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Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley Aug 2019

Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley

Maxwell H. Gluck Equine Research Center Faculty Publications

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …


Imaging Of Glucose Metabolism By 13c-Mri Distinguishes Pancreatic Cancer Subtypes In Mice, Shun Kishimoto, Jeffrey R. Brender, Daniel R. Crooks, Shingo Matsumoto, Tomohiro Seki, Nobu Oshima, Hellmut Merkle, Penghui Lin, Galen Reed, Albert P. Chen, Jan Henrik Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Kazutoshi Yamamoto, Peter L. Choyke, James Mitchell, Andrew N. Lane, Teresa W. M. Fan, W. Marston Linehan, Murali C. Krishna Aug 2019

Imaging Of Glucose Metabolism By 13c-Mri Distinguishes Pancreatic Cancer Subtypes In Mice, Shun Kishimoto, Jeffrey R. Brender, Daniel R. Crooks, Shingo Matsumoto, Tomohiro Seki, Nobu Oshima, Hellmut Merkle, Penghui Lin, Galen Reed, Albert P. Chen, Jan Henrik Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Kazutoshi Yamamoto, Peter L. Choyke, James Mitchell, Andrew N. Lane, Teresa W. M. Fan, W. Marston Linehan, Murali C. Krishna

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic differences among and within tumors can be an important determinant in cancer treatment outcome. However, methods for determining these differences non-invasively in vivo is lacking. Using pancreatic ductal adenocarcinoma as a model, we demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of the metabolism of 13C labeled glucose tracers, which can be imaged without hyperpolarization by using newly developed techniques for noise suppression. Using this method, cancer subtypes that appeared to have similar metabolic profiles based on steady state metabolic measurement can be distinguished from each other. The metabolic maps from …


Understanding The Axonal Response To Injury By In Vivo Imaging In The Mouse Spinal Cord: A Tale Of Two Branches., Binhai Zheng, Ariana O Lorenzana, Le Ma Aug 2019

Understanding The Axonal Response To Injury By In Vivo Imaging In The Mouse Spinal Cord: A Tale Of Two Branches., Binhai Zheng, Ariana O Lorenzana, Le Ma

Department of Neuroscience Faculty Papers

Understanding the basic properties of how axons respond to injury in the mammalian central nervous system (CNS) is of fundamental value for developing strategies to promote neural repair. Axons possess complex morphologies with stereotypical branching patterns. However, current knowledge of the axonal response to injury gives little consideration to axonal branches, nor do strategies to promote axon regeneration. This article reviews evidence from in vivo spinal cord imaging that axonal branches markedly impact the degenerative and regenerative responses to injury. At a major bifurcation point, depending on whether one or both axonal branches are injured, neurons may choose either a …


Host And Viral Mechanisms Of Congenital Zika Syndrome, Brooke Liang, José Paulo Guida, Maria Laura Costa Do Nascimento, Indira U Mysorekar Aug 2019

Host And Viral Mechanisms Of Congenital Zika Syndrome, Brooke Liang, José Paulo Guida, Maria Laura Costa Do Nascimento, Indira U Mysorekar

Open Access Publications

In 2015-2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by


Equine Arteritis Virus Long-Term Persistence Is Orchestrated By Cd8+ T Lymphocyte Transcription Factors, Inhibitory Receptors, And The Cxcl16/Cxcr6 Axis, Mariano Carossino, Pouya Dini, Theodore S. Kalbfleisch, Alan T. Loynachan, Igor F. Canisso, R. Frank Cook, Peter J. Timoney, Udeni B. R. Balasuriya Jul 2019

