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A Two Compartment Pharmacokinetic Model Describes The Intra‐Articular Delivery And Retention Of Rhprg4 Following Acl Transection In The Yucatan Mini Pig, Mark Hurtig, Iman Zaghoul, Heather Sheardown, Tannin A. Schmidt, Lina Liu, Ling Zhang, Khaled A. Elsaid, Gregory D. Jay 2018 University of Guelph

A Two Compartment Pharmacokinetic Model Describes The Intra‐Articular Delivery And Retention Of Rhprg4 Following Acl Transection In The Yucatan Mini Pig, Mark Hurtig, Iman Zaghoul, Heather Sheardown, Tannin A. Schmidt, Lina Liu, Ling Zhang, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re‐establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra‐articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing ∼55 Kg each received 4 mg of 131I‐rhPRG4 delivered by IA injection 5 days following surgical ACL transection. Animals were sequentially euthanized following IA rhPRG4 at 10 mins (time zero), 24, 72 hrs, 6, 13 and 20 days later. The …


No Evidence For Kin Protection In The Expression Of Sickness Behaviors In House Mice, Patricia C. Lopes, Per Block, Alice Pontiggia, Anna K. Lindholm, Barbara König 2018 Chapman University

No Evidence For Kin Protection In The Expression Of Sickness Behaviors In House Mice, Patricia C. Lopes, Per Block, Alice Pontiggia, Anna K. Lindholm, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When infected, animals change their behaviors in several ways, including by decreasing their activity, their food and water intake, and their interest in social interactions. These behavioral alterations are collectively called sickness behaviors and, for several decades, the main hypotheses put forward to explain this phenomenon were that engaging in sickness behaviors facilitated the fever response and improved the likelihood of host survival. However, a new hypothesis was recently proposed suggesting that engaging in sickness behaviors may serve to protect kin. We tested this kin protection hypothesis by combining a field and a laboratory experiment in house mice. In both …


Kinetics Of Dextromethorphan-O-Demethylase Activity And Distribution Of Cyp2d In Four Commonly-Used Subcellular Fractions Of Rat Brain, Barent N. Dubois, Farideh Amirrad, Reza Mehvar 2018 Chapman University

Kinetics Of Dextromethorphan-O-Demethylase Activity And Distribution Of Cyp2d In Four Commonly-Used Subcellular Fractions Of Rat Brain, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

The purpose of this study was to compare the enzymatic kinetics and distribution of cytochrome P450 2D (CYP2D) among different rat brain subcellular fractions.

Rat brains were used to prepare total membrane, crude mitochondrial, purified mitochondrial, and microsomal fractions, in addition to total homogenate. Michaelis–Menten kinetics of the brain CYP2D activity was estimated based on the conversion of dextromethorphan (DXM) to dextrorphan using UPLC-MS/MS. Protein levels of CYP2D and subcellular markers were determined by Western blot.

Microsomal CYP2D exhibited high affinity and low capacity, compared with the mitochondrial CYP2D that had a much lower (∼50-fold) affinity but a higher (∼six-fold) …


Repeat Elements Organise 3d Genome Structure And Mediate Transcription In The Filamentous Fungus Epichloë Festucae, David J. Winter, Austen R. D. Ganley, Carolyn A. Young, Ivan Liachko, Christopher L. Schardl, Pierre-Yves Dupont, Daniel Berry, Arvina Ram, Barry Scott, Murray P. Cox 2018 Massey University, New Zealand

Repeat Elements Organise 3d Genome Structure And Mediate Transcription In The Filamentous Fungus Epichloë Festucae, David J. Winter, Austen R. D. Ganley, Carolyn A. Young, Ivan Liachko, Christopher L. Schardl, Pierre-Yves Dupont, Daniel Berry, Arvina Ram, Barry Scott, Murray P. Cox

