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Mastl Kinase, A Promising Therapeutic Target, Promotes Cancer Recurrence., Ling Wang, Vivian Q. Luong, Peter J. Giannini, Aimin Peng Nov 2014

Mastl Kinase, A Promising Therapeutic Target, Promotes Cancer Recurrence., Ling Wang, Vivian Q. Luong, Peter J. Giannini, Aimin Peng

Journal Articles: College of Dentistry

Mastl kinase promotes mitotic progression and cell cycle reentry after DNA damage. We report here that Mastl is frequently upregulated in various types of cancer. This upregulation was correlated with cancer progression in breast and oral cancer, poor patient survival in breast cancer, and tumor recurrence in head and neck squamous cell carcinoma. We further investigated the role of Mastl in tumor resistance using cell lines derived from the initial and recurrent tumors of the same head and neck squamous cell carcinoma patients. Ectopic expression of Mastl in the initial tumor cells strongly promoted cell proliferation in the presence of …


Simplified Post Processing Of Cine Dense Cardiovascular Magnetic Resonance For Quantification Of Cardiac Mechanics, Jonathan D. Suever, Gregory J. Wehner, Christopher M. Haggerty, Linyuan Jing, Sean M. Hamlet, Cassi M. Binkley, Sage P. Kramer, Andrea C. Mattingly, David K. Powell, Kenneth C. Bilchick, Frederick H. Epstein, Brandon K. Fornwalt Nov 2014

Simplified Post Processing Of Cine Dense Cardiovascular Magnetic Resonance For Quantification Of Cardiac Mechanics, Jonathan D. Suever, Gregory J. Wehner, Christopher M. Haggerty, Linyuan Jing, Sean M. Hamlet, Cassi M. Binkley, Sage P. Kramer, Andrea C. Mattingly, David K. Powell, Kenneth C. Bilchick, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Cardiovascular magnetic resonance using displacement encoding with stimulated echoes (DENSE) is capable of assessing advanced measures of cardiac mechanics such as strain and torsion. A potential hurdle to widespread clinical adoption of DENSE is the time required to manually segment the myocardium during post-processing of the images. To overcome this hurdle, we proposed a radical approach in which only three contours per image slice are required for post-processing (instead of the typical 30-40 contours per image slice). We hypothesized that peak left ventricular circumferential, longitudinal and radial strains and torsion could be accurately quantified using this simplified analysis.

METHODS …


The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger Nov 2014

The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Workers exposed to organic dusts from concentrated animal feeding operations (CAFOs) are at risk for developing airway inflammatory diseases. Available preventative and therapeutic measures for alleviating dust-induced lung disease are inadequate. Because omega-3 fatty acids can mitigate inflammatory processes, we aimed to determine whether nutritional supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) could reduce the airway inflammatory consequences of exposures to organic dust. Aqueous extracts of organic dusts from swine CAFOs (ODE) were utilized. In DHA-pretreated human bronchial epithelial cells, lung fibroblasts, monocyte cell cultures, and precision-cut murine lung slices, we found that DHA pretreatment dose-dependently decreased ODE-induced …


Aquatic Hazard Assessment Of A Commercial Sample Of Naphthenic Acids., James P. Swigert, Carol Lee, Diana C.L. Wong, Russell White, Alan G. Scarlett, Charles E. West, Steven J. Rowland Nov 2014

Aquatic Hazard Assessment Of A Commercial Sample Of Naphthenic Acids., James P. Swigert, Carol Lee, Diana C.L. Wong, Russell White, Alan G. Scarlett, Charles E. West, Steven J. Rowland

More Faculty of Science and Engineering Research

This paper presents chemical composition and aquatic toxicity characteristics of a commercial sample of naphthenic acids (NAs). Naphthenic acids are derived from the refining of petroleum middle distillates and can contribute to refinery effluent toxicity. NAs are also present in oil sands process-affected water (OSPW), but differences in the NAs compositions from these sources precludes using a common aquatic toxicity dataset to represent the aquatic hazards of NAs from both origins. Our chemical characterization of a commercial sample of NAs showed it to contain in order of abundance, 1-ring>2-ring>acyclic>3-ring acids (∼84%). Also present were monoaromatic acids (7%) …


