Digital Commons Network^™

Animal Models For Periodontal Disease, Helieh S. Oz, David A. Puleo

Center for Oral Health Research Faculty Publications

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or …

Β-Lactams Interfering With Pbp1 Induce Panton-Valentine Leukocidin Expression By Triggering Sara And Rot Global Regulators Of Staphylococcus Aureus, Oana Dumitrescu, Priya Choudhury, Sandrine Boisset, Cedric Badiou, Michele Bes, Yvonne Benito, Christiane Wolz, Francois Vandenesch, Jerome Etienne, Ambrose L. Cheung

Dartmouth Scholarship

Previous articles reported that beta-lactam antibiotics increase the expression of Staphylococcus aureus Panton-Valentine leukocidin (PVL) by activating its transcription. We investigated the mechanisms underlying the inductor effect of beta-lactams on PVL expression by determining targets and regulatory pathways possibly implicated in this process. We measured PVL production in the presence of oxacillin (nonselective), imipenem (penicillin-binding protein 1 [PBP1] selective), cefotaxime (PBP2 s

The Hypoxia-Adenosine Link During Myocardial Ischemia—Reperfusion Injury, Diana Panesso, Maria C Montealegre, Sandra Rincón, Maria F Mojica, Louis B Rice, Kavindra V Singh, Barbara E Murray, Cesar A Arias

Faculty, Staff and Student Publications

BACKGROUND: Plasmids containing hylEfm (pHylEfm) were previously shown to increase gastrointestinal colonization and lethality of Enterococcus faecium in experimental peritonitis. The hylEfm gene, predicting a glycosyl hydrolase, has been considered as a virulence determinant of hospital-associated E. faecium, although its direct contribution to virulence has not been investigated. Here, we constructed mutants of the hylEfm-region and we evaluated their effect on virulence using a murine peritonitis model.

RESULTS: Five mutants of the hylEfm-region of pHylEfmTX16 from the sequenced endocarditis strain (TX16 [DO]) were obtained using an adaptation of the PheS* system and were evaluated in a commensal strain TX1330RF to …

Can Oxygen Set Thermal Limits In An Insect And Drive Gigantism?, Wilco C.E.P. Verberk, David T. Bilton

School of Biological and Marine Sciences

BACKGROUND: Thermal limits may arise through a mismatch between oxygen supply and demand in a range of animal taxa. Whilst this oxygen limitation hypothesis is supported by data from a range of marine fish and invertebrates, its generality remains contentious. In particular, it is unclear whether oxygen limitation determines thermal extremes in tracheated arthropods, where oxygen limitation may be unlikely due to the efficiency and plasticity of tracheal systems in supplying oxygen directly to metabolically active tissues. Although terrestrial taxa with open tracheal systems may not be prone to oxygen limitation, species may be affected during other life-history stages, particularly …

A Retinoic Acid–Dependent Checkpoint In The Development Of Cd4+ T Cell–Mediated Immunity, Karina Pino-Lagos, Yanxia Guo, Chrysothemis Brown, Matthew P. Alexander, Raúl Elgueta, Kathryn A. Bennett, Victor De Vries, Elizabeth Nowak, Rune Blomhoff, Shanthini Sockanathan, Roshantha A. Chandraratna, Ethan Dmitrovsky, Randolph J. Noelle

Dartmouth Scholarship

It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4⁺ T cell effector function, migration, and polarity. These findings provide a new perspective of the role of …

The Eagleville Times,Volume 9, Issue 1, Debbie Ryan

Eagleville Times

No abstract provided.

Direct Cloning Of Double-Stranded Rnas From Rnase Protection Analysis Reveals Processing Patterns Of C/D Box Snornas And Provides Evidence For Widespread Antisense Transcript Expression, Manli Shen, Eduardo Eyras, Jie Wu, Amit Khanna, Serene Josiah, Mathieu Rederstorff, Michael Q. Zhang, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

We describe a new method that allows cloning of double-stranded RNAs (dsRNAs) that are generated in RNase protection experiments. We demonstrate that the mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs. Surprisingly, the majority of cloned RNAs from RNase protection experiments were derived from endogenous cellular RNA, indicating widespread antisense expression. The cloned dsRNAs could be mapped to genome areas that show RNA expression on both DNA strands and partially overlapped with experimentally determined argonaute-binding sites. The data suggest a conserved processing pattern …

High In Situ Repeatability Of Behaviour Indicates Animal Personality In The Beadlet Anemone Actinia Equina (Cnidaria)., Mark Briffa, Julie Greenaway

