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The New World Of Pet Prosthetics, Anna Brooks Dec 2018

The New World Of Pet Prosthetics, Anna Brooks

Capstones

When an abandoned dog was found in Brooklyn with his paw gnawed off, the animal shelter had two options: amputate the leg, or put the dog down. But neither seemed like a solution. So they decided to do something different, and fit the dog for a prosthetic leg. Prosthetics for people have been around for millennia, and now these devices are moving into the animal kingdom. This story explores the new world of animal prosthetics, and how these devices have changed the lives of animals like Mr. Stubbs — the first alligator with a prosthetic tail — and saved the …


Expanding The Use Of Spectral Libraries In Proteomics., Eric W Deutsch, Yasset Perez-Riverol, Robert J Chalkley, Mathias Wilhelm, Stephen Tate, Timo Sachsenberg, Mathias Walzer, Lukas Käll, Bernard Delanghe, Sebastian Böcker, Emma L Schymanski, Paul Wilmes, Viktoria Dorfer, Bernhard Kuster, Pieter-Jan Volders, Nico Jehmlich, Johannes P C Vissers, Dennis W Wolan, Ana Y Wang, Luis Mendoza, Jim Shofstahl, Andrew W Dowsey, Johannes Griss, Reza M Salek, Steffen Neumann, Pierre-Alain Binz, Henry Lam, Juan Antonio Vizcaíno, Nuno Bandeira, Hannes Röst Dec 2018

Expanding The Use Of Spectral Libraries In Proteomics., Eric W Deutsch, Yasset Perez-Riverol, Robert J Chalkley, Mathias Wilhelm, Stephen Tate, Timo Sachsenberg, Mathias Walzer, Lukas Käll, Bernard Delanghe, Sebastian Böcker, Emma L Schymanski, Paul Wilmes, Viktoria Dorfer, Bernhard Kuster, Pieter-Jan Volders, Nico Jehmlich, Johannes P C Vissers, Dennis W Wolan, Ana Y Wang, Luis Mendoza, Jim Shofstahl, Andrew W Dowsey, Johannes Griss, Reza M Salek, Steffen Neumann, Pierre-Alain Binz, Henry Lam, Juan Antonio Vizcaíno, Nuno Bandeira, Hannes Röst

Articles, Abstracts, and Reports

The 2017 Dagstuhl Seminar on Computational Proteomics provided an opportunity for a broad discussion on the current state and future directions of the generation and use of peptide tandem mass spectrometry spectral libraries. Their use in proteomics is growing slowly, but there are multiple challenges in the field that must be addressed to further increase the adoption of spectral libraries and related techniques. The primary bottlenecks are the paucity of high quality and comprehensive libraries and the general difficulty of adopting spectral library searching into existing workflows. There are several existing spectral library formats, but none captures a satisfactory level …


Flexible And Fast Mapping Of Peptides To A Proteome With Proteomapper., Luis Mendoza, Eric W Deutsch, Zhi Sun, David S Campbell, David Shteynberg, Robert L Moritz Dec 2018

Flexible And Fast Mapping Of Peptides To A Proteome With Proteomapper., Luis Mendoza, Eric W Deutsch, Zhi Sun, David S Campbell, David Shteynberg, Robert L Moritz

Articles, Abstracts, and Reports

Bottom-up proteomics relies on the proteolytic or chemical cleavage of proteins into peptides, the identification of those peptides via mass spectrometry, and the mapping of the identified peptides back to the reference proteome to infer which possible proteins are identified. Reliable mapping of peptides to proteins still poses substantial challenges when considering similar proteins, protein families, splice isoforms, sequence variation, and possible residue mass modifications, combined with an imperfect and incomplete understanding of the proteome. The ProteoMapper tool enables a comprehensive and rapid mapping of peptides to a reference proteome. The indexer component creates a segmented index for an input …


Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi Dec 2018

Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi

Molecular and Cellular Biochemistry Faculty Publications

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …


Thyrotropin Receptor Blocking Antibodies, Tanja Diana, Paul D. Olivo, George J. Kahaly Dec 2018

Thyrotropin Receptor Blocking Antibodies, Tanja Diana, Paul D. Olivo, George J. Kahaly

