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Articles 81871 - 81900 of 1793418
Full-Text Articles in Entire DC Network
Convergence Research For Microplastic Pollution At The Watershed Scale, Heejun Chang, Elise F. Granek, Amanda Gannon, Jordyn M. Wolfand, Janice Brahney
Convergence Research For Microplastic Pollution At The Watershed Scale, Heejun Chang, Elise F. Granek, Amanda Gannon, Jordyn M. Wolfand, Janice Brahney
Geography Faculty Publications and Presentations
Microplastics are found in Earth’s atmosphere, lithosphere, hydrosphere, pedosphere, and ecosphere. While there is a growing interest and need to solve this grand challenge in both the academic and policy realms, few have engaged with academics, policymakers, and community partners to co-identify the problem, co-design research, and co-produce knowledge in tackling this issue. Using a convergence research framework, we investigated the perception of microplastic pollution among different end users, delivered educational materials to K-12 teachers and practitioners, and identified key sampling points for assessing environmental microplastic concentrations in the Columbia River Basin, United States. Three community partner workshops identified regional …
Stroke Survivors: Predicting Cognitive Outcomes By Stroke Severity, Caregiver Factors, & Social Determinants Of Health, Jason Alexander Blake
Stroke Survivors: Predicting Cognitive Outcomes By Stroke Severity, Caregiver Factors, & Social Determinants Of Health, Jason Alexander Blake
All ETDs from UAB
Physical and cognitive disabilities are common following a stroke, often leading to significant changes in survivors' daily lives and increasing dependency on caregivers. These changes can include involuntary retirement, loss of independence, and decreased social engagement, which may necessitate adjustments in living arrangements and long-term care. This dissertation investigates the predictors of cognitive outcomes in stroke survivors, with a particular focus on the roles of stroke severity and caregiver factors. Utilizing data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) project, this research captures the different predictors of post-stroke cognition through biennial assessments. Through longitudinal studies, this …
The Role Of B Cells In A Mouse Model Of Multiple System Atrophy, Gabrielle Childers
The Role Of B Cells In A Mouse Model Of Multiple System Atrophy, Gabrielle Childers
All ETDs from UAB
Multiple system atrophy (MSA) is a rare, fast progressing, debilitating and ultimately fatal movement disorder. The pathological hallmark of MSA disease is the aggregation and misfolding of alpha-synuclein (α-syn) protein in the cytoplasm of oligodendrocytes, termed glial cytoplasmic inclusions (GCIs). Accumulation of these GCIs result in progressive demyelination and neurodegeneration of the striatonigral and olivopontocerebellar regions of the brain. Currently, no therapeutics have been approved that slow or halt the progression of this devastating disease. Neuroinflammation, has been increasingly appreciated as a key neuropathological feature of disease, especially activation of tissue resident innate immune cells. Recently, evidence of adaptive immune …
Effect Of Combined Oral Contraceptive Pills On Clotting Factor Vii Activity Percentage, Buthaina H. Hammadi, Najlaa B. Al-Awady, Sura Salman Ejam
Effect Of Combined Oral Contraceptive Pills On Clotting Factor Vii Activity Percentage, Buthaina H. Hammadi, Najlaa B. Al-Awady, Sura Salman Ejam
Hilla University College Journal For Medical Science
Background: Combined hormonal pills that are used for contraception are widely used around the world as a straightforward, secure, and reversible approach to contraception. Over time, many side effects of these contraceptive pills have been discovered, including prothrombotic effects, one of which is the effect on clotting factor VII.
Objectives: To evaluate the impact of combined hormonal contraceptives on FVII active state percentage and, consequently, the prothrombotic risk associated with these medications.
