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Articles 2911 - 2940 of 96336
Full-Text Articles in Entire DC Network
The Effects Of Ovine-Derived Reinforced Tissue Matrix Surrounding Silicone-Based Implants In A Rat Prepectoral Reconstruction Model, Sai L Pinni, Cameron Martin, Nicholas Fadell, Xiaochao Xia, Evan Marsh, Lauren Schellhardt, Xiaowei Li, Matthew D Wood, Justin M Sacks
The Effects Of Ovine-Derived Reinforced Tissue Matrix Surrounding Silicone-Based Implants In A Rat Prepectoral Reconstruction Model, Sai L Pinni, Cameron Martin, Nicholas Fadell, Xiaochao Xia, Evan Marsh, Lauren Schellhardt, Xiaowei Li, Matthew D Wood, Justin M Sacks
2020-Current year OA Pubs
Silicone-based implants have been widely used in breast reconstruction but have also been associated with poorly understood complications, including pathologic foreign body responses such as capsular contracture. In this study, we leveraged 3D-printing technology to generate silicone-based implants in a novel, anatomically relevant, prepectoral rat model. We used this model to evaluate the response to an extracellular matrix-based product: ovine-derived reinforced tissue matrix (RTM). Two-piece negative molds were developed through computer-aided design and 3D-printed. The molds were filled with various polydimethylsiloxane mixtures and dip-coated to fabricate implants. Implant material characterization revealed that the implants retained the original 3D-printed mold shape …
Defining The Heterogeneous Molecular Landscape Of Lung Cancer Cell Responses To Epigenetic Inhibition, Chuwei Lin, Catherine M Sniezek, Christopher D Mcgann, Rashmi Karki, Ross M Giglio, Benjamin A Garcia, José L Mcfaline-Figueroa, Devin K Schweppe
Defining The Heterogeneous Molecular Landscape Of Lung Cancer Cell Responses To Epigenetic Inhibition, Chuwei Lin, Catherine M Sniezek, Christopher D Mcgann, Rashmi Karki, Ross M Giglio, Benjamin A Garcia, José L Mcfaline-Figueroa, Devin K Schweppe
2020-Current year OA Pubs
Epigenetic inhibitors exhibit powerful antiproliferative and anticancer activities. However, cellular responses to small-molecule epigenetic inhibition are heterogeneous and dependent on factors such as the genetic background and metabolic state of cells, as well as on-/off-target engagement of individual small-molecule compounds. The molecular study of the extent of this heterogeneity often measures changes in a single cell line. To more comprehensively profile the effects of small-molecule perturbations and their influence on heterogeneous cellular responses, we present a molecular resource based on the quantification of chromatin, proteome, and transcriptome remodeling due to histone deacetylase inhibitors (HDACi) in non-isogenic cell lines. Through quantitative …
N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg
N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg
Marcus Institute of Integrative Health Faculty Papers
INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.
METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of …
Race And Patient-Physician Communication On Blood Pressure Management: Helping Improve Care, Samar A. Nasser, Ashley Pender, Ayan Ali, Kardie Tobb, Keith C. Ferdinand
Race And Patient-Physician Communication On Blood Pressure Management: Helping Improve Care, Samar A. Nasser, Ashley Pender, Ayan Ali, Kardie Tobb, Keith C. Ferdinand
Division of Cardiology Faculty Papers
PURPOSE OF REVIEW: To provide an overview of the relationship of race and ethnicity and patient-physician/clinician communication on blood pressure management.
RECENT FINDINGS: The suboptimal interactions experienced by patients from underrepresented racial and ethnic populations may be improved by enriching relationships among clinicians, population health scientists, policymakers, and community members/leaders. Current care communication and policies for managing hypertension appear to be insufficient. Implementing and disseminating effective strategies to efficiently improve the quality of hypertension care and recognize social determinants of health among minoritized populations is intertwined with enhanced communication.
