Medicine and Health Sciences Commons^™

Toward A Standard Formal Semantic Representation Of The Model Card Report, Muhammad Tuan Amith, Licong Cui, Degui Zhi, Kirk Roberts, Xiaoqian Jiang, Fang Li, Evan Yu, Cui Tao

Faculty, Staff and Student Publications

BACKGROUND: Model card reports aim to provide informative and transparent description of machine learning models to stakeholders. This report document is of interest to the National Institutes of Health's Bridge2AI initiative to address the FAIR challenges with artificial intelligence-based machine learning models for biomedical research. We present our early undertaking in developing an ontology for capturing the conceptual-level information embedded in model card reports.

RESULTS: Sourcing from existing ontologies and developing the core framework, we generated the Model Card Report Ontology. Our development efforts yielded an OWL2-based artifact that represents and formalizes model card report information. The current release of …

Contribution Of Early-Life Unpredictability To Neuropsychiatric Symptom Patterns In Adulthood, Andrea D. Spadoni, Meghan Vinograd, Bruna Cuccurazzu, Katy Torres, Laura M. Glynn, Elysia P. Davis, Tallie Z. Baram, Dewleen G. Baker, Caroline M. Nievergelt, Victoria B. Risbrough

Psychology Faculty Articles and Research

Background

Recent studies in both human and experimental animals have identified fragmented and unpredictable parental and environmental signals as a novel source of early-life adversity. Early-life unpredictability may be a fundamental developmental factor that impacts brain development, including reward and emotional memory circuits, affecting the risk for psychopathology later in life. Here, we tested the hypothesis that self-reported early-life unpredictability is associated with psychiatric symptoms in adult clinical populations.

Methods

Using the newly validated Questionnaire of Unpredictability in Childhood, we assessed early-life unpredictability in 156 trauma-exposed adults, of which 65% sought treatment for mood, anxiety, and/or posttraumatic stress disorder (PTSD) …

Racial Disparities In Hepatitis B Birth Dose In The Washington Metropolitan Region, 2018-2020., Hee-Soon Juon, Donna T Sheler, Jane Pan, Daisy Le, Y Tony Yang

Department of Medical Oncology Faculty Papers

Hepatitis B vaccination protects newborns from contracting the hepatitis B virus that may lead to chronic infection, liver failure, or death. Trends and racial differences in the administration of the hepatitis B (HepB) birth dose in 2018-2020 were examined in the targeted region. A retrospective analysis of electronic birth dose vaccination data of newborns in 2018-2020 was performed. Birth data from six birthing facilities and home delivery records were obtained from the DC Health Department Vital Statistics Division. This data represented 40,269 newborns and included the mother's race and ethnicity, health insurance type, birthing facility, and administration of the HepB …

Differential Susceptibility Of Retinal Neurons To The Loss Of Mitochondrial Biogenesis Factor Nrf1, Takae Kiyama, Ching-Kang Chen, Annie Zhang, Chai-An Mao

Faculty, Staff and Student Publications

The retina, the accessible part of the central nervous system, has served as a model system to study the relationship between energy utilization and metabolite supply. When the metabolite supply cannot match the energy demand, retinal neurons are at risk of death. As the powerhouse of eukaryotic cells, mitochondria play a pivotal role in generating ATP, produce precursors for macromolecules, maintain the redox homeostasis, and function as waste management centers for various types of metabolic intermediates. Mitochondrial dysfunction has been implicated in the pathologies of a number of degenerative retinal diseases. It is well known that photoreceptors are particularly vulnerable …

Antiphospholipid Antibodies And Vitamin D Deficiency In Covid-19 Infection With And Without Venous Or Arterial Thrombosis: A Pilot Case-Control Study, Ruchi Shah, Yaqub Nadeem Mohammed, Tracy J Koehler, Jasmeet Kaur, Margarita Toufeili, Priyanjali Pulipati, Ahmed Alqaysi, Ali Khan, Mahrukh Khalid, Yi Lee, Parveen Dhillon, Anna Thao Dan, Nicholas Kumar, Monica Bowen, Anupam A Sule, Geetha Krishnamoorthy

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with thromboembolism. Antiphospholipid antibody (APLa) formation is one of the mechanisms. Vitamin D deficiency has been associated with thrombosis in antiphospholipid antibody syndrome.

