Digital Commons Network^™

Unraveling Posttranslational Modification Complexity: Advances In Quantitative Histone Proteoform Mass Spectrometry, Karl F Poncha, Alyssa T Paparella, Nicolas L Young

Faculty, Staff and Students Publications

Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM …

Clinical Factors And Diagnoses Associated With Inappropriate Urine Culture Ordering In Primary Care, Marissa Valentine-King, Barbara W Trautner, Michael A Hansen, Roger Zoorob, Lisa C K Danek, Kenneth Muldrew, Forrest Hudson, Robert L Atmar, Larissa Grigoryan

Faculty, Staff and Students Publications

Objective: Evaluate the prevalence and risk factors for inappropriately ordered urine cultures in primary care.

Design: Cross-sectional study using chart reviews.

Setting: Two primary care, safety-net clinics in Houston, Texas.

Patients: Non-pregnant adults without a urinary catheter who had a urine culture and a primary care visit between 11/2018 and 3/2020.

Methods: We classified patients lacking physician documentation of the following symptoms as having an inappropriately ordered urine culture: dysuria, frequency, urgency, hematuria, fever, chills, costovertebral angle tenderness, nephrolithiasis, and pain (suprapubic, pelvic, or flank). We extracted patient demographics, visit-related diagnostic codes, past medical history, and urine culture results. Diagnostic …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Platelet Extravasation In The Microvasculature: An Under-Appreciated Role For Platelets, Justin A Courson, Vahid Afshar-Kharghan, Alan R Burns, Rolando E Rumbaut

Faculty, Staff and Students Publications

In recent years, evidence has accumulated highlighting the presence and role of platelet extravasation - wherein platelets accumulate in tissue parenchyma - at a variety of sites throughout the body. While platelets are traditionally known for their roles in hemostasis and thrombosis, it is evident that platelets are potent mediators of inflammation across an array of physiological and pathological contexts. While anucleate and small in size, platelets contain a rich diversity of molecules in their granules capable of modulating cell proliferation, tissue repair, and a host of immune responses. There is growing evidence that platelet extravasation out of the vascular …

Evolving Burden Of Metabolic Dysfunction-Associated Steatotic Liver Disease And Its Complications In A Us Nationwide Healthcare System, Basim Ali, Ronald Samuel, Jennifer R Kramer, Liang Li, Xian Yu, Yumei Cao, Roxanne Desiderio, George Cholankeril, Steven M Asch, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health problem. Measuring the burden of cirrhosis and its complications in people with MASLD is important to inform health care delivery.

Methods: We aimed to quantify the changes in the burden of MASLD-related cirrhosis and hepatocellular carcinoma (HCC) in a nationwide U.S. healthcare system. We used data from the Veterans Health Administration to examine temporal trends between 2010 and 2021 in the annual incidence and prevalence of cirrhosis and HCC in a large cohort of patients with MASLD, and to compare them to those in patients with hepatitis C …

Survodutide For Treatment Of Obesity: Baseline Characteristics Of Participants In A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial (Synchronize™-1), Carel W Le Roux, Sean Wharton, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide, a novel glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor dual agonist, elicited significant weight loss in a phase 2 trial in individuals with obesity without type 2 diabetes (T2D). Two multinational phase 3 trials are investigating survodutide for obesity management in individuals with or without T2D. We report the baseline characteristics of participants in the SYNCHRONIZE-1 trial in adults with obesity without T2D (ClinicalTrials.gov: NCT06066515).

Materials and methods: Participants aged ≥18 years with BMI ≥30 or ≥27 kg/m2 with ≥1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 …

Gould Edu: Cluster-Randomized Trial Of An Educational Intervention To Improve Lipid-Lowering Guideline Adherence, Christopher P Cannon, Christie M Ballantyne, Deepak L Bhatt, James A De Lemos, Qi Gao, Naishu Kui, Robert S Rosenson, Katherine E Mues, Jason Exter, Shushama Alam, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Background: Adherence to lipid-lowering therapy (LLT) guidelines is suboptimal, leading to poor achievement of low-density lipoprotein cholesterol (LDL-C) goals and elevated risk for atherosclerotic cardiovascular disease (ASCVD) events.