2010-2019 OA Pubs

Autoantibodies (Ab) against the thyroid-stimulating hormone receptor (TSHR) are frequently found in autoimmune thyroid disease (AITD). Autoantibodies to the TSHR (anti-TSHR-Ab) may mimic or block the action of TSH or be functionally neutral. Measurement of anti-TSHR-Ab can be done either via competitive-binding immunoassays or with functional cell-based bioassays. Antibody-binding assays do not assess anti-TSHR-Ab functionality, but rather measure the concentration of total anti-TSHR binding activity. In contrast, functional cell-based bioassays indicate whether anti-TSHR-Ab have stimulatory or blocking activity. Historically bioassays for anti-TSHR-Ab were research tools and were used to study the pathophysiology of Graves' disease and Hashimoto's thyroiditis. In the …


Morphometric Characteristics And Time To Hatch As Efficacious Indicators For Potential Nanotoxicity Assay In Zebrafish, Seyed-Mohammadreza Samaee, Nafiseh Manteghi, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani Dec 2018

Morphometric Characteristics And Time To Hatch As Efficacious Indicators For Potential Nanotoxicity Assay In Zebrafish, Seyed-Mohammadreza Samaee, Nafiseh Manteghi, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani

Pharmaceutical Sciences Faculty Publications

Although the effects of nano-sized titania (nTiO2) on hatching events (change in hatching time and total hatching) in zebrafish have been reported, additional consequences of nTiO2 exposure (i.e., the effects of nTiO2-induced changes in hatching events and morphometric parameters on embryo-larvae development and survivability) have not been reported. To address this knowledge gap, embryos 4 h postfertilization were exposed to nTiO2 (0, 0.01, 10, and 1000 μg/mL) for 220 h. Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from 34 to 202 hpe), and 21 morphometric characteristics (8 times …


Lrrk1 Regulation Of Actin Assembly In Osteoclasts Involves Serine 5 Phosphorylation Of L-Plastin, Mingjue Si, Helen Goodluck, Canjun Zeng, Songqin Pan, Elizabeth M Todd, Sharon Celeste Morley, Xuezhong Qin, Subburaman Mohan, Weirong Xing Dec 2018

Lrrk1 Regulation Of Actin Assembly In Osteoclasts Involves Serine 5 Phosphorylation Of L-Plastin, Mingjue Si, Helen Goodluck, Canjun Zeng, Songqin Pan, Elizabeth M Todd, Sharon Celeste Morley, Xuezhong Qin, Subburaman Mohan, Weirong Xing

Open Access Publications

Mice with disruption of Lrrk1 and patients with nonfunctional mutant Lrrk1 exhibit severe osteopetrosis phenotypes because of osteoclast cytoskeletal dysfunction. To understand how Lrrk1 regulates osteoclast function by modulating cytoskeleton rearrangement, we examined the proteins that are differentially phosphorylated in wild-type mice and Lrrk1-deficient osteoclasts by metal affinity purification coupled liquid chromatography/mass spectrometry (LC/MS) analyses. One of the candidates that we identified by LC/MS is L-plastin, an actin bundling protein. We found that phosphorylation of L-plastin at serine (Ser) residues 5 was present in wild-type osteoclasts but not in Lrrk1-deficient cells. Western blot analyses with antibodies specific for Ser5 phosphorylated …


Law Library Blog (December 2018) : Legal Beagle's Blog Archive, Roger Williams University School Of Law Dec 2018

Law Library Blog (December 2018) : Legal Beagle's Blog Archive, Roger Williams University School Of Law

Law Library Newsletters/Blog

No abstract provided.