Equine Arteritis Virus Long-Term Persistence Is Orchestrated By Cd8+ T Lymphocyte Transcription Factors, Inhibitory Receptors, And The Cxcl16/Cxcr6 Axis, Mariano Carossino, Pouya Dini, Theodore S. Kalbfleisch, Alan T. Loynachan, Igor F. Canisso, R. Frank Cook, Peter J. Timoney, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Equine arteritis virus (EAV) has the unique ability to establish long-term persistent infection in the reproductive tract of stallions and be sexually transmitted. Previous studies showed that long-term persistent infection is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistence is maintained despite the presence of local inflammatory and humoral and mucosal antibody responses. Here, we performed transcriptomic analysis of the ampullae, the primary site of EAV persistence in long-term EAV carrier stallions, to understand the molecular signatures of viral persistence. We demonstrated that the local CD8+ T lymphocyte response is predominantly orchestrated …


A Sparse Covarying Unit That Describes Healthy And Impaired Human Gut Microbiota Development, Arjun S Raman, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Sathish Subramanian, Michael J Barratt, Jeffrey I Gordon, Et Al Jul 2019

A Sparse Covarying Unit That Describes Healthy And Impaired Human Gut Microbiota Development, Arjun S Raman, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Sathish Subramanian, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an "ecogroup" of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of …


Effects Of Microbiota-Directed Foods In Gnotobiotic Animals And Undernourished Children, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Vanderlene L Kung, Jiye Cheng, Robert Y Chen, Sathish Subramanian, Carrie A Cowardin, Martin F Meier, David O'Donnell, Michael Talcott, Larry D Spears, Clay F Semenkovich, Christopher Sawyer, Richard D Head, Michael J Barratt, Jeffrey I Gordon, Et Al Jul 2019

Effects Of Microbiota-Directed Foods In Gnotobiotic Animals And Undernourished Children, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Vanderlene L Kung, Jiye Cheng, Robert Y Chen, Sathish Subramanian, Carrie A Cowardin, Martin F Meier, David O'Donnell, Michael Talcott, Larry D Spears, Clay F Semenkovich, Christopher Sawyer, Richard D Head, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF …


In Vivo Effectiveness And Safety Of Probiotics On Prophylaxis And Treatment Of Oral Candidiasis: A Systematic Review And Meta-Analysis, Lijun Hu, Mimi Zhou, Andrew L. Young, Weiwei Zhao, Zhimin Yan Jul 2019

In Vivo Effectiveness And Safety Of Probiotics On Prophylaxis And Treatment Of Oral Candidiasis: A Systematic Review And Meta-Analysis, Lijun Hu, Mimi Zhou, Andrew L. Young, Weiwei Zhao, Zhimin Yan

All Dugoni School of Dentistry Faculty Articles

BACKGROUND: To systematically review and assess the in vivo effectiveness and safety of probiotics for prophylaxis and treating oral candidiasis.

METHODS: A literature search for studies published in English until August 1, 2018 was conducted in the following databases: PubMed, EMBASE, Cochrane Library, and Web of Science. Randomized controlled clinical trials and experimental mouse animal model studies comparing probiotics (at any dosage and in any form) with control groups (placebo, blank control or other agents) and reporting outcomes of the prophylactic and therapeutic effects were considered for inclusion. A descriptive study and, potentially, a meta-analysis were planned.

RESULTS: Six randomized …


Wilgus, Donald Knight (Fa 1203), Manuscripts & Folklife Archives Jul 2019

Wilgus, Donald Knight (Fa 1203), Manuscripts & Folklife Archives

Folklife Archives Finding Aids

Finding aid only for Folklife Archives Project 1203. Student folk studies projects collected by Professor Donald Knight “D. K.” Wilgus while teaching folk studies classes at Western Kentucky University. Most of the items collected are from south central Kentucky, but also includes items from Indiana, Ohio and Tennessee.


Plasticizer Interaction With The Heart: Chemicals Used In Plastic Medical Devices Can Interfere With Cardiac Electrophysiology., Rafael Jaimes, Damon Mccullough, Bryan Siegel, Luther Swift, Daniel Mcinerney, James Hiebert, Erick A Perez-Alday, Beatriz Trenor, Jiansong Sheng, Javier Saiz, Larisa G Tereshchenko, Nikki Gillum Posnack Jul 2019

Plasticizer Interaction With The Heart: Chemicals Used In Plastic Medical Devices Can Interfere With Cardiac Electrophysiology., Rafael Jaimes, Damon Mccullough, Bryan Siegel, Luther Swift, Daniel Mcinerney, James Hiebert, Erick A Perez-Alday, Beatriz Trenor, Jiansong Sheng, Javier Saiz, Larisa G Tereshchenko, Nikki Gillum Posnack

Pediatrics Faculty Publications

BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients.

METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure.

RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 …


A Guinea Fowl Genome Assembly Provides New Evidence On Evolution Following Domestication And Selection In Galliformes, Alain Vignal, Simon Boitard, Noémie Thébault, Guiguigbaza-Kossigan Dayo, Valentine Yapi-Gnaore, Issaka Youssao Abdou Karim, Cécile Berthouly-Salazar, Nóra Pálinkás-Bodzsár, Daniel Guémené, Francoise Thibaud-Nissen, Wesley C Warren, Michèle Tixier-Boichard, Xavier Rognon Jul 2019

A Guinea Fowl Genome Assembly Provides New Evidence On Evolution Following Domestication And Selection In Galliformes, Alain Vignal, Simon Boitard, Noémie Thébault, Guiguigbaza-Kossigan Dayo, Valentine Yapi-Gnaore, Issaka Youssao Abdou Karim, Cécile Berthouly-Salazar, Nóra Pálinkás-Bodzsár, Daniel Guémené, Francoise Thibaud-Nissen, Wesley C Warren, Michèle Tixier-Boichard, Xavier Rognon

Open Access Publications

The helmeted guinea fowl Numida meleagris belongs to the order Galliformes. Its natural range includes a large part of sub-Saharan Africa, from Senegal to Eritrea and from Chad to South Africa. Archaeozoological and artistic evidence suggest domestication of this species may have occurred about 2,000 years BP in Mali and Sudan primarily as a food resource, although villagers also benefit from its capacity to give loud alarm calls in case of danger, of its ability to consume parasites such as ticks and to hunt snakes, thus suggesting its domestication may have resulted from a commensal association process. Today, it is …


Phospholipases D: Making Sense Of Redundancy And Duplication, Andrew J. Morris Jun 2019

Phospholipases D: Making Sense Of Redundancy And Duplication, Andrew J. Morris

Internal Medicine Faculty Publications

Why have two genes when one would suffice? Evolutionary pressure means that biology, unlike government, is generally intolerant of wasted effort. Therefore, when multiple genes exist presumably they are there to provide some benefit to the organism even if that benefit is not immediately obvious to us scientists. A recent report from Raghu and colleagues (Biosci. Rep. (2018) 38, pii: BSR20181690) [1] sheds some light on one possible reason for the existence of two Phospholipases D genes in chordates when only one is present in invertebrates.


Pathologic Gene Network Rewiring Implicates Ppp1r3a As A Central Regulator In Pressure Overload Heart Failure., Pablo Cordero, Victoria N Parikh, Elizabeth T Chin, Ayca Erbilgin, Michael J Gloudemans, Ching Shang, Yong Huang, Alex C Chang, Kevin S Smith, Frederick Dewey, Kathia Zaleta, Michael Morley, Jeff Brandimarto, Nicole Glazer, Daryl Waggott, Aleksandra Pavlovic, Mingming Zhao, Christine S Moravec, W H Wilson Tang, Jamie Skreen, Christine Malloy, Sridhar Hannenhalli, Hongzhe Li, Scott Ritter, Mingyao Li, Daniel Bernstein, Andrew Connolly, Hakon Hakonarson, Aldons J Lusis, Kenneth B Margulies, Anna A Depaoli-Roach, Stephen B Montgomery, Matthew T Wheeler, Thomas Cappola, Euan A Ashley Jun 2019