Objectives: The purpose of this study was to determine whether an educational intervention targeting physicians improves optimization of LLT over 1 year for patients with ASCVD.

Methods: GOULD (Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management) EDU (Education) was a 1-year extension in a subset of sites in the GOULD prospective, observational registry of United States patients with ASCVD. In a cluster-randomized, stepped-wedge design, sites were randomized to …

Esophageal Myotomy And Risk Of Esophageal Cancer And Mortality In Achalasia: Real-World Cohort Study, Fouad Jaber, Mohamad Ali Ibrahim, Mohammed Jaber, Youssef Soliman, Mai A Khalaf, Tara Keihanian, Fares Ayoub, Mohamed O Othman, Salmaan Jawaid

Faculty, Staff and Students Publications

Background and study aims: Achalasia is associated with increased risk of esophageal cancer, particularly squamous cell carcinoma. Although esophageal myotomy improves dysphagia, its impact on cancer risk and mortality remains unclear.

Patients and methods: We conducted a retrospective cohort study using the TriNetX research network, including adults (≥ 18 years) with achalasia confirmed by esophageal manometry. Patients were categorized based on treatment of those undergoing esophageal myotomy (peroral endoscopic myotomy [POEM] or laparoscopic Heller myotomy [LHM]) and those managed without myotomy. Patients with prior esophagectomy or malignancies associated with increased esophageal cancer risk were excluded. The primary outcome was incident …

Findings And Recommendations From The State Of The Art (Sota) Conference On Nursing Research To Improve Veteran Outcomes, Amelia E Schlak, Sarah Krein, Laura A Petersen, David Atkins, Catherine Battaglia, Elizabeth Burkhart, Renee Colsch, Marguerite Daus, Heather Gilmartin, Nipa Kamdar, Melissa Knox, Ann Kutney-Lee, Christine M Olney, Kathryn Rugen, Tracy Weistreich, Sheila Cox Sullivan, On Behalf The Nursing Sota Planning Committee

Faculty, Staff and Students Publications

The Veterans Health Administration (VHA), the largest employer of nurses in the United States, has more than 120,000 nursing personnel providing care to over 9 million Veterans across diverse settings. Despite nursing's central role in delivering and sustaining care, research on strengthening the nursing workforce and optimizing nursing practice has remained underdeveloped in VHA. To address this gap, VHA's Office of Research and Development, in partnership with the Office of Nursing Services, convened a State of the Art (SOTA) conference in November 2023 focused on nursing. The Nursing SOTA brought together nurses, researchers, operational leaders, and other stakeholders to review …

Relationship Between Number Of Assigned Patients And Rn Time To Administer Medications During The Peak-Time Medication Pass, Chase S Eck, Melissa K Knox, Paras D Mehta, Christine Yang, Laura A Petersen

Faculty, Staff and Students Publications

Background: Inpatient nurse staffing affects patient outcomes. Less is known about the mechanism of this relationship and how lower overall staffing in a unit affects individual RN activities at the bedside.

Objectives: Estimate the relationship between the number of patients assigned to an RN and time spent on medication administration at the peak-time medication pass (PTM), a common nursing task.

Research design: Estimate the association using multivariable linear regression to adjust for patient severity and staff and unit fixed effects.

Subjects: All 9272 RNs administering medications during the PTM on 243 inpatient units in 113 VHA hospitals in 2019.

Measures: …

Using Medication Pass Analysis To Examine Longitudinal Changes In Va Inpatient Nurse Staffing And Workload Before And Through The Covid-19 Pandemic: 2019-2022, Melissa K Knox, Chase S Eck, Lynette Dorsey, Paras D Mehta, Christine Yang, Laura A Petersen

Faculty, Staff and Students Publications

Background: The COVID-19 pandemic resulted in extended disruption to the health care system. National-level data-driven comparisons of inpatient nurse staffing and workload before and during the pandemic have been limited.

Objectives: Assess the extent to which registered nurse (RN) staffing and workload changed from prepandemic levels in a national integrated health care system.