Associative And Non-Associative Learning In The Monodelphis Domestica, Ana C. Ramirez Dec 2018

Associative And Non-Associative Learning In The Monodelphis Domestica, Ana C. Ramirez

Theses and Dissertations

Learning encompasses multiple important processes that vary within organisms and that are affected by different factors. Two of the most important types of learning are associative and non-associative learning. Even though past research has studied animal learning in multiple species, there is limited research on learning in the Monodelphis domestica. It is imperative to further the knowledge on this species since multiple fields use it as an animal model for research. The current study examined both non-associative and associative learning in the Monodelphis. Non-associative learning was explored by using a habituation-dishabituation paradigm, while associative learning was examined using the …


Rapid And Robust Restoration Of Breathing Long After Spinal Cord Injury, Philippa M. Warren, Stephanie C. Steiger, Thomas E. Dick, Peter M. Macfarlane, Warren J. Alilain, Jerry Silver Nov 2018

Rapid And Robust Restoration Of Breathing Long After Spinal Cord Injury, Philippa M. Warren, Stephanie C. Steiger, Thomas E. Dick, Peter M. Macfarlane, Warren J. Alilain, Jerry Silver

Spinal Cord and Brain Injury Research Center Faculty Publications

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess …


Macrophage-Derived Netrin-1 Promotes Abdominal Aortic Aneurysm Formation By Activating Mmp3 In Vascular Smooth Muscle Cells, Tarik Hadi, Ludovic Boytard, Michele Silvestro, Dornazsadat Alebrahim, Samson Jacob, Jordyn Feinstein, Krista Barone, Wes Spiro, Susan Hutchison, Russell Simon, Debra L. Rateri, Florence Pinet, David Fenyo, Mark Adelman, Kathryn J. Moore, Holger K. Eltzschig, Alan Daugherty, Bhama Ramkhelawon Nov 2018

Macrophage-Derived Netrin-1 Promotes Abdominal Aortic Aneurysm Formation By Activating Mmp3 In Vascular Smooth Muscle Cells, Tarik Hadi, Ludovic Boytard, Michele Silvestro, Dornazsadat Alebrahim, Samson Jacob, Jordyn Feinstein, Krista Barone, Wes Spiro, Susan Hutchison, Russell Simon, Debra L. Rateri, Florence Pinet, David Fenyo, Mark Adelman, Kathryn J. Moore, Holger K. Eltzschig, Alan Daugherty, Bhama Ramkhelawon

Physiology Faculty Publications

Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix (ECM) fragmentation and inflammation. However, the mechanisms by which these events are coupled thereby fueling focal vascular damage are undefined. Here we report through single-cell RNA-sequencing of diseased aorta that the neuronal guidance cue netrin-1 can act at the interface of macrophage-driven injury and ECM degradation. Netrin-1 expression peaks in human and murine aneurysmal macrophages. Targeted deletion of netrin-1 in macrophages protects mice from developing AAA. Through its receptor neogenin-1, netrin-1 induces a robust intracellular calcium flux necessary for the transcriptional regulation and persistent catalytic activation of matrix metalloproteinase-3 (MMP3) …


H3k9 Methyltransferases And Demethylases Control Lung Tumor-Propagating Cells And Lung Cancer Progression, S. P. Rowbotham, F Li, A. F. M. Dost, S. M. Louie, B. P. Marsh, P. Pessina, C. R. Anbarasu, Christine Fillmore Brainson, S. J. Tuminello, A. Lieberman, S. Ryeom, T. M. Schlaeger, B. J. Aronow, H. Watanabe, K. K. Wong, C. F. Kim Nov 2018

H3k9 Methyltransferases And Demethylases Control Lung Tumor-Propagating Cells And Lung Cancer Progression, S. P. Rowbotham, F Li, A. F. M. Dost, S. M. Louie, B. P. Marsh, P. Pessina, C. R. Anbarasu, Christine Fillmore Brainson, S. J. Tuminello, A. Lieberman, S. Ryeom, T. M. Schlaeger, B. J. Aronow, H. Watanabe, K. K. Wong, C. F. Kim

Toxicology and Cancer Biology Faculty Publications

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition …


Micu1 Interacts With The D-Ring Of The Mcu Pore To Control Its Ca2+ Flux And Sensitivity To Ru360, Melanie Paillard, György Csordás, Kai-Ting Huang, Peter Várnai, Suresh K. Joseph, György Hajnóczky Nov 2018

