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Articles 1 - 22 of 22
Full-Text Articles in Physiology
Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder
Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …
Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov
Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage. Similar cytoprotective effects were observed after transient shRNA-mediated silencing of Rps19, but not …
Estrogen Receptor Alpha (Esr1)-Dependent Regulation Of The Mouse Oviductal Transcriptome, Katheryn L. Cerny, Rosanne A. C. Ribeiro, Myoungkun Jeoung, Chemyong Ko, Phillip J. Bridges
Estrogen Receptor Alpha (Esr1)-Dependent Regulation Of The Mouse Oviductal Transcriptome, Katheryn L. Cerny, Rosanne A. C. Ribeiro, Myoungkun Jeoung, Chemyong Ko, Phillip J. Bridges
Animal and Food Sciences Faculty Publications
Estrogen receptor-α (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of the transcriptome of this organ is not well defined, especially at the genomic level. The objective of this study was therefore to investigate estradiol- and ESR1-dependent regulation of the transcriptome of the oviduct using transgenic mice, both with (ESR1KO) and without (wild-type, WT) a global deletion of ESR1. Oviducts were collected from ESR1KO and WT littermates at 23 days of age, or ESR1KO and WT mice were treated with 5 IU PMSG to stimulate follicular development and the production of ovarian estradiol, and the …
Substrate Rigidity Regulates The Formation And Maintenance Of Tissues, Wei-Hui Guo, Margo Frey, Nancy Burnham, Yu-Li Wang
Substrate Rigidity Regulates The Formation And Maintenance Of Tissues, Wei-Hui Guo, Margo Frey, Nancy Burnham, Yu-Li Wang
Nancy A. Burnham
The ability of cells to form tissues represents one of the most fundamental issues in biology. However, it is unclear what triggers cells to adhere to one another in tissues and to migrate once a piece of tissue is planted on culture surfaces. Using substrates of identical chemical composition but different flexibility, we show that this process is controlled by substrate rigidity: on stiff substrates, cells migrate away from one another and spread on surfaces, whereas on soft substrates they merge to form tissue-like structures. Similar behavior was observed not only with fibroblastic and epithelial cell lines but also explants …
The Nuclear Factor Of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is A Repressor Of Chondrogenesis, Ann M. Ranger, Louis C. Gerstenfeld, Jinxi Wang, Tamiyo Kon, Hyunsu Bae, Ellen M. Gravallese, Melvin J. Glimcher, Laurie H. Glimcher
The Nuclear Factor Of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is A Repressor Of Chondrogenesis, Ann M. Ranger, Louis C. Gerstenfeld, Jinxi Wang, Tamiyo Kon, Hyunsu Bae, Ellen M. Gravallese, Melvin J. Glimcher, Laurie H. Glimcher
Ellen M. Gravallese
Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate …
A Lipopolysaccharide-Induced Dna-Binding Protein For A Class Ii Gene In B Cells Is Distinct From Nf-Kappa B, Ellen M. Gravallese, Mark R. Boothby, Cynthia M. Smas, Laurie H. Glimcher
A Lipopolysaccharide-Induced Dna-Binding Protein For A Class Ii Gene In B Cells Is Distinct From Nf-Kappa B, Ellen M. Gravallese, Mark R. Boothby, Cynthia M. Smas, Laurie H. Glimcher
Ellen M. Gravallese
Class II (Ia) major histocompatibility complex molecules are cell surface proteins normally expressed by a limited subset of cells of the immune system. These molecules regulate the activation of T cells and are required for the presentation of antigens and the initiation of immune responses. The expression of Ia in B cells is determined by both the developmental stage of the B cell and by certain external stimuli. It has been demonstrated previously that treatment of B cells with lipopolysaccharide (LPS) results in increased surface expression of Ia protein. However, we have confirmed that LPS treatment results in a significant …