SUMMARY: Approaches such as self-affirmation—encouraging patients to reflect on their strengths …
Surviving Staten Island: Black Women’S Narratives Of Resilience, Motherwork, And Embodied Trauma, Jazmin Rivera
Surviving Staten Island: Black Women’S Narratives Of Resilience, Motherwork, And Embodied Trauma, Jazmin Rivera
Student Theses
This oral history dissertation centers the experiences of six Black women who had formative experiences navigating hostile school and community-based settings on Staten Island during the 1970s, 1980s, and early 1990s. Guided by a conceptual framework that draws on Black orality, Black feminist thought, and endarkened feminist epistemology, this study demonstrates how Black women were required to cross geographic and social boundaries to survive hostile conditions in Staten Island communities and schools. Findings from this study highlight Black women’s use of community cultural wealth to inform their survival strategies and resilience. At the same time, their experiences indicate the potential …
Novel Retinal Biomarker Development In Early Alzheimer’S Disease, Swetha Ravichandran
Novel Retinal Biomarker Development In Early Alzheimer’S Disease, Swetha Ravichandran
ETDs from 2020-2029
Alzheimer’s disease is a progressive neurodegenerative disorder that causes damage to the neurons that are present in the brain. Progress in the management and treatment of AD is limited by lack of early diagnostics, which are critical to the development of effective therapies. It is therefore critical to develop non-invasive/cost efficient biomarkers to aid in early diagnosis and interventions to prevent or delay dementia onset. While Positron Emission Tomography (PET) and cerebrospinal fluid assessment have greatest utility, they are not routinely used because they are expensive and invasive, respectively. Retinal imaging offers a promising, low-cost, and non-invasive avenue for detecting …
Early Life Stress Mediates Cardiovascular Disease Risk Through Csf1r And Increases Risk Of Lupus Through Mature B-Cells, Cailin Elizabeth Kellum
Early Life Stress Mediates Cardiovascular Disease Risk Through Csf1r And Increases Risk Of Lupus Through Mature B-Cells, Cailin Elizabeth Kellum
ETDs from 2020-2029
The term Early Life Stress (ELS) encompasses traumatic events occurring before the age of 18 such as physical abuse, verbal abuse, household dysfunctions, sexual abuse, childhood neglect, child maltreatment, and adverse childhood experiences. The traumatic psychological and physical experiences in early life are widely known to cause enduring effects on mental and physical health in adulthood. Of note, individuals with ELS have adverse health outcomes earlier in adulthood and with more severity such as in the case of Systemic Lupus Erythematous (SLE), an autoimmune disease. The risk for autoimmunity and cardiovascular disease (CVD) increases with ELS exposure and CVD is …
Awareness And Knowledge Of Juvenile Idiopathic Arthritis Among Orthodontic And Oral And Maxillofacial Surgery Specialties In The United States., Kavita Nayar
ETDs from 2020-2029
Introduction: Juvenile Idiopathic Arthritis (JIA) is the most common chronic pediatric arthritis, frequently involving the temporomandibular joint (TMJ) and resulting in facial growth disturbances, functional impairment, and complex multidisciplinary treatment needs. Despite its clinical relevance, limited awareness and inconsistent management strategies exist among specialists who are involved in the care of these patients including orthodontists, oral and maxillofacial surgeons and rheumatologists. This study aimed to evaluate the understanding, knowledge and interdisciplinary management practices between board-certified orthodontists and oral and maxillofacial surgeons (OMSs) across the United States regarding JIA. Materials and Methods: A cross-sectional survey was distributed electronically via Qualtrics to …
Lmod1 Modulates Neointimal Lesion Size After Vessel Injury And Stabilizes Smooth Muscle Cell Gene Regulatory Networks During Atherogenic Stress, Sara Wennersten
Lmod1 Modulates Neointimal Lesion Size After Vessel Injury And Stabilizes Smooth Muscle Cell Gene Regulatory Networks During Atherogenic Stress, Sara Wennersten
ETDs from 2020-2029
