Digital Commons Network^™

Wormbase: A Modern Model Organism Information Resource, Todd W. Harris, Tim Schedl, Et Al

Open Access Publications

WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by …

Mirdb: An Online Database For Prediction Of Functional Microrna Targets, Yuhao Chen, Xiaowei Wang

Open Access Publications

MicroRNAs (miRNAs) are small noncoding RNAs that act as master regulators in many biological processes. miRNAs function mainly by downregulating the expression of their gene targets. Thus, accurate prediction of miRNA targets is critical for characterization of miRNA functions. To this end, we have developed an online database, miRDB, for miRNA target prediction and functional annotations. Recently, we have performed major updates for miRDB. Specifically, by employing an improved algorithm for miRNA target prediction, we now present updated transcriptome-wide target prediction data in miRDB, including 3.5 million predicted targets regulated by 7000 miRNAs in five species. Further, we have implemented …

Are We Ready To Share Qualitative Research Data? Knowledge And Preparedness Among Qualitative Researchers, Irb Members, And Data Repository Curators, Jessica Mozersky, Heidi Walsh, Meredith Parsons, Tristan Mcintosh, Kari Baldwin, James M Dubois

Open Access Publications

Data sharing maximizes the value of data, which is time and resource intensive to collect. Major funding bodies in the United States (US), like the National Institutes of Health (NIH), require data sharing and researchers frequently share de-identified quantitative data. In contrast, qualitative data are rarely shared in the US but the increasing trend towards data sharing and open science suggest this may be required in future. Qualitative methods are often used to explore sensitive health topics raising unique ethical challenges regarding protecting confidentiality while maintaining enough contextual detail for secondary analyses. Here, we report findings from semi-structured in-depth interviews …

Atomistic Basis Of Opening And Conduction In Mammalian Inward Rectifier Potassium (Kir2.2) Channels, Eva-Maria Zangerl-Plessl, Sun-Joo Lee, Grigory Maksaev, Harald Bernsteiner, Feifei Ren, Peng Yuan, Anna Stary-Weinzinger, Colin G. Nichols

Open Access Publications

Potassium ion conduction through open potassium channels is essential to control of membrane potentials in all cells. To elucidate the open conformation and hence the mechanism of K+ ion conduction in the classic inward rectifier Kir2.2, we introduced a negative charge (G178D) at the crossing point of the inner helix bundle, the location of ligand-dependent gating. This "forced open" mutation generated channels that were active even in the complete absence of phosphatidylinositol-4,5-bisphosphate (PIP2), an otherwise essential ligand for Kir channel opening. Crystal structures were obtained at a resolution of 3.6 Å without PIP2 bound, or 2.8 Å in complex with …

Splicing Factor Sf3b1 Promotes Endometrial Cancer Progression Via Regulating Ksr2 Rna Maturation, Pooja Popli, Megan M. Richters, Sangappa B. Chadchan, Tae Hoon Kim, Eric Tycksen, Obi Griffith, Premal H. Thaker, Malachi Griffith, Ramakrishna Kommagani

Open Access Publications

No abstract provided.

Diffusion Basis Spectrum Imaging Detects Axonal Loss After Transient Dexamethasone Treatment In Optic Neuritis Mice, Tsen-Hsuan Lin, Jie Zhan, Chunyu Song, Michael Wallendorf, Peng Sun, Xuan Niu, Ruimeng Yang, Anne H Cross, Sheng-Kwei Song

Open Access Publications

Optic neuritis is a frequent first symptom of multiple sclerosis (MS) for which corticosteroids are a widely employed treatment option. The Optic Neuritis Treatment Trial (ONTT) reported that corticosteroid treatment does not improve long-term visual acuity, although the evolution of underlying pathologies is unclear. In this study, we employed non-invasive diffusion basis spectrum imaging (DBSI)-derived fiber volume to quantify 11% axonal loss 2 months after corticosteroid treatment (vs. baseline) in experimental autoimmune encephalomyelitis mouse optic nerves affected by optic neuritis. Longitudinal DBSI was performed at baseline (before immunization), after a 2-week corticosteroid treatment period, and 1 and 2 months after …

A Regulatory Science Initiative To Harmonize And Standardize Digital Pathology And Machine Learning Processes To Speed Up Clinical Innovation To Patients, Hetal Desai Marble, Mike Isaacs, Et Al.

Open Access Publications

No abstract provided.

Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Karen Schwander, Et Al.

Open Access Publications

No abstract provided.

