Medicine and Health Sciences Commons^™

A Model Of The Roles Of Essential Kinases In The Induction And Expression Of Late Long-Term Potentiation, Paul Smolen, Douglas A. Baxter, John H. Byrne

Faculty, Staff and Student Publications

The induction of late long-term potentiation (L-LTP) involves complex interactions among second-messenger cascades. To gain insights into these interactions, a mathematical model was developed for L-LTP induction in the CA1 region of the hippocampus. The differential equation-based model represents actions of protein kinase A (PKA), MAP kinase (MAPK), and CaM kinase II (CAMKII) in the vicinity of the synapse, and activation of transcription by CaM kinase IV (CAMKIV) and MAPK. L-LTP is represented by increases in a synaptic weight. Simulations suggest that steep, supralinear stimulus-response relationships between stimuli (e.g., elevations in [Ca(2+)]) and kinase activation are essential for translating brief …

Cardiac-Specific Elevations In Thyroid Hormone Enhance Contractility And Prevent Pressure Overload-Induced Cardiac Dysfunction, Maria G. Trivieri, Gavin Y. Oudit, Rajan Sah, Benoit-Giles Kerfant, Hui Sun, Anthony O. Gramolini, Yan Pan, Alan D. Wickenden, Walburga Croteau

Dartmouth Scholarship

Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and …

Voltage-Dependent Gating Rearrangements In The Intracellular T1-T1 Interface Of A K+ Channel., Guangyu Wang, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The intracellular tetramerization domain (T1) of most eukaryotic voltage-gated potassium channels (Kv channels) exists as a "hanging gondola" below the transmembrane regions that directly control activation gating via the electromechanical coupling between the S4 voltage sensor and the main S6 gate. However, much less is known about the putative contribution of the T1 domain to Kv channel gating. This possibility is mechanistically intriguing because the T1-S1 linker connects the T1 domain to the voltage-sensing domain. Previously, we demonstrated that thiol-specific reagents inhibit Kv4.1 channels by reacting in a state-dependent manner with native Zn(2+) site thiolate groups in the T1-T1 interface; …

Bifurcation And Singularity Analysis Of A Molecular Network For The Induction Of Long-Term Memory, Hao Song, Paul Smolen, Evyatar Av-Ron, Douglas A. Baxter, John H H. Byrne

Faculty, Staff and Student Publications

Withdrawal reflexes of the mollusk Aplysia exhibit sensitization, a simple form of long-term memory (LTM). Sensitization is due, in part, to long-term facilitation (LTF) of sensorimotor neuron synapses. LTF is induced by the modulatory actions of serotonin (5-HT). Pettigrew et al. developed a computational model of the nonlinear intracellular signaling and gene network that underlies the induction of 5-HT-induced LTF. The model simulated empirical observations that repeated applications of 5-HT induce persistent activation of protein kinase A (PKA) and that this persistent activation requires a suprathreshold exposure of 5-HT. This study extends the analysis of the Pettigrew model by applying …

Abnormal Expression Of Rest/Nrsf And Myc In Neural Stem/Progenitor Cells Causes Cerebellar Tumors By Blocking Neuronal Differentiation, Xiaohua Su, Vidya Gopalakrishnan, Duncan Stearns, Kenneth Aldape, Fredrick F Lang, Gregory Fuller, Evan Snyder, Charles G Eberhart, Sadhan Majumder

Faculty, Staff and Student Publications

Medulloblastoma, one of the most malignant brain tumors in children, is thought to arise from undifferentiated neural stem/progenitor cells (NSCs) present in the external granule layer of the cerebellum. However, the mechanism of tumorigenesis remains unknown for the majority of medulloblastomas. In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes. Previous studies have shown that neither c-Myc nor REST/NRSF alone could cause tumor formation. To determine whether c-Myc and REST/NRSF act together to cause medulloblastomas, we used a …

Hepatic And Renal Cytochrome P450 Gene Regulation During Citrobacter Rodentium Infection In Wild-Type And Toll-Like Receptor 4 Mutant Mice, Terrilyn A Richardson, Melanie Sherman, Leposava Antonovic, Sean S Kardar, Henry W Strobel, Daniel Kalman, Edward T Morgan

