Medicine and Health Sciences Commons^™

De Novo Design Of Antiviral And Antibacterial Peptides With Varying Loop Structures, Guangshun Wang, Karen W. Buckheit, Biswajit Mishra, Tamara Lushnikova, Robert W. Buckheit Jr.

Journal Articles: Pathology and Microbiology

No abstract provided.

Major Families Of Multiresistant Plasmids From Geographically And Epidemiologically Diverse Staphylococci., Julia E.S. Shearer, Joy Wireman, Jessica Hostetler, Heather Forberger, Jon Borman, John Gill, Susan Sanchez, Alexander Mankin, Jacqueline Lamarre, Jodi A. Lindsay, Kenneth W. Bayles, Ainsley Nicholson, Frances O'Brien, Slade O. Jensen, Neville Firth, Ronald A. Skurray, Anne O. Summers

Journal Articles: Pathology and Microbiology

Staphylococci are increasingly aggressive human pathogens suggesting that active evolution is spreading novel virulence and resistance phenotypes. Large staphylococcal plasmids commonly carry antibiotic resistances and virulence loci, but relatively few have been completely sequenced. We determined the plasmid content of 280 staphylococci isolated in diverse geographical regions from the 1940s to the 2000s and found that 79% of strains carried at least one large plasmid >20 kb and that 75% of these large plasmids were 20-30 kb. Using restriction fragment length polymorphism (RFLP) analysis, we grouped 43% of all large plasmids into three major families, showing remarkably conserved intercontinental spread …

Nuclease Modulates Biofilm Formation In Community-Associated Methicillin-Resistant Staphylococcus Aureus., Megan R. Kiedrowski, Jeffrey S. Kavanaugh, Cheryl L. Malone, Joe M. Mootz, Jovanka M. Voyich, Mark S. Smeltzer, Kenneth W. Bayles, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging contributor to biofilm-related infections. We recently reported that strains lacking sigma factor B (sigB) in the USA300 lineage of CA-MRSA are unable to develop a biofilm. Interestingly, when spent media from a USA300 sigB mutant was incubated with other S. aureus strains, biofilm formation was inhibited. Following fractionation and mass spectrometry analysis, the major anti-biofilm factor identified in the spent media was secreted thermonuclease (Nuc). Considering reports that extracellular DNA (eDNA) is an important component of the biofilm matrix, we investigated the regulation and role of Nuc in USA300. The expression of …

Cardiovascular Magnetic Resonance Myocardial Feature Tracking Detects Quantitative Wall Motion During Dobutamine Stress., Andreas Schuster, Shelby Kutty, Asif Padiyath, Victoria Parish, Paul Gribben, David A. Danford, Marcus R. Makowski, Boris Bigalke, Philipp Beerbaum, Eike Nagel

Journal Articles: Pediatrics

BACKGROUND: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) is an established tool to assess hibernating myocardium and ischemia. Analysis is typically based on visual assessment with considerable operator dependency. CMR myocardial feature tracking (CMR-FT) is a recently introduced technique for tissue voxel motion tracking on standard steady-state free precession (SSFP) images to derive circumferential and radial myocardial mechanics.We sought to determine the feasibility and reproducibility of CMR-FT for quantitative wall motion assessment during intermediate dose DS-CMR.

METHODS: 10 healthy subjects were studied at 1.5 Tesla. Myocardial strain parameters were derived from SSFP cine images using dedicated CMR-FT software (Diogenes MRI prototype; …

Tgfb1 Disrupts The Angiogenic Potential Of Microvascular Endothelial Cells Of The Corpus Luteum., Dulce Maroni, John S. Davis

Journal Articles: Obstetrics & Gynecology

Cyclical formation and regression of the ovarian corpus luteum is required for reproduction. During luteal regression, the microvasculature of the corpus luteum is extensively disrupted. Prostaglandin F2α, a primary signal for luteal regression, induces the expression of transforming growth factor β1 (TGFB1) in the corpus luteum. This study determined the actions of TGFB1 on microvascular endothelial cells isolated from the bovine corpus luteum (CLENDO cells). We hypothesized that TGFB1 participates in the disruption of the microvasculature during luteal regression. TGFB1 activated the canonical SMAD signaling pathway in CLENDO cells. TGFB1 (1 ng/ml) significantly reduced both basal and fetal-calf-serum-stimulated DNA synthesis, …

Importance Of Proper Diagnosis For Management: Multifocal Choroiditis Mimicking Ocular Histoplasmosis Syndrome., Elham Hatef, Peykan Turkcuoglu, Mohamed Ibrahim, Yasir J. Sepah, Matthew Shulman, Jangwon Heo, Jeong H. Lee, Roomasa Channa, Afsheen Khwaja, Zubir Rentiya, Syed Mahmood Shah, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

PURPOSE: The study aims to evaluate a series of patients with initial diagnosis of ocular histoplasmosis syndrome (OHS) with progression and response to treatments consistent with multifocal choroiditis (MFC).