Developmental Expression Of A Candidate Mullerian Inhibiting Substance Type Ii Receptor, Jose Teixeira, Wei He, Paresh Shah, Nobuyuki Morikawa, Mary Lee, Elizabeth Catlin, Peter Hudson, John Wing, David Maclaughlin, Patricia Donahoe
Developmental Expression Of A Candidate Mullerian Inhibiting Substance Type Ii Receptor, Jose Teixeira, Wei He, Paresh Shah, Nobuyuki Morikawa, Mary Lee, Elizabeth Catlin, Peter Hudson, John Wing, David Maclaughlin, Patricia Donahoe
Mary M. Lee
We have isolated a candidate Mullerian inhibiting substance (MIS) type II receptor complementary DNA from an embryonic rat urogenital ridge library and have studied its binding to MIS, its developmental pattern of expression and tissue distribution. By in situ hybridization with a full-length riboprobe, the receptor is expressed in the mesenchymal cells surrounding the Mullerian duct at embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat fetal gonads. Expression of the messenger RNA was also seen in the granules cells and seminiferous tubules of pubertal gonads. Northern analysis revealed that the MIS type II …
Developmentally Regulated Polyadenylation Of Two Discrete Messenger Ribonucleic Acids For Mullerian Inhibiting Substance, Mary Lee, Richard Cate, Patricia Donahoe, Gerald Waneck
Developmentally Regulated Polyadenylation Of Two Discrete Messenger Ribonucleic Acids For Mullerian Inhibiting Substance, Mary Lee, Richard Cate, Patricia Donahoe, Gerald Waneck
Mary M. Lee
Mullerian inhibiting substance (MIS) is a 140-kilodalton homodimeric glycoprotein that causes regression of the Mullerian ducts in male embryos, and may also have a role in both males and females in the regulation of germ cell maturation. We examined the ontogeny of MIS messenger RNA (mRNA) in rat testes from midgestation through adulthood and found two discrete MIS mRNA species that are developmentally regulated. The larger 2.0-kilobase species is abundant at embryonic day 14, then decreases in late gestation, and is barely detectable after birth. The smaller 1.8-kilobase species is first noted at embryonic day 18 and is the major …
Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration After Ethylene Dimethanesulphonate Ablation, Antonio Salva, Matthew Hardy, Xiufeng Wu, Chantal Sottas, David Maclaughlin, Patricia Donahoe, Mary Lee
Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration After Ethylene Dimethanesulphonate Ablation, Antonio Salva, Matthew Hardy, Xiufeng Wu, Chantal Sottas, David Maclaughlin, Patricia Donahoe, Mary Lee
Mary M. Lee
The postnatal development of Leydig cell precursors is postulated to be controlled by Sertoli cell secreted factors, which may have a determinative influence on Leydig cell number and function in sexually mature animals. One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines. To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration. Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered …
Mullerian Inhibiting Substance Is Present In Embryonic Testes Of Dogs With Persistent Mullerian Duct Syndrome, Vicki Meyers-Wallen, Mary Lee, T. Manganaro, T. Kuroda, David Maclaughlin, Patricia Donahoe
Mullerian Inhibiting Substance Is Present In Embryonic Testes Of Dogs With Persistent Mullerian Duct Syndrome, Vicki Meyers-Wallen, Mary Lee, T. Manganaro, T. Kuroda, David Maclaughlin, Patricia Donahoe
Mary M. Lee
Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian ducts during a critical period in embryonic development in male mammals. In Persistent Mullerian Duct Syndrome (PMDS), an autosomal recessive trait in humans and dogs, the Mullerian ducts fail to regress in otherwise normal males. Previously we reported that PMDS-affected dogs produce bioactive testicular MIS postnatally. The purpose of the present study was to determine whether PMDS-affected canine embryos appropriately express MIS mRNA and protein during the critical period for Mullerian duct regression. Homozygous (PMDS-affected) and normal canine embryos were removed from timed pregnancies. Gonadal sex and the degree of Mullerian …