Materials and Methods: It is a case-control study involving 50 users of COC of different types and compared with other 50 non-user controls after obtaining their verbal consent. …
A Review Of The Persistent Burden Of Post-Covid Headaches In Children, Hajir Karim Abdul-Husseein
A Review Of The Persistent Burden Of Post-Covid Headaches In Children, Hajir Karim Abdul-Husseein
Hilla University College Journal For Medical Science
This review focuses on the problem of the headache occurrence in children after COVID. Studies indicated that headaches and fatigue are common long-term symptoms in school-age children following COVID-19 infection. The prevalence of persistent post-COVID headaches in children varies between 5% and 25.4%, often lasting for at least 3 months. Exploration of potential pathophysiological mechanisms of post-COVID headaches in children includes the trigemino-vascular system, viral-induced inflammation, immune system dysregulation, and compromised cerebral blood flow. Age-related immune responses and the expression of receptors like ACE2 may also play a role in pediatric headache development. The features of post-COVID headaches in children …
Exploring Educator Psychological Capital Through Participation In A Coordinated School Violence Prevention Approach, Stephanie Lorraine Neff
Exploring Educator Psychological Capital Through Participation In A Coordinated School Violence Prevention Approach, Stephanie Lorraine Neff
Walden Dissertations and Doctoral Studies
This study is a description of how educators’ participation in a coordinated approach to violence prevention contributed to employee wellness and school climate. Using principles of psychological capital (PsyCap) theory, archival focus group and interview data were used to describe educator experiences during implementation of a 3-year coordinated approach to school violence in a mid-sized public school district. Findings of the analysis revealed consistent references to feelings of hope, efficacy, resilience, and optimism throughout the study, but with slight shifts in frequency each year based on both internal (i.e. skill development, relationship-building), and external (i.e. administrative support, policy directives, broader …
Effect Of Access Cavity Preparation And Cement On The Fracture Load Of Translucent Zirconia Crowns, Andrea Fenton, Amir H. Nejat, Edwin Kee, Xiaoming Xu, Albert F. Mcmullen Iii
Effect Of Access Cavity Preparation And Cement On The Fracture Load Of Translucent Zirconia Crowns, Andrea Fenton, Amir H. Nejat, Edwin Kee, Xiaoming Xu, Albert F. Mcmullen Iii
School of Dentistry Faculty Publications
Purpose: To evaluate the effect of endodontic access hole preparation and choice of luting cement on the fracture resistance of translucent zirconia (5Y) crowns. Materials and Methods: Polymethylmethacrylate (PMMA) dies, representing a prepared maxillary molar tooth, were milled. Translucent zirconia crowns were milled from 5Y (Cercon XTML) zirconia discs and sintered. Forty crowns were divided into four groups (n = 10 per group) based on access hole preparation (accessed, non-accessed) and type of luting cement (resin cement, resin modified glass ionomer (RMGI) cement). Crowns were cemented on the PMMA dies with either resin cement (Panavia SA Cement Universal, Kuraray Noritake …
Experiences Of Discrimination And Neighborhood Cohesion In Risk Of Poor Mental Health Outcomes Among Older, Community-Dwelling Participants In The Regards Study, Marquita S. Brooks
Experiences Of Discrimination And Neighborhood Cohesion In Risk Of Poor Mental Health Outcomes Among Older, Community-Dwelling Participants In The Regards Study, Marquita S. Brooks
All ETDs from UAB
Mental health disorders impact approximately 14% of persons aged 65 and older and often are undertreated or underrecognized. Assessment of factors that link environmental, sociocultural, behavioral, and biological factors to overall health and disease is integral to guiding research on health disparities in older populations. Although research suggests associations between environmental factors (i.e., discrimination and neighborhood cohesion) and mental health outcomes, there is limited research on these factors within the U.S. Therefore, our study assessed the relationship between discrimination, neighborhood cohesion, and mental health outcomes in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national, prospective …
Examining Risk And Protective Factors Of African Americans Who Use Substances, Dominique Ashonta Black
Examining Risk And Protective Factors Of African Americans Who Use Substances, Dominique Ashonta Black
All ETDs from UAB
