Digital Commons Network^™

Magel2 Truncation Alters Select Behavioral And Physiological Outcomes In A Rat Model Of Schaaf-Yang Syndrome, Derek L Reznik, Mingxiao V Yang, Pedro Albelda De La Haza, Antrix Jain, Melanie Spanjaard, Susanne Theiss, Christian P Schaaf, Anna Malovannaya, Theresa V Strong, Surabi Veeraragavan, Rodney C Samaco

Faculty, Staff and Students Publications

Previous studies in mice have utilized Magel2 gene deletion models to examine the consequences of its absence. We report the generation, molecular validation and phenotypic characterization of a novel rat model with a truncating Magel2 mutation modeling variants associated with Schaaf-Yang syndrome-causing mutations. Within the hypothalamus, a brain region in which human MAGEL2 is paternally expressed, we demonstrated, at the level of transcript and peptide detection, that rat Magel2 exhibits a paternal, parent-of-origin effect. In evaluations of behavioral features across several domains, juvenile Magel2 mutant rats displayed alterations in anxiety-like behavior and sociability measures. Moreover, the analysis of peripheral organ …

Why Does The X Chromosome Lag Behind Autosomes In Gwas Findings?, Ivan P Gorlov, Christopher I Amos

Faculty, Staff and Students Publications

The X-chromosome is among the largest human chromosomes. It differs from autosomes by a number of important features including hemizygosity in males, an almost complete inactivation of one copy in females, and unique patterns of recombination. We used data from the Catalog of Published Genome Wide Association Studies to compare densities of the GWAS-detected SNPs on the X-chromosome and autosomes. The density of GWAS-detected SNPs on the X-chromosome is 6-fold lower compared to the density of the GWAS-detected SNPs on autosomes. Differences between the X-chromosome and autosomes cannot be explained by differences in the overall SNP density, lower X-chromosome coverage …

Pd-L1 Translocation To The Plasma Membrane Enables Tumor Immune Evasion Through Mib2 Ubiquitination, Xinfang Yu, Wei Li, Haidan Liu, Xu Wang, Cristian Coarfa, Chao Cheng, Xinlian Yu, Zhaoyang Zeng, Ya Cao, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is a transmembrane protein synthesized in the endoplasmic reticulum of tumor cells and transported to the plasma membrane to interact with programmed death 1 (PD-1) expressed on T cell surface. This interaction delivers coinhibitory signals to T cells, thereby suppressing their function and allowing evasion of antitumor immunity. Most companion or complementary diagnostic devices for assessing PD-L1 expression levels in tumor cells used in the clinic or in clinical trials require membranous staining. However, the mechanism driving PD-L1 translocation to the plasma membrane after de novo synthesis is poorly understood. Herein, …

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …

Relief Of Malignant Gastric Outlet Obstruction With Lumen-Apposing Metallic Stent-Assisted Percutaneous Endoscopic Gastrostomy Tube After Roux-En-Y Gastric Bypass, Scott N Berger, Juan D Gomez Cifuentes, Tara Keihanian, Wasif M Abidi, Kalpesh K Patel

Faculty, Staff and Students Publications

No abstract provided.

Automated In Vivo High-Resolution Imaging To Detect Human Papillomavirus-Associated Anal Precancer In Persons Living With Hiv, David Brenes, Alex Kortum, Jennifer Carns, Tinaye Mutetwa, Richard Schwarz, Yuxin Liu, Keith Sigel, Rebecca Richards-Kortum, Sharmila Anandasabapathy, Michael Gaisa, Elizabeth Chiao

Faculty, Staff and Students Publications

INTRODUCTION: In the United States, the effectiveness of anal cancer screening programs has been limited by a lack of trained professionals proficient in high-resolution anoscopy (HRA) and a high patient lost-to-follow-up rate between diagnosis and treatment. Simplifying anal intraepithelial neoplasia grade 2 or more severe (AIN 2+) detection could radically improve the access and efficiency of anal cancer prevention. Novel optical imaging providing point-of-care diagnoses could substantially improve existing HRA and histology-based diagnosis. This work aims to demonstrate the potential of high-resolution microendoscopy (HRME) coupled with a novel machine learning algorithm for the automated, in vivo diagnosis of anal precancer. …

