Digital Commons Network^™

Factors Associated With Condom Use With Non-Commercial Partners Among Sexually-Active Transgender Women In Cambodia: Findings From A National Survey Using Respondent-Driven Sampling., Siyan Yi, Amelia Plant, Sovannary Tuot, Phalkun Mun, Srean Chhim, Navy Chann, Pheak Chhoun, Carinne M. Brody

BACKGROUND: Globally, the prevalence of HIV among transgender women is much higher than that of the general adult population. This can be explained by the persistently low rate of consistent condom use among this population. This study was therefore conducted to explore factors associated with consistent condom use among sexually-active transgender women in Cambodia, specifically with their non-commercial partners.

METHODS: Data used for this study were collected as part of the National Integrated Biological and Behavioral Survey 2016. Participants were recruited from the capital city of Phnom Penh and 12 other provinces with high burden of HIV using the Respondent-Driven …

Buparlisib In Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase Ii Trial., Patrick Y Wen, Mehdi Touat, Brian M Alexander, Ingo K Mellinghoff, Shakti Ramkissoon, Christine S Mccluskey, Kristine Pelton, Sam Haidar, Sankha S Basu, Sarah C Gaffey, Loreal E Brown, Juan Emmanuel Martinez-Ledesma, Shaofang Wu, Jungwoo Kim, Wei Wei, Mi-Ae Park, Jason T Huse, John G Kuhn, Mikael L Rinne, Howard Colman, Nathalie Y R Agar, Antonio M Omuro, Lisa M Deangelis, Mark R Gilbert, John F De Groot, Timothy F Cloughesy, Andrew S Chi, Thomas M Roberts, Jean J Zhao, Eudocia Q Lee, Lakshmi Nayak, James R Heath, Laura L Horky, Tracy T Batchelor, Rameen Beroukhim, Susan M Chang, Azra H Ligon, Ian F Dunn, Dimpy Koul, Geoffrey S Young, Michael D Prados, David A Reardon, W K Alfred Yung, Keith L Ligon

Articles, Abstracts, and Reports

PURPOSE: Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.

METHODS: This study was a multicenter, open-label, multi-arm, phase II trial in patients with PI3K pathway-activated glioblastoma at first or second recurrence. In cohort 1, patients scheduled for re-operation after progression received buparlisib for 7 to 13 days before surgery to evaluate brain penetration and modulation of the PI3K pathway in resected tumor tissue. In cohort 2, patients not eligible for re-operation received buparlisib until progression or unacceptable toxicity. Once …

Coming Together To Define Membrane Contact Sites., Luca Scorrano, Maria Antonietta De Matteis, Scott Emr, Francesca Giordano, György Hajnóczky, Benoît Kornmann, Laura L. Lackner, Tim P. Levine, Luca Pellegrini, Karin Reinisch, Rosario Rizzuto, Thomas Simmen, Harald Stenmark, Christian Ungermann, Maya Schuldiner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Close proximities between organelles have been described for decades. However, only recently a specific field dealing with organelle communication at membrane contact sites has gained wide acceptance, attracting scientists from multiple areas of cell biology. The diversity of approaches warrants a unified vocabulary for the field. Such definitions would facilitate laying the foundations of this field, streamlining communication and resolving semantic controversies. This opinion, written by a panel of experts in the field, aims to provide this burgeoning area with guidelines for the experimental definition and analysis of contact sites. It also includes suggestions on how to operationally and tractably …

A Novel Pathogenic Variant In Osbpl2 Linked To Hereditary Late-Onset Deafness In A Mongolian Family, Ningjin Wu, Husile Husile, Liqing Yang, Yaning Cao, Xing Li, Wenyan Huo, Haihua Bai, Yangjian Liu, Qizhu Wu

Open Access Publications

BACKGROUND: To investigate the clinical features and the underlying causal gene of a family with hereditary late-onset deafness in Inner Mongolia of China, and to provide evidence for the early genetic screening and diagnosis of this disease.

