Rcrab: An R Analytics Tool To Visualize And Analyze The Movement Of Horseshoe Crabs In Long Island Sound, 2019 Sacred Heart University
Rcrab: An R Analytics Tool To Visualize And Analyze The Movement Of Horseshoe Crabs In Long Island Sound, Ismael Youssef, Samah Senbel, Jo-Marie Kasinak, Jennifer Mattei
School of Computer Science & Engineering Faculty Publications
Mark-recapture programs are important for studying the ecology and population dynamics of wildlife. An R shiny analytics tool was developed to track the movement of horseshoe crabs in Long Island Sound based on tag and resight data. The crabs were tagged and recaptured by volunteers of Project Limulus, a community-based research program. The dataset contains tag and recapture location information for 14,065 horseshoe crabs over 18 years. The dataset was initially cleaned by removing records with missing, duplicate or incorrect data. A new data structure was developed to save the data and simplify processing: Three dimensions were used, one ...
Microbiota Of Newborn Calves And Their Mothers Reveals Possible Transfer Routes For Newborn Calves’ Gastrointestinal Microbiota, 2019 University of Veterinary Medicine Vienna
Microbiota Of Newborn Calves And Their Mothers Reveals Possible Transfer Routes For Newborn Calves’ Gastrointestinal Microbiota, Daniela Klein-Jöbstl, Narciso M. Quijada, Monika Dzieciol, Benjamin Feldbacher, Matrin Wagner, Marc Drillich, Stephan Schmitz-Esser, Evelyne Mann
Animal Science Publications
The intestinal microbiota of newborns plays an important role in the development of immunity and metabolism. In livestock animals, knowledge of the intestinal microbiota is essential not only to prevent diseases but also to optimize weight gain and performance. The aim of our study was to examine faecal samples repeatedly within the first two days of life using 16S rRNA gene High Throughput Sequencing. Additionally, samples from the mouths of the calves and the vaginas, colostrum, and faeces of the dams were included to evaluate possible sources of the calf faecal microbiota. The calf faecal microbiota was highly variable during ...
Distribution And Responsiveness Of Rat Anti-Müllerian Hormone During Ovarian Development And Vcd-Induced Ovotoxicity, Connie J. Mark-Kappeler, Nivedita Sen, Aileen F. Keating, I. Glenn Sipes, Patricia B. Hoyer
Anti-Müllerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared ...
Dual Protective Role For Glutathione S-Transferase Class Pi Against Vcd-Induced Ovotoxicity In The Rat Ovary, 2019 Iowa State University
Dual Protective Role For Glutathione S-Transferase Class Pi Against Vcd-Induced Ovotoxicity In The Rat Ovary, Aileen F. Keating, Nivedita Sen, I. Glenn Sipes, Patricia B. Hoyer
The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S-transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extraovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80mg/ Kg/d; 15d, i.p). The present study investigated the pattern of ...
Inhibition Of Pik3 Signaling Pathway Members By The Ovotoxicant 4-Vinylcyclohexene Diepoxide In Rats, 2019 Iowa State University
Inhibition Of Pik3 Signaling Pathway Members By The Ovotoxicant 4-Vinylcyclohexene Diepoxide In Rats, Aileen F. Keating, Shannon M. Fernandez, Connie J. Mark-Kappeler, Nivedita Sen, I. Glenn Sipes, Patricia B. Hoyer
4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that specifically destroys primordial and small primary follicles in the ovaries of rats and mice, is thought to target an oocyte-expressed tyrosine kinase receptor, Kit. This study compared the temporal effect of VCD on protein distribution of KIT and its downstream PIK3-activated proteins, AKT and FOXO3. Postnatal Day 4 Fischer 344 rat ovaries were cultured in control media ± VCD (30 μM) for 2–8 days (d2–d8). KIT, AKT, phosphorylated AKT, FOXO3, and pFOXO3 protein levels were assessed by Western blotting and/or immunofluorescence staining with confocal microscopy. Phosphorylated AKT was decreased (P < 0.05) in oocyte nuclei in primordial (39% decrease) and small primary (37% decrease) follicles within 2 days of VCD exposure. After d4, VCD reduced (P ...
Impact Of Obesity On 7,12-Dimethylbenz[A]Anthracene-Induced Altered Ovarian Connexin Gap Junction Proteins In Female Mice, Shanthi Ganesan, Jackson Nteeba, Aileen F. Keating
The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean ...
