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Full-Text Articles in Medicine and Health Sciences

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews Mar 2019

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews

Tyler Johnson

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …


Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela Feb 2019

Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela

Tyler Johnson

In November-December 2007 a widespread seabird mortality event occurred in Monterey Bay, California, USA, coincident with a massive red tide caused by the dinoflagellate Akashiwo sanguinea. Affected birds had a slimy yellow-green material on their feathers, which were saturated with water, and they were severely hypothermic. We determined that foam containing surfactant-like proteins, derived from organic matter of the red tide, coated their feathers and neutralized natural water repellency and insulation. No evidence of exposure to petroleum or other oils or biotoxins were found. This is the first documented case of its kind, but previous similar events may have gone …


Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews Feb 2019

Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews

Tyler Johnson

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …


The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou Feb 2019

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou

Tyler Johnson

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …


Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn Feb 2019

Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn

Tyler Johnson

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …


Silencing Of The Pink1 Gene Expression By Conditional Rnai Does Not Induce Dopaminergic Neuron Death In Mice., Hongxia Zhou, Björn H Falkenburger, Jörg B Schulz, Kim Tieu, Zuoshang Xu, Xu Gang Xia Feb 2018

Silencing Of The Pink1 Gene Expression By Conditional Rnai Does Not Induce Dopaminergic Neuron Death In Mice., Hongxia Zhou, Björn H Falkenburger, Jörg B Schulz, Kim Tieu, Zuoshang Xu, Xu Gang Xia

Kim Tieu

Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson's disease. The expression of the shRNA …


Temporal Changes In Innate Immune Signals In A Rat Model Of Alcohol Withdrawal In Emotional And Cardiorespiratory Homeostatic Nuclei., Kate Freeman, Anthony Brureau, Rajanikanth Vadigepalli, Mary M Staehle, Melanie M Brureau, Gregory E Gonye, Jan B Hoek, D Craig Hooper, James S Schwaber Feb 2018

Temporal Changes In Innate Immune Signals In A Rat Model Of Alcohol Withdrawal In Emotional And Cardiorespiratory Homeostatic Nuclei., Kate Freeman, Anthony Brureau, Rajanikanth Vadigepalli, Mary M Staehle, Melanie M Brureau, Gregory E Gonye, Jan B Hoek, D Craig Hooper, James S Schwaber

Mary Staehle

BACKGROUND: Chronic alcohol use changes the brain's inflammatory state. However, there is little work examining the progression of the cytokine response during alcohol withdrawal, a period of profound autonomic and emotional upset. This study examines the inflammatory response in the central nucleus of the amygdala (CeA) and dorsal vagal complex (DVC), brain regions neuroanatomically associated with affective and cardiorespiratory regulation in an in vivo rat model of withdrawal following a single chronic exposure.

METHODS: For qRT-PCR studies, we measured the expression of TNF-α, NOS-2, Ccl2 (MCP-1), MHC II invariant chain CD74, and the TNF receptor Tnfrsf1a in CeA and DVC …


Corticosterone Administration Up-Regulated Expression Of Norepinephrine Transporter And Dopamine Β-Hydroxylase In Rat Locus Coeruleus And Its Terminal Regions, Yan Fan, Ping Ping Chen, Ying Li, Kui Cui, Daniel M. Noel, Elizabeth D. Cummins, Daniel J. Peterson, Russell W. Brown, Meng-Yang Zhu Nov 2017

Corticosterone Administration Up-Regulated Expression Of Norepinephrine Transporter And Dopamine Β-Hydroxylase In Rat Locus Coeruleus And Its Terminal Regions, Yan Fan, Ping Ping Chen, Ying Li, Kui Cui, Daniel M. Noel, Elizabeth D. Cummins, Daniel J. Peterson, Russell W. Brown, Meng-Yang Zhu

Russell W. Brown

Stress has been reported to activate the locus coeruleus (LC)-noradrenergic system. In this study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine β-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase in DBH protein levels only appeared in the hippocampus and …


Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari Aug 2017

Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari

Lisa Hoffman

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as …


Functional Local Renin-Angiotensin System In Human And Rat Periodontal Tissue, Carlos Ferreira Santos, Ana Carolina Morandini, Thiago José Dionísio, Flávio A. Faria, Marta C. Lima, Caio M. Figueiredo, Bella L. Colombini-Ishikiriama, Carla Renata Sipert, Rubens P. Maciel, Ana P. Akashi, Gabriela P. Souza, Gustavo P. Garlet, Camila O. Rodini, Sandra L. Amaral, Christiane Becari, Maria C. Salgado, Eduardo B. Oliveira, Isaac Matus, Daniela N. Didier, Andrew S. Greene Jun 2017

Functional Local Renin-Angiotensin System In Human And Rat Periodontal Tissue, Carlos Ferreira Santos, Ana Carolina Morandini, Thiago José Dionísio, Flávio A. Faria, Marta C. Lima, Caio M. Figueiredo, Bella L. Colombini-Ishikiriama, Carla Renata Sipert, Rubens P. Maciel, Ana P. Akashi, Gabriela P. Souza, Gustavo P. Garlet, Camila O. Rodini, Sandra L. Amaral, Christiane Becari, Maria C. Salgado, Eduardo B. Oliveira, Isaac Matus, Daniela N. Didier, Andrew S. Greene

Ana Carolina Morandini

The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression …


The Glia Response After Peripheral Nerve Injury: A Comparison Between Schwann Cells And Olfactory Ensheathing Cells And Their Uses For Neural Regenerative Therapies, Matthew J Barton, James St John, Alison Wright, Jenny Ekberg Jun 2017

The Glia Response After Peripheral Nerve Injury: A Comparison Between Schwann Cells And Olfactory Ensheathing Cells And Their Uses For Neural Regenerative Therapies, Matthew J Barton, James St John, Alison Wright, Jenny Ekberg

Jenny Ekberg

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory …


An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls Sep 2016

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, PhD

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …


Wild Justice Redux: What We Know About Social Justice In Animals And Why It Matters, Jessica Pierce, Marc Bekoff Sep 2016

Wild Justice Redux: What We Know About Social Justice In Animals And Why It Matters, Jessica Pierce, Marc Bekoff

Marc Bekoff, PhD

Social justice in animals is beginning to attract interest in a broad range of academic disciplines. Justice is an important area of study because it may help explain social dynamics among individuals living in tightly- knit groups, as well as social interactions among individuals who only occasionally meet. In this paper, we provide an overview of what is currently known about social justice in animals and offer an agenda for further research. We provide working definitions of key terms, outline some central research questions, and explore some of the challenges of studying social justice in animals, as well as the …


The Ethics Of Wildlife Control In Humanized Landscapes, John Hadidian, Camilla H. Fox, William S. Lynn Aug 2016

The Ethics Of Wildlife Control In Humanized Landscapes, John Hadidian, Camilla H. Fox, William S. Lynn

William S. Lynn, PhD

The 21st century is witness to an unprecedented and rapid growth of human settlements, from urban centers to wilderness vacation resorts. Concurrent with this has been the growing tolerance and acceptance of many wild animals and humans for one another. This has created an expanding ‘zone’ of human-animal contacts, some number of which invariably result in conflicts. While the vast majority of our interactions with wild animals are undoubtedly benign, it is the conflict between wildlife and people that draws particularly close attention from the public. Animals viewed as vertebrate “pests” range from the small to the large, the timid …


Window Into Retinal Studies, Gustavo D. Aguirre Feb 2016

Window Into Retinal Studies, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Professor Gustavo Aguirre discusses the context of his research studies at the University of Pennsylvania, which are currently concentrating on the degenerative disease, retinitis pigmentosa.