Faculty, Staff and Student Publications

Citrobacter rodentium is the rodent equivalent of human enteropathogenic Escherichia coli infection. This study investigated regulation of hepatic and renal cytochrome P450 (P450) mRNAs, hepatic P450 proteins, cytokines, and acute phase proteins during C. rodentium infection. Female C3H/HeOuJ (HeOu) and C3H/HeJ (HeJ) mice [which lack functional toll-like receptor 4 (TLR4)] were infected with C. rodentium by oral gavage and sacrificed 6 days later. Hepatic CYP4A10 and 4A14 mRNAs were decreased in HeOu mice (

A Pdz-Binding Motif As A Critical Determinant Of Rho Guanine Exchange Factor Function And Cell Phenotype, Miaoliang Liu, Arie Horowitz

Dartmouth Scholarship

We identified a Rho guanine exchange factor (GEF) expressed as two splice variants, which differ only in either having or lacking a Postsynaptic density 95, Disk large, Zona occludens-1 (PDZ) motif. The PDZ adaptor protein synectin bound the longer splice variant, Syx1, which was targeted to the plasma membrane in a synectin-dependent manner. The shorter variant, Syx2, was diffusely distributed in the cytoplasm. Fluorescence resonance energy transfer (FRET) imaging revealed similar differences between the spatial patterns of active RhoA in Syx1 versus Syx2-expressing cells. Expression of Syx1 augmented endothelial cell (EC) migration and tube formation, whereas Syx2 expression did not. …

H2-M3-Restricted Cd8+ T Cells Are Not Required For Mhc Class Ib-Restricted Immunity Against Listeria Monocytogenes, Sarah E. F. D'Orazio, Christine A. Shaw, Michael N. Starnbach

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Studies using major histocompatibility complex (MHC)-Ia–deficient mice have shown that MHC-Ib–restricted CD8⁺ T cells can clear infections caused by intracellular pathogens such as Listeria monocytogenes. M3-restricted CD8⁺ T cells, which recognize short hydrophobic N-formylated peptides, appear to comprise a substantial portion of the MHC-Ib–restricted T cell response in the mouse model of L. monocytogenes infection. In this study, we isolated formyltransferase (fmt) mutant strains of L. monocytogenes that lacked the ability to add formyl groups to nascent polypeptides. These fmt mutant Listeria strains did not produce antigens that could be recognized by M3-restricted T …

Loss Of Sparc-Mediated Vegfr-1 Suppression After Injury Reveals A Novel Antiangiogenic Activity Of Vegf-A, Miho Nozaki, Eiji Sakurai, Brian J. Raisler, Judit Z. Baffi, Jassir Witta, Yuichiro Ogura, Rolf A. Brekken, E Helene Sage, Balamurali K. Ambati, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

VEGF-A promotes angiogenesis in many tissues. Here we report that choroidal neovascularization (CNV) incited by injury was increased by excess VEGF-A before injury but was suppressed by VEGF-A after injury. This unorthodox antiangiogenic effect was mediated via VEGFR-1 activation and VEGFR-2 deactivation, the latter via Src homology domain 2-containing (SH2-containing) tyrosine phosphatase-1 (SHP-1). The VEGFR-1-specific ligand placental growth factor-1 (PlGF-1), but not VEGF-E, which selectively binds VEGFR-2, mimicked these responses. Excess VEGF-A increased CNV before injury because VEGFR-1 activation was silenced by secreted protein, acidic and rich in cysteine (SPARC). The transient decline of SPARC after injury revealed a temporal …

Na+/K+ -Atpase Regulates Tight Junction Formation And Function During Mouse Preimplantation Development., Michelle I Violette, Pavneesh Madan, Andrew J Watson

Obstetrics & Gynaecology Publications

Research applied to the early embryo is required to effectively treat human infertility and to understand the primary mechanisms controlling development to the blastocyst stage. The present study investigated whether the Na(+)/K(+)-ATPase regulates tight junction formation and function during blastocyst formation. To investigate this hypothesis, three experimental series were conducted. The first experiments defined the optimal dose and treatment time intervals for ouabain (a potent and specific inhibitor of the Na(+)/K(+)-ATPase) treatment. The results demonstrated that mouse embryos maintained a normal development to the blastocyst stage following a 6-h ouabain treatment. The second experiments investigated the effects of ouabain treatment …