African Americans (AAs) are less likely to report internalized symptoms and substance use compared to other racial groups but tend to report more severe symptoms related to either condition. Research suggests internalized symptoms and substance use share a causal relationship or an underlying factor that contributes to both conditions. Risk factors such as stress, discrimination, and trauma strengthen the relationship between anxiety and substance use in AAs. A higher prevalence of stress, discrimination, and trauma exposure was found in AAs when compared to other racial groups, increasing AAs risk for internalized symptoms and substance use. While it is important to …
Cardiac-Derived Fibroblast Growth Factor 23 Contributes To Physiologic And Pathologic Cardiac Remodeling, Isaac Daniel Campos
Cardiac-Derived Fibroblast Growth Factor 23 Contributes To Physiologic And Pathologic Cardiac Remodeling, Isaac Daniel Campos
All ETDs from UAB
Chronic Kidney Disease (CKD) is a global health risk that increases patients’ risk for premature mortality and is accompanied by pathologic cardiac hypertrophy and fibrosis. Declining kidney function results in elevations of serum phosphate and Fibroblast Growth Factor (FGF) 23, a bone-derived phosphaturic hormone. Hyperphosphatemia and elevated FGF23 are associated with cardiovascular mortality in CKD. FGF23 can directly target cardiac myocytes via FGF Receptor (FGFR) 4 and induce cardiac hypertrophy and blocking FGFR4 signaling in CKD models reduces cardiac hypertrophy, but not fibrosis. FGF23 elevations are also observed following exercise and during pregnancy, two scenarios of physiologic hypertrophy not associated …
Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap
Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap
Dissertations
During sepsis, males often experience worse cardiac outcomes than females. Here, we identified pyruvate dehydrogenase kinase 4 (PDK4) as a key contributor to this disparity. PDK4 is a mitochondrial protein that regulates glucose utilization by inhibiting pyruvate dehydrogenase (PDH). Using a mouse model of endotoxemia, we induced acute inflammation with a sublethal dose of lipopolysaccharide (LPS), which caused cardiac dysfunction and significantly increased myocardial PDK4 expression in males but not females. Cardiac-specific PDK4 overexpression promoted LPS-induced cardiac dysfunction in both sexes, whereas cardiac-specific PDK4 knockout provided protection. In wild-type males, LPS disrupted cardiac metabolism by decreasing PDH activity and fatty …
Targeting Eya1 Phosphatase Activity In Mll-Rearranged Leukemia, Lola Badmus
Targeting Eya1 Phosphatase Activity In Mll-Rearranged Leukemia, Lola Badmus
Dissertations
MLL-rearranged (MLL-r) leukemia is an aggressive subset of acute leukemia, accounting for up to 10% of adult and 70% of infant AML and ALL cases. These leukemias are driven by MLL fusion proteins, which recruit epigenetic cofactors to dysregulate gene expression, leading to poor prognosis and resistance to conventional chemotherapy. Previous lab work identified EYA1’s role in leukemogenesis, establishing it as a therapeutic target in MLL-r leukemia. EYA1, is a transcriptional coactivator and protein tyrosine phosphatase (PTP). Originally a gout medication, benzbromarone (BBR), was identified in an NCI Diversity Set screen as an EYA1-specific PTP inhibitor. BBR provides a tool …
Benefits And Challenges Of Collaborative Networks Addressing Food System Disruptions During The Covid-19 Pandemic, Dikshya Dahal, Tania Schusler
Benefits And Challenges Of Collaborative Networks Addressing Food System Disruptions During The Covid-19 Pandemic, Dikshya Dahal, Tania Schusler
School of Environmental Sustainability: Faculty Publications and Other Works
The COVID-19 pandemic disrupted food systems with disproportionate impacts on marginalized social groups, which in the USA included racial and ethnic minorities, working class families, immigrants, seniors, and people with disabilities, among others. The pandemic also greatly affected the operations of nonprofit organizations, which play important roles in disaster response. We explored how social networks supported non-profit organizations’ efforts to address increased food insecurity and food-related business disruptions during the pandemic in the Chicago region, IL, USA. We used mixed methods including a Social Network Analysis (SNA) of 48 organizations and their reported partners plus focus group discussions with representatives …
Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting
Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting
Faculty, Staff and Student Publications
Background: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear.