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 Nov 2014

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, …


Swelling And Eicosanoid Metabolites Differentially Gate Trpv4 Channels In Retinal Neurons And Glia., Daniel A. Ryskamp, Andrew O. Jo, Amber M M. Frye, Felix Vazquez-Chona, Nanna Macaulay, Wallace B. Thoreson, David Križaj Nov 2014

Swelling And Eicosanoid Metabolites Differentially Gate Trpv4 Channels In Retinal Neurons And Glia., Daniel A. Ryskamp, Andrew O. Jo, Amber M M. Frye, Felix Vazquez-Chona, Nanna Macaulay, Wallace B. Thoreson, David Križaj

Journal Articles: Ophthalmology

Activity-dependent shifts in ionic concentrations and water that accompany neuronal and glial activity can generate osmotic forces with biological consequences for brain physiology. Active regulation of osmotic gradients and cellular volume requires volume-sensitive ion channels. In the vertebrate retina, critical support to volume regulation is provided by Müller astroglia, but the identity of their osmosensor is unknown. Here, we identify TRPV4 channels as transducers of mouse Müller cell volume increases into physiological responses. Hypotonic stimuli induced sustained [Ca(2+)]i elevations that were inhibited by TRPV4 antagonists and absent in TRPV4(-/-) Müller cells. Glial TRPV4 signals were phospholipase A2- and cytochrome P450-dependent, …


The Formin Fmnl3 Assembles Plasma Membrane Protrusions That Participate In Cell–Cell Adhesion, Timothy J. Gauvin, Lorna E. Young, Henry N. Higgs Nov 2014

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 …


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 Nov 2014

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 …


Alzheimer's Therapeutics Targeting Amyloid Beta 1-42 Oligomers I: Abeta 42 Oligomer Binding To Specific Neuronal Receptors Is Displaced By Drug Candidates That Improve Cognitive Deficits, Nicholas J. Izzo, Agnes Staniszewski, Lillian To, Mauro Fa, Andrew F. Teich, Faisal Saeed, Harrison Wostein, Thomas Walko Iii, Anisha Vaswani, Meghan Wardius, Zanobia Syed, Jessica Ravenscroft, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Patricia Finn, Gary Look, Gilbert Rishton, Hank Safferstein, Miles Miller, Conrad Johanson, Edward Stopa, Manfred Windisch, Birgit Hutter-Paier, Mehrdad Shamloo, Ottavio Arancio, Harry Levine Iii, Susan M. Catalano Nov 2014

Alzheimer's Therapeutics Targeting Amyloid Beta 1-42 Oligomers I: Abeta 42 Oligomer Binding To Specific Neuronal Receptors Is Displaced By Drug Candidates That Improve Cognitive Deficits, Nicholas J. Izzo, Agnes Staniszewski, Lillian To, Mauro Fa, Andrew F. Teich, Faisal Saeed, Harrison Wostein, Thomas Walko Iii, Anisha Vaswani, Meghan Wardius, Zanobia Syed, Jessica Ravenscroft, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Patricia Finn, Gary Look, Gilbert Rishton, Hank Safferstein, Miles Miller, Conrad Johanson, Edward Stopa, Manfred Windisch, Birgit Hutter-Paier, Mehrdad Shamloo, Ottavio Arancio, Harry Levine Iii, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce …


Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers Ii: Sigma-2/Pgrmc1 Receptors Mediate Abeta 42 Oligomer Binding And Synaptotoxicity, Nicholas J. Izzo, Jinbin Xu, Chenbo Zeng, Molly J. Kirk, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Gary Look, Gilbert Rishton, Hank Safferstein, Carlos Cruchaga, Alison Goate, Michael A. Cahill, Ottavio Arancio, Robert H. Mach, Rolf Craven, Elizabeth Head, Harry Levine Iii, Tara L. Spires-Jones, Susan M. Catalano Nov 2014

Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers Ii: Sigma-2/Pgrmc1 Receptors Mediate Abeta 42 Oligomer Binding And Synaptotoxicity, Nicholas J. Izzo, Jinbin Xu, Chenbo Zeng, Molly J. Kirk, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Gary Look, Gilbert Rishton, Hank Safferstein, Carlos Cruchaga, Alison Goate, Michael A. Cahill, Ottavio Arancio, Robert H. Mach, Rolf Craven, Elizabeth Head, Harry Levine Iii, Tara L. Spires-Jones, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic …


Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero Nov 2014

Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero

Journal Articles: Eppley Institute

The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF) increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that …


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 Nov 2014

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 …


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 Nov 2014

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 …


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 Nov 2014

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 …


Comparison Of Crystal Structures Of 4-(Benzo[B]Thiophen-2-Yl)-5-(3,4,5-Trimethoxyphenyl)-2H-1,2,3-Triazole And 4-(Benzo[B]Thiophen-2-Yl)-2-Methyl-5-(3,4,5-Trimethoxyphenyl)-2H-1,2,3-Triazole, Narsimha Reddy Penthala, Nikhil Reddy Madadi, Shobanbabu Bommagani, Sean Parkin, Peter A. Crooks Nov 2014

Comparison Of Crystal Structures Of 4-(Benzo[B]Thiophen-2-Yl)-5-(3,4,5-Trimethoxyphenyl)-2H-1,2,3-Triazole And 4-(Benzo[B]Thiophen-2-Yl)-2-Methyl-5-(3,4,5-Trimethoxyphenyl)-2H-1,2,3-Triazole, Narsimha Reddy Penthala, Nikhil Reddy Madadi, Shobanbabu Bommagani, Sean Parkin, Peter A. Crooks

Chemistry Faculty Publications

The title compound, C19H17N3O3S (I), was prepared by a [3 + 2]cyclo­addition azide condensation reaction using sodium azide and l-proline as a Lewis base catalyst. N-Methyl­ation of compound (I) using CH3I gave compound (II), C20H19N3O3S. The benzo­thio­phene ring systems in (I) and (II) are almost planar, with r.m.s deviations from the mean plane = 0.0205 (14) in (I) and 0.016 (2) Å in (II). In (I) and (II), the triazole rings make dihedral angles of 32.68 (5) and 10.43 (8)°, respectively, …


Pharmacokinetic And Pharmacodynamic Interactions Between Antiepileptics And Antidepressants, Domenico Italiano, Edoardo Spina, Jose De Leon Nov 2014

Pharmacokinetic And Pharmacodynamic Interactions Between Antiepileptics And Antidepressants, Domenico Italiano, Edoardo Spina, Jose De Leon

Psychiatry Faculty Publications

INTRODUCTION: Antiepileptic-antidepressant combinations are frequently used by clinicians; their pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions (DIs) have not been well studied but are frequently likely to be clinically relevant.

AREAS COVERED: This article provides a comprehensive review of PK DIs between antiepileptics and antidepressants. In the absence of PD DI studies, PD information on pharmacological mechanisms and studies on efficacy and safety of individual drugs are reviewed.

EXPERT OPINION: The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone and the inhibitory properties of valproic acid and some antidepressants are well understood; correction factors are provided …


Toward A Posthuman Education, Nathan Snaza, Peter Appelbaum, Siân Bayne, Dennis Carlson, Marla Morris, Nikki Rotas, Jennifer Sandlin, Jason Wallin, John A. Weaver Nov 2014

Toward A Posthuman Education, Nathan Snaza, Peter Appelbaum, Siân Bayne, Dennis Carlson, Marla Morris, Nikki Rotas, Jennifer Sandlin, Jason Wallin, John A. Weaver

Curriculum, Foundations & Reading: Faculty Publications

The text of our manifesto will introduce posthumanism to a curriculum studies audience and propose new directions for curriculum theory and educational research more broadly. Following a description of what is variously called the “posthuman condition” or the “posthuman era,” our manifesto outlines the main theoretical features of posthumanism with particular attention to how it challenges or problematizes the nearly ubiquitous assumptions of humanism. In particular, we focus on how posthumanism responds to the history of Western humanism’s justification and encouragement of colonialism, slavery, the objectification of women, the thoughtless slaughter of non-human animals, and ecological devastation. We dwell on …


Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin Nov 2014

Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin

Dartmouth Scholarship

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …


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 Oct 2014

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 …


Transcranial Magnetic Stimulation Of The Prefrontal Cortex In Awake Nonhuman Primates Evokes A Polysynaptic Neck Muscle Response That Reflects Oculomotor Activity At The Time Of Stimulation., Chao Gu, Brian D Corneil Oct 2014