High Fat Diet Induced Obesity Alters Ovarian Phosphatidylinositol-3 Kinase Signaling Gene Expression, 2019 Iowa State University
High Fat Diet Induced Obesity Alters Ovarian Phosphatidylinositol-3 Kinase Signaling Gene Expression, J. Nteeba, J. W. Ross, J. W. Perfield Ii, A. F. Keating
Insulin regulates ovarian phosphatidylinositol-3-kinase (PI3K) signaling, important for primordial follicle viability and growth activation. This study investigated diet-induced obesity impacts on: 1) insulin receptor (Insr) and insulin receptor substrate 1 (Irs1); 2) PI3K components (Kit ligand (Kitlg), kit (c-Kit), protein kinase B alpha (Akt1) and forkhead transcription factor subfamily 3 (Foxo3a)); 3) xenobiotic biotransformation (microsomal epoxide hydrolase (Ephx1), Cytochrome P450 isoform 2E1 (Cyp2e1), Glutathione S-transferase (Gst) isoforms mu (Gstm) and pi (Gstp)) and 4) microRNA’s 184, 205, 103 and 21 gene expression. INSR, GSTM and GSTP protein levels were also measured. Obese mouse ovaries had decreased Irs1, Foxo3a, Cyp2e1 ...
Heat Stress Alters Ovarian Insulin-Mediated Phosphatidylinositol-3 Kinase And Steroidogenic Signaling In Gilt Ovaries, Jackson Nteeba, M. Victoria Sanz-Fernandez, Robert P. Rhoads, Lance H. Baumgard, Jason W. Ross, Aileen F. Keating
Heat Stress (HS) compromises a variety of reproductive functions in several mammalian species. Inexplicably, HS animals are frequently hyperinsulinemic despite marked hyperthermia-induced hypophagia. Our objectives were to determine the effects of HS on insulin signaling and components essential to steroid biosynthesis in the pig ovary. Female pigs (35±4 kg) were exposed to constant thermal neutral (TN; 20°C; 35-50% humidity; n = 6) or HS conditions (35°C; 20-35% humidity; n = 6) for either 7 (n = 10) or 35 d (n = 12). After 7d, HS increased (P < 0.05) ovarian mRNA abundance of the insulin receptor (INSR), insulin receptor substrate 1 (IRS1), protein kinase B subunit 1 (AKT1), low density lipoprotein receptor (LDLR), luteinizing hormone receptor (LHCGR), and aromatase (CYP19a). After 35d, HS increased INSR, IRS1, AKT1, LDLR, LHCGR, CYP19a, and steroidogenic acute regulatory protein (STAR) ovarian mRNA abundance. In addition, after 35d, HS increased ovarian phosphorylated IRS1 (pIRS1), phosphorylated AKT (pAKT), STAR and CYP19a protein abundance. Immunostaining analysis revealed similar localization of INSR and pAKT1 in the cytoplasmic membrane and oocyte cytoplasm, respectively, of all stage follicles, and in theca and granulosa cells. Collectively, these results demonstrate that HS alters ovarian insulin mediated-PI3K signaling pathway members which likely impacts follicle activation and viability. In summary, environmentally-induced HS is an endocrine disrupting exposure that modifies ovarian physiology and potentially compromises production of ovarian hormones essential for fertility and pregnancy maintenance.
A Comparison Of Inflammatory And Oxidative Stress Markers In Adipose Tissue From Weight-Matched Obese Male And Female Mice, Karen J. Nickelson, Kelly L. Stromsdorfer, R. Taylor Pickering, Tzu-Wen Liu, Laura C. Ortinau, Aileen F. Keating, James W. Perfield Ii
Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent ...
Impact Of Obesity On Ovotoxicity Induced By 7,12-Dimethylbenz[A]Anthracene In Mice, 2019 Iowa State University
Impact Of Obesity On Ovotoxicity Induced By 7,12-Dimethylbenz[A]Anthracene In Mice, Jackson Nteeba, Shanthi Ganesan, Aileen F. Keating
Insulin, elevated during obesity, regulates xenobiotic biotransformation enzymes, potentially through phosphatidylinositol 3-kinase (PI3K) signaling, in extraovarian tissues. PI3K regulates oocyte viability, follicular activation, and ovarian chemical biotransformation. 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen and ovotoxicant, destroys all stages of follicles, leading to premature ovarian failure. Obesity has been reported to promote DMBA-induced tumors, but it remains unknown whether obesity affects ovarian xenobiotic metabolism. Therefore, we investigated ovarian expression of xenobiotic metabolism genes—microsomal epoxide hydrolase (Ephx1), glutathione S-transferase (GST) class Pi (Gstp1) and class mu 1 (Gstm1), and PI3K-signaling members (protein kinase B [AKT] alpha [Akt1], beta [Akt2], and ...
Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, 2019 University of Alberta
Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas
Pharmacy Faculty Articles and Research
Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common ...
Phosphoramide Mustard Exposure Induces Dna Adduct Formation And The Dna Damage Repair Response In Rat Ovarian Granulosa Cells, Shanthi Ganesan, Aileen F. Keating
Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response.
Protective Role For Ovarian Glutathione S-Transferase Isoform Pi During 7,12-Dimethylbenz[A]Anthracene-Induced Ovotoxicity, Poulomi Bhattacharya, Aileen F. Keating
7,12-dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all developmental stages. This study investigated a role for the glutathione S-transferase (Gst) isoforms alpha (a), mu (m) and pi (p) and the transcription factors, Ahr and Nrf2, during DMBA-induced ovotoxicity, and their regulation by phosphatidylinositol-3 kinase (PI3K) signaling. Negative regulation of JNK by GSTP during DMBA exposure was also studied. Post-natal day (PND) 4 Fischer 344 rat ovaries were exposed to vehicle control (1% DMSO) ± DMBA (1 μM) or vehicle control (1% DMSO) ± LY294002 (PI3K inhibitor; 20 μM) for 1, 2, 4, or 6 days. Total RNA or protein was ...