Bone Morphogenetic Protein Receptor Type Ia Localization Causes Increased Bmp2 Signaling In Mice Exhibiting Increased Peak Bone Mass Phenotype., Beth Bragdon, Jeremy Bonor, Kathryn L Shultz, Wesley G Beamer, Clifford J Rosen, Anja Nohe Jan 2016

Bone Morphogenetic Protein Receptor Type Ia Localization Causes Increased Bmp2 Signaling In Mice Exhibiting Increased Peak Bone Mass Phenotype., Beth Bragdon, Jeremy Bonor, Kathryn L Shultz, Wesley G Beamer, Clifford J Rosen, Anja Nohe

Clifford J Shultz

Bone morphogenetic protein 2 (BMP2) is a growth factor that initiates osteoblast differentiation. Recent studies show that BMP2 signaling regulates bone mineral density (BMD). BMP2 interacts with BMP receptor type Ia (BMPRIa) and type II receptor leading to the activation of the Smad signaling pathway. BMPRIa must shuttle between distinct plasma membrane domains, enriched of Caveolin-1 alpha and Caveolin-1 beta isoforms, and receptor activation occurs in these domains. Yet it remains unknown whether the molecular mechanism that regulates BMP2 signaling is driving mineralization and BMD. Therefore, the B6.C3H-1-12 congenic mouse model with increased BMD and osteoblast mineralization was utilized in …


An Improved Murine Femur Fracture Device For Bone Healing Studies, Joseph Marturano, Benjamin Cleveland, Melissa Bryne, Shannon O'Connell, John Wixted, Kristen Billiar Dec 2015

An Improved Murine Femur Fracture Device For Bone Healing Studies, Joseph Marturano, Benjamin Cleveland, Melissa Bryne, Shannon O'Connell, John Wixted, Kristen Billiar

Kristen L. Billiar

Murine models are commonly used to investigate bone healing and test new treatments before human trials. Our objective was to design an improved murine femur fracture device and determine optimal mass and velocity settings for maximal likelihood of transverse fracture. Fracture reproducibility was maximized using an adjustable kinetic energy level, a novel mouse positioning system and an electromagnet striker release assembly. Sixty wild-type mice of 8-12-week-old male and female with a weight of 26.4+/-6.1g were subjected to an experimental postmortem fracture in the left and right femur (n=120) using variable kinetic energy inputs. A best-fit prediction equation for transverse fracture …


Influence Of Env And Long Terminal Repeat Sequences On The Tissue Tropism Of Avian Leukosis Viruses, David Brown, Harriet Robinson Dec 2015

Influence Of Env And Long Terminal Repeat Sequences On The Tissue Tropism Of Avian Leukosis Viruses, David Brown, Harriet Robinson

David C. Brown

Adsorption and penetration of retroviruses into eucaryotic cells is mediated by retroviral envelope glycoproteins interacting with host receptors. Recombinant avian leukosis viruses (ALVs) differing only in envelope determinants that interact with host receptors for subgroup A or E ALVs have been found to have unexpectedly distinctive patterns of tissue-specific replication. Recombinants of both subgroups were highly expressed in bursal lymphocytes as well as in cultured chicken embryo fibroblasts. In contrast, the subgroup A but not subgroup E host range allowed high levels of expression in skeletal muscle, while subgroup E but not subgroup A envelope glycoproteins permitted efficient replication in …


Infection Of Peripancreatic Lymph Nodes But Not Islets Precedes Kilham Rat Virus-Induced Diabetes In Bb/Wor Rats, David Brown, Raymond Welsh, Arthur Like Dec 2015

Infection Of Peripancreatic Lymph Nodes But Not Islets Precedes Kilham Rat Virus-Induced Diabetes In Bb/Wor Rats, David Brown, Raymond Welsh, Arthur Like

David C. Brown

A parvovirus serologically identified as Kilham rat virus (KRV) reproducibly induces acute type I diabetes in diabetes-resistant BB/Wor rats. The tissue tropism of KRV was investigated by in situ hybridization with a digoxigenin-labelled plasmid DNA probe containing approximately 1.6 kb of the genome of the UMass isolate of KRV. Partial sequencing of the KRV probe revealed high levels of homology to the sequence of minute virus of mice (89%) and to the sequence of H1 (99%), a parvovirus capable of infecting rats and humans. Of the 444 bases sequenced, 440 were shared by H1. KRV mRNA and DNA were readily …


Biaxial Failure Properties Of Planar Living Tissue Equivalents, Kristen Billiar, Angela Throm, Margo Frey Dec 2015

Biaxial Failure Properties Of Planar Living Tissue Equivalents, Kristen Billiar, Angela Throm, Margo Frey

