Digital Commons Network^™

Poly(Ester Amide) Particles For Controlled Delivery Of Celecoxib., Ian J Villamagna, Trent N Gordon, Mark B Hurtig, Frank Beier, Elizabeth R Gillies

Chemistry Publications

Many potential pharmacological treatments for osteoarthritis can result in undesirable side effects due to the systemic administration of drugs, making the direct delivery of drugs to joints an attractive alternative. Poly(ester amide)s (PEAs) have been shown to exhibit promising properties for the development of particle-based intra-articular delivery vehicles. However, a limited range of PEA structures has been investigated. In this study, we prepared and characterized the properties of two different PEA particles composed of l-phenylalanine, sebacic acid, and either 1,4-butanediol or 1,8-octanediol (PBSe and POSe, respectively). The anti-inflammatory drug celecoxib (CXB) was encapsulated into the particles. Despite minor structural differences, …

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

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

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 …

Mechanism Of Electrospray Supercharging For Unfolded Proteins: Solvent-Mediated Stabilization Of Protonated Sites During Chain Ejection., Insa Peters, Haidy Metwally, Lars Konermann

Chemistry Publications

Proteins that are unfolded in solution produce higher charge states during electrospray ionization (ESI) than their natively folded counterparts. Protein charge states can be further increased by the addition of supercharging agents (SCAs) such as sulfolane. The mechanism whereby these supercharged [M + zH] ^z+ ions are formed under unfolded conditions remains unclear. Here we employed a combination of mass spectrometry (MS), ion mobility spectrometry (IMS), and molecular dynamics (MD) simulations for probing the ESI mechanism under denatured supercharging conditions. ESI of acid-unfolded apo-myoglobin (aMb) in the presence of sulfolane produced charge states around 27+, all the way to fully …

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

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.

An Endogenous Peptide Marker Differentiates Sod1 Stability And Facilitates Pharmacodynamic Monitoring In Sod1 Amyotrophic Lateral Sclerosis, Ilya Gertsman, Joanne Wuu, Melissa Mcalonis-Downes, Majid Ghassemian, Karen Ling, Frank Rigo, Frank Bennett, Michael Benatar, Timothy M. Miller, Sandrine Da Cruz

Open Access Publications

The discovery of novel biomarkers has emerged as a critical need for therapeutic development in amyotrophic lateral sclerosis (ALS). For some subsets of ALS, such as the genetic superoxide dismutase 1 (SOD1) form, exciting new treatment strategies, such as antisense oligonucleotide-mediated (ASO-mediated) SOD1 silencing, are being tested in clinical trials, so the identification of pharmacodynamic biomarkers for therapeutic monitoring is essential. We identify increased levels of a 7-amino acid endogenous peptide of SOD1 in cerebrospinal fluid (CSF) of human SOD1 mutation carriers but not in other neurological cases or nondiseased controls. Levels of peptide elevation vary based on the specific …

Dopamine Receptor Antagonists As Potential Therapeutic Agents For Adpkd., Parama Paul, Sreekumar Ramachandran, Sheng Xia, Jay R. Unruh, Juliana Conkright-Fincham, Rong Li

Manuscripts, Articles, Book Chapters and Other Papers

Autosomal dominant polycystic kidney disease (ADPKD) is caused mostly by mutations in polycystin-1 or polycystin-2. Fluid flow leads to polycystin-dependent calcium influx and nuclear export of histone deacetylase 5 (HDAC5), which facilitates the maintenance of renal epithelial architecture by de-repression of MEF2C target genes. Here, we screened a small-molecule library to find drugs that promotes nuclear export of HDAC5. We found that dopamine receptor antagonists, domperidone and loxapine succinate, stimulate export of HDAC5, even in Pkd1-/-cells. Domperidone targets Drd3 receptor to modulate the phosphorylation of HDAC5. Domperidone treatment increases HDAC5 phosphorylation likely by reducing protein phosphatase 2A (PP2A) activity, thus …