School of Biological and Marine Sciences

'Animal personality' means that individuals differ from one another in either single behaviours or suites of related behaviours in a way that is consistent over time. It is usually assumed that such consistent individual differences in behaviour are driven by variation in how individuals respond to information about their environment, rather than by differences in external factors such as variation in microhabitat. Since behavioural variation is ubiquitous in nature we might expect 'animal personality' to be present in diverse taxa, including animals with relatively simple nervous systems. We investigated in situ startle responses in a sea anemone, Actinia equina, to …

Tdp-43 Potentiates Alpha-Synuclein Toxicity To Dopaminergic Neurons In Transgenic Mice., Tian Tian, Cao Huang, Jianbin Tong, Ming Yang, Hongxia Zhou, Xugang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative diseases. While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. Intriguingly, TDP-43 proteinopathy also coexists with Lewy body and with synucleinopathy in certain disease conditions. Here we reported the effects of TDP-43 on α-synuclein neurotoxicity in transgenic mice. Overexpression of mutant TDP-43 (M337V substitution) in mice caused early death in transgenic founders, but overexpression of normal TDP-43 only induced a moderate loss of cortical neurons in …

The Roles Of Conserved And Nonconserved Cysteinyl Residues In The Oligomerization And Function Of Mammalian Prestin, Benjamin Currall, Danielle Rossino, Heather Jensen Smith, Richard Hallworth

Journal Articles: Eppley Institute

The creation of several prestin knockout and knockin mouse lines has demonstrated the importance of the intrinsic outer hair cell membrane protein prestin to mammalian hearing. However, the structure of prestin remains largely unknown, with even its major features in dispute. Several studies have suggested that prestin forms homo-oligomers that may be stabilized by disulfide bonds. Our phylogenetic analysis of prestin sequences across chordate classes suggested that the cysteinyl residues could be divided into three groups, depending on the extent of their conservation between prestin orthologs and paralogs or homologs. An alanine scan functional analysis was performed of all nine …

The Incidence Of Type-1 Diabetes In Nod Mice Is Modulated By Restricted Flora Not Germ-Free Conditions., Cecile King, Nora Sarvetnick

Journal Articles: Regenerative Medicine

In the NOD mouse, the incidence of type-1 diabetes is thought to be influenced by the degree of cleanliness of the mouse colony. Studies collectively demonstrate that exposure to bacterial antigen or infection in the neonatal period prevents diabetes [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], supporting the notion that immunostimulation can benefit the maturation of the postnatal immune system [11]. A widely accepted extrapolation from this data has been the notion that NOD mice maintained under germ-free conditions have an increased incidence of diabetes. However, evidence supporting this influential concept is surprisingly limited [12]. In this …

Modulation Of Myocardial Mitochondrial Mechanisms During Severe Polymicrobial Sepsis In The Rat, M. Chopra, H. B. Golden, S. Mullapudi, W. Dowhan, D. E. Dostal, Avadhesh C. Sharma

PCOM Scholarly Works

Background: We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoKATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Methodology/Principal Findings: Male Sprague-Dawley rats (350-400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD …

In Vivo Electroporation Of Morpholinos Into The Adult Zebrafish Retina., Ryan Thummel, Travis J. Bailey, David R. Hyde

Biology

Many devastating inherited eye diseases result in progressive and irreversible blindness because humans cannot regenerate dying or diseased retinal neurons. In contrast, the adult zebrafish retina possesses the robust ability to spontaneously regenerate any neuronal class that is lost in a variety of different retinal damage models, including retinal puncture, chemical ablation, concentrated high temperature, and intense light treatment. Our lab extensively characterized regeneration of photoreceptors following constant intense light treatment and inner retinal neurons after intravitreal ouabain injection. In all cases, resident Müller glia re-enter the cell cycle to produce neuronal progenitors, which continue to proliferate and migrate to …

Retention Time Variability As A Mechanism For Animal Mediated Long-Distance Dispersal, Vishwesha Guttal, Frederic Bartumeus, Gregg Hartvigsen, Andrew L. Nevai

Biology

Long-distance dispersal (LDD) events, although rare for most plant species, can strongly influence population and community dynamics. Animals function as a key biotic vector of seeds and thus, a mechanistic and quantitative understanding of how individual animal behaviors scale to dispersal patterns at different spatial scales is a question of critical importance from both basic and applied perspectives. Using a diffusion-theory based analytical approach for a wide range of animal movement and seed transportation patterns, we show that the scale (a measure of local dispersal) of the seed dispersal kernel increases with the organisms' rate of movement and mean seed …

Large-Scale Label-Free Quantitative Proteomics Of The Pea Aphid-Buchnera Symbiosis, Anton Poliakov, Calum W. Russell, Lalit Ponnala, Harold J. Hoops, Qi Sun, Angela E. Douglas, Klaas J. Van Wijk, K.J.