Research design: Longitudinal descriptive analysis. Medication pass analysis using bar code medication administration data for the peak-time medication pass (PTM) assessing year-over-year changes from 2019 to 2022. To assess significance of year-over-year changes in means we used the Welch 2-sample t test.

Subjects: Staff (N=42,999) administering PTM …

Long Covid And Cardiovascular Diseases Among U.S. Adults: Results From The U.S. Medical Expenditure Panel Survey, Geoffrey Y Zhang, John C Lin, Dang Nguyen, Sameed Ahmed M Khatana, Thomas P Giordano

Faculty, Staff and Students Publications

Objective: Long COVID is associated with persistent symptoms including cardiovascular complications; however, the epidemiology and directionality of this association remain unclear.

Methods: Utilizing a retrospective cohort study design with cross-sectional analyses, 8,332 respondents aged 18 and older from the 2022 Medical Expenditure Panel Survey (MEPS) who had a prior COVID-19 infection, were analyzed to determine the temporal association between long COVID and cardiovascular disease (CVD), modeling each as both outcome and exposure in separate analyses.

Results: Long COVID was associated with any CVD diagnosis (OR 1.37; 95% CI: 1.05-1.80), specifically angina (OR 1.81; 95% CI: 1.18-2.77) and myocardial infarction (OR …

Healthcare Transition In Spina Bifida: A National Mixed Method Study, Betsy Hopson, Kathy H Huen, Molly B Richardson, Rhonda G Cady, Jennifer T Queally, Judy Thibadeau, Ellen Fremion

Faculty, Staff and Students Publications

Introduction: Adolescents and young adults (AYA) with spina bifida (SB) face substantial challenges during the transition from pediatric to adult healthcare, including fragmented systems, limited adult provider availability, and gaps in self-management readiness. Despite national guidelines, little is known about how transition practices are implemented across the Spina Bifida Association (SBA) Clinical Care Partner (CCP) network. This study examined clinician perspectives on current practices, barriers, facilitators, and definitions of successful healthcare transition (HCT).

Methods: Using an explanatory sequential mixed methods design, we first conducted a 47-item survey with clinicians from SBA CCP clinics (n = 20/32; 62.5 % response rate). …

Safety And Efficacy Of Vadadustat Versus Darbepoetin Alfa For Chronic Kidney Disease-Related Anemia In Patients Receiving Dialysis By Baseline Erythropoiesis-Stimulating Agent Dose, Alan Jardine, Steven K Burke, Wenli Luo, Todd Minga, Mark J Sarnak, Wolfgang C Winkelmayer, Rajiv Agarwal, Glenn M Chertow, Kai-Uwe Eckardt, Mark J Koury

Faculty, Staff and Students Publications

Introduction: Erythropoiesis-stimulating agents (ESAs) and iron supplementation are standard treatments for chronic kidney disease (CKD)-related anemia. Targeting higher hemoglobin values in CKD increases cardiovascular risk. Whether the increased risk is from higher ESA doses or higher hemoglobin levels is uncertain, but alternative therapies are sought for patients requiring high ESA doses. Phase 3 INNO2VATE trials in patients with dialysis-dependent CKD (DD-CKD) demonstrated vadadustat's noninferiority compared with darbepoetin alfa. To determine vadadustat's potential to treat anemia, including in patients requiring high ESA doses, its safety and efficacy were compared with those of darbepoetin alfa across prespecified baseline ESA dose subgroups in …

Ptpn1 Regulation Via Ybx1-Ptbp1 Interaction Promotes Fibroblast Activation And Fibrotic Remodeling In The Lung, Huibing Liu, Cong Xia, Yingying Zhang, Yulong Gan, Lianhui Cheng, Xuqian Wang, Airu Chang, Wenyu Zhao, Bin Li, Yaxuan Wang, Yajun Li, Ivan Rosas, Juntang Yang, Guoying Yu, Lan Wang