Micu1 Interacts With The D-Ring Of The Mcu Pore To Control Its Ca2+ Flux And Sensitivity To Ru360, Melanie Paillard, György Csordás, Kai-Ting Huang, Peter Várnai, Suresh K. Joseph, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proper control of the mitochondrial Ca2+ uniporter’s pore (MCU) is required to allow Ca2+ dependent activation of oxidative metabolism and to avoid mitochondrial Ca2+ overload and cell death. The MCU’s gatekeeping and cooperative activation is mediated by the Ca2+ sensing MICU1 protein, which has been proposed to form dimeric complexes anchored to the EMRE scaffold of MCU. We unexpectedly find that MICU1 suppresses inhibition of MCU by ruthenium red/Ru360, which bind to MCU’s DIME motif, the selectivity filter. This led us to recognize in MICU1’s sequence, a putative DIME Interacting Domain (DID) which is required for …


A Xenopus Oocyte Model System To Study Action Potentials, Aaron Corbin-Leftwich, Hannah E Small, Helen H Robinson, Carlos A. Villalba-Galea, Linda M Boland Nov 2018

A Xenopus Oocyte Model System To Study Action Potentials, Aaron Corbin-Leftwich, Hannah E Small, Helen H Robinson, Carlos A. Villalba-Galea, Linda M Boland

School of Pharmacy Faculty Articles

Action potentials (APs) are the functional units of fast electrical signaling in excitable cells. The upstroke and downstroke of an AP is generated by the competing and asynchronous action of Na+- and K+-selective voltage-gated conductances. Although a mixture of voltage-gated channels has been long recognized to contribute to the generation and temporal characteristics of the AP, understanding how each of these proteins function and are regulated during electrical signaling remains the subject of intense research. AP properties vary among different cellular types because of the expression diversity, subcellular location, and modulation of ion channels. These complexities, in addition to the …


Cartographic Beasts At The Tail-End Of The Long Renaissance: Style And Sources For The Tabula Geographica Regni Chile (1646), Catherine Burdick Nov 2018

Cartographic Beasts At The Tail-End Of The Long Renaissance: Style And Sources For The Tabula Geographica Regni Chile (1646), Catherine Burdick

Artl@s Bulletin

In mid-seventeenth century Europe, as “plain” Enlightenment mapping conventions displaced Renaissance pictorialism, cartographic beasts passed into disuse. In this paper I analyze a final retreat for mapped fauna, Alonso de Ovalle’s Tabula geographica regni Chile (Rome, 1646), as a tail-end of the pictorial style which characterized the cartography of the long Renaissance. Yet we shall see that this map’s outmoded pictorialism was appropriate to its function as an early conveyance of Chile in Spain, and that Ovalle’s South American critters, adapted from exploration documents, evoked the authority of great voyages before Philip IV.


Dietary Protein Restriction Reduces Circulating Vldl Triglyceride Levels Via Crebh-Apoa5-Dependent And -Independent Mechanisms, J Humberto Treviño-Villarreal, Valeria Tosti, Nicola Veronese, Beatrice Bertozzi, Arnold D Bullock, Robert S Figenshau, Gerald L Andriole, Luigi Fontana, Et Al Nov 2018

Dietary Protein Restriction Reduces Circulating Vldl Triglyceride Levels Via Crebh-Apoa5-Dependent And -Independent Mechanisms, J Humberto Treviño-Villarreal, Valeria Tosti, Nicola Veronese, Beatrice Bertozzi, Arnold D Bullock, Robert S Figenshau, Gerald L Andriole, Luigi Fontana, Et Al

Open Access Publications

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Dietary interventions based on protein restriction (PR) reduce circulating triglycerides (TGs), but underlying mechanisms and clinical relevance remain unclear. Here, we show that 1 week of a protein-free diet without enforced calorie restriction significantly lowered circulating TGs in both lean and diet-induced obese mice. Mechanistically, the TG-lowering effect of PR was due, in part, to changes in very low-density lipoprotein (VLDL) metabolism both in liver and peripheral tissues. In the periphery, PR stimulated VLDL-TG consumption by increasing VLDL-bound APOA5 expression and promoting VLDL-TG hydrolysis and clearance from circulation. The PR-mediated increase …