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

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

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

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, …

Down Syndrome Mouse Models Have An Abnormal Enteric Nervous System, Ellen M Schill, Christina M Wright, Alisha Jamil, Jonathan M Lacombe, Randall J Roper, Robert O Heuckeroth

Open Access Publications

Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung Disease (HSCR), a developmental defect where the enteric nervous system (ENS) is missing from distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Post-surgical problems like enterocolitis and soiling are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in two DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including Dscam and Dyrk1a, which …

An Obligatory Role For Club Cells In Preventing Obliterative Bronchiolitis In Lung Transplants, Zhiyi Liu, Fuyi Liao, Davide Scozzi, Yuka Furuya, Kaitlyn N Pugh, Ramsey Hachem, Delphine L Chen, Marlene Cano, Jonathan M Green, Alexander S Krupnick, Daniel Kreisel, Anne Karina T Perl, Howard J Huang, Steven L Brody, Andrew E Gelman

Open Access Publications

Obliterative bronchiolitis (OB) is a poorly understood airway disease characterized by the generation of fibrotic bronchiolar occlusions. In the lung transplant setting, OB is a pathological manifestation of bronchiolitis obliterans syndrome (BOS), which is a major impediment to long-term recipient survival. Club cells play a key role in bronchiolar epithelial repair, but whether they promote lung transplant tolerance through preventing OB remains unclear. We determined if OB occurs in mouse orthotopic lung transplants following conditional transgene-targeted club cell depletion. In syngeneic lung transplants club cell depletion leads to transient epithelial injury followed by rapid club cell-mediated repair. In contrast, allogeneic …

Extracellular Vesicles As Biological Shuttles For Targeted Therapies., Stefania Raimondo, Gianluca Giavaresi, Aurelio Lorico, Riccardo Alessandro

College of Osteopathic Medicine (TUN) Publications and Research

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)-specialized membrane-bound nanocarriers for intercellular communication-suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, …

Chicken Talk, Kaley Durney

Children's Book and Media Review

No abstract provided.

The Alligator's Smile And Other Poems, Phyllis Rosen

Children's Book and Media Review

No abstract provided.

There Was A Wee Lassie Who Swallowed A Midgie, Jazmin Gomez

Children's Book and Media Review

No abstract provided.

Curious George's 5-Minute Stories, Gabrielle Borg

Children's Book and Media Review

Ill-mannered Lulu wants a brontosaurus for a pet. It is her birthday and she always gets what she wants! After her parents say no, Lulu sets off into the forest alone, hoping to find a brontosaurus herself. She sings a ridiculous and loud song as she skips through the woods. Her singing attracts a big bear, a hungry tiger, and a seething snake. Lulu puts each of these predators in their place with a shout, a wallup, or a bang! She then settles comfortably into her sleeping bag for a night of pleasant dreams. In the morning, the foot of …

Rivers: A Visual History From River To Sea, Cynthia Phillips

Children's Book and Media Review

Norris Kaplan is a sarcastic and cynical Haitian-French Canadian teenager whose snarky witticisms often land him in hot water. After his mother gets a job in Austin, Texas, Norris finds himself in an American high school, cataloging his snap judgments of everyone he meets—the Cheerleaders, the Jocks, the Manic Pixie Dream Girl. But as time goes on, Norris begins to see that not everyone fits into the boxes he puts them in. It’s not until he screws everything up on prom night that Norris realizes it may be time to stop hiding behind his snarky opinions and start letting people …

Xtreme Snakes: Mambas, Haley Singleton

Children's Book and Media Review

Mambas is an informational texts that teaches you the basic information about mambas. The first part of the book is an introduction to mambas and their physiology, while the second half serves to show the different types of mambas and discuss what to do if you are bitten. The book contains a glossary of all the bigger words younger readers might not understand. The book is charming, fun to read, and very informational.