Dynamics Of Gametes And Embryos In The Oviduct: What Can In Vivo Imaging Reveal?, Shang Wang, Irina V Larina

Faculty, Staff and Students Publications

IN BRIEF: In vivo imaging of gametes and embryos in the oviduct enables new studies of the native processes that lead to fertilization and pregnancy. This review article discusses recent advancements in the in vivo imaging methods and insights which contribute to understanding the oviductal function.

ABSTRACT: Understanding the physiological dynamics of gametes and embryos in the fallopian tube (oviduct) has significant implications for managing reproductive disorders and improving assisted reproductive technologies. Recent advancements in imaging of the mouse oviduct in vivo uncovered fascinating dynamics of gametes and embryos in their native states. These new imaging approaches and observations are …

Synthetic Assembly Dna Cloning To Build Plasmids For Multiplexed Transgenic Selection, Counterselection Or Any Other Genetic Strategies Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Alejandro Sarrion-Perdigones, Herman A Dierick

Faculty, Staff and Students Publications

We recently described a drug-based selectable and counterselectable genetic platform for the animal model system Drosophila melanogaster, consisting of four resistance and two sensitivity markers that allow direct selection for, or counterselection against, a desired genotype. This platform eliminates the need to identify modified progeny by traditional laborious screening using dominant eye and body color markers, white⁺ and yellow⁺, respectively. The four resistance markers permit selection of animals using G418 sulfate, Puromycin HCl, Blasticidin S, or Hygromycin B, while the two sensitivity markers allow counterselection of animals against Ganciclovir or Acyclovir, and 5-Fluorocytosine. The six markers …

The Roles Of Cyp1a2 And Cyp2d In Pharmacokinetic Profiles Of Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine And Its Metabolites In Mice, Xuan Qin, Cen Xie, John M Hakenjos, Kevin R Mackenzie, Shelton R Boyd, Mercedes Barzi, Karl-Dimiter Bissig, Damian W Young, Feng Li

Faculty, Staff and Students Publications

Duloxetine (DLX) is widely used to treat major depressive disorder. Little is known about the mechanistic basis for DLX-related adverse effects (e.g., liver injury). Human CYP1A2 and CYP2D6 mainly contributes to DLX metabolism, which was proposed to be involved in its adverse effects. Here, we investigated the roles of Cyp1a2 and Cyp2d on DLX pharmacokinetic profile and tissue distribution using a Cyp1a2 knockout (Cyp1a2-KO) mouse model together with a Cyp2d inhibitor (propranolol). Cyp1a2-KO has the few effects on the systematic exposure (area under the plasma concentration-time curve, AUC) and tissue disposition of DLX and its primary metabolites. Propranolol dramatically increased …

Final Results From A Phase 2b Randomized, Placebo-Controlled Clinical Trial Of Rbx2660: A Microbiota-Based Drug For The Prevention Of Recurrent Clostridioides Difficile Infection, Erik R Dubberke, Robert Orenstein, Sahil Khanna, Beth Guthmueller, Christine Lee

2020-Current year OA Pubs

INTRODUCTION: Effective treatments for recurrent Clostridioides difficile infection (rCDI) are urgently needed. RBX2660 is an investigational microbiota-based live biotherapeutic to reduce CDI recurrence following standard-of-care antibiotic treatment in individuals with rCDI. Here we report the final safety data through 24 months of follow-up as well as final efficacy data, reflecting alignment of the pre-specified statistical analysis plan definitions with the data presented.