Vwa Proteins Of Leptospira Interrogans Induce Hemorrhage In Leptospirosis By Competitive Inhibition Of Vwf/Gpib-Mediated Platelet Aggregation., Jia-Qi Fang, Muhammad Imran, Wei-Lin Hu, David M. Ojcius, Yang Li, Yu-Mei Ge, Kai-Xuan Li, Xu'ai Lin, Jie Yan Nov 2018

Vwa Proteins Of Leptospira Interrogans Induce Hemorrhage In Leptospirosis By Competitive Inhibition Of Vwf/Gpib-Mediated Platelet Aggregation., Jia-Qi Fang, Muhammad Imran, Wei-Lin Hu, David M. Ojcius, Yang Li, Yu-Mei Ge, Kai-Xuan Li, Xu'ai Lin, Jie Yan

All Dugoni School of Dentistry Faculty Articles

BACKGROUD: Leptospira interrogans is the major causative agent of leptospirosis, a worldwide zoonotic disease. Hemorrhage is a typical pathological feature of leptospirosis. Binding of von Willebrand factor (vWF) to platelet glycoprotein-Ibα (GPIbα) is a crucial step in initiation of platelet aggregation. The products of L. interrogans vwa-I and vwa-II genes contain vWF-A domains, but their ability to induce hemorrhage has not been determined.

METHODS: Human (Hu)-platelet- and Hu-GPIbα-binding abilities of the recombinant proteins expressed by L. interrogans strain Lai vwa-I and vwa-II genes (rLep-vWA-I and rLep-vWA-II) were detected by flowcytometry, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Hu-platelet …


Enteric Infection Coupled With Chronic Notch Pathway Inhibition Alters Colonic Mucus Composition Leading To Dysbiosis, Barrier Disruption And Colitis., Ishfaq Ahmed, Badal C. Roy, Rita-Marie T. Raach, Sarah M. Owens, Lijun Xia, Shrikant Anant, Venkatesh Sampath, Shahid Umar Nov 2018

Enteric Infection Coupled With Chronic Notch Pathway Inhibition Alters Colonic Mucus Composition Leading To Dysbiosis, Barrier Disruption And Colitis., Ishfaq Ahmed, Badal C. Roy, Rita-Marie T. Raach, Sarah M. Owens, Lijun Xia, Shrikant Anant, Venkatesh Sampath, Shahid Umar

Manuscripts, Articles, Book Chapters and Other Papers

Intestinal mucus layer disruption and gut microflora modification in conjunction with tight junction (TJ) changes can increase colonic permeability that allows bacterial dissemination and intestinal and systemic disease. We showed previously that Citrobacter rodentium (CR)-induced colonic crypt hyperplasia and/or colitis is regulated by a functional cross-talk between the Notch and Wnt/β-catenin pathways. In the current study, mucus analysis in the colons of CR-infected (108 CFUs) and Notch blocker Dibenzazepine (DBZ, i.p.; 10μmol/Kg b.w.)-treated mice revealed significant alterations in the composition of trace O-glycans and complex type and hybrid N-glycans, compared to CR-infected mice alone that preceded/accompanied alterations in 16S rDNA …


Multistate Infestation With The Exotic Disease-Vector Tick Haemaphysalis Longicornis - United States, August 2017-September 2018, C. B. Beard, James Occi, Denise L. Bonilla, Andrea M. Egizi, Dina M. Fonseca, Gary P. Wormser, William Halperin Nov 2018

Multistate Infestation With The Exotic Disease-Vector Tick Haemaphysalis Longicornis - United States, August 2017-September 2018, C. B. Beard, James Occi, Denise L. Bonilla, Andrea M. Egizi, Dina M. Fonseca, Gary P. Wormser, William Halperin

NYMC Faculty Publications

Haemaphysalis longicornis is a tick indigenous to eastern Asia and an important vector of human and animal disease agents, resulting in such outcomes as human hemorrhagic fever and reduction of production in dairy cattle by 25%. H. longicornis was discovered on a sheep in New Jersey in August 2017 (1). This was the first detection in the United States outside of quarantine. In the spring of 2018, the tick was again detected at the index site, and later, in other counties in New Jersey, in seven other states in the eastern United States, and in Arkansas. The hosts included six …


Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt Nov 2018

Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples.