Beta 1-Integrins Are Required For Hippocampal Ampa Receptor-Dependent Synaptic Transmission, Synaptic Plasticity, And Working Memory, Chi-Shing Chan, Edwin J. Weeber, Lin Zong, Elaine Fuchs, J David Sweatt, Ronald L. Davis

Faculty, Staff and Students Publications

Integrins comprise a large family of cell adhesion receptors that mediate diverse biological events through cell-cell and cell-extracellular matrix interactions. Recent studies have shown that several integrins are localized to synapses with suggested roles in synaptic plasticity and memory formation. We generated a postnatal forebrain and excitatory neuron-specific knock-out of beta1-integrin in the mouse. Electrophysiological studies demonstrated that these mutants have impaired synaptic transmission through AMPA receptors and diminished NMDA receptor-dependent long-term potentiation. Despite the impairment in hippocampal synaptic transmission, the mutants displayed normal hippocampal-dependent spatial and contextual memory but were impaired in a hippocampal-dependent, nonmatching-to-place working memory task. These …

Cutaneous And Presumed Visceral Leishmaniasis In A Soldier Deployed To Afghanistan, James P. Woodrow, Joshua D. Hartzell, Jim Czarnik, David Brett-Major, Glenn Wortmann

Journal Articles: Epidemiology

Leishmaniasis has been frequently diagnosed in US military personnel returning from duty in Southwest Asia. The majority of cases have demonstrated cutaneous disease, although a few cases of visceral disease have been documented. We present the case of an immunocompetent, HIV-negative, US Army soldier who suffered both visceral and cutaneous manifestations of leishmaniasis after returning from deployment in Afghanistan. Overlap of cutaneous and visceral involvement is rare and has not been reported in our cohort. Latent Plasmodium vivax infection may have been an exacerbating cofactor. We discuss this case and present a review of the literature.

Paired-Pulse Depression At Photoreceptor Synapses., Katalin Rabl, Lucia Cadetti, Wallace B. Thoreson

Journal Articles: Ophthalmology

Synaptic depression produced by repetitive stimulation is likely to be particularly important in shaping responses of second-order retinal neurons at the tonically active photoreceptor synapse. We analyzed the time course and mechanisms of synaptic depression at rod and cone synapses using paired-pulse protocols involving two complementary measurements of exocytosis: (1) paired whole-cell recordings of the postsynaptic current (PSC) in second-order retinal neurons and (2) capacitance measurements of vesicular membrane fusion in rods and cones. PSCs in ON bipolar, OFF bipolar, and horizontal cells evoked by stimulation of either rods or cones recovered from paired-pulse depression (PPD) at rates similar to …

Characterization Of Hard2, A Processed Hard1 Gene Duplicate, Encoding A Human Protein N-Alpha-Acetyltransferase., Thomas Arnesen, Matthew J Betts, Frédéric Pendino, David A Liberles, Dave Anderson, Jaime Caro, Xianguo Kong, Jan E Varhaug, Johan R Lillehaug

Department of Medicine Faculty Papers

BACKGROUND: Protein acetylation is increasingly recognized as an important mechanism regulating a variety of cellular functions. Several human protein acetyltransferases have been characterized, most of them catalyzing epsilon-acetylation of histones and transcription factors. We recently described the human protein acetyltransferase hARD1 (human Arrest Defective 1). hARD1 interacts with NATH (N-Acetyl Transferase Human) forming a complex expressing protein N-terminal alpha-acetylation activity. RESULTS: We here describe a human protein, hARD2, with 81 % sequence identity to hARD1. The gene encoding hARD2 most likely originates from a eutherian mammal specific retrotransposition event. hARD2 mRNA and protein are expressed in several human cell lines. …

Statins And The Vasculopathy Of Systemic Sclerosis: Potential Therapeutic Agents?, Chris T. Derk, Sergio A. Jimenez

Department of Medicine Faculty Papers

It has been postulated that endothelial cell injury is the initiating event in the pathogenesis of systemic sclerosis, causing attraction, attachment, migration and infiltration of activated T-cells and subsequent production of cytokines and growth factors. As a result of the action of these cytokines and growth factors, chemoattraction of fibroblasts into the vessel wall and transdifferentiation of resident fibroblasts and smooth muscle cells into myofibroblasts occur leading to fibrosis and exaggerated collagen deposition in the vessel wall. To date, the therapeutic options for the vasculopathy of systemic sclerosis have been limited to drugs that cause vasodilation and inhibit platelet aggregation …

