Digital Commons Network^™

Ras And Beyond: The Many Faces Of The Neurofibromatosis Type 1 Protein, Corina Anastasaki, Paola Orozco, David H Gutmann

Open Access Publications

Neurofibromatosis type 1 is a rare neurogenetic syndrome, characterized by pigmentary abnormalities, learning and social deficits, and a predisposition for benign and malignant tumor formation caused by germline mutations in the NF1 gene. With the cloning of the NF1 gene and the recognition that the encoded protein, neurofibromin, largely functions as a negative regulator of RAS activity, attention has mainly focused on RAS and canonical RAS effector pathway signaling relevant to disease pathogenesis and treatment. However, as neurofibromin is a large cytoplasmic protein the RAS regulatory domain of which occupies only 10% of its entire coding sequence, both canonical and …

Hypoxia Inhibits Colonic Uptake Of The Microbiota-Generated Forms Of Vitamin B1 Via Hif-1Α-Mediated Transcriptional Regulation Of Their Transporters, Subrata Sabui, Kalidas Ramamoorthy, Jose M Romero, Rita D Simoes, James M Fleckenstein, Hamid M Said

Open Access Publications

Hypoxia exerts profound effects on cell physiology, but its effect on colonic uptake of the microbiota-generated forms of vitamin B1 (i.e., thiamin pyrophosphate [TPP] and free thiamine) has not been described. Here, we used human colonic epithelial NCM460 cells and human differentiated colonoid monolayers as in vitro and ex vivo models, respectively, and were subjected to either chamber (1% O

Rxra Dt448/9pp Generates A Dominant Active Variant Capable Of Inducing Maturation In Acute Myeloid Leukemia Cells, Orsola Di Martino, Margaret A. Ferris, Gayla Hadwiger, Soyi Sarkar, Anh Vu, María P. Menéndez-Gutiérrez, Mercedes Ricote, John S Welch

Open Access Publications

RARA and RXRA contribute to myeloid maturation in both mice and humans, and deletion of Rxra and Rxrb augments leukemic growth in mice. While defining the domains of RXRA that are required for anti-leukemic effects in murine KMT2A-MLLT3 leukemia cells, we unexpectedly identified RXRA DT448/9PP as a constitutively active variant capable of inducing maturation and loss of their proliferative phenotype. RXRA DT448/9PP was associated with ligand-independent activity in reporter assays, with enhanced co-activator interactions, reduced engraftment in vivo, and activation of myeloid maturation transcriptional signatures that overlapped with those of cells treated with the potent RXRA agonist bexarotene, suggestive of …

Nevirapine Hair And Plasma Concentrations And Hiv-1 Viral Suppression Among Hiv Infected Ante-Partum And Post-Partum Women Attended In A Mother And Child Prevention Program In Maputo City, Mozambique, Rosa Marlene Cuco, Osvaldo Loquiha, Adelino Juga, Aleny Couto, Bindiya Meggi, Adolfo Vubil, Esperança Sevene, Nafissa Osman, Marleen Temmerman, Olivier Degomme

Obstetrics and Gynaecology, East Africa

Introduction: Prevention of mother to child transmission of HIV (PMTCT) is frequently challenged by irregular access to more effective anti-retroviral therapy. Nevirapine single dose (sdNVP), sdNVP+AZT+3TC for MTCT prophylaxis and NVP+ AZT+3TC for treatment and PMTCT were withdrawn due to low genetic resistance barrier and low efficacy. However current PMTCT lines in Mozambique include DTG+3TC+TDF, TDF+3TC+EFV, DTG +ABC+3TC, and AZT + NVP syrup prophylaxis for exposed babies. We assessed NVP hair and plasma concentrations and association with HIV-1RNA suppression among HIV+ ante-partum and post-partum women under PMTCT in Maputo, Mozambique.

Methods: From December 2013 to November 2014, prospectively …

Targeting Gastrointestinal Cancers With Chimeric Antigen Receptor (Car)-T Cell Therapy, Ross E Staudt, Robert D Carlson, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The immune system is capable of remarkably potent and specific efficacy against infectious diseases. For decades, investigators sought to leverage those characteristics to create immune-based therapies (immunotherapy) that might be far more effective and less toxic than conventional chemotherapy and radiation therapy for cancer. Those studies revealed many factors and mechanisms underlying the success or failure of cancer immunotherapy, leading to synthetic biology approaches, including CAR-T cell therapy. In this approach, patient T cells are genetically modified to express a chimeric antigen receptor (CAR) that converts T cells of any specificity into tumor-specific T cells that can be expanded to …

February 1, 2022 Ereporter, University Of Alabama At Birmingham

eReporter (campus newsletter)

No abstract provided.