METHODS: The PUNCH CD2 clinical trial was a prospective, multicenter, randomized, double-blinded, placebo-controlled, three-arm phase 2b study conducted to evaluate the efficacy and safety of RBX2660 for the reduction of rCDI compared to placebo. Eligible patients were at …

Missed Opportunities In The Diagnosis Of Tuberculosis Meningitis, Niamh Simmons, Margaret A Olsen, Joanna Buss, Thomas C Bailey, Carlos Mejia-Chew

2020-Current year OA Pubs

BACKGROUND: Tuberculosis meningitis (TBM) has high mortality and morbidity. Diagnostic delays can impact TBM outcomes. We aimed to estimate the number of potentially missed opportunities (MOs) to diagnose TBM and determine its impact on 90-day mortality.

METHODS: This is a retrospective cohort of adult patients with a central nervous system (CNS) TB

RESULTS: Of 893 patients with TBM, median age at diagnosis was 50 years (interquartile range, 37-64), 61.3% were male, and 35.2% had Medicaid as primary payer. Overall, 407 (45.6%) had a prior hospital or ED visit with an MO code. In-hospital 90-day mortality was not different between those …

Biallelic Variants In Ogdh Encoding Oxoglutarate Dehydrogenase Lead To A Neurodevelopmental Disorder Characterized By Global Developmental Delay, Movement Disorder, And Metabolic Abnormalities, Ella F Whittle, Madison Chilian, Ehsan Ghayoor Karimiani, Helga Progri, Daniela Buhas, Melis Kose, Rebecca D Ganetzky, Mehran Beiraghi Toosi, Paria Najarzadeh Torbati, Reza Shervin Badv, Ivan Shelihan, Hui Yang, Houda Zghal Elloumi, Sukyeong Lee, Yalda Jamshidi, Alan M Pittman, Henry Houlden, Erika Ignatius, Shamima Rahman, Reza Maroofian, Wan Hee Yoon, Christopher J Carroll

Faculty, Staff and Students Publications

PURPOSE: This study aimed to establish the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.

METHODS: We performed a detailed clinical characterization of 4 unrelated individuals from consanguineous families with a neurodevelopmental disorder. We used exome sequencing or targeted-exome sequencing, cosegregation, in silico protein modeling, and functional analyses of variants in HEK293 cells and Drosophila melanogaster, as well as in proband-derived fibroblast cells.

RESULTS: In the 4 individuals, we identified 3 novel homozygous variants in oxoglutarate dehydrogenase (OGDH) (NM_002541.3), which encodes a subunit of the tricarboxylic acid cycle enzyme …

A Review Of Stellate Ganglion Block As An Adjunctive Treatment Modality, Kennedy Kirkpatrick, Mashfee H Khan, Yi Deng, Krishna B Shah

Faculty, Staff and Students Publications

Peripheral nerve blocks are becoming increasingly used as adjunctive treatment modalities for a variety of conditions refractory to medical management. Right or left stellate ganglion blocks (SGB) are a specific type of peripheral nerve block that target the sympathetic blockade of neuronal impulses using the injection of local anesthetic and steroids into nerve bundles in the cervical area. This review article is intended to summarize the common uses of stellate ganglion blocks and explain the procedural technique, which has evolved with technological advances in ultrasonography. The similarities between these disease processes are centered around sympathetic hyperactivity. This sympathetic overdrive state …

Affare Fatto 2!, Susanna Nocchi, Silvia Bertoni

Books/Book Chapters

Taster. List of contents and first unit of a book for students of Italian as a foreign language.

Affare fatto! 2 is the second volume of a course aimed at learners of Italian who want to reach an intermediate level of competence in the language (B1/B1+ of the CEFR). The book offers material that can be used to attain competences in Italian for Business and for Professional Communication.

Affare fatto! 2 can be used as a textbook in a university course, as a book for professionals who work in Italy or with Italian partners, and as a textbook for those …

Comparison Of Postoperative Outcomes Of Laparoscopic Vs Open Inguinal Hernia Repair, Jennie Meier, Audrey Stevens, Miles Berger, Konstantinos I Makris, Athanasios Bramos, Joan Reisch, C Munro Cullum, Simon C Lee, Celette Sugg Skinner, Herbert Zeh, Cynthia J Brown, Courtney J Balentine

Faculty, Staff and Students Publications

Importance: Advocates of laparoscopic surgery argue that all inguinal hernias, including initial and unilateral ones, should be repaired laparoscopically. Prior work suggests outcomes of open repair are improved by using local rather than general anesthesia, but no prior studies have compared laparoscopic surgery with open repair under local anesthesia.