Biology

Many insects are nutritionally dependent on symbiotic microorganisms that have tiny genomes and are housed in specialized host cells called bacteriocytes. The obligate symbiosis between the pea aphid Acyrthosiphon pisum and the γ-proteobacterium Buchnera aphidicola (only 584 predicted proteins) is particularly amenable for molecular analysis because the genomes of both partners have been sequenced. To better define the symbiotic relationship between this aphid and Buchnera, we used large-scale, high accuracy tandem mass spectrometry (nanoLC-LTQ-Orbtrap) to identify aphid and Buchnera proteins in the whole aphid body, purified bacteriocytes, isolated Buchnera cells and the residual bacteriocyte fraction. More than 1900 aphid and …

A Network Model For Plant-Pollinator Community Assembly, Colin Campbell, Suann Yang, Reka Albert, Katriona Shea

Biology

Community assembly models, usually constructed for food webs, are an important component of our understanding of how ecological communities are formed. However, models for mutualistic community assembly are still needed, especially because these communities are experiencing significant anthropogenic disturbances that affect their biodiversity. Here, we present a unique network model that simulates the colonization and extinction process of mutualistic community assembly. We generate regional source pools of species interaction networks on the basis of statistical properties reported in the literature. We develop a dynamic synchronous Boolean framework to simulate, with few free parameters, the dynamics of new mutualistic community formation …

The Effect Of Consumers And Mutualists Of Vaccinium Membranaceum At Mount St. Helens: Dependence On Successional Context, Suann Yang, Eelke Jongejans, Sylvia Yang, John G. Bishop

Biology

In contrast to secondary succession, studies of terrestrial primary succession largely ignore the role of biotic interactions, other than plant facilitation and competition, despite the expectation that simplified interaction webs and propagule-dependent demographics may amplify the effects of consumers and mutualists. We investigated whether successional context determined the impact of consumers and mutualists by quantifying their effects on reproduction by the shrub Vaccinium membranaceum in primary and secondary successional sites at Mount St. Helens (Washington, USA), and used simulations to explore the effects of these interactions on colonization. Species interactions differed substantially between sites, and the combined effect of consumers …

Suppression Of Gsk-3 Activation By M-Cadherin Protects Myoblasts Against Mitochondria-Associated Apoptosis During Myogenic Differentiation, Y. Wang, Y. Hao, S. E. Alway

Faculty & Staff Scholarship

No abstract provided.

Autophagy In Antigen-Presenting Cells Results In Presentation Of Citrullinated Peptides To Cd4 T Cells, Jamie M. Ireland, Emil R. Unanue

Open Access Publications

Antibody responses to citrullinated self-proteins are found in autoimmunities, particularly in rheumatoid arthritis, where they serve as a diagnostic indicator. We show here that processing of the protein hen egg-white lysozyme (HEL) resulted in citrullination of peptides presented on class II MHC molecules by antigen-presenting cells. The presentation of the citrullinated peptides but not of the unmodified peptides was associated with autophagy. Dendritic cells (DCs), macrophages, and thymic DCs presented citrullinated peptides constitutively. Their treatment with 3-methyladenine (3MA) blocked presentation of citrullinated HEL peptides, but presentation of unmodified peptides was not affected. Presentation of citrullinated peptides was not detected on …

Type I Interferon Is Selectively Required By Dendritic Cells For Immune Rejection Of Tumors, Mark S. Diamond, Michelle Kinder, Hirokazu Matsushita, Mona Mashayekhi, Gavin P. Dunn, Jessica M. Archambault, Hsiaoju Lee, Cora D. Arthur, J Michael White, Ulrich Kalinke, Kenneth M. Murphy, Robert D. Schreiber

Open Access Publications

Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN's actions. However, the specific cells affected by IFN-α/β and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity …

Cd103+ Pulmonary Dendritic Cells Preferentially Acquire And Present Apoptotic Cell-Associated Antigen, A Nicole Desch, Gwendalyn J. Randolph, Kenneth Murphy, Emmanuel L. Gautier, Ross M. Kedl, Mireille H. Lahoud, Irina Caminschi, Ken Shortman, Peter M. Henson, Claudia V. Jakubzick