OBJECTIVE: Measure APLa and vitamin D in hospitalized COVID-19 patients with and without thrombosis to evaluate if thromboembolism is associated with concomitant APLa and vitamin D deficiency.

METHODS: Case-control study. Hospitalized COVID-19 patients with a thromboembolic event (ischemic stroke, myocardial infarction, deep venous thrombosis/pulmonary embolism, Cases n = 20). Controls (n = 20): Age, sex-matched without thromboembolic events. Patients with autoimmune disorders, antiphospholipid antibody syndrome, thrombophilia, anticoagulation therapy, prior thromboembolism, chronic …

Editorial: Physiologic Signals In Neonatal Intensive Care, Eric W Reynolds

Faculty, Staff and Student Publications

No abstract provided.

Trial Of Erythropoietin For Hypoxic-Ischemic Encephalopathy In Newborns, Yvonne W Wu, Robert C Mckinstry, Rakesh Rao, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.

METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after …

De Novo Variants Of Csnk2b Cause A New Intellectual Disability-Craniodigital Syndrome By Disrupting The Canonical Wnt Signaling Pathway, Maria Asif, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

No abstract provided.

Subclinical Magnetic Resonance Imaging Markers Of Cerebral Small Vessel Disease In Relation To Office And Ambulatory Blood Pressure Measurements, Jesus D. Melgarejo, Gladys E. Maestre, Jose Gutierrez, Lutgarde Thijs, Luis J. Mena, Ciro Gaona, Reinier Leendertz, Joseph H. Lee, Carlos A. Chavez, Gustavo Calmon

School of Medicine Publications

Background: Twenty-four-hour and nighttime blood pressure (BP) levels are more strongly associated with cardiovascular risk than office or daytime BP measurements. However, it remains undocumented which of the office and ambulatory BP measurements have the strongest association and predictive information in relation to the presence of type I, or arteriolosclerosis type, cerebral small vessel diseases (CSVD).

Methods: A subset of 429 participants from the Maracaibo Aging Study [aged ≥40 years (women, 73.7%; mean age, 59.3 years)] underwent baseline brain magnetic resonance imaging (MRI) to visualize CSVD, which included log-transformed white matter hyperintensities (log-WMH) volume and the presence (yes/no) of lacunes, …

Triplet Therapy, Transplantation, And Maintenance Until Progression In Myeloma, Paul G Richardson, Susanna J Jacobus, Edie A Weller, Hani Hassoun, Sagar Lonial, Noopur S Raje, Eva Medvedova, Philip L Mccarthy, Edward N Libby, Peter M Voorhees, Robert Z Orlowski, Larry D Anderson, Jeffrey A Zonder, Carter P Milner, Cristina Gasparetto, Mounzer E Agha, Abdullah M Khan, David D Hurd, Krisstina Gowin, Rammurti T Kamble, Sundar Jagannath, Nitya Nathwani, Melissa Alsina, R Frank Cornell, Hamza Hashmi, Erica L Campagnaro, Astrid C Andreescu, Teresa Gentile, Michaela Liedtke, Kelly N Godby, Adam D Cohen, Thomas H Openshaw, Marcelo C Pasquini, Sergio A Giralt, Jonathan L Kaufman, Andrew J Yee, Emma Scott, Pallawi Torka, Amy Foley, Mariateresa Fulciniti, Kyle Hebert, Mehmet K Samur, Kelly Masone, Michelle E Maglio, Andrea A Zeytoonjian, Omar Nadeem, Robert L Schlossman, Jacob P Laubach, Claudia Paba-Prada, Irene M Ghobrial, Aurore Perrot, Philippe Moreau, Hervé Avet-Loiseau, Michel Attal, Kenneth C Anderson, Nikhil C Munshi, Determination Investigators

Faculty, Staff and Students Publications

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown.

METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received …

Long-Term Outcomes For Ibrutinib-Rituximab And Chemoimmunotherapy In Cll: Updated Results Of The E1912 Trial, Tait D Shanafelt, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

Herein, we present the long-term follow-up of the randomized E1912 trial comparing the long-term efficacy of ibrutinib-rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) and describe the tolerability of continuous ibrutinib. The E1912 trial enrolled 529 treatment-naïve patients aged ≤70 years with chronic lymphocytic leukemia (CLL). Patients were randomly assigned (2:1 ratio) to receive IR or 6 cycles of FCR. With a median follow-up of 5.8 years, median progression-free survival (PFS) is superior for IR (hazard ratio [HR], 0.37; P < .001). IR improved PFS relative to FCR in patients with both immunoglobulin heavy chain variable region (IGHV) gene mutated CLL (HR: 0.27; P < .001) and IGHV unmutated CLL (HR: 0.27; P < .001). Among the 354 patients randomized to IR, 214 (60.5%) currently remain on ibrutinib. Among the 138 IR-treated patients who discontinued treatment, 37 (10.5% of patients who started IR) discontinued therapy due to disease progression or death, 77 (21.9% of patients who started IR) discontinued therapy for adverse events (AEs)/complications, and 24 (6.8% of patients who started IR) withdrew for other reasons. Progression was uncommon among patients able to remain on ibrutinib. The median time from ibrutinib discontinuation to disease progression or death among those who discontinued treatment for a reason other than progression was 25 months. Sustained improvement in overall survival (OS) was observed for patients in the IR arm (HR, 0.47; P = .018). In conclusion, IR therapy offers superior PFS relative to FCR in patients with IGHV mutated or unmutated CLL, as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. This trial was registered at www.clinicaltrials.gov as #NCT02048813.

3 Selections From "Upon The Body: Poems Of/To A Black Social Epi, Pt.Ii--Love//Resistance In The Time Of Covid", R. J. Petteway

Amplify: A Journal of Writing-as-Activism

The 3 poems included here are from a collection written between January and August 2020. The full collection—27 poems total—examines intersections of structural racism, racialized police violence, and COVID-19, drawing from generations of creative resistance produced and embodied by Black artists, activists, and scholars like Nina Simone, Langston Hughes, Paul Laurence Dunbar, Audre Lorde, Ida B. Wells, James Baldwin, and W.E.B. DuBois. The collection as a whole is crafted as counternarrative to public health’s ahistoric, apolitical, racist, and homophobic proclivities in times of crisis. The 3 poems here are from Part II, "LOVE//Resistance in the Time of COVID.” These selections …

High Performance Judoka’S Views On Their Athlete Journey And The Need For Athlete Education, Katrina Mcdonald, Anna Stodter, Mathew Dowling, Justin Roberts

Journal of Athlete Development and Experience

High-performance sport has been the subject of controversy and scandal, coming under heavy scrutiny within the broad issue of “Duty of Care” in terms of the welfare and holistic development of athletes. The United Kingdom has many different schemes and mechanisms that are available to athletes to support them in their development on their athlete journey. However, there is a lack of research exploring whether these schemes and mechanisms fulfill athlete needs and facilitate athlete development. Utilizing Charmaz’s constructivist grounded theory method, twelve full-time, high-performance Judoka (Judo athletes) were intensively interviewed, exploring the experience of their journey as an athlete. …

A Survey Of The Mental Health Of Uk Olympic And Paralympic Sport Athletes., Sandra D. Leyland Dr, Alan Currie Prof, Elizabeth Board Dr, Amit D. Mistry Dr, Rod Jaques Dr, Craig Ranson Dr

Journal of Athlete Development and Experience

Abstract

This study examined the prevalence of psychological distress and well-being amongst elite athletes in the UK.

An online survey was emailed to 753 athletes within the English Institute of Sport. Response rate 52.3%. 371 participants (median age 25) completed measures of psychological distress and subjective well-being alongside demographics and sport-related variables.

High or very high psychological distress was reported by 23.7%. Poor subjective well-being was reported by 18.8%. Of those reporting psychological distress, 9% also reported good subjective well-being. The odds of psychological distress and poor well-being increased if the athlete was female (OR 2.03, distress; OR 2.00, poor …

Concomitant Myocardial And Coronary Injury In Systemic Lupus Erythematosus, Amal Elouarradi, Ilham Bensahi, Marwa Ghayate, Fatimazahra Merzouk, Mohamed Sabry

Journal of the Saudi Heart Association

No abstract provided.