Objective: To evaluate postoperative outcomes of open inguinal hernia repair under general or local anesthesia compared with laparoscopic repair.

Design, setting, and participants: This retrospective cohort study identified 107 073 patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent unilateral initial inguinal hernia repair from 1998 to 2019. …

Primary Central Nervous System Germ Cell Tumors In Children And Young Adults: A Review Of Controversies In Diagnostic And Treatment Approach, Kee Kiat Yeo, Sumanth Nagabushan, Girish Dhall, Mohamed S Abdelbaki

2020-Current year OA Pubs

Primary central nervous system (CNS) germ cell tumors (GCT) are a rare heterogenous group of cancers, arising most commonly in the second decade of life. Through several clinical trials conducted around the world by various groups, the treatment approach for CNS GCT has advanced substantially with generally improved overall outcomes. In recent years, the goal of clinical trials has been focused on reduction of the radiotherapy burden and minimization of long-term toxicity. This review summarizes the current diagnostic and treatment regimens for CNS GCT, examines the controversies associated with these approaches, gaps in contemporary knowledge, and underscores the challenges we …

Interview No. 1751, Hernandez

Combined Interviews

Hernandez began working at Farah on April of 1972. Everyone at Farah left 2 moths after and she mentioned that those two months were enough for her to know what was right and what was wrong. Hernandez saw and experience many unjust things in those two months. She didn’t know how bad the situation inside the company was until she started to work there and realized that what the people were saying was right and even worse than what they described it as.

The worse part of the Farah company were the managers and their lack of experience in retail …

Interview No. 1753, Sanchez

Combined Interviews

Sanchez began working at Farah on April of 1969. Everyone at Farah hated their job and at first, she didn’t know why but 2 months after entering she realize what was right and what was wrong. As many others Farah workers on Paisano were tired of the unjust treatment and bad wage, Sanchez felt the exact same way in just a week of getting hired.

At first, she thought that it was so easy the hiring process and that Farah hired anyone who was willing to work. Soon after Sanchez realized that Farah hired many people, because of the amount …

Interview No. 1755, Gandara

Combined Interviews

He says that he stared working with his father after returning from the ARMY. He says that when he was working, they had a union that sometimes will fire people for nothing and they will have to legally open a case against that and he says that in order to get a response you needed to wait a long time. He says that one of his duties in the job was cutting ropes into different sizes. There is another woman interview that is his wife and she says that women were a minority in their job and they had to …

Interview No. 1757, Carrillo

Combined Interviews

Her last name is Carrillo and she was born in Mexico, and she arrived at Cuidad Juarez when she was 5 years old when she turned 12, she moved to, El Paso Texas. She was a home stay person and she helped with all the duties in the house, she is the middle child she has 3 older brothers and 3 younger brothers. Before she was married, she was working at a factory where they packed eggs and she worked in the fields picking pecans. She got married at the age of 22, with her husband that she met in …

Interview No. 1758, Saucido

Combined Interviews

Her last name is Saucido and she was working at Farah and she was part of the strike. Some of her duties at Farah was cutting and cleaning which was a very demanding job. She says that before the union there was no one that could help them and they thought that the union was going to make things better for them, but it wasn’t that way. When they were working, they will have supervisors that were making sure you did your job correctly, but sometimes they were extremely demanding and they will fire many people for either taking long …

Interview No. 1749, Jesse Muñoz Rev.

Combined Interviews

Jesse Munoz was an El Paso priest from Our Lady of the Light Church. He was born in Ciudad Juarez, Mexico, in 1940 during the depression years. When he turned eleven him and his family moved to El Paso, Texas in hopes of a better life and education. At the age of fourteen he took a bus to New York and worked there for over a year. He then had enough money to go to Spain and pay for an education and many years later he came back to El Paso, Texas.