Methods: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We …
Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee
Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee
Faculty, Staff and Student Publications
Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …
Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky
Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky
Faculty, Staff and Student Publications
Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …
Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn
Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn
Department of Surgery Faculty Papers
INTRODUCTION: For primary bilateral inguinal hernias, international guidelines favor a laparoscopic posterior mesh repair due to relatively lower risk of acute and chronic pain, faster recovery, and favorable biomechanical properties compared to open anterior approaches (Lichtenstein, plug and patch, etc.). However, studies comparing open mesh-based bilateral inguinal hernia repairs to bilateral laparoscopic and robotic mesh-based approaches are limited. The Abdominal Core Health Quality Collaborative (ACHQC) registry includes longitudinal data on bilateral inguinal hernia repairs performed via open as well as laparo-endoscopic approaches. We hypothesize that outcomes for bilateral inguinal hernia repair are similar between open and laparo-endoscopic approaches in the …
Audiological Characteristics And Associations With Psychological Inflexibility, Karen Muñoz, Bailey Sorensen, Aryn Kamerer, Michael P. Twohig
Audiological Characteristics And Associations With Psychological Inflexibility, Karen Muñoz, Bailey Sorensen, Aryn Kamerer, Michael P. Twohig
Psychology Faculty Publications
Purpose:
The aim of this study was to describe psychological inflexibility for hearing difficulty for a sample of adults seeking hearing help and explore associations with demographic and audiological characteristics.Method:
Archival data from 226 clinical electronic medical records at one university clinic were analyzed for this retrospective exploratory study. Audiometric test findings and results from the Acceptance and Action Questionnaire–Adult Hearing Loss (AAQ-AHL) were extracted for adult patients seen between June 1, 2022, and February 29, 2024.Results:
The majority had a bilateral hearing loss (64%), 10% had a unilateral hearing loss, and 26% had bilateral pure-tone averages better …The Acute Impact Of Game-Based Physical Education On The Mood States Of Middle School Students, John Nemeth
The Acute Impact Of Game-Based Physical Education On The Mood States Of Middle School Students, John Nemeth
Doctorate in Kinesiology
Mental health disorders represent a massive global health burden, with close to one billion people currently affected. Access to treatment and medical care remains low, especially among children. Increased physical activity (PA) is a widely recognized and accessible method for improving mental health, with substantial evidence supporting its benefits. Physical education (PE) is a structured, school-based environment that promotes PA and increased movement, but research examining its impact on mood is limited. This study examined mood changes in middle school students following PE participation in two game-based activities: handball (team sports) and badminton (partner games). A quasi-experimental design was used …
Moderating Role Of Locus Of Control On The Relationship Between Self-Efficacy And Trust In Ai, Amelia Gillies
Moderating Role Of Locus Of Control On The Relationship Between Self-Efficacy And Trust In Ai, Amelia Gillies
Walden Dissertations and Doctoral Studies
The rapid integration of artificial intelligence (AI) into essential sectors, including healthcare, customer services, and defense, has underscored the importance of user trust in AI systems. Psychological traits such as locus of control (the extent to which individuals attribute outcomes to internal or external factors) and self-efficacy (individuals’ confidence in their ability) have been identified as significant factors influencing trust in these automated systems. Previous studies have independently linked these psychological traits to trust in technology; however, there has been limited exploration of potential moderating effects of locus of control on the relationship between digital technology self-efficacy and trust in …
Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu
Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu
Center for Medical Ethics and Health Policy Staff Publications
Background: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying EDEM2 (endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF.