Pathologic Gene Network Rewiring Implicates Ppp1r3a As A Central Regulator In Pressure Overload Heart Failure., Pablo Cordero, Victoria N Parikh, Elizabeth T Chin, Ayca Erbilgin, Michael J Gloudemans, Ching Shang, Yong Huang, Alex C Chang, Kevin S Smith, Frederick Dewey, Kathia Zaleta, Michael Morley, Jeff Brandimarto, Nicole Glazer, Daryl Waggott, Aleksandra Pavlovic, Mingming Zhao, Christine S Moravec, W H Wilson Tang, Jamie Skreen, Christine Malloy, Sridhar Hannenhalli, Hongzhe Li, Scott Ritter, Mingyao Li, Daniel Bernstein, Andrew Connolly, Hakon Hakonarson, Aldons J Lusis, Kenneth B Margulies, Anna A Depaoli-Roach, Stephen B Montgomery, Matthew T Wheeler, Thomas Cappola, Euan A Ashley

Articles, Abstracts, and Reports

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and …


Environmental Microcystin Targets The Microbiome And Increases The Risk Of Intestinal Inflammatory Pathology Via Nox2 In Underlying Murine Model Of Nonalcoholic Fatty Liver Disease, Sutapa Sarkar, Diana Kimono, Muayad Albadrani, Ratanesh K. Seth, Philip Busbee, Hasan Alghetaa, Dwayne E. Porter, Geoff I. Scott, Bryan Brooks, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh Chatterjee Jun 2019

Environmental Microcystin Targets The Microbiome And Increases The Risk Of Intestinal Inflammatory Pathology Via Nox2 In Underlying Murine Model Of Nonalcoholic Fatty Liver Disease, Sutapa Sarkar, Diana Kimono, Muayad Albadrani, Ratanesh K. Seth, Philip Busbee, Hasan Alghetaa, Dwayne E. Porter, Geoff I. Scott, Bryan Brooks, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh Chatterjee

Faculty Publications

With increased climate change pressures likely to influence harmful algal blooms, exposure to microcystin, a known hepatotoxin and a byproduct of cyanobacterial blooms can be a risk factor for NAFLD associated comorbidities. Using both in vivo and in vitro experiments we show that microcystin exposure in NAFLD mice cause rapid alteration of gut microbiome, rise in bacterial genus known for mediating gut inflammation and lactate production. Changes in the microbiome were strongly associated with inflammatory pathology in the intestine, gut leaching, tight junction protein alterations and increased oxidative tyrosyl radicals. Increased lactate producing bacteria from the altered microbiome was associated …


Intracellular Retention Of Mutant Lysyl Oxidase Leads To Aortic Dilation In Response To Increased Hemodynamic Stress, Vivian S Lee, Carmen M Halabi, Thomas J Broekelmann, Philip C Trackman, Nathan O Stitziel, Robert P Mecham Jun 2019

Intracellular Retention Of Mutant Lysyl Oxidase Leads To Aortic Dilation In Response To Increased Hemodynamic Stress, Vivian S Lee, Carmen M Halabi, Thomas J Broekelmann, Philip C Trackman, Nathan O Stitziel, Robert P Mecham

Open Access Publications

Heterozygous missense mutations in lysyl oxidase (LOX) are associated with thoracic aortic aneurysms and dissections. To assess how LOX mutations modify protein function and lead to aortic disease, we studied the factors that influence the onset and progression of vascular aneurysms in mice bearing a Lox mutation (p.M292R) linked to aortic dilation in humans. We show that mice heterozygous for the M292R mutation did not develop aneurysmal disease unless challenged with increased hemodynamic stress. Vessel dilation was confined to the ascending aorta although both the ascending and descending aortae showed changes in vessel wall structure, smooth muscle cell number and …


Preoperative Stimulation Of Resolution And Inflammation Blockade Eradicates Micrometastases., Dipak Panigrahy, Allison Gartung, Jun Yang, Haixia Yang, Molly M Gilligan, Megan L Sulciner, Swati S Bhasin, Diane R Bielenberg, Jaimie Chang, Birgitta A Schmidt, Julia Piwowarski, Anna Fishbein, Dulce Soler-Ferran, Matthew A Sparks, Steven J Staffa, Vidula Sukhatme, Bruce D Hammock, Mark W Kieran, Sui Huang, Manoj Bhasin, Charles N Serhan, Vikas P Sukhatme Jun 2019