Transcranial Magnetic Stimulation Of The Prefrontal Cortex In Awake Nonhuman Primates Evokes A Polysynaptic Neck Muscle Response That Reflects Oculomotor Activity At The Time Of Stimulation., Chao Gu, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Transcranial magnetic stimulation (TMS) has emerged as an important technique in cognitive neuroscience, permitting causal inferences about the contribution of a given brain area to behavior. Despite widespread use, exactly how TMS influences neural activity throughout an interconnected network, and how such influences ultimately change behavior, remain unclear. The oculomotor system of nonhuman primates (NHPs) offers a potential animal model to bridge this gap. Here, based on results suggesting that neck muscle activity provides a sensitive indicator of oculomotor activation, we show that single pulses of TMS over the frontal eye fields (FEFs) in awake NHPs evoked rapid (within ∼25 …


Latexin Sensitizes Leukemogenic Cells To Gamma-Irradiation-Induced Cell-Cycle Arrest And Cell Death Through Rps3 Pathway, Y. You, R. Wen, R. Pathak, A. Li, W. Li, D. St. Clair, M. Hauer-Jensen, D. Zhou, Ying Liang Oct 2014

Latexin Sensitizes Leukemogenic Cells To Gamma-Irradiation-Induced Cell-Cycle Arrest And Cell Death Through Rps3 Pathway, Y. You, R. Wen, R. Pathak, A. Li, W. Li, D. St. Clair, M. Hauer-Jensen, D. Zhou, Ying Liang

Toxicology and Cancer Biology Faculty Publications

Leukemia is a leading cause of cancer death. Recently, the latexin (Lxn) gene was identified as a potential tumor suppressor in several types of solid tumors and lymphoma, and Lxn expression was found to be absent or downregulated in leukemic cells. Whether Lxn functions as a tumor suppressor in leukemia and what molecular and cellular mechanisms are involved are unknown. In this study, the myeloid leukemogenic FDC-P1 cell line was used as a model system and Lxn was ectopically expressed in these cells. Using the protein pull-down assay and mass spectrometry, ribosomal protein subunit 3 (Rps3) was identified as a …


Copy Number Variation In The Horse Genome, Sharmila Ghosh, Zhipeng Qu, Pranab J. Das, Erica Fang, Rytis Juras, E. Gus Cothran, Sue Mcdonell, Daniel G. Kenney, Teri L. Lear, David L. Adelson, Bhanu P. Chowdhary, Terje Raudsepp Oct 2014

Copy Number Variation In The Horse Genome, Sharmila Ghosh, Zhipeng Qu, Pranab J. Das, Erica Fang, Rytis Juras, E. Gus Cothran, Sue Mcdonell, Daniel G. Kenney, Teri L. Lear, David L. Adelson, Bhanu P. Chowdhary, Terje Raudsepp

Maxwell H. Gluck Equine Research Center Faculty Publications

We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse …


The P38alpha Mitogen-Activated Protein Kinase Limits The Cns Proinflammatory Cytokine Response To Systemic Lipopolysaccharide, Potentially Through An Il-10 Dependent Mechanism, Adam D. Bachstetter, Bin Xing, Linda J. Van Eldik Oct 2014

The P38alpha Mitogen-Activated Protein Kinase Limits The Cns Proinflammatory Cytokine Response To Systemic Lipopolysaccharide, Potentially Through An Il-10 Dependent Mechanism, Adam D. Bachstetter, Bin Xing, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The p38α mitogen-activated protein kinase (MAPK) is a well-characterized intracellular kinase involved in the overproduction of proinflammatory cytokines from glia. As such, p38α appears to be a promising therapeutic target for neurodegenerative diseases associated with neuroinflammation. However, the in vivo role of p38α in cytokine production in the CNS is poorly defined, and prior work suggests that p38α may be affecting a yet to be identified negative feedback mechanism that limits the acute, injury-induced proinflammatory cytokine surge in the CNS.