Smc3 Knockdown Triggers Genomic Instability And P53-Dependent Apoptosis In Human And Zebrafish Cells., Giancarlo Ghiselli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The structural maintenance of chromosome 3 (SMC3) protein is a constituent of a number of nuclear multimeric protein complexes that are involved in DNA recombination and repair in addition to chromosomal segregation. Overexpression of SMC3 activates a tumorigenic cascade through which mammalian cells acquire a transformed phenotype. This has led us to examine in depth how SMC3 level affects cell growth and genomic stability. In this paper the effect of SMC3 knockdown has been investigated. RESULTS: Mammalian cells that are SMC3 deficient fail to expand in a clonal population. In order to shed light on the underlying mechanism, experiments …

No Vaccine Against Hiv Yet--Are We Not Perfectly Equipped?, Mahender Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Enormous effort has been devoted to the development of a vaccine against human immunodeficiency virus (HIV). But it is proving to be an unprecedented challenge to create an effective vaccine mainly due to the high genetic variability of the virus and the necessity of cytotoxic T lymphocytes (CTL) for containing the infection. Currently pursued vaccine strategies appear to induce CTL in nonhuman primate models but in the early clinical trials, these strategies fail to fully control the viral infection. New strategies that can cover the vast genetic diversity of HIV are needed for the development of a potent vaccine.

Determination Of Some Virulence Factors In Staphylococcus Spp. Isolated From Various Clinical Samples, Süheyla Türkyilmaz, Osman Kaya

Turkish Journal of Veterinary & Animal Sciences

The objectives of this study were to identify staphylococci isolated from different animal clinical samples, to examine some of the virulence factors in the isolates, to determine relationships between these virulence factors and coagulase positive Staphylococcus (CoPS)/coagulase negative Staphylococcus (CoNS) strains. A total of 180 strains of Staphylococcus spp. were isolated from bovine mastitis, dogs with otitis externa and chickens with various infections. The isolates were identified as S. aureus (29.4%), S. hyicus (16.7%), S. intermedius (3.9%), S. chromogenes (16.1%), S. lentus (13.3%), S. epidermidis (11.1%), S. simulans (7.8%) and S. haemolyticus (1.7%). The rate of positiveness for deoxyribonuclease (DNase) …

Embryonic Stem Cell-Derived Hematopoietic Stem Cells, Yuan Wang, Frank Yates, Olaia Naveiras, Patricia Ernst, George Q. Daley

Dartmouth Scholarship

Despite two decades of studies documenting the in vitro blood-forming potential of murine embryonic stem cells (ESCs), achieving stable long-term blood engraftment of ESC-derived hematopoietic stem cells in irradiated mice has proven difficult. We have exploited the Cdx-Hox pathway, a genetic program important for blood development, to enhance the differentiation of ESCs along the hematopoietic lineage. Using an embryonic stem cell line engineered with tetracycline-inducible Cdx4 , we demonstrate that ectopic Cdx4 expression promotes hematopoietic mesoderm specification, increases hematopoietic progenitor formation, and, together with HoxB4, enhances multilineage hematopoietic engraftment of lethally irradiated adult mice. Clonal analysis of retroviral integration sites …

Placental Expression Of Angiopoietin-1, Angiopoietin-2 And Tie-2 During Placental Development In An Ovine Model Of Placental Insufficiency-Fetal Growth Restriction., Amy S Erickson Hagen, Ryan J Orbus, Randall B Wilkening, Timothy Regnault, Russell V Anthony

Paediatrics Publications

Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, and often results from functional placental insufficiency. Placentation requires extensive vasculogenesis and subsequent angiogenesis, in both maternal and fetal tissues. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are angiogenic growth factors expressed in the placenta, and compete for binding to a common receptor, Tunica interna endothelial cell kinase-2 (Tie-2). Our objective was to examine Ang-1, Ang-2 and Tie-2 expression in ovine placental tissue obtained from normal and FGR pregnancies throughout gestation. Fetal cotyledon and maternal caruncle tissue concentrations of Ang-1, Ang-2 and Tie-2 mRNA were assessed by real-time reverse transcriptase-polymerase …

