Digital Commons Network^™

Bacterial Sepsis Increases Hippocampal Fibrillar Amyloid Plaque Load And Neuroinflammation In A Mouse Model Of Alzheimer's Disease, Jacob M Basak, Aura Ferreiro, Lucy S Cohen, Patrick W Sheehan, Collin J Nadarajah, Michael F Kanan, Kimberley V Sukhum, Gautam Dantas, Erik S Musiek

2020-Current year OA Pubs

BACKGROUND: Sepsis, a leading cause for intensive care unit admissions, causes both an acute encephalopathy and chronic brain dysfunction in survivors. A history of sepsis is also a risk factor for future development of dementia symptoms. Similar neuropathologic changes are associated with the cognitive decline of sepsis and Alzheimer's disease (AD), including neuroinflammation, neuronal death, and synaptic loss. Amyloid plaque pathology is the earliest pathological hallmark of AD, appearing 10 to 20 years prior to cognitive decline, and is present in 30% of people over 65. As sepsis is also more common in older adults, we hypothesized that sepsis might …

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, And Function, And Cardiovascular Events (From The Atherosclerosis Risk In Communities Study), Aliza Hussain, Olive Tang, Caroline Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron Folsom, Gerardo Heiss, Faiez Zannad, Thomas Mosley, Salim S Virani, Josef Coresh, Eric Boerwinkle, Bing Yu, Jonathan W Cunningham, Amil M Shah, Scott D Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne

Faculty, Staff and Students Publications

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels …

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Enabling Precision Medicine In Cancer Care Through A Molecular Data Warehouse: The Moffitt Experience, Steven A Eschrich, Jamie K Teer, Phillip Reisman, Erin Siegel, Chandan Challa, Patricia Lewis, Katherine Fellows, Everin Malpica, Rodrigo Carvajal, Guillermo Gonzalez, Scott Cukras, Miguel Betin-Montes, Garrick Aden-Buie, Melissa Avedon, Daniel Manning, Aik Choon Tan, Brooke L Fridley, Travis Gerke, Mattias Van Looveren, Amilcar Blake, Jennifer Greenman, Dana E Rollison

Faculty, Staff and Students Publications

PURPOSE: The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research.

METHODS: Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse …

Acetyl-Coa And Metabolite Fluxes Regulate White Adipose Tissue Expansion, Jessica B Felix, Aaron R Cox, Sean M Hartig

Faculty, Staff and Students Publications

White adipose tissue (WAT) depends on coordinated regulation of transcriptional and metabolic pathways to respond to whole-body energy demands. We highlight metabolites that contribute to biosynthetic reactions for WAT expansion. Recent studies have precisely defined how byproducts of carbohydrate and lipid metabolism affect physiological and endocrine functions in adipocytes. We emphasize the critical emerging roles of short-chain fatty acids (SCFAs) and tricarboxylic acid (TCA) cycle metabolites that connect lipogenesis to WAT energy balance and endocrine functions. These insights address how adipocytes use small molecules generated from central carbon metabolism to measure responses to nutritional stress.

Genetics Of Atrial Fibrillation, Jitae A Kim, Mihail G Chelu, Na Li

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained cardiac arrhythmia. In addition to traditional risk factors, it is increasingly recognized that a genetic component underlies atrial fibrillation development. This review aims to provide an overview of the genetic cause of atrial fibrillation and clinical applications, with a focus on recent developments.

RECENT FINDINGS: Genome-wide association studies have now identified around 140 genetic loci associated with atrial fibrillation. Studies into the effects of several loci and their tentative gene targets have identified novel pathways associated with atrial fibrillation development. However, further validations of causality are still needed for many …

A Blood-Based Diagnostic Test Incorporating Plasma Aβ42/40 Ratio, Apoe Proteotype, And Age Accurately Identifies Brain Amyloid Status: Findings From A Multi Cohort Validity Analysis, Tim West, Kristopher M Kirmess, Matthew R Meyer, Mary S Holubasch, Stephanie S Knapik, Yan Hu, John H Contois, Erin N Jackson, Scott E Harpstrite, Randall J Bateman, David M Holtzman, Philip B Verghese, Ilana Fogelman, Joel B Braunstein, Kevin E Yarasheski

2020-Current year OA Pubs

BACKGROUND: The development of blood-based biomarker tests that are accurate and robust for Alzheimer's disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status.