METHODS: To attempt to define this negative feedback mechanism, we used two in vitro and two in vivo models …


Collapse Of An Ecological Network In Ancient Egypt, Justin Yeakel, Mathias Pires, Lars Rudolf, Nathaniel Dominy Oct 2014

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 …


Ticagrelor: Pharmacokinetics, Pharmacodynamics, Clinical Efficacy, And Safety., Paul P. Dobesh, Julie H. Oestreich Oct 2014

Ticagrelor: Pharmacokinetics, Pharmacodynamics, Clinical Efficacy, And Safety., Paul P. Dobesh, Julie H. Oestreich

Journal Articles: Pharmacy Practice

Dual antiplatelet therapy, composed of aspirin plus a P2Y12 -receptor antagonist, is the cornerstone of treatment for patients with acute coronary syndrome (ACS). A number of U.S. Food and Drug Administration-approved P2Y12 -receptor antagonists are available for treating patients with ACS, including the thienopyridine compounds clopidogrel and prasugrel. Ticagrelor, the first of a new class of antiplatelet agents, is a noncompetitive, direct-acting P2Y12 -receptor antagonist. Unlike the thienopyridine compounds, ticagrelor does not require metabolism for activity. Also, whereas clopidogrel and prasugrel are irreversible inhibitors of the P2Y12 receptor, ticagrelor binds reversibly to inhibit receptor signaling and subsequent platelet activation. In …


Ct Perfusion Imaging As An Early Biomarker Of Differential Response To Stereotactic Radiosurgery In C6 Rat Gliomas, Timothy Pok Chi Yeung, Maher Kurdi, Yong Wang, Baraa Al-Khazraji, Laura Morrison, Lisa Hoffman, Dwayne Jackson, Cathie Crukley, Ting-Yim Lee, Glenn Bauman, Slav Yartsev Oct 2014

Ct Perfusion Imaging As An Early Biomarker Of Differential Response To Stereotactic Radiosurgery In C6 Rat Gliomas, Timothy Pok Chi Yeung, Maher Kurdi, Yong Wang, Baraa Al-Khazraji, Laura Morrison, Lisa Hoffman, Dwayne Jackson, Cathie Crukley, Ting-Yim Lee, Glenn Bauman, Slav Yartsev

Medical Biophysics Publications

BACKGROUND: The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model.

METHODS: Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8) or stereotactic radiosurgery (N = 25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute …


Developmental Stress, Condition, And Birdsong: A Case Study In Song Sparrows., Kim L Schmidt, Elizabeth A Macdougall-Shackleton, Shawn P Kubli, Scott A Macdougall-Shackleton Oct 2014

Developmental Stress, Condition, And Birdsong: A Case Study In Song Sparrows., Kim L Schmidt, Elizabeth A Macdougall-Shackleton, Shawn P Kubli, Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

Sexual-selection theory posits that ornaments and displays can reflect a signaler's condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers. Here, we review data on the relationships between birdsong, a sexually selected trait, and developmental and current condition of birds from a long-term study of a population of song sparrows (Melospiza melodia). Field studies of free-living birds indicate that the …


Systematic Review Of Potential Health Risks Posed By Pharmaceutical, Occupational And Consumer Exposures To Metallic And Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide And Its Soluble Salts, Calvin C. Willhite, Nataliya A. Karyakina, Robert A. Yokel, Nagarajkumar Yenugadhati, Thomas M. Wisniewski, Ian M. F. Arnold, Franco Momoli, Daniel Krewski Oct 2014

Systematic Review Of Potential Health Risks Posed By Pharmaceutical, Occupational And Consumer Exposures To Metallic And Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide And Its Soluble Salts, Calvin C. Willhite, Nataliya A. Karyakina, Robert A. Yokel, Nagarajkumar Yenugadhati, Thomas M. Wisniewski, Ian M. F. Arnold, Franco Momoli, Daniel Krewski

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007).

Challenges encountered in carrying out the present review reflected the experimental use of different physical …


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 Oct 2014

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, …


Ethanol-Induced Oxidant Stress Modulates Hepatic Autophagy And Proteasome Activity., Terrence M. Donohue, Paul G. Thomes Oct 2014

Ethanol-Induced Oxidant Stress Modulates Hepatic Autophagy And Proteasome Activity., Terrence M. Donohue, Paul G. Thomes

Journal Articles: Biochemistry & Molecular Biology

In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin-proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, …