The Caenorhabditis Elegans Heterochronic Regulator Lin-14 Is A Novel Transcription Factor That Controls The Developmental Timing Of Transcription From The Insulin/Insulin-Like Growth Factor Gene Ins-33 By Direct Dna Binding, Marta Hristova, Darcy Birse, Yang Hong, Victor Ambros

Dartmouth Scholarship

A temporal gradient of the novel nuclear protein LIN-14 specifies the timing and sequence of stage-specific developmental events in Caenorhabditis elegans. The profound effects of lin-14 mutations on worm development suggest that LIN-14 directly or indirectly regulates stage-specific gene expression. We show that LIN-14 can associate with chromatin in vivo and has in vitro DNA binding activity. A bacterially expressed C-terminal domain of LIN-14 was used to select DNA sequences that contain a putative consensus binding site from a pool of randomized double-stranded oligonucleotides. To identify candidates for genes directly regulated by lin-14, we employed DNA microarray hybridization to compare …

Selective Role For Superoxide In Insp3 Receptor-Mediated Mitochondrial Dysfunction And Endothelial Apoptosis., Muniswamy Madesh, Brian J Hawkins, Tatyana Milovanova, Cunnigaiper D Bhanumathy, Suresh K Joseph, Satish P Ramachandrarao, Kumar Sharma, Tomohiro Kurosaki, Aron B Fisher

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Reactive oxygen species (ROS) play a divergent role in both cell survival and cell death during ischemia/reperfusion (I/R) injury and associated inflammation. In this study, ROS generation by activated macrophages evoked an intracellular Ca2+ ([Ca2+]i) transient in endothelial cells that was ablated by a combination of superoxide dismutase and an anion channel blocker. [Ca2+]i store depletion, but not extracellular Ca2+ chelation, prevented [Ca2+]i elevation in response to O2*- that was inositol 1,4,5-trisphosphate (InsP3) dependent, and cells lacking the three InsP3 receptor (InsP3R) isoforms failed to display the [Ca2+]i transient. Importantly, the O2*--triggered Ca2+ mobilization preceded a loss in mitochondrial membrane …

A Drosophila Deg/Enac Channel Subunit Is Required For Male Response To Female Pheromones, Heping Lin, Kevin J. Mann, Elena Starostina, Ronald D. Kinser, Claudio W. Pikielny

Dartmouth Scholarship

Odorants and pheromones as well as sweet- and bitter-tasting small molecules are perceived through activation of G protein-coupled chemosensory receptors. In contrast, gustatory detection of salty and sour tastes may involve direct gating of sodium channels of the DEG/ENaC family by sodium and hydrogen ions, respectively. We have found that ppk25, a Drosophila melanogaster gene encoding a DEG/ENaC channel subunit, is expressed at highest levels in the male appendages responsible for gustatory and olfactory detection of female pheromones: the legs, wings, and antennae. Mutations in the ppk25 gene reduce or even abolish male courtship response to females in the dark, …

Roles Of Na,K-Atpase In Early Development And Trophectoderm Differentiation., Gerald M Kidder, Andrew J Watson

Obstetrics & Gynaecology Publications

Before implantation into the uterine wall, the mammalian embryo undergoes a period of cell division, cell shape change, and cell differentiation leading to the formation of an outer epithelium, the trophectoderm. The trophectoderm is the part of the embryo that initiates uterine contact and, after transformation to become the trophoblast, uterine invasion. Similar to the kidney nephron, the trophectoderm is a transporting epithelium with distinct apical and basolateral membrane domains; its function is to facilitate transepithelial Na+ and fluid transport for blastocoel formation. That transport is driven by Na,K-adenosine triphosphatase (ATPase) localized in basolateral membranes of the trophectoderm. Preimplantation embryos …

C-Jun N-Terminal Kinase (Jnk) Is Required For Survival And Proliferation Of B-Lymphoma Cells, Murali Gururajan, Roger Chui, Anbu K. Karuppannan, Jiyuan Ke, C. Darrell Jennings, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Several primary murine and human B lymphomas and cell lines were found to constitutively express high levels of the activated form of c-jun N-terminal kinase (JNK), a member of the mitogen-activated protein (MAP) kinase family. Proliferation of murine B lymphomas CH31, CH12.Lx, BKS-2, and WEHI-231 and the human B lymphomas BJAB, RAMOS, RAJI, OCI-Ly7, and OCI-Ly10 was strongly inhibited by SP600125, an anthrapyrazolone inhibitor of JNK, in a dose-dependent manner. The lymphoma cells underwent apoptosis and arrested at the G2/M phase of cell cycle. Furthermore, JNK-specific small interfering RNA (siRNA) inhibited the growth of both murine and human B lymphomas. …