Phenotypic switching of smooth muscle cells (SMCs) from a contractile to a synthetic state underlies the pathogenesis of several cardiovascular disease (CVD) pathologies, including restenosis and atherosclerosis. Leiomodin 1 (LMOD1), an SMC-enriched actin-binding protein, has been previously found to regulate SMC phenotypic modulation in vitro. However, its contribution to CVD development and progression, along with its influence on gene regulatory networks (GRNs) that inform underlying responses to stress, remains incompletely defined. Here, I combine a mouse injury model, bulk RNA sequencing, and GRN inference to define how reduced LMOD1 expression perturbs SMC physiology during vascular wall remodeling and lipid stress. …
Psychosocial Outcomes In Adults With Cleft Lip And Palate: Exploring The Relationship Between Cleft Severity, Mental Health, And Treatment Satisfaction, Haley Hannabass
Psychosocial Outcomes In Adults With Cleft Lip And Palate: Exploring The Relationship Between Cleft Severity, Mental Health, And Treatment Satisfaction, Haley Hannabass
ETDs from 2020-2029
Introduction:This study aimed to examine psychosocial outcomes in adults with cleft lip and palate (CL/P), focusing on how cleft severity (unilateral versus bilateral) influences depression, anxiety, social functioning, oral health–related quality of life, and satisfaction with treatment outcomes. Individuals born with clefts often continue to face psychosocial challenges even after surgical repair, and limited research has compared how these outcomes differ by cleft type in adulthood. Materials and Methods:A cross-sectional design was used, including 24 adults aged 18 years and older who had undergone cleft repair and were finished or in active orthodontic treatment at UAB. Participants completed an online …
Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo
Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo
Department of Neurology Faculty Papers
BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.
METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …
Bridging The Gap Transition From Pediatric Care To Adult Care, Jordan Garcia, Haley Henry, Amina Jamma, Guiliana Jimenez Carrion, Alexis Lowary, Jenna Potts, Josie Ramirez, Iman Siraj
Bridging The Gap Transition From Pediatric Care To Adult Care, Jordan Garcia, Haley Henry, Amina Jamma, Guiliana Jimenez Carrion, Alexis Lowary, Jenna Potts, Josie Ramirez, Iman Siraj
2025
No abstract provided.
Amino Acid Pet Tracers For Cancer Imaging And Response Assessment, Ugur Akca
Amino Acid Pet Tracers For Cancer Imaging And Response Assessment, Ugur Akca
ETDs from 2020-2029
Triple-negative breast cancer (TNBC) and high-grade glioma (HGG) pose significant diagnostic and therapeutic challenges due to their aggressive biology and the limitations of [¹⁸F]FDG PET, which suffers from nonspecific uptake in inflammatory tissues, complicating differentiation of viable tumor from treatment-related effects. Computed Tomography, while strong for structural changes, has limited soft tissue contrast for distinguishing tumor from inflammation, and Magnetic Resonance Imaging, despite superior soft tissue resolution, struggles with differentiating active tumor from post-treatment changes like edema or necrosis due to nonspecific enhancement. These challenges highlight the necessity for complementary and advanced imaging strategies for improved diagnosis and monitoring. This …
Sample Preparation Effects On Liquid Scintillation Counting Quench, Jason Rusch
Sample Preparation Effects On Liquid Scintillation Counting Quench, Jason Rusch
ETDs from 2020-2029
Liquid Scintillation Counting (LSC) is a critical technique in operational health physics, particularly for contamination surveys. However, common, expedient sample preparation choices often introduce unpredictable levels of quench, compromising the accuracy of results. This thesis investigates the impact of common preparation variables including vial material, cap lining, solid sample matrix presence, cocktail volume, and radioactivity. The impact of these sample preparation variables were evaluated using the quench methods on two fundamentally distinct commercial LSC systems, the Perkin Elmer Tri-Carb 4910TR (employing tSIE correction) and the Hidex 600 SL (employing TDCR correction). A total of 320 samples were evaluated on each …
Physiological And Neuroimmune Effects Of Manual Therapy, Murdi S. Alanazi
Physiological And Neuroimmune Effects Of Manual Therapy, Murdi S. Alanazi
ETDs from 2020-2029