Preoperative Stimulation Of Resolution And Inflammation Blockade Eradicates Micrometastases., Dipak Panigrahy, Allison Gartung, Jun Yang, Haixia Yang, Molly M Gilligan, Megan L Sulciner, Swati S Bhasin, Diane R Bielenberg, Jaimie Chang, Birgitta A Schmidt, Julia Piwowarski, Anna Fishbein, Dulce Soler-Ferran, Matthew A Sparks, Steven J Staffa, Vidula Sukhatme, Bruce D Hammock, Mark W Kieran, Sui Huang, Manoj Bhasin, Charles N Serhan, Vikas P Sukhatme

Articles, Abstracts, and Reports

Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed anticancer T cell immunity that was augmented by immune checkpoint blockade, negated by adjuvant chemotherapy, and dependent on inhibition of the COX-1/thromboxane A2 …


Xx Sex Chromosome Complement Promotes Atherosclerosis In Mice, Yasir Alsiraj, Xuqi Chen, Sean E. Thatcher, Ryan E. Temel, Lei Cai, Eric M. Blalock, Wendy Katz, Heba M. Ali, Michael C. Petriello, Pan Deng, Andrew J. Morris, Xuping Wang, Aldons J. Lusis, Arthur P. Arnold, Karen Reue, Katherine L. Thompson, Patrick Tso, Lisa A. Cassis Jun 2019

Xx Sex Chromosome Complement Promotes Atherosclerosis In Mice, Yasir Alsiraj, Xuqi Chen, Sean E. Thatcher, Ryan E. Temel, Lei Cai, Eric M. Blalock, Wendy Katz, Heba M. Ali, Michael C. Petriello, Pan Deng, Andrew J. Morris, Xuping Wang, Aldons J. Lusis, Arthur P. Arnold, Karen Reue, Katherine L. Thompson, Patrick Tso, Lisa A. Cassis

Pharmacology and Nutritional Sciences Faculty Publications

Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating …


Extreme Longevity: Discovering Earth's Oldest Organisms, Emilee Bell Jun 2019

Extreme Longevity: Discovering Earth's Oldest Organisms, Emilee Bell

Children's Book and Media Review

Shuffle back in time with Jonathan, the 100+ year old tortoise, and witness the evolution of the automobile. Rest beneath the shade of centuries-old trees born when the glaciers melted on the American continent. Peek at the ocean organisms that roamed the earth before humans were even a thought. Kenney beguiles the reader with ancient timelines, winding the biological history of the world with the human history, tying said reader tightly and permanently with the longevity of the plants and animals of this world. Each chapter feels like an epic tale: lone organisms surviving chaos, hunters, pollution, and massive social …


Reactive Microglia And Il1Β/Il-1r1-Signaling Mediate Neuroprotection In Excitotoxin-Damaged Mouse Retina, Levi Todd, Isabella Palazzo, Lilianna Suarez, Xiaoyu Liu, Leo Volkov, Thanh V Hoang, Warren A Campbell, Seth Blackshaw, Ning Quan, Andy J Fischer Jun 2019

Reactive Microglia And Il1Β/Il-1r1-Signaling Mediate Neuroprotection In Excitotoxin-Damaged Mouse Retina, Levi Todd, Isabella Palazzo, Lilianna Suarez, Xiaoyu Liu, Leo Volkov, Thanh V Hoang, Warren A Campbell, Seth Blackshaw, Ning Quan, Andy J Fischer

Open Access Publications

BACKGROUND: Microglia and inflammation have context-specific impacts upon neuronal survival in different models of central nervous system (CNS) disease. Herein, we investigate how inflammatory mediators, including microglia, interleukin 1 beta (IL1β), and signaling through interleukin 1 receptor type 1 (IL-1R1), influence the survival of retinal neurons in response to excitotoxic damage.