Mullerian Inhibiting Substance Ontogeny And Its Modulation By Follicle-Stimulating Hormone In The Rat Testes, Tatsuo Kuroda, Mary Lee, Christopher Haqq, David Powell, Thomas Manganaro, Patricia Donahoe
Mullerian Inhibiting Substance Ontogeny And Its Modulation By Follicle-Stimulating Hormone In The Rat Testes, Tatsuo Kuroda, Mary Lee, Christopher Haqq, David Powell, Thomas Manganaro, Patricia Donahoe
Mary M. Lee
Mullerian Inhibiting Substance (MIS) production in rat testes from the late fetal to the adult period and its modulation by gonadotropins in neonatal testes were studied using immunohistochemistry, northern analysis, and a graded organ culture bioassay for MIS. The intense immunohistochemical staining for MIS seen in fetal and newborn testes began to decrease gradually after the third postnatal day, then decreased dramatically on the fifth postnatal day. MIS immunohistochemical activity was then present at a low level until about the 20th postnatal day, after which it was barely detectable. The testes from rats treated with FSH at birth showed a …
Mullerian Inhibiting Substance Inhibits Testosterone Synthesis In Adult Rats, V. Sriraman, E. Niu, J. Matias, Patricia Donahoe, David Maclaughlin, Matthew Hardy, Mary Lee
Mullerian Inhibiting Substance Inhibits Testosterone Synthesis In Adult Rats, V. Sriraman, E. Niu, J. Matias, Patricia Donahoe, David Maclaughlin, Matthew Hardy, Mary Lee
Mary M. Lee
Mullerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Mullerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS. Intratesticular MIS injection achieved high local concentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with a corresponding decline in serum testosterone concentrations to 0.7 +/- 0.1 ng/mL, compared to …
Developmental Changes In Mullerian Inhibiting Substance In The Cynomolgus Monkey, Macaca Fascicularis, Mary Lee, M. Gustafson, Etsuji Ukiyama, Patricia Donahoe, David Maclaughlin, Michael Wexler, Hugh Keeping
Developmental Changes In Mullerian Inhibiting Substance In The Cynomolgus Monkey, Macaca Fascicularis, Mary Lee, M. Gustafson, Etsuji Ukiyama, Patricia Donahoe, David Maclaughlin, Michael Wexler, Hugh Keeping
Mary M. Lee
Mullerian inhibiting substance (MIS) is a glycoprotein hormone produced in Sertoli cells of the fetal and postnatal testis, and granulosa cells of the pubertal ovary. We examined MIS expression in a nonhuman primate, the cynomolgus macaque monkey (Macaca fascicularis), to define an animal model for studying MIS gene regulation. Changes in testicular MIS mRNA with age were assessed by in situ hybridization of prepubertal to adult testes, Northern analysis of pubertal and adult specimens, and determination of serum MIS concentrations from infancy to adulthood. We found that MIS expression was highest in the youngest animals and decreased progressively with increasing …
Mullerian-Inhibiting Substance Type Ii Receptor Expression And Function In Purified Rat Leydig Cells, Mary Lee, C. Seah, P. Masiakos, Chantal Sottas, F. Preffer, Patricia Donahoe, David Maclaughlin, Matthew Hardy
Mullerian-Inhibiting Substance Type Ii Receptor Expression And Function In Purified Rat Leydig Cells, Mary Lee, C. Seah, P. Masiakos, Chantal Sottas, F. Preffer, Patricia Donahoe, David Maclaughlin, Matthew Hardy
Mary M. Lee
Mullerian-inhibiting substance (MIS), a gonadal hormone in the transforming growth factor-beta superfamily, induces Mullerian duct involution during male sexual differentiation. Mice with null mutations of the MIS ligand or receptor develop Leydig cell hyperplasia and neoplasia in addition to retained Mullerian ducts, whereas MIS-overexpressing transgenic mice have decreased testosterone concentrations and Leydig cell numbers. We hypothesized that MIS directly modulates Leydig cell proliferation and differentiated function in the maturing testis. Therefore, highly purified rat Leydig and Sertoli cells were isolated to examine cell-specific expression, binding, and function of the MIS type II receptor. These studies revealed that this receptor is …