Open Access Publications

Cells undergoing programmed cell death (apoptosis) are removed in situ by macrophages and dendritic cells (DCs) through a specialized form of phagocytosis (efferocytosis). In the lung, there are two primary DC subsets with the potential to migrate to the local lymph nodes (LNs) and initiate adaptive immune responses. In this study, we show that only CD103(+) DCs were able to acquire and transport apoptotic cells to the draining LNs and cross present apoptotic cell-associated antigen to CD8 T cells. In contrast, both the CD11b(hi) and the CD103(+) DCs were able to ingest and traffic latex beads or soluble antigen. CD103(+) …

Innate And Cytokine-Driven Signals, Rather Than Microbial Antigens, Dominate In Natural Killer T Cell Activation During Microbial Infection, Manfred Brigl, Raju V.V. Tatituri, Gerald F.M. Watts, Veemal Bhowruth, Elizabeth A. Leadbetter, Nathaniel Barton, Nadia R. Cohen, Fong-Fu Hsu, Gurdyal S. Besra, Michael B. Brenner

Open Access Publications

Invariant natural killer T cells (iNKT cells) are critical for host defense against a variety of microbial pathogens. However, the central question of how iNKT cells are activated by microbes has not been fully explained. The example of adaptive MHC-restricted T cells, studies using synthetic pharmacological α-galactosylceramides, and the recent discovery of microbial iNKT cell ligands have all suggested that recognition of foreign lipid antigens is the main driver for iNKT cell activation during infection. However, when we compared the role of microbial antigens versus innate cytokine-driven mechanisms, we found that iNKT cell interferon-γ production after in vitro stimulation or …

Barth Syndrome Mutations That Cause Tafazzin Complex Lability, Steven M. Claypool, Kevin Whited, Santi Srijumnong, Xianlin Han, Carla M. Koehler

Open Access Publications

Deficits in mitochondrial function result in many human diseases. The X-linked disease Barth syndrome (BTHS) is caused by mutations in the tafazzin gene TAZ1. Its product, Taz1p, participates in the metabolism of cardiolipin, the signature phospholipid of mitochondria. In this paper, a yeast BTHS mutant tafazzin panel is established, and 18 of the 21 tested BTHS missense mutations cannot functionally replace endogenous tafazzin. Four BTHS mutant tafazzins expressed at low levels are degraded by the intermembrane space AAA (i-AAA) protease, suggesting misfolding of the mutant polypeptides. Paradoxically, each of these mutant tafazzins assembles in normal protein complexes. Furthermore, in the …

Cardiac Dysfunction After Cancer Treatment, Michael S Ewer, Sandra M Swain, Daniela Cardinale, Anecita Fadol, Thomas M Suter

The Texas Heart Institute Journal

Onco-cardiology is an evolving discipline that requires the consideration of cardiotoxicity in preclinical, clinical,and therapeutic aspects of protocol development,treatment, and surveillance of patients who have undergone interventions using cardiotoxic agents. Only then can we foster new ways to maximize survival while keeping cardiac damage within acceptable limits. It is to this end that our working together has brought us to our present understanding. In the future, we may expect onco-cardiology to play an even greater role in the care of cancer patients.

Cd34-Positive Stem Cells In The Treatment Of Heart And Vascular Disease In Human Beings, Alexander R Mackie, Douglas W Losordo

The Texas Heart Institute Journal

Bone marrow-derived CD34(+) cells are a well-characterized population of stem cells that have traditionally been used clinically to reconstitute the hematopoietic system after radiation or chemotherapy. More recently, CD34(+) cells have also been shown to induce therapeutic angiogenesis in animal models of myocardial, peripheral, and cerebral ischemia. The mechanism by which CD34(+) cells promote therapeutic angiogenesis is not completely understood, although evidence supports both direct incorporation of the cells into the expanding vasculature and paracrine secretion of angiogenic growth factors that support the developing microvasculature. Phase I and phase II clinical trials have explored the usefulness of CD34(+) cells in …

Heterogeneity Of Left Ventricular Signal Characteristics In Response To Acute Vagal Stimulation During Ventricular Fibrillation In Dogs, Alireza Nazeri, Macarthur A Elayda, Lubomir Dragnev, Christopher M Frank, Jihong Qu, Valtino X Afonso, Abdi Rasekh, Mohammad Saeed, Jie Cheng, Mossaab Shuraih, Ali Massumi, Mehdi Razavi