METHODS: Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3, NTCP, OCT1, OATP1B1, OATP1B3, OATP2B1 and ATP1A1 were quantified with LC-MS/MS in isolated crude membrane fractions of snap-frozen post-mortem fetal and pediatric, and surgical adult liver samples. mRNA expression was quantified using RNA sequencing, and genetic variants with TaqMan assays. We explored relationships between protein expression and age …


Mouse Models Of Preterm Birth: Suggested Assessment And Reporting Guidelines, Ronald Mccarthy, Carmel Martin-Fairey, Dorothy K. Sojka, Erik D. Herzog, Emily S. Jungheim, Molly J. Stout, Justin C. Fay, Mala Mahendroo, Jeff Reese, Jennifer L. Herington, Erin J. Plosa, Elaine L. Shelton, Sarah K. England Nov 2018

Mouse Models Of Preterm Birth: Suggested Assessment And Reporting Guidelines, Ronald Mccarthy, Carmel Martin-Fairey, Dorothy K. Sojka, Erik D. Herzog, Emily S. Jungheim, Molly J. Stout, Justin C. Fay, Mala Mahendroo, Jeff Reese, Jennifer L. Herington, Erin J. Plosa, Elaine L. Shelton, Sarah K. England

Open Access Publications

Preterm birth affects approximately 1 out of every 10 births in the United States, leading to high rates of mortality and long-term negative health consequences. To investigate the mechanisms leading to preterm birth so as to develop prevention strategies, researchers have developed numerous mouse models of preterm birth. However, the lack of standard definitions for preterm birth in mice limits our field's ability to compare models and make inferences about preterm birth in humans. In this review, we discuss numerous mouse preterm birth models, propose guidelines for experiments and reporting, and suggest markers that can be used to assess whether …


Collagen Prolyl 4-Hydroxylase 1 Is Essential For Hif-1Α Stabilization And Tnbc Chemoresistance, Gaofeng Xiong, Rachel L. Stewart, Jie Chen, Tianyan Gao, Timothy L. Scott, Luis M. Samayoa, Kathleen L. O'Connor, Andrew N. Lane, Ren Xu Oct 2018

Collagen Prolyl 4-Hydroxylase 1 Is Essential For Hif-1Α Stabilization And Tnbc Chemoresistance, Gaofeng Xiong, Rachel L. Stewart, Jie Chen, Tianyan Gao, Timothy L. Scott, Luis M. Samayoa, Kathleen L. O'Connor, Andrew N. Lane, Ren Xu

Markey Cancer Center Faculty Publications

Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived …


Ohio River Survey (Fa 656), Manuscripts & Folklife Archives Oct 2018

Ohio River Survey (Fa 656), Manuscripts & Folklife Archives

Folklife Archives Finding Aids

Finding aid only for Folklife Archives Project 656. Kentucky Folklife Program project titled: “Ohio River Survey,” which includes interviews, tape logs, photographs and other documentation of folklife along the Ohio River in Illinois, Indiana and Kentucky. Interviews may include a description of belief, traditional occupation, practice, craft, or tool, informant’s name, age, birth date, and address.


Uncovering The Complex Genetics Of Human Temperament, Igor Zwir, Javier Arnedo, Dragan M Svrakic, Sandor Rozsa, Maribel Martinez, C Robert Cloninger, Et Al Oct 2018

Uncovering The Complex Genetics Of Human Temperament, Igor Zwir, Javier Arnedo, Dragan M Svrakic, Sandor Rozsa, Maribel Martinez, C Robert Cloninger, Et Al

Open Access Publications

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified …


Ras-Related C3 Botulinum Toxin Substrate 1 Promotes Axonal Regeneration After Stroke In Mice, Lin Liu, Hui Yuan, Yanhua Yi, Edward C. Koellhoffer, Yashasvee Munshi, Fan Bu, Yi Zhang, Zhenggang Zhang, Louise D. Mccullough, Jun Li Oct 2018

Ras-Related C3 Botulinum Toxin Substrate 1 Promotes Axonal Regeneration After Stroke In Mice, Lin Liu, Hui Yuan, Yanhua Yi, Edward C. Koellhoffer, Yashasvee Munshi, Fan Bu, Yi Zhang, Zhenggang Zhang, Louise D. Mccullough, Jun Li

Neurology Articles

Neurite plasticity is a critical aspect of brain functional recovery after stroke. Emerging data suggest that Ras-related C3 botulinum toxin substrate 1 (Rac1) plays a central role in axonal regeneration in the injured brain, specifically by stimulating neuronal intrinsic growth and counteracting the growth inhibitory signaling that leads to growth cone collapse. Therefore, we investigated the functional role of Rac1 in axonal regeneration after stroke.

