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Impacts Of Climate Change On Members Of Shallow Water Antarctic Communities, Hannah Elise Oswalt Jan 2025

Impacts Of Climate Change On Members Of Shallow Water Antarctic Communities, Hannah Elise Oswalt

All ETDs from UAB

Human-derived CO2 emissions have lowered the ocean’s pH and increased global temperatures. Low seawater pH can decrease the calcification, growth, and survival of calcifying invertebrates. Furthermore, low pH changes macroalgal growth and stress, possibly altering palatability to consumers. Global warming has decreased sea ice coverage, profoundly influencing photosynthetic organisms by altering subsurface irradiance. Shallow, hard-bottom communities along the Western Antarctic Peninsula are characterized by large macroalgal forests that shelter large numbers of mesograzers. Amphipods and macroalgae have a community-wide mutualistic relationship where macroalgae provide refuge from predatory fish while amphipods remove competing epiphytes. To understand how climate change could impact …


The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco Jan 2025

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …


The Role Of Anthropogenic Influences On A Tropical Lake Ecosystem And Its Surrounding Catchment: A Case Study Of Lake Sentani, Sulung Nomosatryo, Daniel Lipus, Alexander Bartholomäus, Cynthia Henny, Iwan Ridwansyah, Puguh Sujarta, Sizhong Yang, Dirk Wagner, Jens Kallmeyer Jan 2025

The Role Of Anthropogenic Influences On A Tropical Lake Ecosystem And Its Surrounding Catchment: A Case Study Of Lake Sentani, Sulung Nomosatryo, Daniel Lipus, Alexander Bartholomäus, Cynthia Henny, Iwan Ridwansyah, Puguh Sujarta, Sizhong Yang, Dirk Wagner, Jens Kallmeyer

College of Life Sciences Faculty Papers

Lake Sentani is a tropical lake in Indonesia, consisting of four interconnected sub-basins of different water depths. While previous work has highlighted the impact of catchment composition on biogeochemical processes in Lake Sentani, little is currently known about the microbiological characteristics across this unique ecosystem. With recent population growth in this historically rural area, the anthropogenic impact on Lake Sentani and hence its microbial life is also increasing. Therefore, we aimed to explore the influence of environmental and anthropogenic factors on the microbial diversity of Lake Sentani. Here, we present a detailed microbiological evaluation of Lake Sentani, analyzing 49 different …


Gene Model For The Ortholog Of Glys In Drosophila Simulans, Madeline L. Gruys, Madison A. Sharp, Zachary Lill, Caroline Xiong, Amy T. Hark, James J. Youngblom, Chinmay P. Rele, Laura K. Reed Jan 2025

Gene Model For The Ortholog Of Glys In Drosophila Simulans, Madeline L. Gruys, Madison A. Sharp, Zachary Lill, Caroline Xiong, Amy T. Hark, James J. Youngblom, Chinmay P. Rele, Laura K. Reed

Faculty Journal Articles

Gene model for the ortholog of glycogen synthase ( Glys ) in the Drosophila simulans May 2017 (Princeton ASM75419v2/DsimGB2) Genome Assembly (GenBank Accession: GCA_000754195.3 ). This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.


Disrupted Relatedness And Shifting Perceptions Of Others: Changing Moods Over Time For People Diagnosed With Bipolar Disorder, Joanna Farr, Jonathan A. Smith, John E. Rhodes Jan 2025

Disrupted Relatedness And Shifting Perceptions Of Others: Changing Moods Over Time For People Diagnosed With Bipolar Disorder, Joanna Farr, Jonathan A. Smith, John E. Rhodes

The Qualitative Report

For people diagnosed with bipolar disorder, the relationship between mood episodes and interpersonal life is critical. Yet little is known about how their experience of other people changes during and between episodes of depression and mania. This longitudinal study aimed to investigate the experience of interpersonal change during depression, mania and euthymia (stability). Semi-structured interviews were conducted with three women at two time points and were analysed using longitudinal interpretative phenomenological analysis. One longitudinal theme, “Changing sense of others impacts relatedness,” demonstrates profound changes in participants’ experiences of other people within and between episodes. During depression, participants experienced other people …