METHODS: Family data were collected to draw a pedigree. Audiological testing and physical examination of the family members were conducted following questionnaire. Genomic DNA was extracted from peripheral blood of 5 family members (3 patients and 2 normal control) and subjected to whole genome sequencing for identifying deafness casual genes. The pathogenic variant in the deafness gene was further confirmed by Sanger sequencing. …

Alterations In Phosphorylation Of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection., Elizabeth K K Glennon, Laura S Austin, Nadia Arang, Heather S Kain, Fred D Mast, Kamalakannan Vijayan, John D Aitchison, Stefan H I Kappe, Alexis Kaushansky

Articles, Abstracts, and Reports

Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated ribosomal protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast …

H3k27m Induces Defective Chromatin Spread Of Prc2-Mediated Repressive H3k27me2/Me3 And Is Essential For Glioma Tumorigenesis., Ashot S. Harutyunyan, Brian Krug, Haifen Chen, Simon Papillon-Cavanagh, Michele Zeinieh, Nicolas De Jay, Shriya Deshmukh, Carol C L Chen, Jad Belle, Leonie G. Mikael, Dylan M. Marchione, Rui Li, Hamid Nikbakht, Bo Hu, Gael Cagnone, Warren A. Cheung, Abdulshakour Mohammadnia, Denise Bechet, Damien Faury, Melissa K. Mcconechy, Manav Pathania, Siddhant U. Jain, Benjamin Ellezam, Alexander G. Weil, Alexandre Montpetit, Paolo Salomoni, Tomi Pastinen, Chao Lu, Peter W. Lewis, Benjamin A. Garcia, Claudia L. Kleinman, Nada Jabado, Jacek Majewski

Manuscripts, Articles, Book Chapters and Other Papers

Lys-27-Met mutations in histone 3 genes (H3K27M) characterize a subgroup of deadly gliomas and decrease genome-wide H3K27 trimethylation. Here we use primary H3K27M tumor lines and isogenic CRISPR-edited controls to assess H3K27M effects in vitro and in vivo. We find that whereas H3K27me3 and H3K27me2 are normally deposited by PRC2 across broad regions, their deposition is severely reduced in H3.3K27M cells. H3K27me3 is unable to spread from large unmethylated CpG islands, while H3K27me2 can be deposited outside these PRC2 high-affinity sites but to levels corresponding to H3K27me3 deposition in wild-type cells. Our findings indicate that PRC2 recruitment and propagation on …

Dissecting Features Of Epigenetic Variants Underlying Cardiometabolic Risk Using Full-Resolution Epigenome Profiling In Regulatory Elements., Fiona Allum, Åsa K. Hedman, Xiaojian Shao, Warren A. Cheung, Jinchu Vijay, Frédéric Guénard, Tony Kwan, Marie-Michelle Simon, Bing Ge, Cristiano Moura, Elodie Boulier, Lars Rönnblom, Sasha Bernatsky, Mark Lathrop, Mark I. Mccarthy, Panos Deloukas, André Tchernof, T Pastinen, Marie-Claude Vohl, Elin Grundberg

Manuscripts, Articles, Book Chapters and Other Papers

Sparse profiling of CpG methylation in blood by microarrays has identified epigenetic links to common diseases. Here we apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal~400), providing high-resolution methylation profiling (>1.3 M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up …

Binding Of Braco19 To A Telomeric G-Quadruplex Dna Probed By All-Atom Molecular Dynamics Simulations With Explicit Solvent., Babitha Machireddy, Holli-Joi Sullivan, Chun Wu

College of Science & Mathematics Departmental Research

Although BRACO19 is a potent G-quadruplex binder, its potential for clinical usage is hindered by its low selectivity towards DNA G-quadruplex over duplex. High-resolution structures of BRACO19 in complex with neither single-stranded telomeric DNA G-quadruplexes nor B-DNA duplex are available. In this study, the binding pathway of BRACO19 was probed by 27.5 µs molecular dynamics binding simulations with a free ligand (BRACO19) to a DNA duplex and three different topological folds of the human telomeric DNA G-quadruplex (parallel, anti-parallel and hybrid). The most stable binding modes were identified as end stacking and groove binding for the DNA G-quadruplexes and duplex, …