The Texas Heart Institute Journal

Studies have shown that long-term vagal stimulation is protective against ventricular fibrillation; however, the effects of acute vagal stimulation during ventricular fibrillation in the normal heart have not been investigated. We examined the effects of acute vagal stimulation on ventricular fibrillation in a canine model. In 4 dogs, we induced 30-second periods of ventricular fibrillation by means of intraventricular pacing. During 2 of the 4 periods of fibrillation that we analyzed, vagal stimulation was delivered through electrodes in the caudal ends of the vagus nerves. Noncontact unipolar electrograms were recorded from 3 ventricular regions: the basal septum, apical septum, and …

Central Venous Pressure And Pulmonary Capillary Wedge Pressure, Tony S Ma, Biykem Bozkurt, David Paniagua, Biswajit Kar, Kumudha Ramasubbu, Carl F Rothe

The Texas Heart Institute Journal

Heart-failure phenotypes include pulmonary and systemic venous congestion. Traditional heart-failure classification systems include the Forrester hemodynamic subsets, which use 2 indices: pulmonary capillary wedge pressure (PCWP) and cardiac index. We hypothesized that changes in PCWP and central venous pressure (CVP), and in the phenotypes of heart failure, might be better evaluated by cardiovascular modeling. Therefore, we developed a lumped-parameter cardiovascular model and analyzed forms of heart failure in which the right and left ventricles failed disproportionately (discordant ventricular failure) versus equally (concordant failure). At least 10 modeling analyses were carried out to the equilibrium state. Acute discordant pump failure was …

Paclitaxel Induces Thrombomodulin Downregulation In Human Aortic Endothelial Cells, Huang-Joe Wang, Te-Ling Lu, Haimei Huang, Huey-Chun Huang

The Texas Heart Institute Journal

Patients with paclitaxel-eluting stents are at risk of developing stent thrombosis upon premature discontinuation of dual antiplatelet therapy. In this study, we set out to clarify whether paclitaxel can modulate thrombomodulin expression in human aortic endothelial cells. Human aortic endothelial cells were stimulated with paclitaxel. Methoxyphenyl tetrazolium inner salt cell viability assay, Western blot analysis, real-time polymerase chain reaction, and immunohistochemical assay were performed. In human aortic endothelial cells, paclitaxel (10(-5) to 10(-9) mol/L) treatment for 13 hours caused significant cytotoxicity at drug concentrations greater than 10(-7) mol/L. Paclitaxel (10(-5) to 10(-9) mol/L) treatment for 5 hours downregulated thrombomodulin expression …

A Dosing Study Of Bone Marrow Mononuclear Cells For Transendocardial Injection In A Pig Model Of Chronic Ischemic Heart Disease, Guilherme V Silva, Marlos R Fernandes, Cristiano O Cardoso, Ricardo R Sanz, Edie M Oliveira, Pilar Jimenez-Quevedo, Javier Lopez, Franca S Angeli, Yi Zheng, James T Willerson, Emerson C Perin

The Texas Heart Institute Journal

We studied the effect of the dose of bone marrow mononuclear cells, delivered via transendocardial injection, upon capillary density and fibrosis in pigs with chronic ischemic heart disease.

Pigs (n = 16) that had undergone ameroid constrictor placement (left circumflex coronary artery) to induce chronic ischemia were divided equally into 4 groups on the basis of bone marrow mononuclear cell dose: control (saline injection) and 50, 100, or 200 × 106 bone marrow mononuclear cells. Thirty days after ameroid placement, each pig received 13 transendocardial NOGA-guided injections. An implantable loop recorder monitored possible arrhythmias caused by cell transplantation. Thirty days …

Micro-Ultrasonographic Imaging Of Atherosclerotic Progression And Correlation With Inflammatory Markers In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Ya Yang, Yan-Hong Wang, Jin-Jie Xie, Li Song, Zheng Wang, Yao-Zhong Zhang, Yan-Wen Qin, Zhi-An Li, Xiao-Shan Zhang

The Texas Heart Institute Journal

We studied prospectively whether atherosclerotic progression in apolipoprotein-E knockout mice could be noninvasively and accurately measured by use of high-resolution ultrasonographic biomicroscopy. We examined the correlation between the ultrasonographic characterization of ascending aortic atherosclerotic plaque and plasma C-reactive protein, interleukin-1, and interleukin-6 levels in these mice.

In 4 age groups (8, 16, 24, and 32 wk) of 8 male knockout mice each (atherosclerotic groups) and age-matched male C57BL/6 mice (control groups), we used ultrasonographic biomicroscopy to measure maximal plaque thickness or intima-media thickness in the ascending aorta. We compared the findings with corresponding histologic measurements, and we measured plasma C-reactive …