Mir-4521 Plays A Tumor Repressive Role In Growth And Metastasis Of Hepatocarcinoma Cells By Suppressing Phosphorylation Of Fak/Akt Pathway Via Targeting Fam129a, Munawar Ayesha, Abbasi Majid, Dongting Zhao, Frederick T. Greenaway, Naimeng Yan, Qinlong Liu, Shuqing Liu, Ming Zhong Sun

Chemistry

Introduction: Globally, hepatocellular carcinoma (HCC) is the sixth most common malignancy and it has the fourth highest mortality. MicroRNAs play a significant part in biological processes in cell formation and advancement by targeting genes in many cancers including HCC. Objective: In the present study we examine the involvement of miR-4521 and FAM129A correlations in HCC occurrence and progression. Methods: Expression levels of miR-4521 and FAM129A in HCC tissues and cells were detected. Immunohistochemistry was carried out to detect expression of FAM129A, MMP9 and TIMP-1 in HCC tissues. Western blot assays were used to examine expression levels of different genes involve …

Eukaryotic Initiation Factor 3 Interactions With Structural Elements Of Barley Yellow Dwarf Virus Untranslated Regions Reveal Details Of A New Cap-Independent Translation Initiation Model, Paul S. Powell

Dissertations, Theses, and Capstone Projects

Barley Yellow Dwarf Virus (BYDV) is a positive strand RNA plant virus that translates without using a 5′ 7-methylguanosine cap or a 3′ poly-adenosine tail, features that are required for canonical mRNA translation. BYDV’s non-canonical translation relies on RNA structures in the 5′ and 3′ untranslated regions (UTRs) to recruit eukaryotic initiation factors (eIFs) and ribosomes. BYDV’s 3′ translation enhancer (BTE) is a cruciform structure capable of recruiting the cap-binding complex eIF4F, the large scaffolding complex eIF3, and the 40S ribosomal subunit. Together eIF3, eIF4F, and BTE influence factor binding and 40S recruitment on the 5′ UTR and play a …

The College Experience Podcast: Connecting Student Services For College Success, Lucila Sanchez

Dissertations, Theses, and Capstone Projects

What do we know about orienting college students on how to successfully manage the college experience? With this podcast, I aim to answer that question. The podcast aims to serve two purposes. The first purpose is to transmit the information to the students. The secondary purpose is to support student development by increasing knowledge about a wide range of topics as well as available services and resources. The goal is for students to become more aware of how they can access and use these services most effectively and how to manage their time to access essential services that support their …

Making Sense Of Pre-Symbolic Trauma: A Qualitative Study On The Lived Experiences Of Adults Who Were Born Extremely Prematurely, Noia Efrat

Dissertations, Theses, and Capstone Projects

The psychological experiences of adults (n=5) who were born at or before the threshold for extreme prematurity (weeks) was examined using Interpretive Phenomenological Analysis (IPA) (Smith, Flowers & Larkin, 2009). Subjects were interviewed to learn about how their extreme prematurity has become organized and integrated on the levels of fantasy, identity and personality. Results showed that dysregulation and the propensity to self-contain on both somatic and affective levels were common themes across cases, supporting current research connecting the ongoing impacts of prematurity to the context of overstimulation and fundamental absence in the first months of life in the NICU. Despite …

Representation Learning For Chemical Activity Predictions, Mohamed S. Ayed

Dissertations, Theses, and Capstone Projects

Computational prediction of a phenotypic response upon the chemical perturbation on a biological system plays an important role in drug discovery and many other applications. Chemical fingerprints derived from chemical structures are a widely used feature to build machine learning models. However, the fingerprints ignore the biological context, thus, they suffer from several problems such as the activity cliff and curse of dimensionality. Fundamentally, the chemical modulation of biological activities is a multi-scale process. It is the genome-wide chemical-target interactions that modulate chemical phenotypic responses. Thus, the genome-scale chemical-target interaction profile will more directly correlate with in vitro and in …