Homozygous Frameshift Mutations In Fat1 Cause A Syndrome Characterized By Colobomatous-Microphthalmia, Ptosis, Nephropathy And Syndactyly., Najim Lahrouchi, Aman George, Ilham Ratbi, Ronen Schneider, Siham C Elalaoui, Shahida Moosa, Sanita Bharti, Ruchi Sharma, Mones Abu-Asab, Felix Onojafe, Najlae Adadi, Elisabeth M Lodder, Fatima-Zahra Laarabi, Yassine Lamsyah, Hamza Elorch, Imane Chebbar, Alex V Postma, Vassilios Lougaris, Alessandro Plebani, Janine Altmueller, Henriette Kyrieleis, Vardiella Meiner, Helen Mcneill, Kapil Bharti, Stanislas Lyonnet, Bernd Wollnik, Alexandra Henrion-Caude, Amina Berraho, Friedhelm Hildebrandt, Connie R Bezzina, Brian P Brooks, Abdelaziz Sefiani

Open Access Publications

A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic …

Follicular Lymphoma Patients With Kir2dl2 And Kir3dl1 And Their Ligands (Hla-C1 And Hla-Bw4) Show Improved Outcome When Receiving Rituximab, Amy K Erbe, Wei Wang, Lakeesha Carmichael, Anna Hoefges, Bartosz Grzywacz, Patrick K Reville, Erik A Ranheim, Jacquelyn A Hank, Kyungmann Kim, Songwon Seo, Eneida A Mendonca, Yiqiang Song, Vaishalee P Kenkre, Fangxin Hong, Randy D Gascoyne, Elisabeth Paietta, Sandra J Horning, Jeffrey S Miller, Brad Kahl, Paul M Sondel

Open Access Publications

BACKGROUND: The ECOG-ACRIN Cancer Research Group evaluated rituximab treatment schedules for patients with newly-diagnosed low-tumor-burden follicular-lymphoma (FL). All patients received 4-weekly rituximab treatments as induction therapy. Clinically-responding patients were randomized to receive rituximab every 13 weeks ("maintenance") vs. no additional rituximab until progression ("non-maintenance"). Based on "time-to-rituximab-failure (TTRF)", the study-committee reported there was no overall-benefit for maintenance rituximab in this setting. Tumor-reactive mAbs, like rituximab, trigger natural killer (NK) cells. NK-cell responses are regulated, in part, by interactions between killer immunoglobulin-like receptors (KIRs) on NK cells and their interactions with KIR-ligands. In a separate study of children with neuroblastoma treated …

Association Of The Infant Gut Microbiome With Early Childhood Neurodevelopmental Outcomes: An Ancillary Study To The Vdaart Randomized Clinical Trial, Joanne E. Sordillo, Susan Korrick, Nancy Laranjo, Vincent Carey, George M. Weinstock, Diane R. Gold, George O'Connor, Megan Sandel, Leonard B. Bacharier, Avraham Beigelman, Robert Zeiger, Augusto A. Litonjua, Scott T. Weiss

Open Access Publications

Importance: In animal models, the early life gut microbiome influences later neurodevelopment. Corresponding data in human populations are lacking.

Objective: To study associations between the gut microbiome in infants and development at preschool age measured by the Ages and Stages Questionnaire, third edition (ASQ-3).

Design, Setting, and Participants: This ancillary cohort study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART) used data from 715 participants who had development assessed at 3 years of age by the ASQ-3, which included scores in 5 domains (gross motor skills, fine motor skills, problem solving, communication, and personal and social skills). A total …

Heart Failure Symptom Biology In Response To Ventricular Assist Device Implantation., Christopher S Lee, James O Mudd, Karen S Lyons, Quin E Denfeld, Corrine Y Jurgens, Bradley E Aouizerat, Jill M Gelow, Christopher V Chien, Emily Aarons, Kathleen L Grady

Articles, Abstracts, and Reports

BACKGROUND: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF), particularly in response to left ventricular assist device (LVAD) implantation.

OBJECTIVE: The aim of this study was to quantify the degree to which symptoms and biomarkers change in parallel from before implantation through the first 6 months after LVAD implantation in advanced HF.