Delayed treatment with a specific Rac1 inhibitor, NSC 23766, worsened functional recovery, which was assessed by the pellet reaching test from day 14 to day 28 after stroke. It additionally reduced axonal density in the …


Knockdown Of Crispld2 In Zebrafish Identifies A Novel Network For Nonsyndromic Cleft Lip With Or Without Cleft Palate Candidate Genes, Brett T Chiquet, Qiuping Yuan, Eric C Swindell, Lorena Maili, Robert Plant, Jeffrey Dyke, Ryan Boyer, John F Teichgraeber, Matthew R Greives, John B Mulliken, Ariadne Letra, Susan H Blanton, Jacqueline T Hecht Oct 2018

Knockdown Of Crispld2 In Zebrafish Identifies A Novel Network For Nonsyndromic Cleft Lip With Or Without Cleft Palate Candidate Genes, Brett T Chiquet, Qiuping Yuan, Eric C Swindell, Lorena Maili, Robert Plant, Jeffrey Dyke, Ryan Boyer, John F Teichgraeber, Matthew R Greives, John B Mulliken, Ariadne Letra, Susan H Blanton, Jacqueline T Hecht

Faculty, Staff and Student Publications

Orofacial development is a multifaceted process involving tightly regulated genetic signaling networks, that when perturbed, lead to orofacial abnormalities including cleft lip and/or cleft palate. We and others have shown an association between the cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) gene and nonsyndromic cleft lip with or without cleft palate (NSCLP). Further, we demonstrated that knockdown of Crispld2 in zebrafish alters neural crest cell migration patterns resulting in abnormal jaw and palate development. In this study, we performed RNA profiling in zebrafish embryos and identified 249 differentially expressed genes following knockdown of Crispld2. In silico pathway analysis identified …


Timing And Mechanism Of Conceptus Demise In A Complement Regulatory Membrane Protein Deficient Mouse, Michael P Triebwasser, Xiaobo Wu, Paula Bertram, Dennis E Hourcade, Donald Michael Nelson, John P Atkinson Oct 2018

Timing And Mechanism Of Conceptus Demise In A Complement Regulatory Membrane Protein Deficient Mouse, Michael P Triebwasser, Xiaobo Wu, Paula Bertram, Dennis E Hourcade, Donald Michael Nelson, John P Atkinson

Open Access Publications

PROBLEM: Crry is a widely expressed type 1 transmembrane complement regulatory protein in rodents which protects self-tissue by downregulating C3 activation. Crry

METHOD OF STUDY: We investigated the basis of Crry

RESULTS: We narrowed the critical period of the complement effect from 6.5 to 8.5 days post-coitus (dpc), which is immediately after the conceptus is exposed to maternal blood. Deposition by 5.5 dpc of maternal C3b on the placental vasculature lacking Crry

CONCLUSION: Our data are most consistent with the deposition of C3b being responsible for the failure of the allantois to fuse to the chorion leading to subsequent conceptus …


Translational Evaluation Of Acid/Base And Electrolyte Alterations In Rodent Model Of Focal Ischemia, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Hilary A. Seifert, Christopher C. Leonardo, Craig T. Ajmo, Elspeth A. Foran, Justin F. Fraser, Keith R. Pennypacker Oct 2018

Translational Evaluation Of Acid/Base And Electrolyte Alterations In Rodent Model Of Focal Ischemia, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Hilary A. Seifert, Christopher C. Leonardo, Craig T. Ajmo, Elspeth A. Foran, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

BACKGROUND AND PURPOSE: Acid/base and electrolytes could provide clinically valuable information about cerebral infarct core and penumbra. We evaluated associations between acid/base and electrolyte changes and outcomes in 2 rat models of stroke, permanent, and transient middle cerebral artery occlusion.

