Digital Commons Network^™

Castration-Resistant Prostate Cancer: Androgen Receptor Inactivation Induces Telomere Dna Damage, And Damage Response Inhibition Leads To Cell Death, Vidyavathi Reddy, Asm Iskander, Clara Hwang, George Divine, Mani Menon, Evelyn R. Barrack, Prem-Veer Reddy, Sahn-Ho Kim

Urology Articles

Telomere stability is important for cell viability, as cells with telomere DNA damage that is not repaired do not survive. We reported previously that androgen receptor (AR) antagonist induces telomere DNA damage in androgen-sensitive LNCaP prostate cancer cells; this triggers a DNA damage response (DDR) at telomeres that includes activation of ATM, and blocking ATM activation prevents telomere DNA repair and leads to cell death. Remarkably, AR antagonist induces telomere DNA damage and triggers ATM activation at telomeres also in 22Rv1 castration-resistant prostate cancer (CRPC) cells that are not growth inhibited by AR antagonist. Treatment with AR antagonist enzalutamide (ENZ) …

Do Teachers Participating In A Therapy Dog Program Perceive An Impact On Students’ Attitudes And Behaviors Toward Reading?, Jenna M. Dragani-Reagan

PCOM Psychology Dissertations

No abstract provided.

Inflammatory Serine Proteases Play A Critical Role In The Early Pathogenesis Of Diabetic Cardiomyopathy., Mikhail A Kolpakov, Kunal Sikder, Amrita Sarkar, Shaswati Chaki, Sanket K Shukla, Xinji Guo, Zhao Qi, Carlos Barbery, Abdelkarim Sabri, Khadija Rafiq

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM.

METHODS: Eight weeks old mice with deletion of dipeptidyl peptidase I (DPPI), an enzyme involved in the maturation of major ISPs, and wild type (WT) mice controls were injected with streptozotocin (50 mg/kg for 5 days intraperitoneally) and studied after …

Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case

Journal Articles: Eppley Institute

While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O₂^-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O₂^- with no evident changes in hydrogen peroxide (H₂O₂), peroxynitrite (ONOO^-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions …

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …

Hope For Paws New York: Rescue, Rehabilitation And Veterinary Hospital, Jasmine Arndt

Architecture Theses and Projects

Hope for Paws has made it their mission to rescue any and all animals, no matter the size, shape, breed or species. Their goal is to rehabilitate them, foster them out, and get them adopted into loving forever homes, where they will never know the abuse and neglect that they had previously known. But is there a better system? Hope for Paws runs the rescue missions, pays for the vet bills, find the fosters, and works with the fosters to find them their forever homes. They accomplish this while they still care for all they rescue and check in on …

Developmental Expression Of Monocarboxylate Transporter 1 And 4 In Rat Liver, Michael Ng, Justin Louie, Jieyun Cao, Melanie A. Felmlee

School of Pharmacy Faculty Articles

PURPOSE: Monocarboxylate transporters (MCT) are proton-coupled integral membrane proteins that control the influx and efflux of endogenous monocarboxylates such as lactate, acetate and pyruvate. They also transport and mediate the clearance of drugs such as valproate and gamma-hydroxybutyrate. CD147 functions as ancillary protein that chaperones MCT1 and MCT4 to the cell membrane. There is limited data on the maturation of MCT and CD147 expression in tissues related to drug distribution and clearance. The objective of the present study was to quantify hepatic MCT1, MCT4, and CD147 mRNA, whole cell and membrane protein expression from birth to sexual maturity.