Manual therapy (MT) is widely used across healthcare disciplines for the management of musculoskeletal conditions. Emerging evidence indicates that MT may also influence broader physiological systems such as the nervous and the immune systems. However, the mechanisms underlying these effects are still not well understood, and limited evidence exists regarding the neuroimmune effect of MT in neurologically impaired populations such as multiple sclerosis (MS). The overall aim of this dissertation was to investigate the physiological effects of MT, synthesizing current evidence across mechanistic domains, and generating pilot data to inform future research. This dissertation was structured around four manuscripts. The …
Clinical Decision Support Using Medical Imaging Artificial Intelligence, Yun-Chi Lin
Clinical Decision Support Using Medical Imaging Artificial Intelligence, Yun-Chi Lin
ETDs from 2020-2029
Medical imaging plays a central role in modern clinical decision-making, yet its effective integration with artificial intelligence (AI) remains challenged by real-world clinical constraints. This dissertation investigates how medical imaging-based AI frameworks can be strategically designed to support clinical decision-making for two distinct but clinically critical scenarios: acute pandemic care and chronic neurodegenerative disease management. In acute pandemic settings, such as the COVID-19 crisis, healthcare systems face an urgent need for rapid risk stratification under conditions of data scarcity and operational stress including surges in patient volume and limited medical resources. This work explores strategies for developing deep learning models …
Investigating Stromal Cell-Mediated Biomechanics For Angiogenesis And Reperfusion In A 3d Microfluidic Model For Ischemic Vascular Disease, Vaishali Bala
ETDs from 2020-2029
Peripheral artery disease (PAD) affects millions worldwide, causing tissue ischemia and impaired healing due to insufficient blood flow. Current therapeutic strategies to promote revascularization remain limited, largely because the mechanical regulation of angiogenesis is poorly understood. While biochemical growth factors like VEGF have been extensively studied, the role of mechanical forces generated by stromal cells in the perivascular matrix remains underexplored. This dissertation investigated how stromal cell contractility drives vascular growth through mechanotransduction pathways and modulation of endothelial cell-cell junctions. Using 3D fibrin or fibrin-collagen-I-based microtissues and compartmentalized microfluidic devices, we characterized the mechanical phenotypes of multiple fibroblast populations and …
Editorial: Advancing Musculoskeletal Health: Bridging Basic And Clinical Research On Biomechanical Properties Of Joints, Ligaments, Tendons, And Associated Structures, Xin Jin, Snehal S. Shetye, Mengcun Chen
Editorial: Advancing Musculoskeletal Health: Bridging Basic And Clinical Research On Biomechanical Properties Of Joints, Ligaments, Tendons, And Associated Structures, Xin Jin, Snehal S. Shetye, Mengcun Chen
Center for Translational Medicine Faculty Papers
No abstract provided.
Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner
Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation …
Integrated Proteomics To Understand The Role Of Neuritin-1 (Nrn1) As A Molecular Mediator Of Synaptic Resilience In Alzheimer’S Disease, Derian Pugh
ETDs from 2020-2029
Alzheimer’s disease (AD) is the leading cause of dementia in adults over the age of 65, and currently affects approximately 6.9 million people in the United States. By 2060, the number of people age 65 and older with AD is projected to reach 13.8 million, barring the development of disease-altering therapies to prevent, slow or cure AD. Thus, there is a need for progress in the understanding of AD pathophysiology, as well as in the development of diagnostic and therapeutic interventions. Approximately one-third of individuals without dementia at the time of death are found to harbor high levels of amyloid-beta …
Cbct Evaluation Of Planned Vs. Achieved Expansion And Buccal Bone Thickness In Phase I Orthodontic Cases Treated With Clear Aligners, Jared Teeples
Cbct Evaluation Of Planned Vs. Achieved Expansion And Buccal Bone Thickness In Phase I Orthodontic Cases Treated With Clear Aligners, Jared Teeples
ETDs from 2020-2029
Introduction: Within orthodontics, CBCT technology has been used to analyze tooth movement with both fixed appliances and clear aligners. However, little research has evaluated alveolar bone remodeling outcomes in growing patients treated with clear aligner expansion. Methods: This study compared pre-treatment (T0) and post-treatment (T1) CBCTs of Phase I patients treated with clear aligners who had expansion planned in the Invisalign® ClinCheck. CBCTs were collected and analyzed, including 27 maxillary and 22 mandibular arches. The aims were (1) to compare planned vs. actual expansion and (2) to evaluate the arch width (AW) and alveolar bone changes before and after treatment. …