METHODS: Retrospective review of nine patients referred for management of recurrent OHS lesions. Serology panel was conducted to rule out autoimmune and infectious causes.

RESULTS: Clinical examination revealed multiple small, punched-out peripheral chorioretinal scars, and peripapillary atrophy. Histoplasma antigen/antibody was negative in all patients. Fluorescein angiography and optical coherence tomography confirmed active inflammation in five patients. Immunomodulatory therapy (IMT) was initiated to control active inflammation. While on IMT, visual acuity stabilized …

Inhibition Of Phosphorylated C-Met In Rhabdomyosarcoma Cell Lines By A Small Molecule Inhibitor Su11274., Jinxuan Hou, Jixin Dong, Lijun Sun, Liying Geng, J. Wang, Jialin C. Zheng, Yan Li, Julia A. Bridge, Steven H. Hinrichs, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: c-Met is a receptor tyrosine kinase (RTK) that is over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. In this study, we investigated the role of c-Met in rhabdomyosarcoma (RMS) using its small molecule inhibitor SU11274, which has been hypothesized to be a potential therapeutic target for RMS.

METHODS: The expression level of phosphorylated c-Met in RMS cell lines (RD, CW9019 and RH30) and tumor tissues was assessed by phospho-RTK array and immunohistochemistry, respectively. The inhibition effects of SU11274 on RMS cells were studied with regard to intracellular signaling, cell proliferation, cell cycle …

A Positive Feedback Synapse From Retinal Horizontal Cells To Cone Photoreceptors., Skyler L. Jackman, Norbert Babai, James J. Chambers, Wallace B. Thoreson, Richard H. Kramer

Journal Articles: Ophthalmology

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca(2+) and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca(2+), whereas negative feedback is mediated by a change in HC membrane …

Myd88 Is Pivotal For Immune Recognition Of Citrobacter Koseri And Astrocyte Activation During Cns Infection., Shuliang Liu, Tammy Kielian

Journal Articles: Pathology and Microbiology

Citrobacter koseri (C. koseri) is a Gram-negative bacterium that can cause a highly aggressive form of neonatal meningitis, which often progresses to establish multi-focal brain abscesses. The roles of Toll-like receptor 4 (TLR4) and its signaling adaptor MyD88 during CNS C. koseri infection have not yet been examined, which is important since recent evidence indicates that innate immune responses are tailored towards specific pathogen classes. Here TLR4 WT (C3H/FeJ) and TLR4 mutant (C3H/HeJ) mice as well as MyD88 KO animals were infected intracerebrally with live C. koseri, resulting in meningitis and ventriculitis with accompanying brain abscess formation. MyD88 KO mice …

Quantal Amplitude At The Cone Ribbon Synapse Can Be Adjusted By Changes In Cytosolic Glutamate., Theodore M. Bartoletti, Wallace B. Thoreson

Journal Articles: Ophthalmology

PURPOSE: Vision is encoded at photoreceptor synapses by the number of released vesicles and size of the post-synaptic response. We hypothesized that elevating cytosolic glutamate could enhance quantal size by increasing glutamate in vesicles.

METHODS: We introduced glutamate (10-40 mM) into cone terminals through a patch pipette and recorded excitatory post-synaptic currents (EPSCs) from horizontal or OFF bipolar cells in the Ambystoma tigrinum retinal slice preparation.