METHODS: Liver …

Serological Proteomic Screening And Evaluation Of A Recombinant Egg Antigen For The Diagnosis Of Low-Intensity Schistosoma Mansoni Infections In Endemic Area In Brazil, Vanessa Silva-Moraes, Lisa Marie Shollenberger, William Castro-Borges, Ana Lucia Teles Rabello, Donald A. Harn, Lia Carolina Soares Medeiros, Wander De Jesus Jeremias, Liliane Maria Vidal Siqueira, Caroline Stephane Salviano Pereira, Maria Luysa Camargos Pedrosa, Nathalie Bonatti Franco Almeida, Aureo Almeida, Jose Roberto Lambertucci, Nidia Francisca De Figueiredo Carneiro, Paulo Marcos Zech Coelho, Refaella Fortini Queiroz Grenfell

Biological Sciences Faculty Publications

Background

Despite decades of use of control programs, schistosomiasis remains a global public health problem. To further reduce prevalence and intensity of infection, or to achieve the goal of elimination in low-endemic areas, there needs to be better diagnostic tools to detect low-intensity infections in low-endemic areas in Brazil. The rationale for development of new diagnostic tools is that the current standard test Kato-Katz (KK) is not sensitive enough to detect low-intensity infections in low-endemic areas. In order to develop new diagnostic tools, we employed a proteomics approach to identify biomarkers associated with schistosome-specific immune responses in hopes of developing …

Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with an internal tandem duplication in Fms-related tyrosine kinase 3 (FLT3-ITD) is identified as a subgroup with poor outcome and intrinsic resistance to chemotherapy and therefore urgent need for development of novel therapeutic strategies.

Methods: The antitumor effects of melatonin alone or combined with sorafenib were evaluated via flow cytometry and immunoblotting assays in FLT-ITD AML cells. Also, the ex vivo and in vivo models were used to test the synergistic effects of melatonin and sorafenib against leukemia with FLT3/ITD mutation.

Results: Our study shows for the first time that melatonin inhibits proliferation and induces apoptosis …

The Puppets Look Like Flowers At Last, Evie Metz

Theses and Dissertations

The urge to uncover aspects of human condition permeates my work, from the fundamental curiosity of a child tearing apart their doll to uncover what lies within to continuing a quest in uncovering basic human urges through my puppet animated dramas and tragedies. There is a controversial line between the childlike and the adult-like that can be ambiguous, and at some times more discernible while other times less. I create handcrafted stop-frame puppet animations that explore self-conscious emotions such as embarrassment, shame, and envy within unpredictable life scenarios. These are animations about inner life, attempting to resolve conflicting elements of …

Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges To Clinical Application, Henry Caplan, Scott D Olson, Akshita Kumar, Mitchell George, Karthik S Prabhakara, Pamela Wenzel, Supinder Bedi, Naama E Toledano-Furman, Fabio Triolo, Julian Kamhieh-Milz, Guido Moll, Charles S Cox

Faculty, Staff and Student Publications

For several decades, multipotent mesenchymal stromal cells (MSCs) have been extensively studied for their therapeutic potential across a wide range of diseases. In the preclinical setting, MSCs demonstrate consistent ability to promote tissue healing, down-regulate excessive inflammation and improve outcomes in animal models. Several proposed mechanisms of action have been posited and demonstrated across an array of in vitro models. However, translation into clinical practice has proven considerably more difficult. A number of prominent well-funded late-phase clinical trials have failed, thus calling out for new efforts to optimize product delivery in the clinical setting. In this review, we discuss novel …

Don't Touch Me Like That: Masculinity, Touch, And The Role Of Affect In Media Representations Of Animal Attacks, Carolyn Grace Block

Electronic Theses and Dissertations Archive

This dissertation analyzes masculinity and touch in three highly publicized cases where men intentionally interacted with wild animals and were harmed in the process. I focus predominately on the first week of media coverage following Steve The Crocodile Hunter Irwin who was killed by a massive stingray while filming for a television series off the Great Barrier Reef, Roy Horn of the famed Las Vegas magician duo Siegfried and Roy who was mauled by one of his performing tigers in front of a live audience, and Antoine Yates, an African American man bitten by the pet tiger he kept in …

Elmer's Walk, Leah Christopher

Children's Book and Media Review

While life swarms on around him, Elmer the elephant enjoys the beauty and peace of nature. A beautiful spider web doesn’t entice the monkeys to pause, but Elmer observes it thoughtfully. Elmer points out an interesting log to the crocodiles—but they keep on moving. He invites the snake to admire the colorful flowers to no avail. Even the lion won’t delay his nap to look at the waterfall. Rush, rush, rush—no one has time to appreciate nature with Elmer. Eventually, Elmer finds and joins his cousin Wilbur in watching the sun setting and stars rising in the night sky. But …