METHODS: Excitotoxic retinal damage was induced via intraocular injections of NMDA. Microglial phenotype and neuronal survival were assessed by immunohistochemistry. Single-cell RNA sequencing was performed to obtain transcriptomic profiles. Microglia were ablated by using clodronate liposome or PLX5622. Retinas were treated with IL1β prior to NMDA damage and cell …


Cyclin C Regulated Oxidative Stress Responsive Transcriptome In Mus Musculus Embryonic Fibroblasts, David C Stieg, Kai-Ti Chang, Katrina F Cooper, Randy Strich Jun 2019

Cyclin C Regulated Oxidative Stress Responsive Transcriptome In Mus Musculus Embryonic Fibroblasts, David C Stieg, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The transcriptional changes that occur in response to oxidative stress help direct the decision to maintain cell viability or enter a cell death pathway. Cyclin C-Cdk8 is a conserved kinase that associates with the RNA polymerase II Mediator complex that stimulates or represses transcription depending on the locus. In response to oxidative stress, cyclin C, but not Cdk8, displays partial translocation into the cytoplasm. These findings open the possibility that cyclin C relocalization is a regulatory mechanism governing oxidative stress-induced transcriptional changes. In the present study, the cyclin C-dependent transcriptome was determined and compared to transcriptional changes occurring in oxidatively …


Pet First Aid And C.P.R., Central Washington University, Gretchen Taussig-Simpson Jun 2019

Pet First Aid And C.P.R., Central Washington University, Gretchen Taussig-Simpson

Brooks Library Events

Learn how to keep your pet safe and healthy.


The Current State Of Animal Models And Genomic Approaches Towards Identifying And Validating Molecular Determinants Of Mycobacterium Tuberculosis Infection And Tuberculosis Disease, Allison N Bucsan, Smriti Mehra, Shabaana A Khader, Deepak Kaushal Jun 2019

The Current State Of Animal Models And Genomic Approaches Towards Identifying And Validating Molecular Determinants Of Mycobacterium Tuberculosis Infection And Tuberculosis Disease, Allison N Bucsan, Smriti Mehra, Shabaana A Khader, Deepak Kaushal

2010-2019 OA Pubs

Animal models are important in understanding both the pathogenesis of and immunity to tuberculosis (TB). Unfortunately, we are beginning to understand that no animal model perfectly recapitulates the human TB syndrome, which encompasses numerous different stages. Furthermore, Mycobacterium tuberculosis infection is a very heterogeneous event at both the levels of pathogenesis and immunity. This review seeks to establish the current understanding of TB pathogenesis and immunity, as validated in the animal models of TB in active use today. We especially focus on the use of modern genomic approaches in these models to determine the mechanism and the role of specific …


Genetic Approaches To Metabolic Bone Diseases, Fadil M Hannan, Paul J Newey, Michael P Whyte, Rajesh V Thakker Jun 2019

Genetic Approaches To Metabolic Bone Diseases, Fadil M Hannan, Paul J Newey, Michael P Whyte, Rajesh V Thakker

Open Access Publications

Metabolic bone diseases comprise a diverse group of disorders characterized by alterations in skeletal homeostasis, and are often associated with abnormal circulating concentrations of calcium, phosphate or vitamin D metabolites. These diseases commonly have a genetic basis and represent either a monogenic disorder due to a germline or somatic single gene mutation, or an oligogenic or polygenic disorder that involves variants in more than one gene. Germline single gene mutations causing Mendelian diseases typically have a high penetrance, whereas the genetic variations causing oligogenic or polygenic disorders are each associated with smaller effects with additional contributions from environmental factors. Recognition …


High Fat Diet Alters Gut Microbiota But Not Spatial Working Memory In Early Middle-Aged Sprague Dawley Rats, Nikita Girish Deshpande, Juhi Saxena, Tristan G. Pesaresi, Casey Dylan Carrell, Grayson Breneman Ashby, Min-Ken Liao, Linnea Ruth Freeman May 2019