Plant Pathology Faculty Publications

Structural features of genomes, including the three-dimensional arrangement of DNA in the nucleus, are increasingly seen as key contributors to the regulation of gene expression. However, studies on how genome structure and nuclear organisation influence transcription have so far been limited to a handful of model species. This narrow focus limits our ability to draw general conclusions about the ways in which three-dimensional structures are encoded, and to integrate information from three-dimensional data to address a broader gamut of biological questions. Here, we generate a complete and gapless genome sequence for the filamentous fungus, Epichloë festucae. We use Hi-C …


Vancomycin Delays Clindamycin-Induced Fatality In The Hamster Model Of Clostridioides [Clostridium] Difficile Infection, Amelia E. Fox-King, Chrisabelle Mefferd, Jacqueline R. Phan, Nancy O. Nou, Ernesto Abel-Santos, Brian P. Hedlund 2018 University of Nevada, Las Vegas

Vancomycin Delays Clindamycin-Induced Fatality In The Hamster Model Of Clostridioides [Clostridium] Difficile Infection, Amelia E. Fox-King, Chrisabelle Mefferd, Jacqueline R. Phan, Nancy O. Nou, Ernesto Abel-Santos, Brian P. Hedlund

LSAMP Poster Presentations

Antibiotics can leave the host gut microbiome susceptible to Clostridioides [Clostridium] difficile colonization and lethal toxin production. For instance, clindamycin-induced susceptibility to C. difficile infection (CDI) results in rapid fatality in hamster models, yet vancomycin has been shown to offer increased survival in hamsters challenged with C. difficile. We aim to develop an antibiotic treatment that will facilitate CDI susceptibility without prompt fatality in hamster models. An antibiotic regimen starting with a continuous vancomycin treatment along with a single clindamycin dosage is thought to reduce the major disruption in the indigenous gut microbiome and prevent clindamycin-induced death. …


Simulating Antibiotic Resistance In The Computer Lab And Biology Lab: Ideas For Undergraduate Projects, Anne E. Yust 2018 The New School

Simulating Antibiotic Resistance In The Computer Lab And Biology Lab: Ideas For Undergraduate Projects, Anne E. Yust

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.


Nocardia Brasiliensis Infection After Hurricane Irma: Two Case Reports, Sarah Al-Obaydi MD, James DeMaio, Nemer Dabage MD 2018 HCA Healthcare

Nocardia Brasiliensis Infection After Hurricane Irma: Two Case Reports, Sarah Al-Obaydi Md, James Demaio, Nemer Dabage Md

Infectious Disease

Background: Although an increase in skin and soft tissue infections has been well documented after natural disasters, cases of Nocardia brasiliensis infection have not been included in prior reports. We present two cases of N. brasiliensis lymphadenitis that occurred in Manatee County, Florida after Hurricane Irma.

Methods: Case 1-A 75 year old immune competent male may have injured his arm while retrieving a golf ball approximately four weeks after Hurricane Irma. Ten days later he presented to the hospital with an abscess on his left forearm and a lymphadenitis extending nearly to the axilla. Despite treatment with vancomycin, the lymph …


Adapting Cell-Free Protein Synthesis As A Platform Technology For Education, Grace W. Chu, Max Z. Levine, Nicole E. Gregorio, Javin P. Oza 2018 California State University, Los Angeles

Adapting Cell-Free Protein Synthesis As A Platform Technology For Education, Grace W. Chu, Max Z. Levine, Nicole E. Gregorio, Javin P. Oza

STAR Program Research Presentations

Cell-free protein synthesis (CFPS) has emerged as an enabling biotechnology for research and biomanufacturing as it allows for the production of protein without the need for a living cell. Applications of CFPS include the construction of libraries for functional genomics and structural biology, the production of personalized medicine, and the expression of virus-like particles. The absence of a cell wall provides an open platform for direct manipulation of the reaction conditions and biological machinery. This project focuses on adapting the CFPS biotechnology to the classroom, making a hands-on bioengineering approach to learning protein synthesis accessible to students grades K-16 through …