Bispectral Index (Bis) Monitor: Applying The Evidence For Appropriate Application And Use, Mandy Christensen-Geraci, Becky Templin

Nursing DNP Projects

Abstract

Background: Accurate monitoring of sedation and proper utilization of the BIS Monitor in intensive care unit (ICU) patients can result in decreased use of sedative medications, which can lead to decreased time to extubation, thereby reducing costs and even perhaps the length of hospital stay. The purpose of this project was to provide education to medical intensive care unit (MICU) nurses to increase their knowledge and confidence using the BIS monitor.

Methods: A middle range theory, specifically the Synergy Model for Patient Care was used as a conceptual framework for designing the intervention and The Johns Hopkins Evidence-Based (JHNEBP) …

2022-07-13_Michiganoverview_Covidvaccinestats, Michigan Department Of Health & Human Services

Michigan COVID-19 Vaccine Data

The COVID Vaccine Dashboard page was obtained from Michigan's main COVID-19 page: https://www.michigan.gov/coronavirus/resources/covid-19-vaccine/covid-19-dashboard.

First-dose tracker above is for entire Michigan Population. Coverage maps below are for age 5+.

Previously reported numbers of administered vaccine doses may change as new data are received. A possible lag in reporting vaccine doses will result in increases in numbers previously reported.

This report is created by the Michigan Department of Health and Human Services Division of Immunization from data reported to the Michigan Care Improvement Registry (MCIR).

The dashboard contained the tabs Primary Series Doses Administered, Primary Series Doses by Vaccine, …

Mortality Prediction Analysis Among Covid-19 Inpatients Using Clinical Variables And Deep Learning Chest Radiography Imaging Features., Xuan V Nguyen, Engin Dikici, Sema Candemir, Robyn L Ball, Luciano M Prevedello

Faculty Research 2022

The emergence of the COVID-19 pandemic over a relatively brief interval illustrates the need for rapid data-driven approaches to facilitate clinical decision making. We examined a machine learning process to predict inpatient mortality among COVID-19 patients using clinical and chest radiographic data. Modeling was performed with a de-identified dataset of encounters prior to widespread vaccine availability. Non-imaging predictors included demographics, pre-admission clinical history, and past medical history variables. Imaging features were extracted from chest radiographs by applying a deep convolutional neural network with transfer learning. A multi-layer perceptron combining 64 deep learning features from chest radiographs with 98 patient clinical …

2022-07-13 Michiganoverview_Covidbedppe, Michigan Department Of Health & Human Services

Michigan COVID-19 Hospital Data

Contains the tables Statewide Hospital Capacity Report for COVID-19, COVID-19 Metrics, Statewide Hospital Available PPE Tracking for COVID-19, as well as the tables PPE Days On Hand and Patient Census.

Three Dimensions Of Covid-19 Risk Perceptions And Their Socioeconomic Correlates In The United States: A Social Media Analysis, Shan Qiao Ph.D., Zhenlong Li Ph.D., Chen Liang Ph.D., Xiaoming Li Ph.D., Caroline Rudisill Ph.D.

Faculty Publications

Social media analysis provides an alternate approach to monitoring and understanding risk perceptions regarding COVID-19 over time. Our current understandings of risk perceptions regarding COVID-19 do not disentangle the three dimensions of risk perceptions (perceived susceptibility, perceived severity, and negative emotion) as the pandemic has evolved. Data are also limited regarding the impact of social determinants of health (SDOH) on COVID-19-related risk perceptions over time. To address these knowledge gaps, we extracted tweets regarding COVID-19-related risk perceptions and developed indicators for the three dimensions of risk perceptions based on over502 million geotagged tweets posted by over 4.9 million Twitter users …

Antithrombin-Iii Mitigates Thrombin-Mediated Endothelial Cell Contraction And Sickle Red Blood Cell Adhesion In Microscale Flow, William J. Wulftange, Erdem Kucukal, Yuncheng Man, Ran An, Karamoja Monchamp, Charlotte D. Sevrain, Himanshu R. Dashora, Allison Bode, Jane A. Little, Umut A. Gurkan