Modulation Of Stemness And Differentiation Regulators By Valproic Acid In Medulloblastoma Neurospheres, Natália Hogetop Freire, Alice Laschuk Herlinger, Julia Vanini, Matheus Dalmolin, Marcelo A C Fernandes, Carolina Nör, Vijay Ramaswamy, Caroline Brunetto De Farias, André Tesainer Brunetto, Algemir Lunardi Brunetto, Lauro José Gregianin, Mariane Da Cunha Jaeger, Michael D Taylor, Rafael Roesler Jan 2025

Modulation Of Stemness And Differentiation Regulators By Valproic Acid In Medulloblastoma Neurospheres, Natália Hogetop Freire, Alice Laschuk Herlinger, Julia Vanini, Matheus Dalmolin, Marcelo A C Fernandes, Carolina Nör, Vijay Ramaswamy, Caroline Brunetto De Farias, André Tesainer Brunetto, Algemir Lunardi Brunetto, Lauro José Gregianin, Mariane Da Cunha Jaeger, Michael D Taylor, Rafael Roesler

Faculty, Staff and Students Publications

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest. These effects were accompanied by enhanced H3K9 histone acetylation (H3K9ac) and decreased expression of the MYC oncogene. VPA impaired the expansion of MB neurospheres enriched in stemness markers and reduced MYC while increasing TP53 …


Ubr5 In Tumor Biology: Exploring Mechanisms Of Immune Regulation And Possible Therapeutic Implications In Mpnst, Diana Akinyi Odhiambo, Selina Fan, Angela C Hirbe Jan 2025

Ubr5 In Tumor Biology: Exploring Mechanisms Of Immune Regulation And Possible Therapeutic Implications In Mpnst, Diana Akinyi Odhiambo, Selina Fan, Angela C Hirbe

2020-Current year OA Pubs

Malignant peripheral nerve sheath tumor (MPNST) is a rare but aggressive soft-tissue sarcoma characterized by poor response to therapy. The primary treatment remains surgical resection with negative margins. Nonetheless, in the setting of neurofibromatosis type 1 (NF1), the five-year survival rate is at 20-50%, with recurrence occurring in up to 50% of individuals. For patients with metastatic and unresectable disease, current treatment options include cytotoxic chemotherapy, which offers minimal benefit, and most patients die within five years of diagnosis. Despite advances in targeted therapy focusing on inhibiting Ras signaling and its downstream effectors, clinical trials report minimal clinical benefit, highlighting …


Executive Committee - Agenda, 1/7/2025, Academic Senate Jan 2025

Executive Committee - Agenda, 1/7/2025, Academic Senate

Academic Senate Agendas

No abstract provided.


Sialylation Of Tnfr1 By St6gal1 Modulates Receptor Dynamics And Determines Cell Fate, Jihye Hwang Jan 2025

Sialylation Of Tnfr1 By St6gal1 Modulates Receptor Dynamics And Determines Cell Fate, Jihye Hwang

All ETDs from UAB

Abnormal glycosylation has long been identified as a key feature of cancer. Aberrant glycan structures on tumor cells arise from the dysregulation of select glycosyltransferases. For example, sialyltransferase ST6GAL1 is notable for its high expression in various cancers, including breast, colon, ovarian, and pancreatic. ST6GAL1 introduces α2-6-linkage sialylation to N-glycans on proteins, endowing cancer cells with stem cell-like properties. This modification contributes to resistance to apoptosis mediated by death receptors like TNFR1. Despite its significance in cancer, the regulatory mechanisms controlling ST6GAL1 expression remain largely unexplored. Additionally, it is unclear whether the apoptosis-resistant effect of sialylation is caused by an …