Mechanisms Of Ovarian Atresia Induced By Xenobiotic Exposures, 2019 Iowa State University
Mechanisms Of Ovarian Atresia Induced By Xenobiotic Exposures, Jason W. Ross, Aileen F. Keating
The focus of this chapter is the mechanisms of apoptosis that occur during “normal” (physiologically-induced) or “abnormal” (chemical- or pathology-induced) attrition of ovarian oocytes. One of the primary functions of the ovary is development and maturation of oocytes, which occur within a follicular structure. During fetal development of the ovary, primordial germ cells (oogonia) are formed and become oocytes when they stop dividing, and are arrested at the diplotene stage (prophase) of the first meiotic division. At this stage the oocyte is surrounded by a single layer of flattened somatic cells (pre-granulosa cells) and a basement membrane to form primordial ...
Ovarian Expressed Microsomal Epoxide Hydrolase: Role In Detoxification Of 4-Vinylcyclohexene Diepoxide And Regulation By Phosphatidylinositol-3 Kinase Signaling, Poulomi Bhattacharya, Nivedita Sen, Patricia B. Hoyer, Aileen F. Keating
4-vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a ...
Glutathione S-Transferase Class Mu Regulation Of Apoptosis Signal-Regulating Kinase 1 Protein During Vcd-Induced Ovotoxicity In Neonatal Rat Ovaries, Poulomi Bhattacharya, Jill A. Madden, Nivedita Sen, Patricia B. Hoyer, Aileen F. Keating
4-vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-related kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also ...
Disruption Of Female Reproductive Function By Endotoxins, 2019 Iowa State University
Disruption Of Female Reproductive Function By Endotoxins, K. L. Bidne, M. J. Dickson, J. W. Ross, L. H. Baumgard, A. F. Keating
Endotoxemia can be caused by obesity, environmental chemical exposure, abiotic stressors, and bacterial infection. Circumstances that deleteriously impact intestinal barrier integrity can induce endotoxemia and controlled experiments have identified negative impacts of lipopolysaccharide (LPS; an endotoxin mimetic) on folliculogenesis, puberty onset, estrus behavior, ovulation, meiotic competence, luteal function and ovarian steroidogenesis. In addition, neonatal LPS exposures have transgenerational female reproductive impacts, raising concern about early life contacts to this endogenous reproductive toxicant. Aims of this review are to identify physiological stressors causing endotoxemia, to highlight potential mechanism(s) by which LPS compromises female reproduction, and identify knowledge gaps regarding how ...
Involvement Of A Volatile Metabolite During Phosphoramide Mustard-Induced Ovotoxicity, 2019 Iowa State University
Involvement Of A Volatile Metabolite During Phosphoramide Mustard-Induced Ovotoxicity, Jill A. Madden, Patricia B. Hoyer, Patrick J. Devine, Aileen F. Keating
The finite ovarian follicle reserve can be negatively impacted by chemical exposures including the anti-neoplastic agent, cyclophosphamide (CPA). CPA requires bioactivation to phosphoramide mustard (PM) to elicit its therapeutic effects however; in addition to being the tumor-targeting metabolite, PM is also ovotoxic. In addition, PM can break down to a cytotoxic, volatile metabolite, chloroethylaziridine (CEZ). The aim of this study was initially to characterize PMinduced ovotoxicity in growing follicles. Using PND4 Fisher 344 rats, ovaries were cultured for 4 days before being exposed once to PM (10 or 30 μM). Following eight additional days in culture, relative to control (1 ...
Impact Of 7,12-Dimethylbenz[A]Anthracene Exposure On Connexin Gap Junction Proteins In Cultured Rat Ovaries, 2019 Iowa State University
Impact Of 7,12-Dimethylbenz[A]Anthracene Exposure On Connexin Gap Junction Proteins In Cultured Rat Ovaries, Shanthi Ganesan, Aileen F. Keating
7,12-dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles in a concentration-dependent manner. The impact of DMBA on connexin (CX) proteins that mediate communication between follicular cell types along with pro-apoptotic factors p53 and Bax were investigated. Postnatal day (PND) 4 Fisher 344 rat ovaries were cultured for 4 days in vehicle medium (1% DMSO) followed by a single exposure to vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and cultured for 4 or 8 days. RT-PCR was performed to quantify Cx37, Cx43, p53 and Bax mRNA level. Western blotting and immunofluorescence staining were performed to determine ...
Acute 7,12-Dimethylbenz[A]Anthracene Exposure Causes Differential Concentration-Dependent Follicle Depletion And Gene Expression In Neonatal Rat Ovaries, Jill A. Madden, Patricia B. Hoyer, Patrick J. Devine, Aileen F. Keating
Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or ...