Cysteine Protease Activity In Allergen Recognition And Initiation Of Th2 Allergic Responses, Audrey Rae Meloun
Cysteine Protease Activity In Allergen Recognition And Initiation Of Th2 Allergic Responses, Audrey Rae Meloun
ETDs from 2020-2029
Allergens are non-infectious environmental proteins that can trigger T helper 2 (Th2) cell-mediated inflammation in atopic individuals. Allergens are structurally diverse and typically lack pathogen-associated molecules patterns (PAMPs), which are recognized by pathogen recognition receptors (PRRs). PRRs are the canonical sensors of the innate immune system that typically detect PAMPs in microbes, initiating signaling pathways that drive pathogen clearance. Because allergens generally do not activate PRRs in the same way as infectious agents, alternative detection mechanisms are likely responsible for their recognition and the subsequent initiation of Th2 cell-mediated inflammation. House Dust Mite (HDM), a major indoor allergen, and other …
Development Of Human Trophoblast Cell Surface Antigen-2 (Trop-2) Specific Radiopharmaceutical Tracers, Arnav Vipulkumar Patel
Development Of Human Trophoblast Cell Surface Antigen-2 (Trop-2) Specific Radiopharmaceutical Tracers, Arnav Vipulkumar Patel
ETDs from 2020-2029
Trophoblast cell surface antigen 2 (Trop2) is closely related to the development and progression of triple-negative breast cancers (TNBC) and is also being investigated as a pan-cancer biomarker. Trop-2 tumorigenesis is mediated by the calcium ion signaling pathways. By accurately predicting and targeting Trop-2 for immunotherapy, precision therapy is crucial. Trop-2 is overexpressed in tumor tissues compared to normal tissues, which makes it a promising molecular target for cancer-targeted therapy. This thesis reports the development and preclinical evaluation of two novel Trop-2-specific radiopharmaceutical tracers derived from the clinically approved antibody-drug conjugate Sacituzumab Govitecan (SG): a full antibody drug conjugate-based tracer …
Beyond Neurons: Impact Of Cannabidiol On Glial Cells In Ischemic Stroke, Victória Linden De Rezende, Khiany Mathias, Cinara Ludvig Gonçalves, Rafael Mariano De Bitencourt, Tatiana Barichello, Fabricia Petronilho
Beyond Neurons: Impact Of Cannabidiol On Glial Cells In Ischemic Stroke, Victória Linden De Rezende, Khiany Mathias, Cinara Ludvig Gonçalves, Rafael Mariano De Bitencourt, Tatiana Barichello, Fabricia Petronilho
Faculty, Staff and Student Publications
Ischemic stroke triggers a complex cascade of events involving inflammation, oxidative stress, and glial cell dysfunction, all of which contribute to neuronal damage and impaired recovery. Glial cells (e.g., astrocytes, microglia, and oligodendrocytes) play key roles in neuroinflammatory responses, making them attractive targets for therapeutic modulation. Cannabidiol, a non-psychoactive phytocannabinoid from Cannabis sativa, exhibits anti-inflammatory, antioxidant, and neuroprotective properties. Preclinical evidence indicates that cannabidiol attenuates glial reactivity, reduces pro-inflammatory signaling, mitigates oxidative stress, and preserves blood-brain and intestinal barrier integrity in stroke models. Moreover, cannabidiol modulates key molecular pathways (e.g., nuclear factor-κB, tumor necrosis factor, and calcium-related signaling), contributing to …
Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting
Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting
Faculty, Staff and Student Publications
Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …
Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting
Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting
Faculty, Staff and Student Publications
Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …
Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin
Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin
Faculty, Staff and Student Publications
Background/Objectives: The bacterial cell division machinery is emerging as an attractive target for antimicrobial compounds. FtsZ, a highly conserved essential division protein, is the target for a number of small molecules such as benzamides. Recent studies show that benzodioxane-benzamides (BDOBs) are among the most potent inhibitors of FtsZ function in Gram-positive bacteria, although their ability to inhibit Gram-negative FtsZ, in particular Escherichia coli FtsZ, has been more controversial.