Development Of Momordica Saponin-Based Vaccine Adjuvants, Hyunjung Kim Jan 2025

Development Of Momordica Saponin-Based Vaccine Adjuvants, Hyunjung Kim

All ETDs from UAB

Vaccine adjuvants are indispensable substances that help induce a fast, potent, and durable immune response when administered with vaccine antigens. Among the FDA-approved vaccine adjuvants for human use, three of the most recently approved ones contain saponin adjuvant QS-21. To address QS-21’s inherent drawbacks, we investigated the adjuvant activity of a series of saponin-based semisynthetic vaccine adjuvants, including VSA-1 and VSA-2, prepared from natural Momordica saponins I and II in one-step. The natural saponins precursors are isolated from the widely available and inexpensive seeds of Momordica cochinchinensis SPRENG. In general, VSA adjuvants can enhance both humoral and cellular immune responses …


Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham Jan 2025

Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham

All ETDs from UAB

Immunoglobulin A1 (IgA1) is the second most abundantly produced immunoglobulin in circulation per day and plays a key role in human immunity. Two molecular complexities of IgA1 make accurately studying the protein challenging. The first is that IgA1 exists in three main molecular forms in the serum of humans: monomeric (mIgA1, 80-90% of serum IgA1), polymeric (pIgA1, 10-20% of serum IgA1), and IgA1-containing immune complexes (IgA1-IC, <0.5% of serum IgA1). The second complexity is that the hinge-region of IgA1 is extensively O-glycosylated and exhibits a high level of variation in its O-glycans, particularly in the degree of sialylation. In context of the autoimmune disease IgA nephropathy (IgAN), patients have elevated levels of IgA1 that has reduced levels of galactose (Gal) in the IgA1 hinge-region (Gal-deficient IgA1). This Gal-deficient IgA1 forms immune complexes with IgG autoantibodies (IgA1-IC), deposits in the glomeruli, and induces kidney injury. While it is established that these large IgA1-IC (>700 kDa) formed in the circulation are pathogenic, there remains a gap in knowledge about other blood proteins that may be associating with IgA1 in complexes. It is also necessary to understand the native …


A Mixed Methods Approach To Understanding What Knowledge Alabama K-12 In-Service Educators Hold In Regard To School-Based Trauma-Informed Practices, Katherine Busch Jan 2025

A Mixed Methods Approach To Understanding What Knowledge Alabama K-12 In-Service Educators Hold In Regard To School-Based Trauma-Informed Practices, Katherine Busch

All ETDs from UAB

Childhood trauma is prevalent in epidemic proportions, with data showing 40%-90% of individuals experiencing one or more childhood traumatic events that permanently changes neurobiology and stress response. These stress responses can manifest in behaviors that lead to problems in schools, including behavior issues, special education referrals, suspensions or expulsions, and decreased academic achievement. In adulthood, these traumatic stressors increase the odds of engaging in risky behaviors and developing chronic health conditions. Schools can be places of healing, promoting resilience and utilizing trauma-informed practices to help children and educators. Emerging studies show promise in the benefits of school-based trauma-informed practices, but …


Where The Black Women At? Exploring The Narratives & Experiences Of Black Women In Higher Education Leadership, Jasmine P. Jean Jan 2025

Where The Black Women At? Exploring The Narratives & Experiences Of Black Women In Higher Education Leadership, Jasmine P. Jean

All ETDs from UAB

WHERE THE BLACK WOMEN AT? EXPLORING THE NARRATIVES & EXPERIENCES OF BLACK WOMEN IN HIGHER EDUCATION LEADERSHIP JASMINE P. PARKER JEAN HIGHER EDUCATION ADMINISTRATION ABSTRACT This thesis explores the experiences of Black Women in mid- and senior-level leadership roles in higher education, with a focus on the unique challenges they face due to the intersection of race and gender. Black Women remain significantly underrepresented in leadership positions across the academic landscape, despite earning higher education degrees at high rates. The study seeks to amplify the voices of Black Women leaders, providing insight into the barriers they encounter, the strategies they …


Transcriptomic Transformations And Epigenetic Elements: The Heart Of The Matter Across Diverse Cardiac Pathophysiologies, Sayan Bakshi Jan 2025

Transcriptomic Transformations And Epigenetic Elements: The Heart Of The Matter Across Diverse Cardiac Pathophysiologies, Sayan Bakshi