METHODS: This was a prospective cohort study of 101 patients receiving an LVAD for the management of advanced HF. Data on symptoms (dyspnea, early and subtle symptoms [HF Somatic Perception Scale], pain severity [Brief Pain Inventory], wake disturbance [Epworth Sleepiness Scale], …

Informativeness Of Dental Morphology In Ancestry Estimation In African Americans, Jessica M. Gross, Heather J H Edgar

Pathology Research and Scholarship

OBJECTIVES: Our objective is to assess the informativeness of dental morphology in estimating biogeographic ancestry in African Americans.

MATERIALS AND METHODS: The data are 62 dental morphological traits scored as nondichotomized and dichotomized in 797 individuals, 992,601 SNPs from 271 individuals, and 645 STRs from 177 individuals. Each dataset consists of Africans, Europeans, and African Americans. For each dataset, we summed Fisher Information (FI), then used STRUCTURE to estimate ancestry.

RESULTS: Total FI was highest for SNPs, followed by STRs, nondichotomized dental traits, and dichotomized dental traits. For both genetic datasets, Africans and Europeans fell into two distinctive clusters with …

Neoantigen Screening Identifies Broad Tp53 Mutant Immunogenicity In Patients With Epithelial Cancers., Parisa Malekzadeh, Anna Pasetto, Paul F Robbins, Maria R Parkhurst, Biman C Paria, Li Jia, Jared J Gartner, Victoria Hill, Zhiya Yu, Nicholas P Restifo, Abraham Sachs, Eric Tran, Winifred Lo, Robert Pt Somerville, Steven A Rosenberg, Drew C Deniger

Articles, Abstracts, and Reports

No abstract provided.

Stress-Induced Epinephrine Enhances Lactate Dehydrogenase A And Promotes Breast Cancer Stem-Like Cells, Bai Cui, Yuanyuan Luo, Pengfei Tian, Fei Peng, Jinxin Lu, Yongliang Yang, Qitong Su, Bing Liu, Jiachuan Yu, Xi Luo, Liu Yin, Wei Cheng, Fan An, Bin He, Dapeng Liang, Sijin Wu, Peng Chu, Luyao Song, Xinyu Liu, Huandong Luo, Binhua P. Zhou

Molecular and Cellular Biochemistry Faculty Publications

Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress–induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A–dependent (LDHA-dependent) metabolic rewiring. Chronic stress–induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress–induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological …

Effect Of Conditioning Regimen Dose Reduction In Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation., Claudio G. Brunstein, Marcelo C. Pasquini, Soyoung Kim, Mingwei Fei, Kehinde Adekola, Ibrahim A. Ahmed, Mahmoud Aljurf, Vaibhav Agrawal, Jeffrey J. Auletta, Minoo Battiwalla, Nelli Bejanyan, Joseph Bubalo, Jan Cerny, Lynette Chee, Stefan O. Ciurea, Cesar Freytes, Shahinaz M. Gadalla, Robert Peter Gale, Siddhartha Ganguly, Shahrukh K. Hashmi, Peiman Hematti, Gerhard Hildebrandt, Leona A. Holmberg, Oscar B. Lahoud, Heather Landau, Hillard M. Lazarus, Marcos De Lima, Vikram Mathews, Richard Maziarz, Taiga Nishihori, Maxim Norkin, Richard Olsson, Ran Reshef, Seth Rotz, Bipin Savani, Harry C. Schouten, Sachiko Seo, Baldeep M. Wirk, Jean Yared, Shin Mineishi, John Rogosheske, Miguel-Angel Perales

Manuscripts, Articles, Book Chapters and Other Papers

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m2. Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) …

Levels And Patterns Of Self-Reported And Objectively-Measured Free-Living Physical Activity Among Prostate Cancer Survivors: A Prospective Cohort Study, Lee Smith, Jung Ae Lee, Junbae Mun, Ratna Pakpahan, Kellie R Imm, Sonya Izadi, Adam S Kibel, Graham A Colditz, Robert L Grubb Iii, Kathleen Y Wolin, Siobhan Sutcliffe, Lin Yang

Open Access Publications

BACKGROUND: No prior study has measured or compared self-reported and objectively measured physical activity trajectories in prostate cancer survivors before and after treatment.