Faculty Scholarship

Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII …

Describing And Assessing A New Method Of Approximating Categorical Individual-Level Income Using Community-Level Income From The Census (Weighting By Income Probabilities), Uriel Kim, Siran M. Koroukian, Kurt C. Stange, James C. Spilsbury, Weichuan Dong, Johnie Rose

Faculty Scholarship

Objective: To assess a new approach (weighting by “income probabilities [IP]”) that uses US Census data from the patients' communities to approximate individual-level income, an important but often missing variable in health services research. Data Sources: Community (census tract level) income data came from the 2017 5-year American Community Survey (ACS). The patient data included those diagnosed with cancer in 2017 in Ohio (n = 65,759). The reference population was the 2017 5-year ACS Public Use Microdata Sample (n = 564,357 generalizing to 11,288,350 Ohioans). Study Design/Methods: We applied the traditional approach of income approximation using median census tract income …

Three Dimensions Of Covid-19 Risk Perceptions And Their Socioeconomic Correlates In The United States: A Social Media Analysis, Shan Qiao, Zhenlong Li, Caroline Rudsill

Faculty Publications

Social media analysis provides an alternate approach to monitoring and understanding risk perceptions regarding COVID-19 over time. Our current understandings of risk perceptions regarding COVID-19 do not disentangle the three dimensions of risk perceptions (perceived susceptibility, perceived severity, and negative emotion) as the pandemic has evolved. Data are also limited regarding the impact of social determinants of health (SDOH) on COVID-19-related risk perceptions over time. To address these knowledge gaps, we extracted tweets regarding COVID-19-related risk perceptions and developed indicators for the three dimensions of risk perceptions based on over 502 million geotagged tweets posted by over 4.9 million Twitter …

Coping Strategies For Inner Conflicts Between Gay Bear Identity And Health Concerns, Chichun Lin, Darren D. Moore

The Qualitative Report

Gay bear refers to a burly gay man with a hirsute body and face. Chinese gay bear men are highly homogeneous and strictly emphasize a uniform bear appearance; however, obesity is an obvious health issue in this population. This study aims to explore the Chinese gay bear men's inner conflicts between bear identity and health concerns. Eleven Chinese gay bear men including four Taiwanese, two mainland Chinese, two Hong Kong, two Malaysian, and one Singaporean were interviewed. The study used a thematic analysis approach and found three coping strategies including (a) Eat healthy but maintain a minimal bear standard; (b) …

Gut Bacterial Isoamylamine Promotes Age-Related Cognitive Dysfunction By Promoting Microglial Cell Death, Yun Teng, Jingyao Mu, Fangyi Xu, Xiangcheng Zhang, Mukesh K Sriwastva, Qiaohong M Liu, Xiaohong Li, Chao Lei, Kumaran Sundaram, Xin Hu, Lifeng Zhang, Juw Won Park, Jae Yeon Hwang, Eric C Rouchka, Xiang Zhang, Jun Yan, Michael L Merchant, Huang-Ge Zhang

Faculty, Staff and Student Publications

The intestinal microbiome releases a plethora of small molecules. Here, we show that the Ruminococcaceae metabolite isoamylamine (IAA) is enriched in aged mice and elderly people, whereas Ruminococcaceae phages, belonging to the Myoviridae family, are reduced. Young mice orally administered IAA show cognitive decline, whereas Myoviridae phage administration reduces IAA levels. Mechanistically, IAA promotes apoptosis of microglial cells by recruiting the transcriptional regulator p53 to the S100A8 promoter region. Specifically, IAA recognizes and binds the S100A8 promoter region to facilitate the unwinding of its self-complementary hairpin structure, thereby subsequently enabling p53 to access the S100A8 promoter and enhance S100A8 expression. …

The Lived Experience Of Postpartum Anxiety During Covid-19: A Hermeneutic Phenomenological Study, Walker Ladd Phd, Jenny De Decker