All ETDs from UAB

Cardiovascular disease (CVD) comprises a complex array of disorders affecting the heart and blood vessels, representing the leading cause of mortality worldwide. This multifaceted nature of CVD has prompted extensive research into its molecular underpinnings and etiological diversity. Despite significant advances, the majority of CVD management strategies are guideline-based symptomatic treatment. This necessitates extensive research studies on therapeutic interventions aimed at disease prevention or cure. In this dissertation, we have employed next-generation sequencing (NGS) techniques to elucidate the cardiac transcriptional and epigenetic landscape across various conditions, including ischemic heart failure (IHF), Cardiogenic shock (CS), and diabetic heart failure (DHF). Our …


Keep Your Head Up King, Your Crown Is Slippin': An Anti-Deficit Critical Phenomenological Analysis Of Black Male Stem Educators' Experiences, Desmond R. Parker Jan 2025

Keep Your Head Up King, Your Crown Is Slippin': An Anti-Deficit Critical Phenomenological Analysis Of Black Male Stem Educators' Experiences, Desmond R. Parker

All ETDs from UAB

Black males comprise approximately 3% to 5% of the overall K-12 teaching workforce. The science, technology, engineering, and mathematics (STEM) fields are overrepresented in this shortage. This research project aimed to shed light on the experiences of Black male STEM educators to better understand what garnered their interests in STEM, and what ultimately led them to step into the STEM classroom. This study used a critical anti-deficit framework and hermeneutic phenomenological philosophy to understand the experiences of 10 Black male STEM educators in Alabama ranging from three to 30 years of teaching experience. Research data were collected through two semi-structured …


Targeting Streptococcus Mutans Diadenylate Cyclase For The Prevention Of Dental Caries, Edwin Miguel Rojas Jan 2025

Targeting Streptococcus Mutans Diadenylate Cyclase For The Prevention Of Dental Caries, Edwin Miguel Rojas

All ETDs from UAB

Streptococcus mutans (S. mutans) is the primary etiological agent involved in the initiation and progression of dental caries. S. mutans forms robust biofilms on the tooth surface, and current preventative treatments, such as oral rinses, eliminate both pathogenic and commensal oral species. Therefore, there is an urgent need for therapeutics which selectively inhibit S. mutans biofilms while keeping the oral microbiome intact. The diadenylate cyclase (DAC) enzyme in S. mutans plays a key role in biofilm formation. DAC converts adenosine triphosphate (ATP) into cyclic di-AMP (c-di-AMP), a secondary messenger involved in several cellular pathways. Increased levels of c-di-AMP have shown …


Characterization Of Dhdds Rp59 Knock-In Mouse Models Of Retinitis Pigmentosa, Mai Ngoc Nguyen Jan 2025

Characterization Of Dhdds Rp59 Knock-In Mouse Models Of Retinitis Pigmentosa, Mai Ngoc Nguyen

All ETDs from UAB

Cis-prenyltransferase (CPT), a prenyl chain elongation enzyme made up of two copies of dehydrodolichyl diphosphate synthase (DHDDS) and two copies of Nogo-B Receptor (NgBR), condenses metabolites from the mevalonate pathway to create dolichol, a sugar carrier required for glycosylation in all cells of the body. However, certain missense mutations in DHDDS cause non-syndromic retinitis pigmentosa (RP59). Three missense mutations, K42E, T206A, and R98W have been found in RP59 patients that present the cardinal phenotypes of RP – diminished ERG responses, attenuated retinal vessels, bone spicule-like pigmentation, and retinal thinning due to photoreceptor loss. However, no global changes in glycosylation are …


Evaluations Of Hand-Arm Vibration (Hav) Exposure And Related Vascular And Musculoskeletal Heath Effects Among Groundskeeping Workers In Southeastern U.S., Nathan Chen Jan 2025

Evaluations Of Hand-Arm Vibration (Hav) Exposure And Related Vascular And Musculoskeletal Heath Effects Among Groundskeeping Workers In Southeastern U.S., Nathan Chen