P38 Mitogen-Activated Protein Kinase (Mapk) First Regulates Filamentous Actin At The 8-16-Cell Stage During Preimplantation Development., Andrew J M Paliga, David R Natale, Andrew J Watson

Obstetrics & Gynaecology Publications

BACKGROUND INFORMATION: The MAPK (mitogen-activated protein kinase) superfamily of proteins consists of four separate signalling cascades: the c-Jun N-terminal kinase or stress-activated protein kinases (JNK/SAPK); the ERKs (extracellular-signal-regulated kinases); the ERK5 or big MAPK1; and the p38 MAPK group of protein kinases, all of which are highly conserved. To date, our studies have focused on defining the role of the p38 MAPK pathway during preimplantation development. p38 MAPK regulates actin filament formation through the downstream kinases MAPKAPK2/3 (MAPK-activated protein kinase 2/3) or MAPKAPK5 [PRAK (p38 regulated/activated kinase)] and subsequently through HSP25/27 (heat-shock protein 25/27). We recently reported that 2-cell-stage murine …

Tcpf Is A Soluble Colonization Factor And Protective Antigen Secreted By El Tor And Classical O1 And O139 Vibrio Cholerae Serogroups, Thomas J. Kirn, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae causes diarrhea by colonizing the human small bowel and intoxicating epithelial cells. Colonization is a required step in pathogenesis, and strains defective for colonization are significantly attenuated. The best-characterized V. cholerae colonization factor is the toxin-coregulated pilus (TCP). It has been demonstrated that TCP is required for V. cholerae colonization in both humans and mice. TCP enhances bacterial interactions that allow microcolony formation and thereby promotes survival in the intestine. We have recently discovered that the TCP biogenesis apparatus also serves as a secretion system, mediating the terminal step in the extracellular secretion pathway of TcpF. TcpF was …

A Critical Role For The Programmed Death Ligand 1 In Fetomaternal Tolerance, Indira Guleria, Arezou Khosroshahi, Mohammed Javeed Ansari, Antje Habicht, Miyuki Azuma, Hideo Yagita, Randolph J. Noelle

Dartmouth Scholarship

Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell

Mitogen-Activated Protein Kinase (Mapk) Blockade Of Bovine Preimplantation Embryogenesis Requires Inhibition Of Both P38 And Extracellular Signal-Regulated Kinase (Erk) Pathways., Pavneesh Madan, Michele D Calder, Andrew J Watson

Obstetrics & Gynaecology Publications

Blastocyst formation, as a critical period during development, is an effective indicator of embryonic health and reproductive efficiency. Out of a number of mechanisms underlying blastocyst formation, highly conserved mitogen-activated protein kinase (MAPK) signaling has emerged as a major mechanism involved in regulating murine preimplantation embryo development. The objective of our study was to ascertain the role of MAPK signaling in regulating bovine development to the blastocyst stage. Using reverse transcriptase PCR and immunohistochemical staining procedures we have demonstrated that mRNA transcripts and polypeptides encoding p38 MAPK pathway constituents are detectable in preimplantation bovine embryos from the one-cell to the …

Organization And Signal Processing Of The Descending Tracts In The Cervical Spinal Cord, Yanmei Tie

Doctoral Dissertations

This dissertation addresses the research for the development of spinal cord-computer interface (SCCI). The main objective of SCCI is to generate voluntary motor control signals for individuals with spinal cord injury (SCI).

In the neuroscience aspect, organization of the fibers in the descending tracts of the dorsolateral funiculus of the cervical spinal cord was investigated in cats. The spinal cord was penetrated with silicon substrate microelectrodes at 400 μm intervals in the medio-lateral direction at the C5/C6 and C6/C7 segmental borders. The stimulus consisted of a 20 ms train of charge-balanced biphasic pulses at 330 Hz. The evoked activities from …