Genome-Wide Association Study Of Opioid Cessation, Jiayi W Cox, Richard M Sherva, Kathryn L Lunetta, Emma C Johnson, Nicholas G Martin, Louisa Degenhardt, Arpana Agrawal, Elliot C Nelson, Henry R Kranzler, Joel Gelernter, Lindsay A Farrer

Open Access Publications

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in

The Cartilage Matrisome In Adolescent Idiopathic Scoliosis, Carol A. Wise, Diane Sepich, Aki Ushiki, Anas M. Khanshour, Yared H. Kidane, Nadja Makki, Christina A. Gurnett, Ryan S. Gray, Jonathan J. Rios, Nadav Ahituv, Lila Solnica-Krezel

Open Access Publications

No abstract provided.

Histopathologic, Immunophenotypic, And Proteomics Characteristics Of Low-Grade Phyllodes Tumor And Fibroadenoma: More Similarities Than Differences, Lingxin Zhang, Chen Tang, John D. Pfeifer, Richard M. Caprioli, Audra M. Judd, Nathan H. Patterson, Michelle L. Reyzer, Jeremy L. Norris, Horacio M. Maluf

Open Access Publications

No abstract provided.

Gata2 Regulates Constitutive Pd-L1 And Pd-L2 Expression In Brain Tumors, Yujie Fu, Connor J. Liu, Dale K. Kobayashi, Tanner M. Johanns, Jay A. Bowman-Kirigin, Maximilian O. Schaettler, Diane D. Mao, Diane Bender, Diane G. Kelley, Ravindra Uppaluri, Wenya Linda Bi, Ian F. Dunn, Yu Tao, Jingqin Luo, Albert H. Kim, Gavin P. Dunn

Open Access Publications

No abstract provided.

Design And Rationale Of The Hapin Study: A Multicountry Randomized Controlled Trial To Assess The Effect Of Liquefied Petroleum Gas Stove And Continuous Fuel Distribution, Thomas Clasen, Victor G. Davila-Roman, Et Al.

Open Access Publications

No abstract provided.

Midkine Activation Of Cd8+ T Cells Establishes A Neuron–Immune–Cancer Axis Responsible For Low-Grade Glioma Growth, Xiaofan Guo, Yuan Pan, Min Xiong, Shilpa Sanapala, Corina Anastasaki, Olivia Cobb, Sonika Dahiya, David H. Gutmann

Open Access Publications

No abstract provided.

Feasibility And Safety Of Focused Ultrasound-Enabled Liquid Biopsy In The Brain Of A Porcine Model, Christopher Pham Pacia, Lifei Zhu, Yaoheng Yang, Yimei Yue, Arash Nazeri, H. Michael Gach, Michael R. Talcott, Eric C. Leuthardt, Hong Chen

Open Access Publications

No abstract provided.

Gene Expression In Meniscal Tears At The Time Of Arthroscopic Partial Meniscectomy Predicts The Progression Of Osteoarthritis Within 6 Years Of Surgery, Joseph D. Lamplot, Muhammad Farooq Rai, William P. Tompkins, Michael V. Friedman, Eric J. Schmidt, Linda J. Sandell, Robert H. Brophy

Open Access Publications

No abstract provided.

Ldha-Mediated Ros Generation In Chondrocytes Is A Potential Therapeutic Target For Osteoarthritis, Manoj Arra, Gaurav Swarnkar, Ke Ke, Jesse E. Otero, Jun Ying, Xin Duan, Takashi Maruyama, Muhammad Farooq Rai, Regis J. O'Keefe, Gabriel Mbalaviele, Jie Shen, Yousef Abu-Amer

Open Access Publications

No abstract provided.

Interpreting Pathways To Discover Cancer Driver Genes With Moonlight, Antonio Colaprico, Matthew H. Bailey, Et Al.

Open Access Publications

No abstract provided.

Proteomic Resistance Biomarkers For Pi3k Inhibitor In Triple Negative Breast Cancer Patient-Derived Xenograft Models, Zhanfang Guo, Tina Primeau, Jingqin Luo, Cynthia Zhang, Hua Sun, Jeremy Hoog, Feng Gao, Shixia Huang, Dean P Edwards, Sherri R Davies, Rebecca Aft, Li Ding, Matthew J Ellis, Shunqiang Li, Cynthia X Ma

Open Access Publications

PI3K pathway activation is frequently observed in triple negative breast cancer (TNBC). However, single agent PI3K inhibitors have shown limited anti-tumor activity. To investigate biomarkers of response and resistance mechanisms, we tested 17 TNBC patient-derived xenograft (PDX) models representing diverse genomic backgrounds and varying degrees of PI3K pathway signaling activities for their tumor growth response to the pan-PI3K inhibitor, BKM120. Baseline and post-treatment PDX tumors were subjected to reverse phase protein array (RPPA) to identify protein markers associated with tumor growth response. While BKM120 consistently reduced PI3K pathway activity, as demonstrated by reduced levels of phosphorylated AKT, percentage tumor growth …

Simultaneous Immunization With Omp25 And L7/L12 Provides Protection Against Brucellosis In Mice, Sonal Gupta, Surender Mohan, Vikas Kumar Somani, Somya Aggarwal, Rakesh Bhatnagar

Open Access Publications

Currently used

Pkis Deep Dive Yields A Chemical Starting Point For Dark Kinases And A Cell Active Brsk2 Inhibitor, Tigist Y. Tamir, David H. Drewry, Carrow Wells, M. Ben Major, Alison D. Axtman

Open Access Publications

No abstract provided.