Iac Gene Expression In The Indole-3-Acetic Acid-Degrading Soil Bacterium Enterobacter Soli Lf7, Isaac V. Greenhut, Beryl L. Slezak, Johan H. J. Leveau 2018 University of Kentucky

Iac Gene Expression In The Indole-3-Acetic Acid-Degrading Soil Bacterium Enterobacter Soli Lf7, Isaac V. Greenhut, Beryl L. Slezak, Johan H. J. Leveau

Plant and Soil Sciences Faculty Publications

We show for soil bacterium Enterobacter soli LF7 that the possession of an indole-3-acetic acid catabolic (iac) gene cluster is causatively linked to the ability to utilize the plant hormone indole-3-acetic acid (IAA) as a carbon and energy source. Genome-wide transcriptional profiling by mRNA sequencing revealed that these iac genes, chromosomally arranged as iacHABICDEFG and coding for the transformation of IAA to catechol, were the most highly induced (>29-fold) among the relatively few (iac cluster were genes for a major facilitator superfamily protein (mfs) and enzymes of the β-ketoadipate pathway (pcaIJD-catBCA), which channels …


Implementing Strategies To Reduce Central Line-Associated Blood Stream Infections On An Inpatient Pediatric Unit, Sherryann St. Pierre, Nicole Manchester, Jessica Howe, Melanie Lord, Mark Parker, Suneela Nayak, Ruth Hanselman, Stephen Tyzik, Amy Sparks, Barbara Bush Children's Hospital 2018 Maine Medical Center

Implementing Strategies To Reduce Central Line-Associated Blood Stream Infections On An Inpatient Pediatric Unit, Sherryann St. Pierre, Nicole Manchester, Jessica Howe, Melanie Lord, Mark Parker, Suneela Nayak, Ruth Hanselman, Stephen Tyzik, Amy Sparks, Barbara Bush Children's Hospital

Operations Transformation

STRATEGIES TO REDUCE CENTRAL LINE ASSOCIATED BLOODSTREAM INFECTIONS

Every central line associated bloodstream infection (CLABSI) leads to poor outcomes, increased mortality and increased healthcare costs. A pediatric care team in an academic tertiary medical center set a goal to reduce the number of these infections on their unit.

The team’s research showed that daily bathing greatly decreases CLABSI. Their baseline metrics demonstrated an unacceptable level of those with central lines being bathed. A root cause analysis revealed that patient and family refusal was the leading cause for those who did not bathe.

A performance improvement plan was initiated that consisted …


Capsid Structure Of Dsrna Fungal Viruses, Daniel Luque, Carlos P. Mata, Nobuhiro Suzuki, Said A. Ghabrial, José R. Castón 2018 Centro Nacional de Biotecnología, Spain

Capsid Structure Of Dsrna Fungal Viruses, Daniel Luque, Carlos P. Mata, Nobuhiro Suzuki, Said A. Ghabrial, José R. Castón

Plant Pathology Faculty Publications

Most fungal, double-stranded (ds) RNA viruses lack an extracellular life cycle stage and are transmitted by cytoplasmic interchange. dsRNA mycovirus capsids are based on a 120-subunit T = 1 capsid, with a dimer as the asymmetric unit. These capsids, which remain structurally undisturbed throughout the viral cycle, nevertheless, are dynamic particles involved in the organization of the viral genome and the viral polymerase necessary for RNA synthesis. The atomic structure of the T = 1 capsids of four mycoviruses was resolved: the L-A virus of Saccharomyces cerevisiae (ScV-L-A), Penicillium chrysogenum virus (PcV), Penicillium stoloniferum virus F (PsV-F), and Rosellinia necatrix …


Contributions Of The Gp120 Variable Loops To Envelope Glycoprotein Trimer Stability In Primate Lentiviruses, Dane M. Bowder 2018 University of Nebraska-Lincoln