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial pneumonia of unknown etiology. Its pathogenesis involves complex multicellular interactions and signaling pathways, with fibroblast-to-myofibroblast transition (FMT) being critical for fibrogenesis. Although the transcription factor Y-box binding protein 1 (YBX1) regulates processes such as cell proliferation, transcription, translation, and DNA repair, its role in IPF remains undefined. Here, we demonstrate that YBX1 overexpression significantly promotes transforming growth factor-β1 (TGF-β1)-induced pulmonary FMT, leading to substantially increased extracellular matrix (ECM) deposition in primary human (PHLFs) and mouse (PMLFs) lung fibroblasts. Conversely, YBX1 inhibition markedly suppresses TGF-β1-driven aberrant fibroblast migration and activation. Mechanistically, YBX1 …

A Practical Approach To The Management Of Percutaneous Coronary Intervention Complications, Tanawat Attachaipanich, Hafeez Ul Hassan Virk, Muzamil Khawaja, Mahboob Alam, Ravi S Hira, Jacob A Doll, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Introduction: Despite advances in stent design, pharmacotherapy, and procedural techniques that have improved percutaneous coronary intervention (PCI) outcomes and reduced PCI-related complications, these events still occur and are associated with adverse outcomes. Moreover, complex PCI procedures, which predispose to increased risk of complications, are increasingly performed. Understanding risk factors, underlying mechanisms, evidence-based management, and preventive strategies are essential to optimize procedural outcomes. This review aims to summarize current evidence and highlight gaps in knowledge related to PCI-associated complications.

Methods: This narrative review used a focused PubMed search through October 2025, prioritizing randomized trials, large observational studies, guidelines, and consensus statements. …

The ‘Obesity Paradox’ In Patients Undergoing Transcatheter Aortic Valve Implantation. A Specialized Narrative Review, Johao Escobar, Iqra Riaz, Muzamil Khawaja, Hafeez Ul Hassan Virk, Joshua Hahn, Fu''Ad Al-Azzam, Zhen Wang, Mahboob Alam, Markus Strauss, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Obesity has long been identified as a noteworthy risk factor for cardiovascular diseases, including aortic stenosis. Nevertheless, an unexplained phenomenon known as the obesity paradox has arisen in the context of transcatheter aortic valve implantation (TAVI), inquiring conventional beliefs. The obesity paradox refers to better clinical outcomes observed in obese individuals undergoing TAVI. These include reduced all-cause mortality, lower rates of procedural complications, and improved long-term survival rates compared to their lean counterparts. Several theories have been proposed to explain the obesity paradox in TAVI. One of the most popular is the adipose tissue-mediated cardioprotective effect hypothesis. It is known …

Duration Of Antimicrobial Therapy In Cardiovascular Implantable Electronic Device Associated Systemic Infections: A Retrospective Analysis, Emily Y Xiao, Patrick T Lynch, Sarwat Khalil, Derrick A Draeger, Alexandra M Lewis, Faiz M Baqai, Mihail G Chelu, M Rizwan Sohail

Faculty, Staff and Students Publications

Background: While the need for complete device removal is well-established for cardiovascular implantable electronic device (CIED) infections, there is insufficient evidence on the optimal duration of antimicrobial therapy.

Objectives: To examine how antimicrobial duration affects clinical outcomes of patients presenting with CIED-associated bacteremia and lead endocarditis.

Design: This is a retrospective cohort study conducted at a quaternary care hospital in Houston, TX, USA.

Methods: Patients who underwent device removal for a primary indication of bacteremia or lead endocarditis over a 10-year period were stratified by prescribed duration of antibiotics as ⩽2 weeks or >2 weeks post-extraction. Measured outcomes included all-cause …

Mindful Diagnostics In Culture-Negative Endocarditis: Early Noninvasive Diagnosis Of Tropheryma Whipplei By Plasma Microbial Cell-Free Dna, Ashita Jain, Sarwat Khalil, Muhammad R Sohail, Laura C Lelenwa, Enrique Garcia-Sayan, Kenneth K Liao, Ahmed Hamdi, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

Tropheryma whipplei was identified by plasma microbial cell-free DNA sequencing within 4 days in severe culture-negative endocarditis after antibiotics had already been started. The result supported earlier diagnostic clarification and antimicrobial de-escalation before valve pathology was available, illustrating a practical diagnostic-stewardship role for noninvasive sequencing in high-acuity endocarditis.

