tornado days (number of days in which at least one tornado occurred) annually. Tornadoes and tornado outbreaks were most commonly produced from linear storms, defined as radar signatures at least 75 km long and approximately 3 times as long as wide. Most (78%) tornadoes occurred in England. The probability of a tornado within 10 km of a point was highest in the south, southeast, and west of England. On average, there were 2.5 tornado outbreaks every year. Where intensity was known, 95% of tornadoes were classified as F0 or F1 with the remainder classified as F2. There were no tornadoes rated F3 or greater during this time period. Tornadoes occurred throughout the year with a maximum from May through October. Finally, tornadoes tended to occur in low-CAPE, high-shear environments. Tornadoes in the British Isles were difficult to predict using only sounding-derived parameters because there were no clear thresholds between null, tornadic, outbreak, and significant tornado cases

“I Won’t Use the Term Dumbing It Down, but You Have to Take the Scientific Jargon Out”: A Qualitative Study of Environmental Health Partners’ Communication Practices and Needs

Effective research translation and science communication are necessary for successful implementation of water resources management initiatives. This entails active involvement of stakeholders through collaborative partnerships and knowledge-sharing practices. To follow up a recent study with the National Institute of Environmental Health Sciences (NIEHS)–funded Center for Oceans and Human Health and Climate Change Interactions (OHHC2I) project investigators, the center’s Community Engagement Core (CEC) documented center partners’ science communication practices and needs to inform a collaborative training and improve investigator-partner bidirectional communication. Thirteen (13) individuals participated in 10 semi-structured qualitative interviews focused on their research translation needs, science communication and dissemination tactics, and interactions and experiences with scientists. Based on our findings, we recommend a collaborative, scientist-stakeholder training to include plain language development, dissemination tactics, communication evaluation, stakeholder and intended audience engagement, and strategies for effective transdisciplinary partnerships. This work contributes to the knowledge and understanding of stakeholder engagement practices specifically focused on science communication that can enhance relationship-building between academia and partners involved in environmental health–focused initiatives in the context of South Carolina but applicable elsewhere

Effects of preovulatory estradiol on uterine environment and conceptus survival from fertilization to maternal recognition of pregnancy

Preovulatory estradiol is known to impact embryo quality and survival. The objective of this study was to determine the effects of preovulatory estradiol on the uterine environment and conceptus survival through maternal recognition of pregnancy. Beef cows/heifers were AIed following induced ovulation. Cows were grouped into high and low preovulatory estradiol. Conceptuses were collected on day 16 nonsurgically (Rep 1; n = 20), or following slaughter (Rep 2; n = 29). Blood was collected to determine plasma glucose concentrations, and uterine luminal fluid (ULF) was analyzed for protein, glucose, and interferon tau (IFNT) concentrations. Total cellular RNA was extracted from caruncular (CAR) and intercaruncular (INCAR) endometrial tissue. There was no effect of preovulatory estradiol on conceptus recovery rate (P = 0.38) or on apoptosis rate in the trophectoderm (P = 0.64). Cows in which a conceptus was recovered had greater concentrations of protein in the ULF (P = 0.04). Animals with elevated preovulatory estradiol had greater endometrial abundance of SLC2A1 (P = 0.05) and SLC5A1 (P = 0.04) in both INCAR and CAR tissue. Presence of a conceptus also tended to increase (P = 0.10) abundance of SLC5A1 in INCAR. In CAR tissue, cows with a conceptus had decreased SLC2A4 abundance (P = 0.05). In summary, conceptus recovery rates, apoptosis in the trophectoderm, IFNT, glucose, and protein concentration in ULF did not differ between cows that did or did not have an increase in preovulatory estradiol concentrations. Thus, there is no indication of increased conceptus survival to day 16 of pregnancy based on estradiol concentrations

Effects of preovulatory estradiol on uterine environment and conceptus survival from fertilization to maternal recognition of pregnancy