High Fat Diet Alters Gut Microbiota But Not Spatial Working Memory In Early Middle-Aged Sprague Dawley Rats, Nikita Girish Deshpande, Juhi Saxena, Tristan G. Pesaresi, Casey Dylan Carrell, Grayson Breneman Ashby, Min-Ken Liao, Linnea Ruth Freeman

Open Access Fund Publications

As the global population ages, and rates of dementia rise, understanding lifestyle factors that play a role in the development and acceleration of cognitive decline is vital to creating therapies and recommendations to improve quality of later life. Obesity has been shown to increase risk for dementia. However, the specific mechanisms for obesity-induced cognitive decline remain unclear. One potential contributor to diet-induced cognitive changes is neuroinflammation. Furthermore, a source of diet-induced inflammation to potentially increase neuroinflammation is via gut dysbiosis. We hypothesized that a high fat diet would cause gut microbe dysbiosis, and subsequently: neuroinflammation and cognitive decline. Using 7-month …


Altered Detrusor Contractility And Voiding Patterns In Mice Lacking The Mechanosensitive Trek-1 Channel., Ricardo H. Pineda, Joseph Hypolite, Sanghee Lee, Alonso Carrasco, Nao Iguchi, Randall B. Meacham, Anna P. Malykhina May 2019

Altered Detrusor Contractility And Voiding Patterns In Mice Lacking The Mechanosensitive Trek-1 Channel., Ricardo H. Pineda, Joseph Hypolite, Sanghee Lee, Alonso Carrasco, Nao Iguchi, Randall B. Meacham, Anna P. Malykhina

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Previously published results from our laboratory identified a mechano-gated two-pore domain potassium channel, TREK-1, as a main mechanosensor in the smooth muscle of the human urinary bladder. One of the limitations of in vitro experiments on isolated human detrusor included inability to evaluate in vivo effects of TREK-1 on voiding function, as the channel is also expressed in the nervous system, and may modulate micturition via neural pathways. Therefore, in the present study, we aimed to assess the role of TREK-1 channel in bladder function and voiding patterns in vivo by using TREK-1 knockout (KO) mice.

METHODS: Adult C57BL/6 …


A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker May 2019

A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker

Pharmaceutical Sciences Faculty Publications

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.


A Consensus Guide To Capturing The Ability To Inhibit Actions And Impulsive Behaviors In The Stop-Signal Task., Frederick Verbruggen, Adam R Aron, Guido Ph Band, Christian Beste, Patrick G Bissett, Adam T Brockett, Joshua W Brown, Samuel R Chamberlain, Christopher D Chambers, Hans Colonius, Lorenza S Colzato, Brian D Corneil, James P Coxon, Annie Dupuis, Dawn M Eagle, Hugh Garavan, Ian Greenhouse, Andrew Heathcote, René J Huster, Sara Jahfari, J Leon Kenemans, Inge Leunissen, Chiang-Shan R Li, Gordon D Logan, Dora Matzke, Sharon Morein-Zamir, Aditya Murthy, Martin Paré, Russell A Poldrack, K Richard Ridderinkhof, Trevor W Robbins, Matthew Roesch, Katya Rubia, Russell J Schachar, Jeffrey D Schall, Ann-Kathrin Stock, Nicole C Swann, Katharine N Thakkar, Maurits W Van Der Molen, Luc Vermeylen, Matthijs Vink, Jan R Wessel, Robert Whelan, Bram B Zandbelt, C Nico Boehler Apr 2019