Kristen L. Billiar

Quantification of the mechanical properties of living tissue equivalents (LTEs) is essential for assessing their ultimate functionality as tissue substitutes, yet their delicate nature makes failure testing problematic. For this study, we evaluated the validity of using an inflation device for quantifying the biaxial tensile failure properties of extremely delicate fibroblast-populated collagen gels (CGs) and fibrin gels (FGs). Small samples were circularly clamped and then inflated until rupture. Each sample assumed an approximately spherical shape and burst at its center indicating effective clamping. After two weeks in culture, all LTEs tested were fragile, but the FGs were significantly stronger and …


Human Cryptochrome Exhibits Light-Dependent Magnetosensitivity, Lauren Foley, Robert Gegear, Steven Reppert Dec 2015

Human Cryptochrome Exhibits Light-Dependent Magnetosensitivity, Lauren Foley, Robert Gegear, Steven Reppert

Robert J. Gegear

Humans are not believed to have a magnetic sense, even though many animals use the Earth's magnetic field for orientation and navigation. One model of magnetosensing in animals proposes that geomagnetic fields are perceived by light-sensitive chemical reactions involving the flavoprotein cryptochrome (CRY). Here we show using a transgenic approach that human CRY2, which is heavily expressed in the retina, can function as a magnetosensor in the magnetoreception system of Drosophila and that it does so in a light-dependent manner. The results show that human CRY2 has the molecular capability to function as a light-sensitive magnetosensor and reopen an area …


Cd4+ Regulatory T Cells Require Ctla-4 For The Maintenance Of Systemic Tolerance, Randall Friedline, David Brown, Hai Nguyen, Hardy Kornfeld, Jinhee Lee, Yi Zhang, Mark Appleby, Sandy Der, Joonsoo Kang, Cynthia Chambers Dec 2015

Cd4+ Regulatory T Cells Require Ctla-4 For The Maintenance Of Systemic Tolerance, Randall Friedline, David Brown, Hai Nguyen, Hardy Kornfeld, Jinhee Lee, Yi Zhang, Mark Appleby, Sandy Der, Joonsoo Kang, Cynthia Chambers

David C. Brown

Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3(+) regulatory T cells. CTLA-4-deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4-deficient and -sufficient bone marrow (BM)-derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4(-/-) T cells in trans by CTLA-4-sufficient T cells is …


Defining Behavioral And Molecular Differences Between Summer And Migratory Monarch Butterflies, Haisun Zhu, Robert Gegear, Amy Casselman, Sriramana Kanginakudru, Steven Reppert Dec 2015

Defining Behavioral And Molecular Differences Between Summer And Migratory Monarch Butterflies, Haisun Zhu, Robert Gegear, Amy Casselman, Sriramana Kanginakudru, Steven Reppert

Robert J. Gegear

BACKGROUND: In the fall, Eastern North American monarch butterflies (Danaus plexippus) undergo a magnificent long-range migration. In contrast to spring and summer butterflies, fall migrants are juvenile hormone deficient, which leads to reproductive arrest and increased longevity. Migrants also use a time-compensated sun compass to help them navigate in the south/southwesterly direction en route for Mexico. Central issues in this area are defining the relationship between juvenile hormone status and oriented flight, critical features that differentiate summer monarchs from fall migrants, and identifying molecular correlates of behavioral state. RESULTS: Here we show that increasing juvenile hormone activity to induce summer-like …


Dermal Collagen Matrices For Ventral Hernia Repair: Comparative Analysis In A Rat Model, G. Broderick, Joyce Mcintyre, M. Noury, Heather Strom, Charles Psoinos, A. Christakas, Kristen Billiar, Zachary Hurwitz, Janice Lalikos, Ronald Ignotz, Raymond Dunn Dec 2015

Dermal Collagen Matrices For Ventral Hernia Repair: Comparative Analysis In A Rat Model, G. Broderick, Joyce Mcintyre, M. Noury, Heather Strom, Charles Psoinos, A. Christakas, Kristen Billiar, Zachary Hurwitz, Janice Lalikos, Ronald Ignotz, Raymond Dunn

Kristen L. Billiar

PURPOSE: The purpose of this study was to compare inflammatory responses, tissue integration, and strength of the acellular dermal collagen matrices AlloDerm((R))* Regenerative Tissue Matrix, Permacol**Surgical Implant (Permacol), and CollaMend*** Implant in a rat model for ventral hernia repair.