All ETDs from UAB

Long-term, excessive exposure to hand-arm vibration (HAV) may induce vascular, neurological, and musculoskeletal disorders, collectively known as hand-arm vibration syndrome (HAVS). However, concerns arise when adopting the currently available guidelines and standards to protect workers who regularly use vibrating tools due to the lack of standardized exposure assessment methods for HAV and reliable health indicators for HAVS. The existing exposure-response relationship addressed in ISO 5349-1 was developed based on epidemiological studies predominantly performed in temperate zones. Thus, this dissertation aimed to evaluate the HAV exposure levels and vascular and muscular health effects from vibration exposure among groundskeepers in the southeastern …


The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop Jan 2025

The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop

All ETDs from UAB

Circadian rhythms are crucial endogenous cycles with period of ~24 hours that evolved to adapt to light – dark driven changes in environmental conditions. At a molecular level, circadian rhythms are generated by the actions of clock genes that form a transcriptional- translational feedback loop and regulate the rhythmic expression of downstream clock-controlled genes. Cumulatively, the actions of these molecular clocks regulate rhythmicity of physiological and behavioral processes and are extensively characterized within the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Like SCN neurons, dopaminergic neurons of the SN are intrinsically pacemaking, though it is unknown if this intrinsic firing …


Impact Of Point-Of-Care Testing On Diagnosis, Treatment, And Surveillance Of Vaccine-Preventable Viral Infections, Kirthika Lakshmanan, Benjamin M. Liu Jan 2025

Impact Of Point-Of-Care Testing On Diagnosis, Treatment, And Surveillance Of Vaccine-Preventable Viral Infections, Kirthika Lakshmanan, Benjamin M. Liu

Student Publications

With the advent of a variety of vaccines against viral infections, there are multiple viruses that can be prevented via vaccination. However, breakthrough infections or uncovered strains can still cause vaccine-preventable viral infections (VPVIs). Therefore, timely diagnosis, treatment, and surveillance of these viruses is critical to patient care and public health. Point-of-care (POC) viral diagnostics tools have brought significant improvements in the detection and management of VPVIs. These cutting-edge technologies enable prompt and accurate results, enhancing patient care by facilitating timely treatment decisions. This review delves into the advancements in POC testing, including antigen/antibody detection and molecular assays, while focusing …


Yap Overcomes Mechanical Barriers To Induce Mitotic Rounding And Adult Cardiomyocyte Division, Yuka Morikawa, Jong H Kim, Rich Gang Li, Lin Liu, Shijie Liu, Vaibhav Deshmukh, Matthew C Hill, James F Martin Jan 2025

Yap Overcomes Mechanical Barriers To Induce Mitotic Rounding And Adult Cardiomyocyte Division, Yuka Morikawa, Jong H Kim, Rich Gang Li, Lin Liu, Shijie Liu, Vaibhav Deshmukh, Matthew C Hill, James F Martin

Faculty, Staff and Students Publications

Background: Many specialized cells in adult organs acquire a state of cell cycle arrest and quiescence through unknown mechanisms. Our limited understanding of mammalian cell cycle arrest is derived primarily from cell culture models. Adult mammalian cardiomyocytes, a classic example of cell cycle arrested cells, exit the cell cycle postnatally and remain in an arrested state for the life of the organism. Cardiomyocytes can be induced to re-enter the cell cycle by YAP5SA, an active form of the Hippo signaling pathway effector YAP.

Methods: We performed clonal analyses to determine the cell cycle kinetics of YAP5SA cardiomyocytes. We also performed …


Microtubules Sequester Acetylated Yap In The Cytoplasm And Inhibit Heart Regeneration, Shijie Liu, Vaibhav Deshmukh, Fansen Meng, Yidan Wang, Yuka Morikawa, Jeffrey D Steimle, Rich Gang Li, Jun Wang, James F Martin Jan 2025

Microtubules Sequester Acetylated Yap In The Cytoplasm And Inhibit Heart Regeneration, Shijie Liu, Vaibhav Deshmukh, Fansen Meng, Yidan Wang, Yuka Morikawa, Jeffrey D Steimle, Rich Gang Li, Jun Wang, James F Martin

Faculty, Staff and Students Publications

Background: The Hippo pathway effector YAP (Yes-associated protein) plays an essential role in cardiomyocyte proliferation and heart regeneration. In response to physiological changes, YAP moves in and out of the nucleus. The pathophysiological mechanisms regulating YAP subcellular localization after myocardial infarction remain poorly defined.

