Digital Commons Network^™

Fish Sound Production In The Presence Of Harmful Algal Blooms In The Eastern Gulf Of Mexico, Carrie C. Wall, Chad Lembke, Chuanmin Hu, David A. Mann

Marine Science Faculty Publications

This paper presents the first known research to examine sound production by fishes during harmful algal blooms (HABs). Most fish sound production is species-specific and repetitive, enabling passive acoustic monitoring to identify the distribution and behavior of soniferous species. Autonomous gliders that collect passive acoustic data and environmental data concurrently can be used to establish the oceanographic conditions surrounding sound-producing organisms. Three passive acoustic glider missions were conducted off west-central Florida in October 2011, and September and October 2012. The deployment period for two missions was dictated by the presence of red tide events with the glider path specifically set …

Functional And Developmental Identification Of A Molecular Subtype Of Brain Serotonergic Neuron Specialized To Regulate Breathing Dynamics, Rachael D. Brust, Andrea E. Corcoran, George B. Richerson, Eugene Nattie, Susan M. Dymecki

Dartmouth Scholarship

Serotonergic neurons modulate behavioral and physiological responses from aggression and anxiety to breathing and thermoregulation. Disorders involving serotonin (5HT) dysregulation are commensurately heterogeneous and numerous. We hypothesized that this breadth in functionality derives in part from a developmentally determined substructure of distinct subtypes of 5HT neurons each specialized to modulate specific behaviors. By manipulating developmentally defined subgroups one by one chemogenetically, we find that the Egr2-Pet1 subgroup is specialized to drive increased ventilation in response to carbon dioxide elevation and acidosis. Furthermore, this subtype exhibits intrinsic chemosensitivity and modality-specific projections-increasing firing during hypercapnic acidosis and selectively projecting to respiratory chemosensory …

Mtorc2 Is Required For Rit-Mediated Oxidative Stress Resistance, Weikang Cai, Douglas A. Andres

Molecular and Cellular Biochemistry Faculty Publications

Rit, a member of the Ras family of GTPases, has been shown to promote cell survival in response to oxidative stress, in part by directing an evolutionarily conserved p38 MAPK-Akt survival cascade. Aberrant Rit signaling has recently been implicated as a driver mutation in human cancer, adding importance to the characterization of critical Rit effector pathways. However, the mechanism by which Rit-p38 signaling regulated Akt activity was unknown. Here, we identify mTORC2 as a critical downstream mediator of Rit-dependent survival signaling in response to reactive oxygen species (ROS) stress. Rit interacts with Sin1 (MAPKAP1), and Rit loss compromises ROS-dependent mTORC2 …

Bacterial Rna:Dna Hybrids Are Activators Of The Nlrp3 Inflammasome, Sivapriya Kailasan Vanaja, Vijay A. K. Rathinam, Maninjay K. Atianand, Parisa Kalantari, Brian M. Skehan, Katherine A. Fitzgerald, John M. Leong

Katherine A. Fitzgerald

Enterohemorrhagic Escherichia coli (EHEC) is an extracellular pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome. The proinflammatory cytokine, interleukin-1beta, has been linked to hemolytic uremic syndrome. Here we identify the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome as an essential mediator of EHEC-induced IL-1beta. Whereas EHEC-specific virulence factors were dispensable for NLRP3 activation, bacterial nucleic acids such as RNA:DNA hybrids and RNA gained cytosolic access and mediated inflammasome-dependent responses. Consistent with a direct role for RNA:DNA hybrids in inflammasome activation, delivery of synthetic EHEC RNA:DNA hybrids into the cytosol triggered NLRP3-dependent responses, …

Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …

Cd151-Α3Β1 Integrin Complexes Suppress Ovarian Tumor Growth By Repressing Slug-Mediated Emt And Canonical Wnt Signaling, Lauren A. Baldwin, John T. Hoff, Jason Lefringhouse, Michael Zhang, Changhe Jia, Zeyi Liu, Sonia Erfani, Hongyan Jin, Mei Xu, Qing-Bai She, John R. Van Nagell Jr., Chi Wang, Li Chen, Rina Plattner, David M. Kaetzel, Jia Luo, Michael Lu, Dava West, Chunming Liu, Fred R. Ueland, Ronny Drapkin, Binhua P. Zhou, Xiuwei H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by …