METHODS: Rats were randomized into four groups and abdominal wall defects repaired with an inlay graft of AlloDerm, Permacol, or CollaMend. Rats were sacrificed at six time points and the defect area was removed and analyzed for tissue integration and physical strength.

RESULTS: Variable cell infiltration was seen for the three implant groups. At of the all time points examined, cellular …


Identification Of Experimentally Induced Colitis By In Vitro Nuclear Magnetic Resonance., R H Rolandelli, S H Saul, R G Settle, D O Jacobs, Raymond Singer, G L Wolf, J L Rombeau Sep 2015

Identification Of Experimentally Induced Colitis By In Vitro Nuclear Magnetic Resonance., R H Rolandelli, S H Saul, R G Settle, D O Jacobs, Raymond Singer, G L Wolf, J L Rombeau

Raymond L Singer MD

The present study determined whether in vitro nuclear magnetic resonance could be used to assess experimentally induced colitis in rats. Acute colitis was induced in 6 Sprague-Dawley rats by acetic acid enema, while 6 control animals received saline enemas. All animals were sacrificed 24 hours post-enema, and NMR relaxation times, T1 and T2, of colonic samples were determined on a 10 MHz spin analyzer (RADX, Houston, TX). Colonic water content was determined on the same samples by desiccation. Colitis animals showed significantly higher T1 and T2 relaxation times and tissue water content than controls. T1 and T2 times correlated significantly …


Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor Aug 2015

Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor

Janet M. Stavnezer

Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is …


The Fly Camta Transcription Factor Potentiates Deactivation Of Rhodopsin, A G Protein-Coupled Light Receptor, Junhai Han, Ping Gong, Keith Reddig, Mirna Mitra, Peiyi Guo, Hong-Sheng Li Jul 2015

The Fly Camta Transcription Factor Potentiates Deactivation Of Rhodopsin, A G Protein-Coupled Light Receptor, Junhai Han, Ping Gong, Keith Reddig, Mirna Mitra, Peiyi Guo, Hong-Sheng Li

Peiyi Guo

Control of membrane-receptor activity is required not only for the accuracy of sensory responses, but also to protect cells from excitotoxicity. Here we report the isolation of two noncomplementary fly mutants with slow termination of photoresponses. Genetic and electrophysiological analyses of the mutants revealed a defect in the deactivation of rhodopsin, a visual G protein-coupled receptor (GPCR). The mutant gene was identified as the calmodulin-binding transcription activator (dCAMTA). The known rhodopsin regulator Arr2 does not mediate this visual function of dCAMTA. A genome-wide screen identified five dCAMTA target genes. Of these, overexpression of the F box gene dFbxl4 rescued the …


Mutation Of A Tadr Protein Leads To Rhodopsin And Gq-Dependent Retinal Degeneration In Drosophila, Lina Ni, Peiyi Guo, Keith Reddig, Mirna Mitra, Hong-Sheng Li Jul 2015

Mutation Of A Tadr Protein Leads To Rhodopsin And Gq-Dependent Retinal Degeneration In Drosophila, Lina Ni, Peiyi Guo, Keith Reddig, Mirna Mitra, Hong-Sheng Li

Peiyi Guo

The Drosophila photoreceptor is a model system for genetic study of retinal degeneration. Many gene mutations cause fly photoreceptor degeneration, either because of excessive stimulation of the visual transduction (phototransduction) cascade, or through apoptotic pathways that in many cases involve a visual arrestin Arr2. Here we report a gene named tadr (for torn and diminished rhabdomeres), which, when mutated, leads to photoreceptor degeneration through a different mechanism. Degeneration in the tadr mutant is characterized by shrunk and disrupted rhabdomeres, the light sensory organelles of photoreceptor. The TADR protein interacted in vitro with the major light receptor Rh1 rhodopsin, and genetic …


3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner Jul 2015

3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner

Richard A. Malthaner

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the …


3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner Jul 2015

3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner

Richard A. Malthaner

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the …