METHODS: We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic …

Expression And Regulatory Roles Of Lncrnas In G-Cimp-Low Vs G-Cimp-High Glioma: An In-Silico Analysis, Indrani Datta, Houtan Noushmehr, Chaya Brodie, Laila M. Poisson

Public Health Sciences Articles

BACKGROUND: Clinically relevant glioma subtypes, such as the glioma-CpG island methylator phenotype (G-CIMP), have been defined by epigenetics. In this study, the role of long non-coding RNAs in association with the poor-prognosis G-CMIP-low phenotype and the good-prognosis G-CMIP-high phenotype was investigated. Functional associations of lncRNAs with mRNAs and miRNAs were examined to hypothesize influencing factors of the aggressive phenotype.

METHODS: RNA-seq data on 250 samples from TCGA's Pan-Glioma study, quantified for lncRNA and mRNAs (GENCODE v28), were analyzed for differential expression between G-CIMP-low and G-CIMP-high phenotypes. Functional interpretation of the differential lncRNAs was performed by Ingenuity Pathway Analysis. Spearman rank …

Oncolytic Hsv-1 G207 Immunovirotherapy For Pediatric High-Grade Gliomas, Gregory K Friedman, Mohamed S Abdelbaki, Et Al

Open Access Publications

BACKGROUND: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue.

METHODS: We conducted a phase 1 trial of G207, which used a 3+3 design with four dose cohorts of children and adolescents with biopsy-confirmed recurrent or progressive supratentorial brain tumors. Patients underwent stereotactic placement …

Highly Accurate Chip-Based Resequencing Of Sars-Cov-2 Clinical Samples, Kendall Hoff, Xun Ding, Lucas Carter, John Duque, Ju-Yu Lin, Samantha Dung, Priyanka Singh, Jiayi Sun, Filip Crnogorac, Radha Swaminathan, Emily N. Alden, Xuechen Zhu, Ryota Shimada, Marijan Posavi, Noah Hull, Darrell L. Dinwiddie, Adam M. Halasz, Glenn Mcgall, Wei Zhou, Jeremy S. Edwards

Pediatrics Research and Scholarship

SARS-CoV-2 has infected over 128 million people worldwide, and until a vaccine is developed and widely disseminated, vigilant testing and contact tracing are the most effective ways to slow the spread of COVID-19. Typical clinical testing only confirms the presence or absence of the virus, but rather, a simple and rapid testing procedure that sequences the entire genome would be impactful and allow for tracing the spread of the virus and variants, as well as the appearance of new variants. However, traditional short read sequencing methods are time consuming and expensive. Herein, we describe a tiled genome array that we …

Proteomic Investigation Of Glyceraldehyde-Derived Intracellular Ages And Their Potential Influence On Pancreatic Ductal Cells, Lakmini Senavirathna, Cheng Ma, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

Glyceraldehyde-derived advanced glycation end products (AGEs) play an important role in the pathogenesis of many diseases including cancer. Accumulation of intracellular AGEs could stimulate cancer induction and facilitate cancer progression. We evaluated the toxic effect of glyceraldehyde-derived intracellular AGEs on normal and malignant pancreatic ductal cells by assessing the cell viability, toxicity, and oxidative stress, followed by proteomic analysis. Our functional studies showed that pancreatic cancer cells (PANC-1 and MIA PaCa-2) were more resistant to glyceraldehyde treatment compared to normal pancreatic ductal epithelial cells (HPDE), while cytotoxicity effects were observed in all cell types. Furthermore, using 13C isotopic labeled glyceraldehyde, …

Sars-Cov-2 Requires Cholesterol For Viral Entry And Pathological Syncytia Formation, David W. Sanders, Alex S. Holehouse, Et Al

Open Access Publications

Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ~6000 drugs and >30 spike variants. Together with quantitative cell biology …

A Microbiota-Directed Food Intervention For Undernourished Children, Robert Y Chen, Matthew C Hibberd, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.

METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference …

Tocilizumab In Hospitalized Patients With Severe Covid-19 Pneumonia, Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S Aziz, Nichola Cooper, Ivor S Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants …

Dorsal Anterior Cingulate Cortex Encodes The Integrated Incentive Motivational Value Of Cognitive Task Performance, Debbie M Yee, Jennifer L Crawford, Bidhan Lamichhane, Todd S Braver

2020-Current year OA Pubs

Humans can seamlessly combine value signals from diverse motivational incentives, yet it is not well understood how these signals are "bundled" in the brain to modulate cognitive control. The dorsal ACC (dACC) is theorized to integrate motivational value dimensions in the service of goal-directed action, although this hypothesis has yet to receive rigorous confirmation. In the present study, we examined the role of human dACC in motivational incentive integration. Healthy young adult men and women were scanned with fMRI while engaged in an experimental paradigm that quantifies the combined effects of liquid (e.g., juice, neutral, saltwater) and monetary incentives on …

Genetic And Non-Genetic Factors Affecting The Expression Of Covid-19-Relevant Genes In The Large Airway Epithelium, Silva Kasela, Victor E Ortega, Molly Martorella, Suresh Garudadri, Jenna Nguyen, Elizabeth Ampleford, Anu Pasanen, Srilaxmi Nerella, Kristina L Buschur, Igor Z Barjaktarevic, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Alejandro P Comellas, Christopher B Cooper, David J Couper, Gerard J Criner, Jeffrey L Curtis, Meilan K Han, Nadia N Hansel, Eric A Hoffman, Robert J Kaner, Jerry A Krishnan, Fernando J Martinez, Merry-Lynn N Mcdonald, Deborah A Meyers, Robert Paine, Stephen P Peters, Mario Castro, Loren C Denlinger, Serpil C Erzurum, John V Fahy, Elliot Israel, Nizar N Jarjour, Bruce D Levy, Xingnan Li, Wendy C Moore, Sally E Wenzel, Charles Langelier, Prescott G Woodruff, Tuuli Lappalainen, Stephanie A Christenson

Faculty, Staff and Student Publications

BACKGROUND: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression.

METHODS: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with …

Evolution Of Genetic Networks For Human Creativity, I Zwir, C Del-Val, C R Cloninger, Et Al

Open Access Publications

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and …

Optimized Polyepitope Neoantigen Dna Vaccines Elicit Neoantigen-Specific Immune Responses In Preclinical Models And In Clinical Translation, Lijin Li, Xiuli Zhang, Xiaoli Wang, Samuel W Kim, John M Herndon, Michelle K Becker-Hapak, Beatriz M Carreno, Nancy B Myers, Mark A Sturmoski, Michael D Mclellan, Christopher A Miller, Tanner M Johanns, Benjamin R Tan, Gavin P Dunn, Timothy P Fleming, Ted H Hansen, S Peter Goedegebuure, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation.

METHODS: We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer …

Usability Of Electronic Health Record-Generated Discharge Summaries: Heuristic Evaluation., Patrice Dolhonde Tremoulet, Priyanka D Shah, Alisha A Acosta, Christian W Grant, Jon T Kurtz, Peter Mounas, Michael Kirchhoff, Elizabeth Wade

College of Science & Mathematics Departmental Research

BACKGROUND: Obtaining accurate clinical information about recent acute care visits is extremely important for outpatient providers. However, documents used to communicate this information are often difficult to use. This puts patients at risk of adverse events. Elderly patients who are seen by more providers and have more care transitions are especially vulnerable.

OBJECTIVE: This study aimed to (1) identify the information about elderly patients' recent acute care visits needed to coordinate their care, (2) use this information to assess discharge summaries, and (3) provide recommendations to help improve the quality of electronic health record (EHR)-generated discharge summaries, thereby increasing patient …

Dexmedetomidine Or Propofol For Sedation In Mechanically Ventilated Adults With Sepsis, Christopher G Hughes, Patrick T Mailloux, John W Devlin, Joshua T Swan, Robert D Sanders, Antonio Anzueto, James C Jackson, Aimee S Hoskins, Brenda T Pun, Onur M Orun, Rameela Raman, Joanna L Stollings, Amy L Kiehl, Matthew S Duprey, Lan N Bui, Hollis R O'Neal, Allison Snyder, Michael A Gropper, Kalpalatha K Guntupalli, Gregg J Stashenko, Mayur B Patel, Nathan E Brummel, Timothy D Girard, Robert S Dittus, Gordon R Bernard, E Wesley Ely, Pratik P Pandharipande, Mends2 Study Investigators

Faculty, Staff and Students Publications

BACKGROUND: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.