Understanding The Proton Transport In Non-Aqueous Histidine-Based Nanostructures, Jiang Bian

Dissertations, Theses, and Capstone Projects

Over the past two decades, proton transport has been extensively studied because of the many applications to the development of new technological devices. In particular, understanding proton transport permits the design of new materials with desired properties for constructing effective proton exchange membranes (PEM) in fuel cells. Current PEM technology involves biocummulative perfluorinated membranes that operate under hydrated conditions, for which the proton conductivity is limited by the usually high temperature that fuel cells operate. Therefore, it is of great interest to study the alternative systems that have the potential to conduct protons, in particular, those that are able to …

Adapting Small Unmanned Aerial Systems For Behavioral Research With Coastal Marine Mammals, Eric Angel Ramos

Dissertations, Theses, and Capstone Projects

Marine mammals inhabit aquatic worlds where their subsurface behavior, cryptic surface profiles, and movements make them difficult to study. New tools are needed to study coastal marine mammals in a world increasing impacted by climate change related shifts in weather and animal distribution patterns. Unmanned aerial systems (UAS) are important remote-sensing tools for studying a range of wildlife including terrestrial and aquatic flora and fauna. These systems offer flexible platforms for adding sensor packages needed for different applications, for example, most are equipped with high-resolution cameras and GPS sensors. The vantage point from an aerial platform dramatically improves the ability …

An In Silico Approach To Investigate The Structural And Biochemical Basis Of The Rna Binding Functions Of Nucleolin, Avdar San

Dissertations, Theses, and Capstone Projects

Nucleolin (NCL) is a stress responsive multifunctional nucleolar protein and accounts for 10% of the total nucleolar protein content. NCL belongs to the class of RNA binding proteins (RBPs) that regulate many important cellular processes through their interactions with different RNA molecules. The dysregulation of RBPs and the RNA metabolism pathways they intersect is a known driver of tumorigenesis. NCL regulates ribosome biogenesis, chromatin remodeling, microRNA processing, and gene expression on multiple levels. The RNA-protein interactions of NCL are primarily driven by its four RNA binding domains (RBDs). NCL is known to interact with a growing list of primary-miRNA (pri-miRNA) …

Maternal Wellness: Self, Matrescence, Obstetric Violence, And Self-Care, Vanessa V. Vales-Lewis

Dissertations, Theses, and Capstone Projects

In this dissertation, I engage in a self-study through an examination of my experience of matrescence (i.e., the transition to motherhood). I discuss my praxis in the development of a self-study on maternal wellness as it applies to my well-being as both a researcher and the researched. In Chapter 1, I preface this study by highlighting critical scholars and the bricoleurs who have been foundational in my undertaking of this work on a narrative study on maternal wellness. Using bricolage as part of a research methodological framework that involved key scholarly methodologies of authentic inquiry, emergence and contingence, and narratology, …

Committed To The Fragment: Feminist Literature And The Promise Of Wellness, Lynne Beckenstein

Dissertations, Theses, and Capstone Projects

“I have never been able to blind myself” to the cruelty of a world that “destroys its own young in passing…out of not noticing or caring about the destruction,” Audre Lorde tells us in her 1980 “mythobiography” Zami: A New Spelling of My Name. This quality, Lorde says, “according to one popular definition of mental health, makes me mentally unhealthy.” In rejecting psychological self-possession as a sign of wellness, this passage also rejects it as one of sovereignty’s conditions. At the time of Lorde’s writing, this version of sovereignty already dominated the landscape of therapeutic culture in the United States, …

Role Of Metals In Human Immune System: Study Of Metal-Dependent Structural Changes Of S100a12 Protein, Aleksey Aleshintsev

Dissertations, Theses, and Capstone Projects

S100A12 protein belongs to the S100 family of calcium-binding proteins and participates in the innate immune system. Antimicrobial proteins from the S100 family of the proteins (S100A12, S100A8/A9, etc.) are secreted and expressed by neutrophils during microbial infection and perform their antimicrobial activity through metal sequestration. While most S100 proteins function intracellularly, S100A12 is highly expressed and secreted into the extracellular space by neutrophils during infection. Sequestration of Zn²⁺ by S100A12 is aided by the nanomolar zinc binding affinity of the protein at neutral pH conditions, which is further enhanced upon calcium-binding. The Zn²⁺ binding scaffold in S100A12 …

Surveilling The Fat Disidencia: Policing The Bodies Of Plus-Size Black Women On Instagram, Daniela V. Verdejo Salazar

Dissertations, Theses, and Capstone Projects

Instagram has shaped how we network and share content with others, making interactions far more accessible for everyone who uses this platform daily. Unfortunately, it has also given space to some surveilling mechanisms that tend to police and norm how users and their bodies should present themselves to the rest of the world.