Coral Spawning In The Gulf Of Oman And Relationship To Latitudinal Variation In Spawning Season In The Northwest Indian Ocean, E. J. Howells, D. Abrego, G. O. Vaughan, J. A. Burt

All Works

Despite a wealth of information on sexual reproduction in scleractinian corals, there are regional gaps in reproductive records. In the Gulf of the Oman in the Arabian Sea, reproductive timing was assessed in four common species of broadcast spawning corals using field surveys of gamete maturity and aquarium observations of spawning activity. The appearance of mature gametes within the same month for Acropora downingi, A. hemprichii, Cyphastrea microphthalma and Platygyra daedalea (≥ 75% of colonies, n = 848) indicated a synchronous and multi-specific spawning season. Based on gamete disappearance and direct observations, spawning predominantly occurred during April in 2013 (75- …

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

The Ethics Of Animal Research: A Survey Of Pediatric Health Care Workers, Ari Joffe, Meredith Bara, Natalie Anton, Nathan Nobis

Experimentation Collection

Introduction: Pediatric health care workers (HCW) often perform, promote, and advocate use of public funds for animal research (AR). We aim to determine whether HCW consider common arguments (and counterarguments) in support (or not) of AR convincing.

Design: After development and validation, an e-mail survey was sent to all pediatricians and pediatric intensive care unit nurses and respiratory therapists (RTs) affiliated with a Canadian University. We presented questions about demographics, support for AR, and common arguments (with their counterarguments) to justify the moral permissibility (or not) of AR. Responses are reported using standard tabulations. Responses of pediatricians and nurses/RTs were …

Transcription Of The Streptococcus Pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated By Previously Unknown Upstream Elements, Marina Falaleeva, Oliwia W. Zurek, Robert L. Watkins, Robert W. Reed, Hadeel Ali, Paul Sumby, Jovanka M. Voyich, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

The important human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the hasABC operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an …

Selection Of Reference Genes For Expression Analysis Using Quantitative Real-Time Pcr In The Pea Aphid, Acyrthosiphon Pisum (Harris) (Hemiptera, Aphidiae), Chunxiao Yang, Huipeng Pan, Yong Liu, Xuguo Zhou

Entomology Faculty Publications

To facilitate gene expression study and obtain accurate qRT-PCR analysis, normalization relative to stable expressed housekeeping genes is required. In this study, expression profiles of 11 candidate reference genes, including actin (Actin), elongation factor 1 α (EF1A), TATA-box-binding protein (TATA), ribosomal protein L12 (RPL12), β-tubulin (Tubulin), NADH dehydrogenase (NADH), vacuolar-type H+-ATPase (v-ATPase), succinate dehydrogenase B (SDHB), 28S ribosomal RNA (28S), 16S ribosomal RNA (16S), and 18S ribosomal RNA (18S) from the pea aphid Acyrthosiphon pisum, …

The Formin Fmnl3 Assembles Plasma Membrane Protrusions That Participate In Cell–Cell Adhesion, Timothy J. Gauvin, Lorna E. Young, Henry N. Higgs

Dartmouth Scholarship

FMNL3 is a vertebrate-specific formin protein previously shown to play a role in angiogenesis and cell migration. Here we define the cellular localization of endogenous FMNL3, the dynamics of GFP-tagged FMNL3 during cell migration, and the effects of FMNL3 suppression in mammalian culture cells. The majority of FMNL3 localizes in a punctate pattern, with >95% of these puncta being indistinguishable from the plasma membrane by fluorescence microscopy. A small number of dynamic cytoplasmic FMNL3 patches also exist, which enrich near cell–cell contact sites and fuse with the plasma membrane at these sites. These cytoplasmic puncta appear to be part of …

Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives

David Grünwald

The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3sigma) to be similarly regulated by Nup98. The expression …