Methods: Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and Nω-nitro-L-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid …
Maternal Loss Of Mouse Nlrp2 Alters The Transcriptome And Dna Methylome In Gv Oocytes And Impairs Zygotic Genome Activation In Embryos, Zahra Anvar, Michael D Jochum, Imen Chakchouk, Momal Sharif, Hannah Demond, Alvin K To, Daniel C Kraushaar, Ying-Wooi Wan, Michael C Mari, Simon Andrews, Gavin Kelsey, Ignatia B Van Den Veyver
Maternal Loss Of Mouse Nlrp2 Alters The Transcriptome And Dna Methylome In Gv Oocytes And Impairs Zygotic Genome Activation In Embryos, Zahra Anvar, Michael D Jochum, Imen Chakchouk, Momal Sharif, Hannah Demond, Alvin K To, Daniel C Kraushaar, Ying-Wooi Wan, Michael C Mari, Simon Andrews, Gavin Kelsey, Ignatia B Van Den Veyver
Center for Medical Ethics and Health Policy Staff Publications
Background: NLRP2 is a subcortical maternal complex (SCMC) protein of mammalian oocytes and preimplantation embryos. SCMC proteins are encoded by maternal effect genes and play a pivotal role in the maternal-to-zygotic transition (MZT), early embryogenesis, and epigenetic (re)programming. Maternal inactivation of genes encoding SCMC proteins has been linked to infertility and subfertility in mice and humans, but the underlying molecular mechanisms for the diverse functions of SCMC proteins, and specifically the role of NLRP2, are incompletely understood.
Results: We profiled the DNA methylome of pre-ovulatory germinal-vesicle (GV) oocytes from Nlrp2-null, heterozygous (Het), and wild-type (WT) female mice and assessed the …
Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy
Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy
Faculty, Staff and Student Publications
Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.
A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker
A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker
Center for Medical Ethics and Health Policy Staff Publications
Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we identified T730 (T720 in mice) as a critical residue associated with pathogenesis. Using a CHD7 T730 missense variant (Chd7T720A) and a frameshift null allele (Chd7fs) in a mouse model, we found that Chd7fs/fs mice were non-viable, while Chd7fs/+ mice exhibited haploinsufficiency-related circling behavior. Notably, Chd7fs/T720A mice died before postnatal …
Correlations Within And Between Highly Multiplexed Proteomic Assays Of Human Plasma, Mary R Rooney, Jingsha Chen, Christie M Ballantyne, Ron C Hoogeveen, Eric Boerwinkle, Bing Yu, Keenan A Walker, Pascal Schlosser, Elizabeth Selvin, Nilanjan Chatterjee, David Couper, Morgan E Grams, Josef Coresh
Correlations Within And Between Highly Multiplexed Proteomic Assays Of Human Plasma, Mary R Rooney, Jingsha Chen, Christie M Ballantyne, Ron C Hoogeveen, Eric Boerwinkle, Bing Yu, Keenan A Walker, Pascal Schlosser, Elizabeth Selvin, Nilanjan Chatterjee, David Couper, Morgan E Grams, Josef Coresh
Faculty, Staff and Students Publications
Introduction: The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established.
Methods: Among 102 participants in the Atherosclerosis Risk in Communities Study (mean age 74 years, 53% women, 47% Black), we used split plasma samples to measure platform precision. CV and Spearman correlations were calculated for each assay. Cross-platform agreement was assessed for overlapping proteins.
Results: SomaScan 11k demonstrated a median correlation of 0.85 for the 10 778 assays and a median CV of …
Oral Pcsk9 Inhibitors: Can Novel Therapies Overcome Barriers To Effective Ldl-Cholesterol Management?, Christie M Ballantyne, Alberico L Catapano, Khurram Nasir
Oral Pcsk9 Inhibitors: Can Novel Therapies Overcome Barriers To Effective Ldl-Cholesterol Management?, Christie M Ballantyne, Alberico L Catapano, Khurram Nasir
Faculty, Staff and Students Publications
No abstract provided.
Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso
Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso
Faculty, Staff and Students Publications
Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …
Adipocyte/Tumor Cell Crosstalk Via Igf-1/Txnip Axis Promotes Malignancy And Endocrine Resistance In Breast Cancer, Amanda Caruso, Felice Maria Accattatis, Cinzia Giordano, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone
Adipocyte/Tumor Cell Crosstalk Via Igf-1/Txnip Axis Promotes Malignancy And Endocrine Resistance In Breast Cancer, Amanda Caruso, Felice Maria Accattatis, Cinzia Giordano, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone
Faculty, Staff and Students Publications
Background: Despite significant improvements in the outcome of Estrogen Receptor (ER) α-positive breast cancer (BC) following the use of endocrine therapies, resistance remains a major challenge. Clinical studies proved that obesity, in addition to promote BC progression, is associated with a reduced efficacy to these treatments, but mechanisms remain unclear.
Methods: We used co-culture systems followed by validation through an ‘ex vivo’ model of human mammary obese (Ob) adipocytes and obese endocrine-resistant metastatic Patient-Derived Organoids (PDOs). Transcriptomics with MixOmics-MINT and MetaCore Functional Tools along with lentiviral and pharmacological approaches provide insights into mechanisms. Clinical relevance was investigated using public datasets, …
An Antibody Biomarker Associated With Onchocerca Volvulus Microfilariae Identified By Proteomic Analysis Of Parasite Tissues Isolated From Paraffin Embedded O. Volvulus Nodules By Laser Capture Microdissection, Sarah E Greene, Kerstin Fischer, Lucia S Di Maggio, Bruce A Rosa, Yuefang Huang, Irina Diekmann, Byoung-Kyu Cho, Jessica Lukowski, Young A Goo, Makedonka Mitreva, Nicholas Opoku, Gary J Weil, Peter U Fischer
An Antibody Biomarker Associated With Onchocerca Volvulus Microfilariae Identified By Proteomic Analysis Of Parasite Tissues Isolated From Paraffin Embedded O. Volvulus Nodules By Laser Capture Microdissection, Sarah E Greene, Kerstin Fischer, Lucia S Di Maggio, Bruce A Rosa, Yuefang Huang, Irina Diekmann, Byoung-Kyu Cho, Jessica Lukowski, Young A Goo, Makedonka Mitreva, Nicholas Opoku, Gary J Weil, Peter U Fischer
2020-Current year OA Pubs
Onchocerciasis (river blindness), a neglected tropical disease caused by the filarial nematode Onchocerca volvulus, impacts millions of people in sub-Saharan Africa. The WHO coordinates global efforts to eliminate onchocerciasis and has prioritized development of improved diagnostic tests to aid these efforts. To find new microfilarial-associated diagnostic targets to help identify active infections, we used laser capture microdissection to isolate embryonic stages from histologic sections of O. volvulus worms in subcutaneous nodules excised from onchocerciasis patients. Proteomic analysis identified 2,512 O. volvulus proteins in those tissues, including 264 found only in the microfilariae (Mf). From this pool of diagnostic candidates, we …
Three Dimensional Multiscalar Neurovascular Nephron Connectivity Map Of The Human Kidney Across The Lifespan, Liam Mclaughlin, Bo Zhang, Siddharth Sharma, Amanda L Knoten, Madhurima Kaushal, Jeffrey M Purkerson, Heidie L Huyck, Gloria S Pryhuber, Joseph P Gaut, Sanjay Jain
Three Dimensional Multiscalar Neurovascular Nephron Connectivity Map Of The Human Kidney Across The Lifespan, Liam Mclaughlin, Bo Zhang, Siddharth Sharma, Amanda L Knoten, Madhurima Kaushal, Jeffrey M Purkerson, Heidie L Huyck, Gloria S Pryhuber, Joseph P Gaut, Sanjay Jain
2020-Current year OA Pubs
The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation from birth through aging. We discovered an extensive nerve network connecting different nephron segments and organizing glomeruli into distinct communities. These communities are linked through "mother glomeruli" that serve as control centers, creating a repeating pattern …