METHODS: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale …

A Risk Assessment Tool For Resumption Of Research Activities During The Covid-19 Pandemic For Field Trials In Low Resource Settings, Suzanne M Simkovich, Victor G Davila-Roman, Lisa De Las Fuentes, Et Al.

2020-Current year OA Pubs

RATIONALE: The spread of severe acute respiratory syndrome coronavirus-2 has suspended many non-COVID-19 related research activities. Where restarting research activities is permitted, investigators need to evaluate the risks and benefits of resuming data collection and adapt procedures to minimize risk.

OBJECTIVES: In the context of the multicountry Household Air Pollution Intervention (HAPIN) trial conducted in rural, low-resource settings, we developed a framework to assess the risk of each trial activity and to guide protective measures. Our goal is to maximize the integrity of reseach aims while minimizing infection risk based on the latest scientific understanding of the virus.

METHODS: We …

Functional Interpretation Of Atad3a Variants In Neuro-Mitochondrial Phenotypes, Zheng Yie Yap, Yo Han Park, Saskia B Wortmann, Adam C Gunning, Shlomit Ezer, Sukyeong Lee, Lita Duraine, Ekkehard Wilichowski, Kate Wilson, Johannes A Mayr, Matias Wagner, Hong Li, Usha Kini, Emily Davis Black, Kristin G Monaghan, James R Lupski, Sian Ellard, Dominik S Westphal, Tamar Harel, Wan Hee Yoon

Faculty, Staff and Students Publications

BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

METHODS: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3a Gal4 …

Proteogenomic And Metabolomic Characterization Of Human Glioblastoma, Liang-Bo Wang, Alla Karpova, Marina A Gritsenko, Jennifer E Kyle, Song Cao, Yize Li, Dmitry Rykunov, Antonio Colaprico, Joseph H Rothstein, Runyu Hong, Vasileios Stathias, Macintosh Cornwell, Francesca Petralia, Yige Wu, Boris Reva, Karsten Krug, Pietro Pugliese, Emily Kawaler, Lindsey K Olsen, Wen-Wei Liang, Xiaoyu Song, Yongchao Dou, Michael C Wendl, Wagma Caravan, Wenke Liu, Daniel Cui Zhou, Jiayi Ji, Chia-Feng Tsai, Vladislav A Petyuk, Jamie Moon, Weiping Ma, Rosalie K Chu, Karl K Weitz, Ronald J Moore, Matthew E Monroe, Rui Zhao, Xiaolu Yang, Seungyeul Yoo, Azra Krek, Alexis Demopoulos, Houxiang Zhu, Matthew A Wyczalkowski, Joshua F Mcmichael, Brittany L Henderson, Caleb M Lindgren, Hannah Boekweg, Shuangjia Lu, Jessika Baral, Lijun Yao, Kelly G Stratton, Lisa M Bramer, Erika Zink, Sneha P Couvillion, Kent J Bloodsworth, Shankha Satpathy, Weiva Sieh, Simina M Boca, Stephan Schürer, Feng Chen, Maciej Wiznerowicz, Karen A Ketchum, Emily S Boja, Christopher R Kinsinger, Ana I Robles, Tara Hiltke, Mathangi Thiagarajan, Alexey I Nesvizhskii, Bing Zhang, D R Mani, Michele Ceccarelli, Xi S Chen, Sandra L Cottingham, Qing Kay Li, Albert H Kim, David Fenyö, Kelly V Ruggles, Henry Rodriguez, Mehdi Mesri, Samuel H Payne, Adam C Resnick, Pei Wang, Richard D Smith, Antonio Iavarone, Milan G Chheda, Jill S Barnholtz-Sloan, Karin D Rodland, Tao Liu, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM …

Pfmfr3: A Multidrug-Resistant Modulator In Plasmodium Falciparum, Frances Rocamora, Purva Gupta, Eva S Istvan, Madeline R Luth, Emma F Carpenter, Krittikorn Kümpornsin, Erika Sasaki, Jaeson Calla, Nimisha Mittal, Krypton Carolino, Edward Owen, Manuel Llinás, Sabine Ottilie, Daniel E Goldberg, Marcus C S Lee, Elizabeth A Winzeler

2020-Current year OA Pubs

In malaria, chemical genetics is a powerful method for assigning function to uncharacterized genes. MMV085203 and GNF-Pf-3600 are two structurally related napthoquinone phenotypic screening hits that kill both blood- and sexual-stage

Obstructive Sleep Apnea And Dementia-Common Gene Associations Through Network-Based Identification Of Common Driver Genes, Hyun-Hwan Jeong, Arvind Chandrakantan, Adam C Adler

Faculty, Staff and Students Publications

BACKGROUND: Obstructive Sleep Apnea (OSA) occurs in 7% of the adult population. The relationship between neurodegenerative diseases such as dementia and sleep disorders have long attracted clinical attention; however, no comprehensive data exists elucidating common gene expression between the two diseases. The objective of this study was to (1) demonstrate the practicability and feasibility of utilizing a systems biology approach called network-based identification of common driver genes (NICD) to identify common genomic features between two associated diseases and (2) utilize this approach to identify genes associated with both OSA and dementia.

METHODS: This study utilized 2 public databases (PCNet, DisGeNET) …

Noninvasive Hemoglobin Level Prediction In A Mobile Phone Environment: State Of The Art Review And Recommendations., Kamrul Hasan Md, Masanul Aziz Md, Ishrak Islam Zarif Md, Mahmudul Hasan, Mma Hashem, Shion Guha Phd, Richard R Love, Sheikh Ahamed

Health Services and Informatics Research

BACKGROUND: There is worldwide demand for an affordable hemoglobin measurement solution, which is a particularly urgent need in developing countries. The smartphone, which is the most penetrated device in both rich and resource-constrained areas, would be a suitable choice to build this solution. Consideration of a smartphone-based hemoglobin measurement tool is compelling because of the possibilities for an affordable, portable, and reliable point-of-care tool by leveraging the camera capacity, computing power, and lighting sources of the smartphone. However, several smartphone-based hemoglobin measurement techniques have encountered significant challenges with respect to data collection methods, sensor selection, signal analysis processes, and machine-learning …

Dietary Intake Is Associated With Neuropsychological Impairment In Women With Hiv, Leah H. Rubin, Deborah R. Gustafson, Lakshmi Warrior, Lila Sheira, Kathryn C. Fitzgerald, Raha Dastgheyb, Kathleen M. Weber, Phyllis C. Tien, Audrey French, Amanda B. Spence, Anjali Sharma, Dionna W. Williams, Cory J. White, Eric C. Seaberg, Edward A. Frongillo Jr., Sheri D. Weiser

Faculty Publications

Background

Diet is a modifiable risk factor that may influence cognition in people with HIV.

Objectives

We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.

Methods

An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = …

The Structure, Function And Evolution Of A Complete Human Chromosome 8, Glennis A Logsdon, Milinn Kremitzki, Tina A Graves-Lindsay, Et Al

Open Access Publications

The complete assembly of each human chromosome is essential for understanding human biology and evolution

Structure, Function And Inhibition Of Critical Protein-Protein Interactions Involving Mixed Lineage Leukemia 1 And Its Fusion Oncoproteins, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master regulator for transcription of important genes (e.g., Hox genes) for embryonic development and hematopoiesis. However, it is largely dispensable in matured cells. Dysregulation of MLL1 leads to overexpression of certain Hox genes and eventually leukemia initiation. Chromosome translocations involving MLL1 cause ~ 75% of acute leukemia in infants and 5-10% in children and adults with a poor prognosis. Targeted therapeutics against oncogenic fusion MLL1 (onco-MLL1) are therefore needed. Onco-MLL1 consists of the N-terminal DNA-interacting domains …