Preovulatory estradiol is known to impact embryo quality and survival. The objective of this study was to determine the effects of preovulatory estradiol on the uterine environment and conceptus survival through maternal recognition of pregnancy. Beef cows/heifers were AIed following induced ovulation. Cows were grouped into high and low preovulatory estradiol. Conceptuses were collected on day 16 nonsurgically (Rep 1; n = 20), or following slaughter (Rep 2; n = 29). Blood was collected to determine plasma glucose concentrations, and uterine luminal fluid (ULF) was analyzed for protein, glucose, and interferon tau (IFNT) concentrations. Total cellular RNA was extracted from caruncular (CAR) and intercaruncular (INCAR) endometrial tissue. There was no effect of preovulatory estradiol on conceptus recovery rate (P = 0.38) or on apoptosis rate in the trophectoderm (P = 0.64). Cows in which a conceptus was recovered had greater concentrations of protein in the ULF (P = 0.04). Animals with elevated preovulatory estradiol had greater endometrial abundance of SLC2A1 (P = 0.05) and SLC5A1 (P = 0.04) in both INCAR and CAR tissue. Presence of a conceptus also tended to increase (P = 0.10) abundance of SLC5A1 in INCAR. In CAR tissue, cows with a conceptus had decreased SLC2A4 abundance (P = 0.05). In summary, conceptus recovery rates, apoptosis in the trophectoderm, IFNT, glucose, and protein concentration in ULF did not differ between cows that did or did not have an increase in preovulatory estradiol concentrations. Thus, there is no indication of increased conceptus survival to day 16 of pregnancy based on estradiol concentrations

Characterization of Ceriporiopsis subvermispora Bicupin Oxalate Oxidase Expressed in Pichia pastoris

Oxalate oxidase (E.C. 1.2.3.4) catalyzes the oxygen-dependent oxidation of oxalate to carbon dioxide in a reaction that is coupled with the formation of hydrogen peroxide. Although there is currently no structural information available for oxalate oxidase fromCeriporiopsis subvermispora (CsOxOx), sequence data and homology modeling indicate that it is the first manganese-containing bicupin enzyme identified that catalyzes this reaction. Interestingly, CsOxOx shares greatest sequence homology with bicupin microbial oxalate decarboxylases (OxDC). We show that CsOxOx activity directly correlates with Mn content and other metals do not appear to be able to support catalysis. EPR spectra indicate that the Mn is present as Mn(II), and are consistent with the coordination environment expected from homology modeling with known X-ray crystal structures of OxDC from Bacillus subtilis. EPR spin-trapping experiments support the existence of an oxalate-derived radical species formed during turnover. Acetate and a number of other small molecule carboxylic acids are competitive inhibitors for oxalate in the CsOxOx catalyzed reaction. The pH dependence of this reaction suggests that the dominant contribution to catalysis comes from the monoprotonated form of oxalate binding to a form of the enzyme in which an active site carboxylic acid residue must be unprotonated

Investigation of the deposition and emission of mercury in arctic snow during an atmospheric mercury depletion event

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94701/1/jgrd14741.pd

Examining the Evidence for Chytridiomycosis in Threatened Amphibian Species

Extinction risks are increasing for amphibians due to rising threats and minimal conservation efforts. Nearly one quarter of all threatened/extinct amphibians in the IUCN Red List is purportedly at risk from the disease chytridiomycosis. However, a closer look at the data reveals that Batrachochytrium dendrobatidis (the causal agent) has been identified and confirmed to cause clinical disease in only 14% of these species. Primary literature surveys confirm these findings; ruling out major discrepancies between Red List assessments and real-time science. Despite widespread interest in chytridiomycosis, little progress has been made between assessment years to acquire evidence for the role of chytridiomycosis in species-specific amphibian declines. Instead, assessment teams invoke the precautionary principle when listing chytridiomycosis as a threat. Precaution is valuable when dealing with the world's most threatened taxa, however scientific research is needed to distinguish between real and predicted threats in order to better prioritize conservation efforts. Fast paced, cost effective, in situ research to confirm or rule out chytridiomycosis in species currently hypothesized to be threatened by the disease would be a step in the right direction. Ultimately, determining the manner in which amphibian conservation resources are utilized is a conversation for the greater conservation community that we hope to stimulate here