Cannabinoid Receptor 2 Agonist Attenuates Pain Related Behavior In Rats With Chronic Alcohol/High Fat Diet Induced Pancreatitis, Liping Zhang, Robert H. Kline Iv, Terry A. Mcnearney, Michael P. Johnson, Karin Westlund High

Physiology Faculty Publications

BACKGROUND: Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in …

Novel Mutations And Mutation Combinations Of Ryanodine Receptor In A Chlorantraniliprole Resistant Population Of Plutella Xylostella (L.), Lei Guo, Pei Liang, Xuguo Zhou, Xiwu Gao

Entomology Faculty Publications

A previous study documented a glycine to glutamic acid mutation (G4946E) in ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this study, a field population collected in Yunnan province, China, exhibited a 2128-fold resistance to chlorantraniliprole. Sequence comparison between resistant and susceptible P. xylostella revealed three novel mutations including a glutamic acid to valine substitution (E1338D), a glutamine to leucine substitution (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly conserved regions of RyR. Frequency analysis of all four mutations in this field population showed that the three …

Kynurenine Aminotransferase Iii And Glutamine Transaminase L Are Identical Enzymes That Have Cysteine S-Conjugate Beta-Lyase Activity And Can Transaminate L-Selenomethionine, John T. Pinto, Boris F. Krasnikov, Steven Alcutt, Melanie E. Jones, Thambi Dorai, Arthur J L Cooper

NYMC Faculty Publications

Three of the four kynurenine aminotransferases (KAT I, II, and IV) that synthesize kynurenic acid, a neuromodulator, are identical to glutamine transaminase K (GTK), α-aminoadipate aminotransferase, and mitochondrial aspartate aminotransferase, respectively. GTK/KAT I and aspartate aminotransferase/KAT IV possess cysteine S-conjugate β-lyase activity. The gene for the former enzyme, GTK/KAT I, is listed in mammalian genome data banks as CCBL1 (cysteine conjugate beta-lyase 1). Also listed, despite the fact that no β-lyase activity has been assigned to the encoded protein in the genome data bank, is a CCBL2 (synonym KAT III). We show that human KAT III/CCBL2 possesses cysteine S-conjugate β-lyase …

Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found …

Validation Of Reference Housekeeping Genes For Gene Expression Studies In Western Corn Rootworm (Diabrotica Virgifera Virgifera), Thaís Barros Rodrigues, Chitvan Khajuria, Haichuan Wang, Natalie Matz, Danielle Cunha Cardoso, Fernando Hercos Valicente, Xuguo Zhou, Blair Siegfried

Entomology Faculty Publications

Quantitative Real-time PCR (qRT-PCR) is a powerful technique to investigate comparative gene expression. In general, normalization of results using a highly stable housekeeping gene (HKG) as an internal control is recommended and necessary. However, there are several reports suggesting that regulation of some HKGs is affected by different conditions. The western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), is a serious pest of corn in the United States and Europe. The expression profile of target genes related to insecticide exposure, resistance, and RNA interference has become an important experimental technique for study of western corn rootworms; however, lack …

Collapse Of An Ecological Network In Ancient Egypt, Justin Yeakel, Mathias Pires, Lars Rudolf, Nathaniel Dominy

Dartmouth Scholarship

The dynamics of ecosystem collapse are fundamental to determining how and why biological communities change through time, as well as the potential effects of extinctions on ecosystems. Here, we integrate depictions of mammals from Egyptian antiquity with direct lines of paleontological and archeological evidence to infer local extinctions and community dynamics over a 6,000-y span. The unprecedented temporal resolution of this dataset enables examination of how the tandem effects of human population growth and climate change can disrupt mammalian communities. We show that the extinctions of mammals in Egypt were nonrandom and that destabilizing changes in community composition coincided with …

Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster., Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen

Faculty Publications

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …

Huwe1 Is A Molecular Link Controlling Raf-1 Activity Supported By The Shoc2 Scaffold, Eun Ryoung Jang, Ping Shi, Jamal Bryant, Jing Chen, Vikas Dukhande, Matthew S. Gentry, Hyein Jang, Myoungkun Jeoung, Emilia Galperin