The Rabbit Listened, Erica Sonzogni

Children's Book and Media Review

Taylor builds an amazing tower out of blocks, but it is suddenly knocked down. The chicken wants Taylor to talk about it, the bear wants Taylor to yell about it, and the elephant wants Taylor to rebuild it. More animals suggest different ways that Taylor can handle this problem. Finally, the rabbit shows up. He sits in silence next to Taylor and simply listens. The rabbit stays with Taylor as he experiences different emotions all related to his ruined tower. After a while, Taylor wants to begin rebuilding his tower, and the rabbit helps, supporting Taylor the whole time.

The Crocodile And The Scorpion, Lindsey Smith

Children's Book and Media Review

Neither having ever had a friend before, the Crocodile and Scorpion decide to give friendship a try. Unfortunately for them, their small brains make that difficult. The Scorpion goes down to the river but knows he can’t get across, so he asks the Crocodile for a ride on his back. The two mutually decide not to hurt one another, and so the Crocodile agrees. Before making it to the other side, however, everything falls apart when both break their promises, and in the end, both animals become victims of their rash behavior.

The Circus Ship, Jazmin Gomez

Children's Book and Media Review

When a circus ship sinks off the shore of Maine, the fifteen animals that were aboard drag themselves out of the water and stagger into the local village. The residents do not take a liking to them at first, but when the circus tiger saves a young girl from a burning building, they all start living in harmony. One day, the greedy circus owner shows up in search of the animals, but the townspeople hide them in plain sight. The owner leaves empty-handed and the animals are left to a peaceful life with the village folk.

Outrageous Animal Adaptations, Haley Singleton

Children's Book and Media Review

This fascinating book is full of animals that have strange adaptations. It has a variety of animals and unique adaptations that leave you in wonder at the natural world. It includes animals from every animal class, and each animal has a description describing their unique adaptation and how it helps them survive. The types of adaptations are varied, which keeps the book engaging and interesting. The book also has an introduction that talks about Charles Darwin and his Theory of Evolution. The book is a fun read, with lots of great pictures and many different animals who all have really …

Miss Annie: Freedom!, Megan Hall

Children's Book and Media Review

Miss Annie is a five-month-old kitten with big dreams for the future. She lives in a house with master, mistress, and little mistress. She is happy in their home, and they take good care of her. Master, mistress, and little mistress try to keep Miss Annie out of trouble by closing doors, hiding yarn, and making sure she stays inside. But despite their efforts, Annie is drawn to the outdoors with trees to climb, mice to catch, and many things to see. One day Annie meets a friend that tells her the outside world is not all she believes it …

Meet My Family: Animal Babies And Their Families, Sydnee Burr

Children's Book and Media Review

Meet My Family explores a large variety of baby animals and their families. Coleman's illustrations are the star of the show, as each baby animal and their parents are both interesting and adorable. While being both informative and entertaining in nature, the animals seem to have been chosen specifically to represent specific family dynamics. For example, raccoon's have never met their father, orangutans don't have a steady home, and Chinstrap Penguins have two dads.

Fall Animal Fun, Beverly Jones

Children's Book and Media Review

In the cherished and beautiful season of fall, the leaves are not the only things that are changing. Animals all around the world go through many changes during fall. Some animals travel south to warmer temperatures. Some animals hibernate, and some animals eat an abundance of food to store up for the winter. Nature's creatures living within the vibrant colors of fall make for an amazing autumnal experience.

Archie Sloth To The Rescue!, Jazmin Gomez

Children's Book and Media Review

Archie is not like other sloths. He doesn’t like to rest. He prefers to dance, swing, jump, and juggle. His friends are unenthusiastic about his playfulness and tell him to take his energy elsewhere. Traveling into the jungle, Archie finds other animals who are also different from their herds. He learns from them that it’s not a bad thing to be different. As he heads back to rejoin his pack, he comes upon a tiger that is ready to eat the sloths! With all his skill and liveliness, Archie is able to save his friends.