Contributions Of The Gp120 Variable Loops To Envelope Glycoprotein Trimer Stability In Primate Lentiviruses, Dane M. Bowder

School of Biological Sciences: Dissertations, Theses, and Student Research

Human Immunodeficiency Virus (HIV) is the etiological agent of AIDS and is responsible for the AIDS pandemic worldwide. According to UNAIDS, as of 2016, there were approximately 36.7 million people living with HIV globally, and 1.8 million new infections that year. While antiretroviral therapies and education continue to reduce these numbers, a preventative vaccine is still required to curb this epidemic. The envelope glycoprotein trimer of HIV, which is the sole protein on the surface of the virus and facilitates entry of the virus into host cells, is of keen interest to the HIV vaccine and drug-development field. Recently, the …


Evaluation Of A Human Papillomavirus Genotyping Assay For Cervical Cancer Screening In Tanzania, Kandali S. Kapie 2018 University of Nebraska-Lincoln

Evaluation Of A Human Papillomavirus Genotyping Assay For Cervical Cancer Screening In Tanzania, Kandali S. Kapie

School of Biological Sciences: Dissertations, Theses, and Student Research

Abstract: Mucosal high-risk Human papillomavirus (HR-HPV) has been identified as the primary factor in causing cervical cancer, the most common cancer in women of low and middle-income countries (LMICs). Cervical cancer screening, incorporating the HPV test shown to be more advantageous than screening by visual inspection with acetic acid (VIA) alone. However, due to resources constrain these countries could not afford the available HPV tests. We, therefore, validated a cost-effective Multiplex PCR HPV (mPCR) assay, a recently developed assay for detecting sixteen genital HPV, fourteen HR-HPV and 2 low-risk genotypes. We postulate that this HPV multiplex assay will be at …


Future Warming And Acidification Result In Multiple Ecological Impacts To A Temperate Coralline Alga, Megan J. Huggett, Kathryn Mcmahon, Rachele Bernasconi 2018 Edith Cowan University

Future Warming And Acidification Result In Multiple Ecological Impacts To A Temperate Coralline Alga, Megan J. Huggett, Kathryn Mcmahon, Rachele Bernasconi

Research outputs 2014 to 2021

Coralline algae are a crucial component of reef systems, stabilising reef substrate, providing habitat and contributing to accretion. Coralline algae and their surface microbial biofilms are also important as settlement cues for marine invertebrates, yet few studies address the impact of future environmental conditions on interactions between coralline algae, reef microbes and settlement by larvae of marine invertebrates. We exposed the temperate coralline algal species Amphiroa gracilis to warming and/or acidification scenarios for 21 days. Algae became bleached but photosystem II function was not measurably impacted. Settlement by larvae of the sea urchin Heliocidaris erythrogramma was reduced and the structure …


Using Clinical Decision Support Within The Electronic Health Record To Reduce Incorrect Prescribing For Acute Sinusitis, Regina Ginzburg, Justin J. Conway, Eve Waltermaurer, Wendy Song, Samantha P. Jellinek-Cohen 2018 College of Pharmacy and Health Sciences, St. John's University; Institute for Family Health

Using Clinical Decision Support Within The Electronic Health Record To Reduce Incorrect Prescribing For Acute Sinusitis, Regina Ginzburg, Justin J. Conway, Eve Waltermaurer, Wendy Song, Samantha P. Jellinek-Cohen

Journal of Patient-Centered Research and Reviews

Purpose: Acute sinusitis has viral etiology in more than 90% of cases, but antibiotics are prescribed for more than 80% of adults in the United States. While applications of computer-assisted guidelines have been found effective in reducing inaccurate prescribing for acute respiratory infections, there is a paucity of research focused specifically on the utilization of electronic best practice alerts (BPA) in improving treatment for acute sinusitis.