Isolation Of The Rat Gene For Mullerian Inhibiting Substance, Christopher Haqq, Mary Lee, Richard Tizard, Mark Wysk, Janice Demarinis, Patricia Donahoe, Richard Cate
Isolation Of The Rat Gene For Mullerian Inhibiting Substance, Christopher Haqq, Mary Lee, Richard Tizard, Mark Wysk, Janice Demarinis, Patricia Donahoe, Richard Cate
Mary M. Lee
Mullerian inhibiting substance (MIS), a testicular glycoprotein also known as anti-Mullerian hormone, plays a key role in male sexual development by causing regression of the Mullerian duct, the anlagen of the uterus, the Fallopian tubes, and part of the vagina. MIS is also expressed in the postnatal ovary, but its precise function is still not known. We report here the complete nucleotide sequence of the rat MIS gene. Rat MIS is encoded in five exons and is synthesized as a precursor of 553 amino acids, containing a 24-amino-acid leader. Based on homology with human MIS, we predict that the rat …
Effect Of E. Coli Endotoxin On Mammalian Cell Growth And Recombinant Protein Production, J. Epstein, Mary Lee, C. Kelly, Patricia Donahoe
Effect Of E. Coli Endotoxin On Mammalian Cell Growth And Recombinant Protein Production, J. Epstein, Mary Lee, C. Kelly, Patricia Donahoe
Mary M. Lee
No abstract provided.
Mullerian Inhibiting Substance Messenger Ribonucleic Acid Expression In Granulosa And Sertoli Cells Coincides With Their Mitotic Activity, Seiichi Hirobe, Wei He, Mary Lee, Patricia Donahoe
Mullerian Inhibiting Substance Messenger Ribonucleic Acid Expression In Granulosa And Sertoli Cells Coincides With Their Mitotic Activity, Seiichi Hirobe, Wei He, Mary Lee, Patricia Donahoe
Mary M. Lee
In males, Mullerian inhibiting substance (MIS) mRNA was first detected on the medial aspect of the urogenital ridge early on the morning of day 13 of gestation before testicular differentiation was evident, and localized to the more obvious Sertoli cells later on embryonic day 13. MIS transcripts remained at maximal levels between 14.5 and 17.5 days gestation, while the Mullerian duct involutes, and remained high until birth. MIS gene expression decreased progressively after birth and, as germ cell meiosis increased, became barely detectable in the Sertoli cells of the seminiferous tubules. In female rats, MIS mRNA was first detected in …
Endogenous Inhibitor Proteins That Connect Ser/Thr Kinases And Phosphatases In Cell Signaling., Masumi Eto, David L Brautigan
Endogenous Inhibitor Proteins That Connect Ser/Thr Kinases And Phosphatases In Cell Signaling., Masumi Eto, David L Brautigan
Department of Molecular Physiology and Biophysics Faculty Papers
Protein phosphatase activity acts as a primary determinant of the extent and duration of phosphorylation of cellular proteins in response to physiological stimuli. Ser/Thr protein phosphatase-1 (PP1) belongs to the PPP superfamily, and is associated with regulatory subunits that confer substrate specificity, allosteric regulation, and subcellular compartmentalization. In addition, all eukaryotic cells contain multiple heat-stable proteins that originally were thought to inhibit phosphatase catalytic subunits released from the regulatory subunits, as a fail-safe mechanism. However, discovery of C-kinase-activated PP1 inhibitor, Mr of 17 kDa (CPI-17) required fresh thinking about the endogenous inhibitors as specific regulators of particular phosphatase complexes, acting …
The Caenorhabditis Elegans F-Box Protein Sel-10 Promotes Female Development And May Target Fem-1 And Fem-3 For Degradation By The Proteasome, Sibylle Jager, Hillel T. Schwartz, H. Robert Horvitz, Barbara Conradt
The Caenorhabditis Elegans F-Box Protein Sel-10 Promotes Female Development And May Target Fem-1 And Fem-3 For Degradation By The Proteasome, Sibylle Jager, Hillel T. Schwartz, H. Robert Horvitz, Barbara Conradt
Dartmouth Scholarship