The Qualitative Report

The experience of pregnancy and postpartum anxiety disorders results in adverse birth outcomes and the disrupted development of infants and children. Since the COVID-19 Pandemic, the Centers for Disease Control and Prevention (CDC) has designated pregnant and postpartum women as more vulnerable to COVID-19 (CDC, 2021), and perinatal mood and anxiety disorders rates have increased. However, research regarding the lived experience of women with postpartum anxiety (PPA) during a global pandemic remains lacking. Using van Manen’s hermeneutic phenomenological research method, we interviewed eight women self-identifying as having had PPA during the COVID-19 pandemic. Analysis revealed five themes describing the lived …

Automating 4dct-Ventilation Imaging Generation Using Ai-Based Advanced Lung Contours, Yingxuan Chen, Sohrab Pahlavan, Paul Jacobs, Farnoush Forghani, Edward Castillo, Richard Castillo, Yevgeniy Vinogradskiy

Conference Presentation Abstracts

Purpose: Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional lung. A novel form of lung functional imaging applied for functional avoidance uses 4DCT imaging to calculating 4DCT-based lung ventilation (4DCT-ventilation). The process of generating 4DCT-ventilation images requires advanced lung segmentation (consisting of a standard lung with airway and vasculature removed) which is a manual and time-consuming process. The purpose of this work is to automate 4DCT-ventilation imaging generation using AI-based auto-segmentation techniques for advanced lung contouring.

Methods: 429 patients with 4DCT data from two institutions were used. Three methods …

Addressing The Gap In Data Communication From Home Health Care To Primary Care During Care Transitions: Completeness Of An Interoperability Data Standard, Paulina Sockolow, Edgar Y Chou, Subin Park

Department of Medicine Faculty Papers

In a future where home health care is no longer an information silo, patient information will be communicated along transitions in care to improve care. Evidence-based practice in the United States supports home health care patients to see their primary care team within the first two weeks of hospital discharge to reduce rehospitalization risk. We sought to identify a parsimonious set of home health care data to be communicated to primary care for the post-hospitalization visit. Anticipating electronic dataset communication, we investigated the completeness of the international reference terminology, Logical Observation Identifiers Names and Codes (LOINC), for coverage of the …

The Intrinsically Disordered Protein Tgist From Toxoplasma Gondii Inhibits Stat1 Signaling By Blocking Cofactor Recruitment, Zhou Huang, Hejun Liu, Jay Nix, Rui Xu, Catherine R Knoverek, Gregory R Bowman, Gaya K Amarasinghe, L David Sibley

2020-Current year OA Pubs

Signal transducer and activator of transcription (STAT) proteins communicate from cell-surface receptors to drive transcription of immune response genes. The parasite Toxoplasma gondii blocks STAT1-mediated gene expression by secreting the intrinsically disordered protein TgIST that traffics to the host nucleus, binds phosphorylated STAT1 dimers, and occupies nascent transcription sites that unexpectedly remain silenced. Here we define a core region within internal repeats of TgIST that is necessary and sufficient to block STAT1-mediated gene expression. Cellular, biochemical, mutational, and structural data demonstrate that the repeat region of TgIST adopts a helical conformation upon binding to STAT1 dimers. The binding interface is …

The Testis-Specific E3 Ubiquitin Ligase Rnf133 Is Required For Fecundity In Mice, Kaori Nozawa, Yoshitaka Fujihara, Darius J Devlin, Ricardo E Deras, Katarzyna Kent, Irina V Larina, Kohei Umezu, Zhifeng Yu, Courtney M Sutton, Qiuji Ye, Laura K Dean, Chihiro Emori, Masahito Ikawa, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: Ubiquitination is a post-translational modification required for a number of physiological functions regulating protein homeostasis, such as protein degradation. The endoplasmic reticulum (ER) quality control system recognizes and degrades proteins no longer needed in the ER through the ubiquitin-proteasome pathway. E2 and E3 enzymes containing a transmembrane domain have been shown to function in ER quality control. The ER transmembrane protein UBE2J1 is a E2 ubiquitin-conjugating enzyme reported to be essential for spermiogenesis at the elongating spermatid stage. Spermatids from Ube2j1 KO male mice are believed to have defects in the dislocation step of ER quality control. However, associated …