At the time Rev. Munoz came back to …

Interview No. 1752, Valenzuela

Combined Interviews

Her last name is Valenzuela and she was born and raised in El Paso, Texas. After she graduated from high school, she got her first fulltime job at Farah. She was working in setting pockets, that involved a lot of hard work and many hours of work. The training that she was, was how to use the machine but like her many other people wants trained well. She says that many supervisors where over them all day long. She says that thru out the day they get 2 breaks from their job and they can rest on site and can …

Interview No. 1762, Leyva Bustamante

Combined Interviews

In April of 1970, Leyva started working at Farah. Everyone at Farah despised their job, and she didn't understand why at first, but after two months, she realized what was right and what was wrong. Leyva, like many other Farah employees on Paisano, was fed up with the unfair treatment and low pay after only a week on the job.

She initially assumed that the hiring process was simple and that Farah employed anyone who was willing to work. Soon after, Leyva recognized that Farah had employed a large number of individuals, and that they needed to balance the number …

Interview No. 1756, Eva Valdez

Combined Interviews

Eva was offered to join the strike during her time working at Farah Manufacturing Company, she first felt kind of scared because she didn’t want to be part of a strike. Eva didn’t understand what the union strike was about but she would later find out.

Eva’s first days at the Farah Manufacturing Company were filled with patches and jeans. She mentioned that she had to put patches in clothing items all day for long periods of time. For her work she would get pay less than $1.60 an hour. Some of her women coworkers had been working there for …

Interview No. 1768, Arieta

Combined Interviews

When Arieta initially started working there, she said that everyone at Farah detested their jobs. She didn't get the issues at Farah in Paisano that made every employee dread reporting to work each day. After a few days had passed, she received her first check and found she had been paid very little before the manager informed her that her pay would be increasing. She came to the realization that the contract she signed when she first started working there was also a complete fabrication that the bosses didn't regard.

She initially believed that Farah employed anyone who was willing …

Interview No. 1761, Rios

Combined Interviews

Everyone at Farah hated their job, that’s how Rios described it when she first started working there. She didn’t understand the problems happening at Farah at Paisano that made every worker hate going to work every day. A couple of days pass, she received her first check and realized that she got payed very little, when the manager told her that she would be getting payed more. She realized that she started her work there as a lie and that the contract that she sign was also a total lie that the managers didn’t respect.

At first, she thought that …

Interview No. 1765, Garcia

Combined Interviews

Garcia has lived and worked in El Paso, Texas. She mentioned that poverty in Mexico is worse than the poverty in the United States. Garcia left Mexico 5 years ago to get a better life in the USA. She left her children with her mother and got on the train to get to El Paso, Texas. She first arrived to Ciudad Juarez, Mexico and stayed with a family during a couple of weeks, while she gathered her papers to get a passport. After she got her passport she went to El Paso and started working and sending money back to …

Interview No. 1777, Tarango

Combined Interviews

Tarangos fathers’ parents were from Mexico and they passed away when she was very little. She never got to meet them. Her grandparent where from Leon Guanajuato, Mexico as well as his dad. Tarango mentioned that most of his family on her dads’ side were shoe makers back in Mexico, which was all he talked about to Tarango about. Sometimes he would talk about God or the Bible, but mostly about the shoe repair shop they had in Mexico. When Tarango’s dad came to the United States in the 1911 and he didn’t know English very well, but he managed …

Interview No. 1770, Del Hierro

Combined Interviews

Nearly all of Farah's employees were exhausted and tired of work. That was when Del Hierro started working there. She didn’t understand the problem in Farah of Paisano that was causing all workers to be reluctant to go to work every day. A few days went by and she received her first check and when the manager told her she would be paid more, she realized she had barely been paid, and realized that the contract she signed was also a complete lie and not respected by her manager.

At first, she thought the hiring process would be so easy …