Marrowquant Across Aging And Aplasia: A Digital Pathology Workflow For Quantification Of Bone Marrow Compartments In Histological Sections, Josefine Tratwal, Erica L Scheller, Et Al

Open Access Publications

The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microenvironment, the so-called "red-to-yellow" transition. Following hematopoietic recovery, such as upon BM transplantation, a "yellow-to-red" transition occurs and functional hematopoiesis is restored. Gold Standards to estimate BM cellular composition are pathologists' assessment of hematopoietic cellularity in hematoxylin and eosin (H&E) stained histological sections as well as volumetric measurements of marrow adiposity with contrast-enhanced micro-computerized tomography (CE-μCT) upon osmium-tetroxide lipid staining. Due to user-dependent …

Genetic Architecture Of Circulating Very-Long-Chain (C24:0 And C22:0) Ceramide Concentrations, Sharon Cresci, Ruibo Zhang, Qiong Yang, Meredith S Duncan, Vanessa Xanthakis, Xuntian Jiang, Ramachandran S Vasan, Jean E Schaffer, Linda R Peterson

Open Access Publications

OBJECTIVE: Total ceramide concentrations are linked with increased insulin resistance and cardiac dysfunction. However, recent studies have demonstrated that plasma concentrations of specific very-long-chain fatty ceramides (C24:0 and C22:0) are associated with a reduced incidence of coronary heart disease and all-cause mortality. We hypothesized that specific genetic loci are associated with plasma C22:0 and C24:0 concentrations.

METHODS: Heritability and genome-wide association studies of plasma C24:0 and C22:0 ceramide concentrations were performed among 2,217 participants in the Framingham Heart Study Offspring Cohort, adjusting for cardiovascular risk factor covariates and cardiovascular drug treatment.

RESULTS: The multivariable-adjusted heritability for C22:0 and C24:0 ceramides …

The At(N) Framework For Alzheimer's Disease In Adults With Down Syndrome, Michael S Rafii, Beau M Ances, Et Al

Open Access Publications

The National Institute on Aging in conjunction with the Alzheimer's Association (NIA-AA) recently proposed a biological framework for defining the Alzheimer's disease (AD) continuum. This new framework is based upon the key AD biomarkers (amyloid, tau, neurodegeneration, AT[N]) instead of clinical symptoms and represents the latest understanding that the pathological processes underlying AD begin decades before the manifestation of symptoms. By using these same biomarkers, individuals with Down syndrome (DS), who are genetically predisposed to developing AD, can also be placed more precisely along the AD continuum. The A/T(N) framework is therefore thought to provide an objective manner by which …

Eflornithine Plus Sulindac For Prevention Of Progression In Familial Adenomatous Polyposis, Carol A. Burke, Paul E. Wise, Et Al

Open Access Publications

No abstract provided.

Cerebral Small Vessel Disease Genomics And Its Implications Across The Lifespan, Muralidharan Sargurupremraj, Andrew C. Heath, Pamela A.F. Madden, Et Al.

Open Access Publications

No abstract provided.

The Current State Of Hiv And Aging: Findings Presented At The 10th International Workshop On Hiv And Aging, Stephanie Shiau, Jane A. O'Halloran, Et Al.

Open Access Publications

No abstract provided.

Chemical Inhibition Of Papd5/7 Rescues Telomerase Function And Hematopoiesis In Dyskeratosis Congenita, Siddharth Shukla, Ho-Chang Jeong, Christopher M. Sturgeon, Roy Parker, Luis Francisco Zirnberger Batista

Open Access Publications

No abstract provided.

Primary Cilia Control Glucose Homeostasis Via Islet Paracrine Interactions, Jing W. Hughes, Jung Hoon Cho, Hannah E. Conway, Michael R. Digruccio, Xue Wen Ng, Henry F. Roseman, Damien Abreu, Fumihiko Urano, David W. Piston

Open Access Publications

No abstract provided.

Alterations In Plasma Triglycerides And Ceramides: Links With Cardiac Function In Humans With Type 2 Diabetes, Linda R. Peterson, Xuntian Jiang, Ling Chen, Anne C. Goldberg, Marsha S. Farmer, Daniel S. Ory, Jean E. Schaffer

Open Access Publications

No abstract provided.