Methods: We identified YAP acetylation at site K265 by in vitro acetylation followed by mass spectrometry analysis. We used adeno-associated virus to express YAP-containing mutations that either abolished acetylation (YAP-K265R) or mimicked acetylation (YAP-K265Q) and studied how acetylation regulates YAP subcellular localization in mouse hearts. We generated a cell line with YAP-K265R mutation and investigated the …


The Gip Receptor Activates Futile Calcium Cycling In White Adipose Tissue To Increase Energy Expenditure And Drive Weight Loss In Mice, Xinxin Yu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G Straub, Valentina Pirro, Margo P Emont, Brian A Droz, Kyla Ai Collins, Chanmin Joung, Mackenzie J Pearson, Corey M James, Gopal J Babu, Vissarion Efthymiou, Ashley Vernon, Mary Elizabeth Patti, Yu A An, Evan D Rosen, Matthew P Coghlan, Ricardo J Samms, Philipp E Scherer, Christine M Kusminski Jan 2025

The Gip Receptor Activates Futile Calcium Cycling In White Adipose Tissue To Increase Energy Expenditure And Drive Weight Loss In Mice, Xinxin Yu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G Straub, Valentina Pirro, Margo P Emont, Brian A Droz, Kyla Ai Collins, Chanmin Joung, Mackenzie J Pearson, Corey M James, Gopal J Babu, Vissarion Efthymiou, Ashley Vernon, Mary Elizabeth Patti, Yu A An, Evan D Rosen, Matthew P Coghlan, Ricardo J Samms, Philipp E Scherer, Christine M Kusminski

Faculty, Staff and Student Publications

Obesity is a chronic disease that contributes to the development of insulin resistance, type 2 diabetes (T2D), and cardiovascular risk. Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) co-agonism provide an improved therapeutic profile in individuals with T2D and obesity when compared with selective GLP-1R agonism. Although the metabolic benefits of GLP-1R agonism are established, whether GIPR activation impacts weight loss through peripheral mechanisms is yet to be fully defined. Here, we generated a mouse model of GIPR induction exclusively in the adipocyte. We show that GIPR induction in the fat cell protects mice from diet-induced …


Rpa And Rad27 Limit Templated And Inverted Insertions At Dna Breaks, Yang Yu, Xin Wang, Jordan Fox, Qian Li, Yang Yu, P J Hastings, Kaifu Chen, Grzegorz Ira Jan 2025

Rpa And Rad27 Limit Templated And Inverted Insertions At Dna Breaks, Yang Yu, Xin Wang, Jordan Fox, Qian Li, Yang Yu, P J Hastings, Kaifu Chen, Grzegorz Ira

Faculty, Staff and Students Publications

Formation of templated insertions at DNA double-strand breaks (DSBs) is very common in cancer cells. The mechanisms and enzymes regulating these events are largely unknown. Here, we investigated templated insertions in yeast at DSBs using amplicon sequencing across a repaired locus. We document very short (most ∼5-34 bp), templated inverted duplications at DSBs. They are generated through a foldback mechanism that utilizes microhomologies adjacent to the DSB. Enzymatic requirements suggest a hybrid mechanism wherein one end requires Polδ-mediated synthesis while the other end is captured by nonhomologous end joining (NHEJ) or by alternative end joining (Alt-EJ). This process is exacerbated …


A Regularized Bayesian Dirichlet-Multinomial Regression Model For Integrating Single-Cell-Level Omics And Patient-Level Clinical Study Data, Yanghong Guo, Lei Yu, Lei Guo, Lin Xu, Qiwei Li Jan 2025

A Regularized Bayesian Dirichlet-Multinomial Regression Model For Integrating Single-Cell-Level Omics And Patient-Level Clinical Study Data, Yanghong Guo, Lei Yu, Lei Guo, Lin Xu, Qiwei Li