A Consensus Guide To Capturing The Ability To Inhibit Actions And Impulsive Behaviors In The Stop-Signal Task., Frederick Verbruggen, Adam R Aron, Guido Ph Band, Christian Beste, Patrick G Bissett, Adam T Brockett, Joshua W Brown, Samuel R Chamberlain, Christopher D Chambers, Hans Colonius, Lorenza S Colzato, Brian D Corneil, James P Coxon, Annie Dupuis, Dawn M Eagle, Hugh Garavan, Ian Greenhouse, Andrew Heathcote, René J Huster, Sara Jahfari, J Leon Kenemans, Inge Leunissen, Chiang-Shan R Li, Gordon D Logan, Dora Matzke, Sharon Morein-Zamir, Aditya Murthy, Martin Paré, Russell A Poldrack, K Richard Ridderinkhof, Trevor W Robbins, Matthew Roesch, Katya Rubia, Russell J Schachar, Jeffrey D Schall, Ann-Kathrin Stock, Nicole C Swann, Katharine N Thakkar, Maurits W Van Der Molen, Luc Vermeylen, Matthijs Vink, Jan R Wessel, Robert Whelan, Bram B Zandbelt, C Nico Boehler

Brain and Mind Institute Researchers' Publications

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the …


Systematic Review Of Gastrointestinal Nematodes Of Horses From Australia, Muhammad A. Saeed, Ian Beveridge, Ghazanfar Abbas, Anne Beasley, Jenni Bauquier, Edwina Wilkes, Caroline Jacobson, Kris J. Hughes, Charles El-Hage, Ryan O'Handley, John Hurley, Lucy Cudmore, Peter Carrigan, Lisa Walter, Brett Tennent-Brown, Martin K. Nielsen, Abdul Jabbar Apr 2019

Systematic Review Of Gastrointestinal Nematodes Of Horses From Australia, Muhammad A. Saeed, Ian Beveridge, Ghazanfar Abbas, Anne Beasley, Jenni Bauquier, Edwina Wilkes, Caroline Jacobson, Kris J. Hughes, Charles El-Hage, Ryan O'Handley, John Hurley, Lucy Cudmore, Peter Carrigan, Lisa Walter, Brett Tennent-Brown, Martin K. Nielsen, Abdul Jabbar

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control.

Methods: Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, …


Development And Evaluation Of A One-Step Multiplex Real-Time Taqman® Rt-Qpcr Assay For The Detection And Genotyping Of Equine G3 And G14 Rotaviruses In Fecal Samples, Mariano Carossino, Maria E. Barrandeguy, Erdal Erol, Yanqiu Li, Udeni B. R. Balasuriya Apr 2019

Development And Evaluation Of A One-Step Multiplex Real-Time Taqman® Rt-Qpcr Assay For The Detection And Genotyping Of Equine G3 And G14 Rotaviruses In Fecal Samples, Mariano Carossino, Maria E. Barrandeguy, Erdal Erol, Yanqiu Li, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Background: Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and has a negative impact on equine breeding enterprises worldwide. Among ERVA strains infecting foals, the genotypes G3P[12] and G14P[12] are the most prevalent, while infections by strains with other genomic arrangements are infrequent. The identification of circulating strains of ERVA is critical for diagnostic and surveillance purposes, as well as to understand their molecular epidemiology. Current genotyping methods available for ERVA and rotaviruses affecting other animal species rely on Sanger sequencing and are significantly time-consuming, costly and labor intensive. Here, we developed the first one-step …


Evaluating Educational Training Impact On Pre-Service Students’ Attitudes Towards Human-Animal Relationships, Yuleinys A. Castillo, Denise Silcox, Lynn K. Fisher Apr 2019

Evaluating Educational Training Impact On Pre-Service Students’ Attitudes Towards Human-Animal Relationships, Yuleinys A. Castillo, Denise Silcox, Lynn K. Fisher

School of Rehabilitation Services & Counseling Faculty Publications

Experts suggest that human-animal relationships can bring benefits to households, work environments, and training facilities. Animals can also have a positive impact on humans’ psychological well-being, interpersonal relationships, and interaction with human services providers. Even though human services providers need to understand clients’ holistic experiences, animals are often excluded from treatment and services. Therefore, human services students, who have exposure to the human animal bond, can be more effective providers and understand the role of animals in society. This study evaluated the impact of information about the human-animal bond on attitudes towards animals among pre-service human services students. In addition, …