My Best Friend Is A Goldfish, Megan Hall

Children's Book and Media Review

Having a best friend isn’t always easy, but it is always worth the struggle. After an argument with his best friend, a boy tries to become best friends with a dog, a cat, a goldfish, and a hamster. Although they are fun to play with for a brief amount of time, he realizes they do not have enough in common to be best friends. My Best Friend Is a Goldfish teaches the importance of sticking with our friends through thick and thin.

Knock, Knock, Leah Christopher

Children's Book and Media Review

Bear is snuggling down for a long winter of hibernation. But other forest animals keep pestering him, knocking on the door and scooting inside with food and decorations. After each knock at the door, Bear grows more impatient. How is he ever going to get some sleep? With his den filled to the brim, a frustrated Bear is ready to tell the giddy bunch all to get out. When he sees the cause for the celebration—“Happy Hibernation!”—he realizes his friends are going to miss him, and he will miss them, too. And once spring arrives, Bear is ready to party …

Shell, Beak, Tusk: Shared Traits And The Wonders Of Adaptation, Maryn Wheeler

Children's Book and Media Review

In a world of predators and prey, animals have adapted to survive. Animals have specific traits to help them eat, while other traits protect them from being eaten. This vivid picture book explores convergent evolution where similar traits are seen in unrelated animals. Each informative page compares animals from different environments who share a helpful trait such as spines, shells, or tall ears. Animals use these survival traits in parallel ways even though they are distinct species. When a trait works, it works in multiple circumstances!

Kiss Of The Spindle, Lisa Packard

Children's Book and Media Review

Doctor Isla Cooper is cursed to sleep as though dead from midnight to six in the morning. The curse affects her job, especially since she is supposed to work at night. Unfortunately, time is running out before the curse becomes permanent. She discovers the witch who cursed her is across the sea and must travel there immediately. She meets Captain Daniel Pickett on his ship and there is an undeniable attraction, but she doesn't want to tie him down with her problems. Daniel insists on helping her no matter what, and with the help of four other passengers, he is …

Trickiest! 19 Sneaky Animals, Rachel Iba

Children's Book and Media Review

Trickiest! examines the odd survival traits of nineteen different animals. Each animal has been specially designed to survive in their environmental niche. Predators have come up with very creative ways to hide from or lure their prey. Likewise, prey have developed amazing ways to escape from predators. Everything from extreme camouflage to tails falling off can be found in this book of bizarre animal behaviors.

The Squirrels' Busy Year: A First Science Storybook, Ariel Woodbury

Children's Book and Media Review

Winter is cold. The squirrels cuddle in their nest to stay warm when they aren't out looking for the acorns they've buried. Spring is warm. The squirrels are out looking for food like the yummy maple tree buds and bulbs that they dig up from the ground. Summer is hot. There is thunder and lightning. Fall is cool. Now that there are acorns, the squirrels are busy collecting them to save underground for winter.

A Herpesvirus Encoded Qa-1 Mimic Inhibits Natural Killer Cell Cytotoxicity Through Cd94/Nkg2a Receptor Engagement, Xiaoli Wang, Sytse J. Piersma, Christopher A. Nelson, Ya-Nan Dai, Ted Christensen, Eric Lazear, Liping Yang, Marjolein Sluijter, Thorbald Van Hall, Ted H. Hansen, Wayne M. Yokoyama, Daved H. Fremont

Open Access Publications

A recurrent theme in viral immune evasion is the sabotage of MHC-I antigen presentation, which brings virus the concomitant issue of 'missing-self' recognition by NK cells that use inhibitory receptors to detect surface MHC-I proteins. Here, we report that rodent herpesvirus Peru (RHVP) encodes a Qa-1 like protein (pQa-1) via RNA splicing to counteract NK activation. While pQa-1 surface expression is stabilized by the same canonical peptides presented by murine Qa-1, pQa-1 is GPI-anchored and resistant to the activity of RHVP pK3, a ubiquitin ligase that targets MHC-I for degradation. pQa-1 tetramer staining indicates that it recognizes CD94/NKG2A receptors. Consistently, …

Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At …

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …

Platypuses: Web-Footed Billed Mammals, Jamie Greenwood

Children's Book and Media Review

Platypuses: Web-Footed Billed Mammals includes an introduction and four chapters, titled “Meet the Platypus,” “What Do Platypuses Look Like,” “Where Do Platypuses Live,” “Platypus Hunting Behavior,” and “The Life Cycle of Platypuses.” Each chapter opens with factual information on the chapter’s individual subject. The information is brief, to the point, easy to understand, and captivating. In each chapter the author compares a platypus with a similar animal and with a dissimilar animal. The end of the book provides a chart that lists the similar and dissimilar traits between platypuses and all the other animals with which it was previously compared.

Going For A Sea Bath, Cynthia Phillips

Children's Book and Media Review

It’s time for her bath, but Leanne would rather continue to play in the ocean waves. The bathtub is too boring. Suddenly her father has a brilliant idea. Why not bring the ocean to her? Soon enough, the tub is filled to the brim with sea creatures of all kinds. Now the tub is not so boring. But when the ten octopi are brought in, Leanne realizes that maybe a bath in the sea would be better.

Dinner Time, Karen Abbott

Children's Book and Media Review

Animals get hungry too! In this hungry picture book, readers follow a dinner menu up the jungle food chain as one animal eats another from one page to the next. Each hungry creature eats the last before winding on their own way into the jungle and meeting the next predator who greets them and gobbles them. All but the last apex predator, who chooses to eat without conversation!

A Is For Australian Animals, Megan Hall

Children's Book and Media Review

When we think of Australian animals, a kangaroo or a koala most often come to mind. But have you ever heard of a Quokka or a Yabby? A Is for Australian Animals covers thirty-eight of the captivating and interesting animals found only in Australia. For each letter of the alphabet, the author describes one or two Australian animals that start with that letter. Each page has a description of that animal and includes additional facts for those who want to learn more. There are many amazing animals to be discovered only in Australia.

Rare But Recurrent Ros1 Fusions Resulting From Chromosome 6q22 Microdeletions Are Targetable Oncogenes In Glioma., Monika A Davare, Jacob J Henderson, Anupriya Agarwal, Jacob P Wagner, Sudarshan R Iyer, Nameeta Shah, Randy Woltjer, Romel Somwar, Stephen W Gilheeney, Ana Decarvalo, Tom Mikkelson, Erwin G Van Meir, Marc Ladanyi, Brian J Druker

Articles, Abstracts, and Reports

PURPOSE: Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.

EXPERIMENTAL DESIGN: Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset. Functional validation of the oncogenic potential and inhibitory sensitivity of discovered ROS1 fusions was performed using three independent cell-based model systems, and an

RESULTS:

CONCLUSIONS: Our findings highlight that CNS tumors should be specifically interrogated for these rare intrachromosomal 6q22 microdeletion …

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

World's Best (And Worst) Animal Jokes, Mavanee Farnsworth

Children's Book and Media Review

World’s Best (and Worst) Animal Jokes really lives up to its name. This joke book is filled with everything animal. There are many different types of jokes, from question-and-answer to knock-knock jokes. There are great, laugh-out-loud jokes, as well as others labeled as “groaner jokes” that are meant to make you sigh and laugh. Each page has several fun jokes that will get the reader thinking about other animal jokes that could be found on the next page. There are many types of animals included, ranging from ocean creatures to cave creatures to mountain creatures. Animal lovers will love laughing …

Possum And The Summer Storm, Robyn Lee

Children's Book and Media Review

Possum’s family watches as their home washes away in a rainstorm, leaving them with nowhere to live. A friendly neighbor notices their situation and volunteers to help rebuild the Possum family home, prompting a community effort. Each forest animal helps build the kind of home they are used to, until eventually the Possum home is roomy enough for everyone to take shelter when the next storm hits.