The Caenorhabditis elegans F-box protein SEL-10 and its human homolog have been proposed to regulate LIN-12 Notch signaling by targeting for ubiquitin-mediated proteasomal degradation LIN-12 Notch proteins and SEL-12 PS1 presenilins, the latter of which have been implicated in Alzheimer's disease. We found that sel-10 is the same gene as egl-41, which previously had been defined by gain-of-function mutations that semidominantly cause masculinization of the hermaphrodite soma. Our results demonstrate that mutations causing loss-of-function of sel-10 also have masculinizing activity, indicating that sel-10 functions to promote female development. Genetically, sel-10 acts upstream of the genes fem-1, fem-2, and fem-3 and …
Minus-End Capture Of Preformed Kinetochore Fibers Contributes To Spindle Morphogenesis, Alexey Khodjakov, Lily Copenagle, Michael B. Gordon, Duane A. Compton, Tarun M. Kapoor
Minus-End Capture Of Preformed Kinetochore Fibers Contributes To Spindle Morphogenesis, Alexey Khodjakov, Lily Copenagle, Michael B. Gordon, Duane A. Compton, Tarun M. Kapoor
Dartmouth Scholarship
Near-simultaneous three-dimensional fluorescence/differential interference contrast microscopy was used to follow the behavior of microtubules and chromosomes in living alpha-tubulin/GFP-expressing cells after inhibition of the mitotic kinesin Eg5 with monastrol. Kinetochore fibers (K-fibers) were frequently observed forming in association with chromosomes both during monastrol treatment and after monastrol removal. Surprisingly, these K-fibers were oriented away from, and not directly connected to, centrosomes and incorporated into the spindle by the sliding of their distal ends toward centrosomes via a NuMA-dependent mechanism. Similar preformed K-fibers were also observed during spindle formation in untreated cells. In addition, upon monastrol removal, centrosomes established a transient …
Asymmetry Of The Central Apparatus Defines The Location Of Active Microtubule Sliding In Chlamydomonas Flagella, Matthew J. Wargo, Elizabeth F. Smith
Asymmetry Of The Central Apparatus Defines The Location Of Active Microtubule Sliding In Chlamydomonas Flagella, Matthew J. Wargo, Elizabeth F. Smith
Dartmouth Scholarship
Regulation of ciliary and flagellar motility requires spatial control of dynein-driven microtubule sliding. However, the mechanism for regulating the location and symmetry of dynein activity is not understood. One hypothesis is that the asymmetrically organized central apparatus, through interactions with the radial spokes, transmits a signal to regulate dynein-driven microtubule sliding between subsets of doublet microtubules. Based on this model, we hypothesized that the orientation of the central apparatus defines positions of active microtubule sliding required to control bending in the axoneme. To test this, we induced microtubule sliding in axonemes isolated from wild-type and mutant Chlamydomonas cells, and then …
Embryonic Chicken Fibroblast Collagen Binding Proteins: Distribution, Role In Substratum Adhesion, And Relationship To Integrins, Roy C. Ogle, A. Jeannette Potts, Marchall Yacoe, Charles D. Little
Embryonic Chicken Fibroblast Collagen Binding Proteins: Distribution, Role In Substratum Adhesion, And Relationship To Integrins, Roy C. Ogle, A. Jeannette Potts, Marchall Yacoe, Charles D. Little
Medical Diagnostics & Translational Sciences Faculty Publications
Collagen binding proteins (CBP) are hydrophobic, cell surface polypeptides, isolated by collagen affinity chromatography. Antibodies to CBPs inhibit the attachment of embryonic chicken heart fibroblasts to native type I collagen fibrils in a dose-dependent manner. The CBP antibodies also induce rounding and detachment of cells adherent to a planar substratum. This process of antibody-mediated substratum detachment resulted in a clustering of CBP and cell-associated extracellular matrix at the cell surface, and the rearrangement of filamentous actin. Other functional studies showed that cells grown within a three-dimensional gel of type I collagen cannot be immunostained at the cell surface with CBP …