Methods: Here, we use genetic and cytological methods to demonstrate that FtsZ of efflux pump-disabled E. coli can be efficiently targeted by BDOBs.
Results: We show that engineered mutants …
Payload Diversification Overcomes Resistance And Guides Sequential Antibody-Drug Conjugate Therapy In Breast Cancer, Dileep Reddy Rampa, Minji Seo, Nanae Ogata, Zhaoxuan Yang, Nithya Sridhar, Fujii Takeo, Chalothorn Wannaphut, Jennifer A Maynard, Kyoji Tsuchikama, George W Sledge, Naoto T Ueno, Jangsoon Lee
Payload Diversification Overcomes Resistance And Guides Sequential Antibody-Drug Conjugate Therapy In Breast Cancer, Dileep Reddy Rampa, Minji Seo, Nanae Ogata, Zhaoxuan Yang, Nithya Sridhar, Fujii Takeo, Chalothorn Wannaphut, Jennifer A Maynard, Kyoji Tsuchikama, George W Sledge, Naoto T Ueno, Jangsoon Lee
Faculty, Staff and Student Publications
Purpose: Antibody-drug conjugates (ADCs) have transformed the treatment of breast cancer. FDA-approved ADCs such as trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd) have demonstrated clinical benefit; however, drug resistance will almost inevitably emerge in the metastatic setting, and there is no established strategy for selecting subsequent ADCs after disease progression to the first exposure to the ADC. This study aimed to define mechanisms of acquired resistance and evaluate rational sequencing approaches.
Experimental design: We generated breast cancer cell lines resistant to T-DXd (TDXd-R) and SG (SG-R). We assessed antigen expression, internalization, and resistance pathways, including efflux transporter …
Expression Spectrum Of Te-Driven Transcripts In Human Adult Tissues, Benpeng Miao, Xinlong Luo, Amina Ademovic, Yushan Yang, Tao P Wu, Bo A Zhang
Expression Spectrum Of Te-Driven Transcripts In Human Adult Tissues, Benpeng Miao, Xinlong Luo, Amina Ademovic, Yushan Yang, Tao P Wu, Bo A Zhang
Faculty, Staff and Students Publications
Background
Transposable elements (TEs) are vital components of eukaryotic genomes and have played a critical role in genome evolution. Although most TEs are silenced in the mammalian genome, increasing evidence suggests that certain TEs are actively involved in gene regulation during early developmental stages. However, the extent to which human TEs drive gene transcription in adult tissues remains largely unexplored.
Results
In this study, we systematically analyze 17,329 human transcriptomes to investigate how TEs influence gene transcription across 47 adult tissues. Our findings reveal that TE-driven transcripts are broadly expressed in human tissues, contributing to both housekeeping functions and tissue-specific …
Beyond The Rash: Cutaneous Peripheral T-Cell Lymphoma As A Diagnostic Pitfall In Primary Care, Jared Hensley, Aura Calderon, Blake Martin, Cristina Kochi, Andres Suarez Parraga
Beyond The Rash: Cutaneous Peripheral T-Cell Lymphoma As A Diagnostic Pitfall In Primary Care, Jared Hensley, Aura Calderon, Blake Martin, Cristina Kochi, Andres Suarez Parraga
School of Medicine Publications
Cutaneous manifestations of T-cell lymphomas may resemble common dermatologic or infectious conditions, increasing the risk of delayed recognition. We report a 78-year-old woman with known peripheral T-cell lymphoma (PTCL) who presented with a rapidly progressive, diffuse erythematous rash accompanied by cervical lymphadenopathy. Initial evaluation prioritized more common etiologies; however, inpatient medicine broadened the differential diagnosis, prompting early hematology and oncology consultation. Contrast-enhanced CT of the neck demonstrated multiple enlarged, partially necrotic left cervical lymph nodes consistent with disease progression. After multidisciplinary discussions and consideration of prognosis, the patient elected palliative-focused management with oncology follow-up. This case underscores the importance of …