Molecular and Cellular Biochemistry Faculty Publications

Scaffold proteins play a critical role in controlling the activity of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Shoc2 is a leucine-rich repeat scaffold protein that acts as a positive modulator of ERK1/2 signaling. However, the precise mechanism by which Shoc2 modulates the activity of the ERK1/2 pathway is unclear. Here we report the identification of the E3 ubiquitin ligase HUWE1 as a binding partner and regulator of Shoc2 function. HUWE1 mediates ubiquitination and, consequently, the levels of Shoc2. Additionally, we show that both Shoc2 and HUWE1 are necessary to control the levels and ubiquitination of the Shoc2 signaling partner, …

Natural Selection On Thermal Performance In A Novel Thermal Environment, Michael L. Logan, Robert M. Cox, Ryan Calsbeek

Dartmouth Scholarship

Tropical ectotherms are thought to be especially vulnerable to climate change because they are adapted to relatively stable temperature regimes, such that even small increases in environmental temperature may lead to large decreases in physiological performance. One way in which tropical organisms may mitigate the detrimental effects of warming is through evolutionary change in thermal physiology. The speed and magnitude of this response depend, in part, on the strength of climate-driven selection. However, many ectotherms use behavioral adjustments to maintain preferred body temperatures in the face of environmental variation. These behaviors may shelter individuals from natural selection, preventing evolutionary adaptation …

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Katherine A. Fitzgerald

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis. Deficiency of …

Chronic Alcohol-Induced Microrna-155 Contributes To Neuroinflammation In A Tlr4-Dependent Manner In Mice, Dora Lippai, Shashi Bala, Timea Csak, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

INTRODUCTION: Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-alpha (TNFalpha), monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1beta). Toll-like receptor-4 (TLR4) pathway induced nuclear factor-kappaB (NF-kappaB) activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs) play crucial role in fine tuning gene expression and miR-155 is a major regulator of inflammation in immune cells after TLR stimulation. AIM: To evaluate the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation. METHODS: Wild type (WT), miR-155- and TLR4-knockout (KO) mice received 5% ethanol-containing or isocaloric …

Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo

Gyongyi Szabo

Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Recent studies demonstrated that Toll-like receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD and NASH. In this review, we emphasize the importance of gut-derived endotoxin and its recognition by TLR4 in the liver. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of individual cell types to the inflammation is …

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Gyongyi Szabo

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis. Deficiency of …

Myeloid Derived Hypoxia Inducible Factor 1-Alpha Is Required For Protection Against Pulmonary Aspergillus Fumigatus Infection, Kelly M. Shepardson, Anupam Jhingran, Alayna Caffrey, Joshua J. Obar, Benjamin T. Suratt, Brent L. Berwin, Tobias M. Hohl, Robert A. Cramer

Dartmouth Scholarship

Hypoxia inducible factor 1α (HIF1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A. fumigatus stabilizes HIF1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcinolone. Utilizing myeloid deficient HIF1α mice, we observed that HIF1α is required for survival and fungal clearance early following pulmonary challenge with A. fumigatus. Unlike previously reported research with bacterial …

Annotated Bibliography: Attitudes Toward Animal Research (1998-2013), Erich Yahner

BIBLIOGRAPHIES

No abstract provided.

Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both …

P19ink4d And P18ink4c Cyclin-Dependent Kinase Inhibitors In The Male Reproductive Axis, Gregory Buchold, Patricia Magyar, Ramamani Arumugam, Mary Lee, Deborah O'Brien

Mary M. Lee

The loss of the cyclin-dependent kinase inhibitors (CKIs) p18(Ink4c) and p19(Ink4d) leads to male reproductive defects (Franklin et al., 1998. Genes Dev 12: 2899-2911; Zindy et al., 2000. Mol Cell Biol 20: 372-378; Zindy et al., 2001. Mol Cell Biol 21: 3244-3255). In order to assess whether these inhibitors directly or indirectly affect male germ cell differentiation, we examined the expression of p18(Ink4c) and p19(Ink4d) in spermatogenic and supporting cells in the testis and in pituitary gonadotropes. Both p18(Ink4c) and p19(Ink4d) are most abundant in the testis after 18 days of age and are expressed in purified populations of spermatogenic …