Midterm Outcomes Of The Self-Expanding Navitor Transcatheter Heart Valve: A Systematic Review And Meta-Analysis., Sahar Samimi, Chloe Kharsa, Mangesh Kritya, Joe Aoun, Syed Zaid, Nadeen N Faza, Stephen H Little, Neal S Kleiman, Michael J Reardon, Sachin S Goel

Faculty, Staff and Students Publications

• A 19-study meta-analysis (7743 patients) found high Navitor technical/device success.
• ≥Moderate PVL was low: 1.3% at 30 days and 0.6% at 1 year.
• Pacemaker implantation was 16.7% at 30 days and 20.4% at 1 year.
• Thirty-day outcomes were favorable: all-cause mortality 1.5% and stroke 1.7%.

Editorial: New Insights On Vascular And Metabolic Diabetic Complications, Hua Mao, John D Imig, Ricardo Espinosa-Tanguma

Faculty, Staff and Students Publications

No abstract provided.

Comparing Rotational Thromboelastometry And Standard Coagulation Assays For Predicting Intraoperative Bleeding In Pediatric Liver Transplantation, Kirby Deshotels, Trung Nguyen, Jun Teruya, Muhammed Umair M Mian, Kelby Fuller, Sanjiv Harpavat, Anna Banc-Husu, Amir Navaei, John Goss, Moreshwar Desai, Arun Saini

Faculty, Staff and Students Publications

Background: Utility of preoperative rotational thromboelastometry (ROTEM) over standard coagulation assays (SCAs) in predicting intraoperative bleeding during orthotopic liver transplantation (OLT) in children with liver failure (LF) remains unclear.

Methods: In this single-center retrospective cohort of pediatric OLT recipients, we compared the predictive values of preoperative ROTEM parameters (intrinsic pathway (INTEM) maximum clot firmness (MCF), extrinsic pathway (EXTEM) clotting time (CT), INTEM CT, and fibrinogen-based (FIBTEM) MCF) and the corresponding SCAs (platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and fibrinogen level, respectively) for significant intraoperative bleeding (blood loss of > 22 mL/kg; i.e., ≥ 85th percentile for …

Definitions Of Arginine Availability: A Critical Metabolic Marker Of Physiological Processes, Mustafa Tosur, Farook Jahoor, Ashok Balasubramanyam

Faculty, Staff and Students Publications

No abstract provided.

Modulation Of Corneal Sensory Processing And Pain Responses By Dry Eye And Corneal Wounding, Ebru Yaman, Yangluowa Qu, Kaylin C Arpaia, Fairouz Elsaeidi, Uma Lakshmi Balakrishnan, Lance He, Henry Skrehot, Jehan Alam, Rui Chen, Mary Ann Stepp, Cintia S De Paiva, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Background: Dry eye disease (DED) is a multifactorial disorder of the ocular surface in which tear film instability, epithelial barrier disruption, and neurosensory dysfunction contribute to symptom generation. Although several contributing factors have been identified, how different forms of ocular surface stress affect sensory pathways and behavioral responses remains unclear.

Purpose: This study aimed to evaluate corneal barrier function, sensory responses, and pain-related behaviors across acute and chronic dry eye and corneal injury models, and to assess stimulus-specific responses associated with TRPV1 and TRPM8 mediated pathways.

Methods: Female C57BL/6 J wild type and Mmp9KO mice were evaluated in acute desiccating …

Strategies And Challenges For The Recruitment Of Young Healthy Participants In The Dietary Approaches To Longevity And Health (Dial Health) Pilot Trial, Hannah E Cabre, Courtney M Peterson, Gareth R Dutton, Kimberly L Drews, Stephanie T Broyles, Robert Dubin, Laura Q Rogers, Catherine Champagne, Dennis T Villareal, Daniel S Hsia, Leanne M Redman, Corby K Martin

Faculty, Staff and Students Publications

Background: Understanding the impact of nutrition on human aging requires long-term trials in young, healthy, unmedicated adults. As part of the Dietary Approaches for Longevity and Health (DiAL Health) pilot project, we evaluated strategies for recruiting this population for aging-related dietary intervention studies.