METHODS: Clinically localized prostate cancer patients treated with radical prostatectomy were recruited between 2011 and 2014. Of the 350 participants enrolled at the main site, 310 provided self-reported physical activity at baseline before radical prostatectomy, and 5 weeks, 6 months, and 12 months after radical prostatectomy. A subset of participants (n = 81) provided objectively measured physical activity at all study time points by wearing an accelerometer for 7 days each. Changes in activity over time were …

Genetics Of Group A Streptococci, Kyu Hong Cho, Gary C Port, Michael Caparon

Open Access Publications

No abstract provided.

Genetic Susceptibility To Alopecia., Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams

Pediatrics Faculty Publications

Background: Injury is one of the most prevalent potentially emotionally traumatic events that children experience and can lead to persistent impaired physical and emotional health. There is a need for interventions that promote full physical and emotional recovery and that can be easily accessed by all injured children. Based on research evidence regarding post-injury recovery, we created the Cellie Coping Kit for Children with Injury intervention to target key mechanisms of action and refined the intervention based on feedback from children, families, and experts in the field. The Cellie Coping Kit intervention is parent-guided and includes a toy (for engagement), …

Plaidoh: A Novel Method For Functional Prediction Of Long Non-Coding Rnas Identifies Cancer-Specific Lncrna Activities, Sarah C Pyfrom, Hong Luo, Jacqueline E Payton

Open Access Publications

BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit remarkable cell-type specificity and disease association. LncRNA's functional versatility includes epigenetic modification, nuclear domain organization, transcriptional control, regulation of RNA splicing and translation, and modulation of protein activity. However, most lncRNAs remain uncharacterized due to a shortage of predictive tools available to guide functional experiments.

RESULTS: To address this gap for lymphoma-associated lncRNAs identified in our studies, we developed a new computational method, Predicting LncRNA Activity through Integrative Data-driven 'Omics and Heuristics (PLAIDOH), which has several unique features not found in other methods. PLAIDOH integrates transcriptome, subcellular localization, enhancer landscape, genome architecture, chromatin interaction, …

A Visual Interactive Analytic Tool For Filtering And Summarizing Large Health Data Sets Coded With Hierarchical Terminologies (Viads)., Xia Jing, Matthew Emerson, David Masters, Matthew Brooks, Jacob Buskirk, Nasseef Abukamail, Chang Liu, James J. Cimino, Jay H. Shubrook, Sonsoles De Lacalle, Yuchun Zhou, Vimla L. Patel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

BACKGROUND: Vast volumes of data, coded through hierarchical terminologies (e.g., International Classification of Diseases, Tenth Revision-Clinical Modification [ICD10-CM], Medical Subject Headings [MeSH]), are generated routinely in electronic health record systems and medical literature databases. Although graphic representations can help to augment human understanding of such data sets, a graph with hundreds or thousands of nodes challenges human comprehension. To improve comprehension, new tools are needed to extract the overviews of such data sets. We aim to develop a visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS) as an online, and publicly …

Reinterpretation Of The Substrate Specificity Of The Voltage-Sensing Phosphatase During Dimerization., Martin Kruse, Susy C Kohout, Bertil Hille

Cooper Medical School of Rowan University Departmental Research

Voltage-sensing phosphatases (VSPs) cleave both 3- and 5-phosphates from inositol phospholipids in response to membrane depolarization. When low concentrations of Ciona intestinalis VSP are expressed in Xenopus laevis oocytes, the 5-phosphatase reaction can be observed during large membrane depolarizations. When higher concentrations are expressed, the 5-phosphatase activity is observed with smaller depolarizations, and the 3-phosphatase activity is revealed with strong depolarization. Here we ask whether this apparent induction of 3-phosphatase activity is attributable to the dimerization that has been reported when VSP is expressed at higher concentrations. Using a simple kinetic model, we show that these enzymatic phenomena can be …