RESULTS: Elevating cytosolic glutamate in cone terminals enhanced EPSCs as well as quantal miniature EPSCs (mEPSCs). Enhancement was prevented by inhibiting vesicular glutamate transport with 1S,3R-1-aminocyclopentane-1,3-dicarboxylate in the patch pipette. A low affinity glutamate …

Lateral Mobility Of Presynaptic L-Type Calcium Channels At Photoreceptor Ribbon Synapses., Aaron J. Mercer, Minghui Chen, Wallace B. Thoreson

Journal Articles: Ophthalmology

At most synapses, presynaptic Ca(2+) channels are positioned near vesicle release sites, and increasing this distance reduces synaptic strength. We examined the lateral membrane mobility of presynaptic L-type Ca(2+) channels at photoreceptor ribbon synapses of the tiger salamander (Ambystoma tigrinum) retina. Movements of individual Ca(2+) channels were tracked by coupling quantum dots to an antibody against the extracellular α(2)δ(4) Ca(2+) channel subunit. α(2)δ(4) antibodies labeled photoreceptor terminals and colocalized with antibodies to synaptic vesicle glycoprotein 2 and voltage-gated Ca(2+) channel 1.4 (Ca(V)1.4) α(1) subunits. The results show that Ca(2+) channels are dynamic and move within a confined region beneath the …

Renal Thrombotic Microangiopathy In Mice With Combined Deletion Of Endocytic Recycling Regulators Ehd3 And Ehd4., Manju George, Mark A. Rainey, Mayumi Naramura, Kirk W. Foster, Melissa S. Holzapfel, Laura L. Willoughby, Guoguang Ying, Rasna M. Goswami, Channabasavaiah B. Gurumurthy, Vimla Band, Simon C. Satchell, Hamid Band

Journal Articles: Eppley Institute

Eps15 Homology Domain-containing 3 (EHD3), a member of the EHD protein family that regulates endocytic recycling, is the first protein reported to be specifically expressed in the glomerular endothelium in the kidney; therefore we generated Ehd3(-/-) mice and assessed renal development and pathology. Ehd3(-/-) animals showed no overt defects, and exhibited no proteinuria or glomerular pathology. However, as the expression of EHD4, a related family member, was elevated in the glomerular endothelium of Ehd3(-/-) mice and suggested functional compensation, we generated and analyzed Ehd3(-/-); Ehd4(-/-) mice. These mice were smaller, possessed smaller and paler kidneys, were proteinuric and died between …

Loss Of Neuronal Integrity During Progressive Hiv-1 Infection Of Humanized Mice., Prasanta Dash, Santhi Gorantla, Howard Gendelman, Jaclyn Knibbe, George P. Casale, Edward Makarov, Adrian A. Epstein, Harris A. Gelbard, Michael D. Boska, Larisa Y. Poluektova

Journal Articles: Radiology

Neuronal damage induced by ongoing human immunodeficiency virus type 1 (HIV-1) infection was investigated in humanized NOD/scid-IL-2Rγ(c)(null) mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4(+) T-cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and …

Neuroinflammation Leads To Region-Dependent Alterations In Astrocyte Gap Junction Communication And Hemichannel Activity., Nikolay Karpuk, Maria Burkovetskaya, Teresa Fritz, Amanda Angle, Tammy Kielian

Journal Articles: Pathology and Microbiology

Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, …

Safety And Efficacy Of Abt-089 In Pediatric Attention-Deficit/Hyperactivity Disorder: Results From Two Randomized Placebo-Controlled Clinical Trials., Timothy E. Wilens, Laura M. Gault, Ann Childress, Christopher J. Kratochvil, Lindsey Bensman, Coleen M. Hall, Evelyn Olson, Weining Z. Robieson, Tushar S. Garimella, Walid M. Abi-Saab, George Apostol, Mario D. Saltarelli

Journal Articles: Psychiatry

OBJECTIVE: To assess the safety and efficacy of ABT-089, a novel α(4)β(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD).

METHOD: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085-0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV: Home …

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 …

Microrna-183 Family Expression In Hair Cell Development And Requirement Of Micrornas For Hair Cell Maintenance And Survival, Michael D. Weston, Marsha L. Pierce, Heather Jensen Smith, Bernd Fritzsch, Sonia Rocha-Sanchez, Kirk W. Beisel, Garrett A. Soukup

Journal Articles: Eppley Institute

MicroRNAs (miRNAs) post-transcriptionally repress complementary target gene expression and can contribute to cell differentiation. The coordinate expression of miRNA-183 family members (miR-183, miR-96, and miR-182) has been demonstrated in sensory cells of the mouse inner ear and other vertebrate sensory organs. To further examine hair cell miRNA expression in the mouse inner ear, we have analyzed miR-183 family expression in wild type animals and various mutants with defects in neurosensory development. miR-183 family member expression follows neurosensory cell specification, exhibits longitudinal (basal-apical) gradients in maturating cochlear hair cells, and is maintained in sensory neurons and most hair cells into adulthood. …