Faculty, Staff and Student Publications

The abundance of various cell types can vary significantly among patients with varying phenotypes and even those with the same phenotype. Recent scientific advancements provide mounting evidence that other clinical variables, such as age, gender, and lifestyle habits, can also influence the abundance of certain cell types. However, current methods for integrating single-cell-level omics data with clinical variables are inadequate. In this study, we propose a regularized Bayesian Dirichlet-multinomial regression framework to investigate the relationship between single-cell RNA sequencing data and patient-level clinical data. Additionally, the model employs a novel hierarchical tree structure to identify such relationships at different cell-type …


Causal Models And Prediction In Cell Line Perturbation Experiments, James P Long, Yumeng Yang, Shohei Shimizu, Thong Pham, Kim-Anh Do Jan 2025

Causal Models And Prediction In Cell Line Perturbation Experiments, James P Long, Yumeng Yang, Shohei Shimizu, Thong Pham, Kim-Anh Do

Faculty, Staff and Student Publications

In cell line perturbation experiments, a collection of cells is perturbed with external agents and responses such as protein expression measured. Due to cost constraints, only a small fraction of all possible perturbations can be tested in vitro. This has led to the development of computational models that can predict cellular responses to perturbations in silico. A central challenge for these models is to predict the effect of new, previously untested perturbations that were not used in the training data. Here we propose causal structural equations for modeling how perturbations effect cells. From this model, we derive two estimators for …


Genetics And Biology Of Pancreatic Ductal Adenocarcinoma, Haoqiang Ying, Alec C Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A Depinho Jan 2025

Genetics And Biology Of Pancreatic Ductal Adenocarcinoma, Haoqiang Ying, Alec C Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and …


Development Of Sacb-Based Counterselection For Efficient Allelic Exchange In Fusobacterium Nucleatum, Peng Zhou, Bibek G C, Bo Hu, Chenggang Wu Jan 2025

Development Of Sacb-Based Counterselection For Efficient Allelic Exchange In Fusobacterium Nucleatum, Peng Zhou, Bibek G C, Bo Hu, Chenggang Wu

Faculty, Staff and Student Publications

Fusobacterium nucleatum, prevalent in the oral cavity, is significantly linked to overall human health. Our molecular comprehension of its role in oral biofilm formation and its interactions with the host under various pathological circumstances has seen considerable advancements in recent years, primarily due to the development of various genetic tools for DNA manipulation in this bacterium. Of these, counterselection-based unmarked in-frame mutation methods have proved notably effective. Under suitable growth conditions, cells carrying a counterselectable gene die, enabling efficient selection of rare, defined allelic exchange mutants. The sacB gene from Bacillus subtilis, encoding levansucrase, is a widely used …


Profiles Of Major Amish Settlements In North America: A Guide For Researchers And Service Providers, Cory Anderson, Rachel Bacon Jan 2025

Profiles Of Major Amish Settlements In North America: A Guide For Researchers And Service Providers, Cory Anderson, Rachel Bacon

Journal of Amish and Plain Anabaptist Studies

Amish populations cluster in ethnic enclaves, or “settlements,” which are located across much of North America, notably in the regions of the Mid-Atlantic, Great Lakes, Midwest, and Upper South. This article profiles 38 of the largest and best known Amish settlements. The profiles include (1) a recent population tally and population projections to 2050, (2) population density maps, (3) settlement history, (4) socio-economic attributes, (5) religious affiliations, and (6) an overview of the physical and economic landscape. The purpose of this article is to provide scholars and service providers an informative introduction to the different settlements. This article can help …


Latine Immigrant Survivors Of Sexual Assault: Clinical Considerations For Aid And Empowerment, Jasmine Pochini Jan 2025

Latine Immigrant Survivors Of Sexual Assault: Clinical Considerations For Aid And Empowerment, Jasmine Pochini

Counseling Psychology | Master's Theses

This thesis project attempts to ascertain the impact of sexual assault on Latine immigrants in the United States with the aid of a literature review and subsequent manual of clinical and sociocultural recommendations. The historical and political background of immigration in the U.S. is discussed, providing a background for the difficulties that Latine immigrants have faced for decades. All facets of immigration are explored, as well as the hostility that many immigrants face due to anti-immigrant sentiment. This combined with the acculturation process proves to have drastic effects on mental health. Sexual assault is then explored, identifying background and statistical …