METHODS: Three-month old Sprague-Dawley rats underwent permanent or transient middle cerebral artery occlusion. Pre- and post-middle cerebral artery occlusion venous samples for permanent and transient models provided pH, carbon dioxide, oxygen, glucose, and electrolyte values of ionized calcium, potassium, and sodium. Multiple regression determined predictors of infarct volume from these values, and Kaplan-Meier curve analyzed morality between permanent and transient …


A Requirement For Slc15a4 In Imiquimod-Induced Systemic Inflammation And Psoriasiform Inflammation In Mice, Alexis D. Griffith, Asifa K. Zaidi, Ashley Pietro, Matthew Hadiono, Jessica S. Yang, Rachel Davis, Daniel L. Popkin Sep 2018

A Requirement For Slc15a4 In Imiquimod-Induced Systemic Inflammation And Psoriasiform Inflammation In Mice, Alexis D. Griffith, Asifa K. Zaidi, Ashley Pietro, Matthew Hadiono, Jessica S. Yang, Rachel Davis, Daniel L. Popkin

Faculty Publications

There is competing evidence that plasmacytoid dendritic cells (pDC), the most potent source of IFN-I, may initiate psoriasis. We targeted pDC function using the slc15a4 loss-of-function mouse whose pDC are unresponsive to TLR agonists. slc15a4 treated with the topical TLR7-agonist imiquimod (IMQ) demonstrated decreased epidermal thickening 24 hours post-treatment which was more pronounced by day 5 as compared to wildtype mice. These findings were specific to the acute IMQ model and not the protracted IL23 model that drives inflammation downstream of TLR activation. Systemically, slc15a4 was required for IMQ-induced weight loss and cutaneous accumulation of CD4+ and Siglec H+, but …


Quantifying Climate Sensitivity And Climate-Driven Change In North American Amphibian Communities, David A. W. Miller, Evan H Campbell Grant, Erin Muths, Staci M. Amburgey, Michael J. Adams, Maxwell B. Joseph, J. Hardin Waddle, Pieter T. J. Johnson, Maureen E. Ryan, Benedikt R. Schmidt, Daniel L. Calhoun, Courtney L. Davis, Robert N. Fisher, David M. Green, Blake R. Hossack, Tracy A. G. Rittenhouse, Susan C. Walls, Larissa L. Bailey, Sam S. Cruickshank, Gary M. Fellers, Thomas A. Gorman, Carola A. Haas, Ward Hughson, David S. Pilliod, Steve J. Price, Andrew M. Ray, Walt Sadinski, Daniel Saenz, William J. Barichivich, Adrianne Brand Sep 2018

Quantifying Climate Sensitivity And Climate-Driven Change In North American Amphibian Communities, David A. W. Miller, Evan H Campbell Grant, Erin Muths, Staci M. Amburgey, Michael J. Adams, Maxwell B. Joseph, J. Hardin Waddle, Pieter T. J. Johnson, Maureen E. Ryan, Benedikt R. Schmidt, Daniel L. Calhoun, Courtney L. Davis, Robert N. Fisher, David M. Green, Blake R. Hossack, Tracy A. G. Rittenhouse, Susan C. Walls, Larissa L. Bailey, Sam S. Cruickshank, Gary M. Fellers, Thomas A. Gorman, Carola A. Haas, Ward Hughson, David S. Pilliod, Steve J. Price, Andrew M. Ray, Walt Sadinski, Daniel Saenz, William J. Barichivich, Adrianne Brand

Forestry and Natural Resources Faculty Publications

Changing climate will impact species’ ranges only when environmental variability directly impacts the demography of local populations. However, measurement of demographic responses to climate change has largely been limited to single species and locations. Here we show that amphibian communities are responsive to climatic variability, using > 500,000 time-series observations for 81 species across 86 North American study areas. The effect of climate on local colonization and persistence probabilities varies among eco-regions and depends on local climate, species life-histories, and taxonomic classification. We found that local species richness is most sensitive to changes in water availability during breeding and changes in …