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …

Gene Therapy Targeting Sarm1 Blocks Pathological Axon Degeneration In Mice, Stefanie Geisler, Shay X. Huang, Amy Strickland, Ryan A. Doan, Daniel W. Summers, Xianrong Mao, Jiwoong Park, Aaron Diantonio, Jeffrey Milbrandt

Open Access Publications

Axonal degeneration (AxD) following nerve injury, chemotherapy, and in several neurological disorders is an active process driven by SARM1, an injury-activated NADase. Axons of SARM1-null mice exhibit greatly delayed AxD after transection and in models of neurological disease, suggesting that inhibiting SARM1 is a promising strategy to reduce pathological AxD. Unfortunately, no drugs exist to target SARM1. We, therefore, developed SARM1 dominant-negatives that potently block AxD in cellular models of axotomy and neuropathy. To assess efficacy in vivo, we used adeno-associated virus-mediated expression of the most potent SARM1 dominant-negative and nerve transection as a model of severe AxD. While axons …

Gen-1 Immunotherapy For The Treatment Of Ovarian Cancer, Premal H Thaker, Nicholas Borys, Jason Fewell, Khursheed Anwer

2010-2019 OA Pubs

GEN-1 is a gene-based immunotherapy, comprising a human IL-12 gene expression plasmid and a synthetic plasmid delivery system, delivered intraperitoneally (ip.) to produce local and persistent levels of a pleiotropic immunocytokine, IL-12, at the tumor site in patients with advanced ovarian cancer. The goal of local and persistent IL-12 delivery is to remodel the highly immunosuppressive tumor microenvironment to favor immune stimulation while avoiding serious systemic toxicities, a major limitation of recombinant IL-12 therapy. Safe and sustained local production of IL-12 and related immunocytokines at the tumor site could produce potentially more favorable immunological changes in the tumor microenvironment and …

The History And Future Of Digital Health In The Field Of Behavioral Medicine., Danielle Arigo, Danielle E Jake-Schoffman, Kathleen Wolin, Ellen Beckjord, Eric B Hekler, Sherry L Pagoto

College of Science & Mathematics Departmental Research

Since its earliest days, the field of behavioral medicine has leveraged technology to increase the reach and effectiveness of its interventions. Here, we highlight key areas of opportunity and recommend next steps to further advance intervention development, evaluation, and commercialization with a focus on three technologies: mobile applications (apps), social media, and wearable devices. Ultimately, we argue that future of digital health behavioral science research lies in finding ways to advance more robust academic-industry partnerships. These include academics consciously working towards preparing and training the work force of the twenty first century for digital health, actively working towards advancing methods …

Dynamic Light Scattering Optical Coherence Tomography To Probe Motion Of Subcellular Scatterers., Nico J J Arezza, Marjan Razani, Michael C Kolios

Medical Biophysics Publications

Optical coherence tomography (OCT) is used to provide anatomical information of biological systems but can also provide functional information by characterizing the motion of intracellular structures. Dynamic light scattering OCT was performed on intact, control MCF-7 breast cancer cells and cells either treated with paclitaxel to induce apoptosis or deprived of nutrients to induce oncosis. Autocorrelations (ACs) of the temporal fluctuations of OCT intensity signals demonstrate a significant decrease in decorrelation time after 24 h in both the paclitaxel-treated and nutrient-deprived cell groups but no significant differences between the two groups. The acquired ACs were then used as input for …

Genetic Associations Of Hemoglobin In Children With Chronic Kidney Disease In The Pedigfr Consortium, Meredith A Atkinson, Rui Xiao, Anna Köttgen, Elke Wühl, Craig S Wong, Matthias Wuttke, Aysun K Bayazit, Salim Çalişkan, Bradley A Warady, Franz Schaefer, Susan L Furth

Pediatrics Research and Scholarship

BACKGROUND: Genome-wide association studies (GWAS) in healthy populations have identified variants associated with erythrocyte traits, but genetic causes of hemoglobin variation in children with CKD are incompletely understood.

METHODS: The Pediatric Investigation of Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE), and Cardiovascular Comorbidity in Children with CKD (4C). We performed cross-sectional and longitudinal association studies of single-nucleotide polymorphisms (SNPs) in 1125 patients.

RESULTS: Children of European (n = 725) or …