Methods: This observational cohort study examined prescribing behavior for sinusitis at a single Federally Qualified Health Center 1 year prior and during the first year of implementation of a BPA in the electronic health …


Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif 2018 University of Nebraska-Lincoln

Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV) infections contribute to the bovine respiratory disease complex (BRDC), which is a multi-factorial disorder involving co-infections of viruses and bacteria including mycoplasma. BRDC causes great economic losses to the United States feedlot industry. BVDV infection induces immunosuppression in infected animals. BVDV Npro binds and degrades the transcription factor interferon regulatory factor-3 (IRF-3) and effectively blocks type I interferon (type I IFN) expression in host cells. BRSV nonstructural proteins, NS1 and NS2, block activation of IRF-3. In calves, concurrent infection with BVDV and BRSV resulted in more severe clinical …


Direct Cell-To-Cell Transmission Of Respiratory Viruses: The Fast Lanes, Nicolás P. Cifuentes-Muñoz, Rebecca Ellis Dutch, Roberto Cattaneo 2018 University of Kentucky

Direct Cell-To-Cell Transmission Of Respiratory Viruses: The Fast Lanes, Nicolás P. Cifuentes-Muñoz, Rebecca Ellis Dutch, Roberto Cattaneo

Molecular and Cellular Biochemistry Faculty Publications

Virus particles protect genomes from hostile environments within and outside the host, eventually delivering these genomes to target tissues to initiate infection. Complex processes requiring significant energy and time are necessary to assemble these virus particles, but only a small portion of released virus will successfully infect new target cells (Fig 1A). While the science of virology has developed based on the isolation and purification of viral particles, it is becoming increasingly clear that direct cell-to-cell transmission of viruses and/or viral components is also highly relevant [1,2].

Direct cell-to-cell spread of infections has several advantages. The first is efficiency: genomic …


Snf1 Cooperates With The Cwi Mapk Pathway To Mediate The Degradation Of Med13 Following Oxidative Stress, Stephen D Willis, David C Stieg, Kai Li Ong, Ravina Shah, Alexandra K. Strich, Julianne H Grose, Katrina F Cooper 2018 Rowan University

Snf1 Cooperates With The Cwi Mapk Pathway To Mediate The Degradation Of Med13 Following Oxidative Stress, Stephen D Willis, David C Stieg, Kai Li Ong, Ravina Shah, Alexandra K. Strich, Julianne H Grose, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Eukaryotic cells, when faced with unfavorable environmental conditions, mount either pro-survival or pro-death programs. The conserved cyclin C-Cdk8 kinase plays a key role in this decision. Both are members of the Cdk8 kinase module that, along with Med12 and Med13, associate with the core Mediator complex of RNA polymerase II. In Saccharomyces cerevisiae, oxidative stress triggers Med13 destruction, which releases cyclin C into the cytoplasm to promote mitochondrial fission and programmed cell death. The SCFGrr1 ubiquitin ligase mediates Med13 degradation dependent on the cell wall integrity pathway, MAPK Slt2. Here we show that the AMP kinase Snf1 activates a second …


Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson 2018 University of Kentucky

Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism …


Fungal Endophytes In A Seed-Free Host: New Species That Demonstrate Unique Community Dynamics, Brett Steven Younginger 2018 Portland State University

Fungal Endophytes In A Seed-Free Host: New Species That Demonstrate Unique Community Dynamics, Brett Steven Younginger

Dissertations and Theses

Fungal endophytes are highly diverse, cryptic plant endosymbionts that form asymptomatic infections within host tissue. They represent a large fraction of the millions of undescribed fungal taxa on our planet with some demonstrating mutualistic benefits to their hosts including herbivore and pathogen defense and abiotic stress tolerance. Other endophytes are latent saprotrophs or pathogens, awaiting host plant senescence to begin alternative stages of their life cycles. Most, however, are likely plant commensals with no observable benefits to their hosts while under study. Yet, when considering the context-dependence that may determine plant resistance to pathogen attack, the consortium of endophytes present …


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