Methods: We analyzed recruitment costs to enroll 70 participants (ages 25-49, BMI 22.0-29.9 kg/m2) across two DiAL Health sites and used NHANES data (2017-March 2020) to estimate the proportion of U.S. adults meeting partial trial eligibility. Additionally, a formative study surveyed 492 U.S. adults (≥18 years) to assess interest in aging-focused dietary trials.

Results: Of 2049 applicants …

Differences In Gene Expression May Contribute To The Racial Differences In The Risk Of Masld, Ivan P Gorlov, Olga Y Gorlova, Aaron P Thrift

Faculty, Staff and Students Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), exhibits marked racial disparities in incidence, progression, and clinical outcomes. While diet, lifestyle, and socioeconomic factors have been shown to influence these disparities, biological mechanisms underlying racial differences in MASLD risk remain poorly understood. We hypothesized that race-associated variation in hepatic gene expression may contribute to differential susceptibility and progression of MASLD. To test this hypothesis, we analyzed publicly available gene expression data from liver biopsies obtained from over 300 Black and White individuals undergoing bariatric surgery. Gene expression profiles were compared across four histological stages: …

Sewers To Solutions: A Guide To Wastewater Pathogen Monitoring, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Wastewater-based epidemiology (WBE) is the analysis of wastewater to detect pathogen levels or activity for public health awareness or action. Pioneered in the 1940s, WBE underwent a resurgence during the COVID-19 pandemic, providing important information about number of cases, outbreaks, and seasonal impact. With advancements in detection technologies and growing interest in environmental surveillance, WBE is poised to become a standard practice in public health monitoring. Here, we provide an overview of the current state of the art of pathogen WBE, including methods of molecular detection, analysis of wastewater data, real-world applications and programs, public health interventions, and benefits and …

Editorial: Advances In Phage Applications: Deciphering Phage Biological And Ecological Mechanisms Through Metagenomics, Tasha M Santiago-Rodriguez, Gary A Toranzos

Faculty, Staff and Students Publications

No abstract provided.

Identification Of Cand1 As A Dna-Dependent Protein Kinase-Regulated Coactivator Of Androgen Receptor And The Arv7 Splice Variant, Ross A Hamilton, Basil Paul, Ping Yi, Kimal Rajapakshe, Anil K Panigrahi, Sandra L Grimm, Cristian Coarfa, Anna Malovannaya, Nancy L Weigel, David M Lonard, Charles E Foulds

Faculty, Staff and Students Publications

ARv7, the most prevalent androgen receptor (AR) variant in castration-resistant prostate cancer, lacks the ligand binding domain (LBD), rendering it resistant to LBD-targeted therapies. Identifying new therapeutic targets requires defining the coregulators and associated regulatory enzymes that govern AR and ARv7 transcriptional activity. Here, we have developed a cell-free DNA pulldown assay employing androgen response elements (AREs) to isolate and characterize the AR- and ARv7-associated coregulator complexes formed on DNA. Mass spectrometry analyses of ARE DNA pulldowns revealed previously unrecognized AR and ARv7 associating coregulators, such as cullin-associated NEDD8-dissociated protein 1 (CAND1), in addition to previously known coregulators. ARv7 showed …

Genomic And Structural Analysis Of Major Antigenic Proteins’ Variability In The Human Relapsing Fever Spirochete Borrelia Persica, Dor Shwartz, Yaarit Nachum-Biala, Reinhard K Straubinger, Ofir Segev, Asaf Levy, Job E Lopez, Gad Baneth

Faculty, Staff and Students Publications

Antigenic variation enables immune evasion of pathogens, yet the mechanisms for the rapid change in their antigens without loss of structural and functional features are not fully known. Tick-borne relapsing fever (TBRF) spirochetes of the genus Borrelia can be used as a model because their variable major proteins (Vmps) drive antigenic variation followed by recurrent waves of bacteremia. In this study we generated the genome of Borrelia persica LMU-C01 and evaluated Vmp structure across relapsing fever Borrelia species. Borrelia persica was found to have a genome of 1.7Mb with one linear chromosome, 12 linear and one circular plasmids. Telomeric hairpin …