The body can be understood as a manifestation, a presence, and a performance. As Judith Butler argues, the body is also a political space where ideas of resistance and vulnerability take place, and I will understand the body as a combination of the physical manifestation of it …

Structural And Biochemical Investigations Of The Initiation Of Dna Replication In Bacteriophage Lambda And Escherichia Coli, Jillian D. Chase

Dissertations, Theses, and Capstone Projects

Faithful transmission of genetic information is requisite for the propagation of all life. DNA replication in each of the three domains of life requires the separation of double stranded DNA (dsDNA) into single stranded DNA (ssDNA) which then serves as a template for genomic duplication of each original DNA strand. Initiation of replication events occurs by tightly regulated processes during which specialized proteins are loaded at a specific locus within the genome, termed the origin of replication, in preparation of bidirectional replication events. A replicative helicase must be loaded or assembled on both strands of DNA at the origin to …

Girl Friends, Camila Santander

Dissertations, Theses, and Capstone Projects

Friendships between women are common and essential parts of women's lives; however, they are often overlooked. This capstone project titled Girl Friends is a film on which eight women are interviewed and asked about their friendships with other women. They discuss the importance of having female friends and how they create love, support, and companionship. The interviewees also talk about female friendships and romantic partners coexisting, the pressures to find a romantic partner to find fulfillment, as opposed to good friends. Additionally, they describe how friendships between women can be competitive and catty, and how female relationships can change as …

Conservation, Comparative Genomics And Species Delimitation Of The Reindeer Lichens (Cladonia), Jordan R. Hoffman

Dissertations, Theses, and Capstone Projects

The genus Cladonia represents one of the most speciose genera of lichenized fungi, with more than 500 known species encompassing a diverse array of morphologies and habits. These lichens form keystone species in many habitats, serving a variety of ecological roles. However, despite being among of the more well studied lichens, there is much still unknown or under-studied about them. As is the case with most lichen study systems, phylogenetic study has been limited to a small number of partial loci, while adoption of next-generation sequence methods has been slow. As a consequence, there are still knowledge gaps in Cladonia …

Paddling Along The Voltage Gated Sodium Channel Galaxy With Sea Anemone Toxins: Structural Studies Of The Interaction Between The Paddle Motif From Nav1.5div And Sea Anemone Toxin, Adel K. Hussein

Dissertations, Theses, and Capstone Projects

Voltage gated sodium channels (VGSC) are membrane proteins that serve an important function in the central nervous system (CNS), peripheral nervous system (PNS), and cardiac muscles amongst others. The main function of VGSC is in the propagation of electrical signals by depolarizing excitable cells. Nine mammalian VGSC subtypes have been characterized, Na_V1.1 – Na_V1.9, that are expressed in a tissue specific manner, each with unique gating properties. Numerous diseases have been linked to defects in VGSC including epilepsy, mental retardation, long QT syndrome, and Brugada disease. Furthermore, these channels are one of the primary targets of …

Understanding Species Interactions And Their Impacts In Restored Communities, Jennifer Zhu

Dissertations, Theses, and Capstone Projects

Species interactions may mediate the ability of organisms to survive in a community and provide valued services but are rarely fully considered in restoration planning. To address this, I considered how service provisioning will change as restored marsh communities mature and the value of incorporating antipredator training into captive-rearing programs.

For chapter 1, I explored how a facultative mutualism between Atlantic ribbed mussels Geukensia demissa and cordgrass Spartina alterniflora may enhance marsh growth and nitrogen cycling in a eutrophic setting. I created experimental plots in Jamaica Bay, NY, that contained live mussels, mussel shells, or no mussels (control) and measured …

February Cvm Library Newsletter

CVM Library Newsletters

February CVM Library Newsletter

Mule Deer Do More With Less: Comparing Their Nutritional Requirements And Tolerances With White-Tailed Deer, Anna R. Staudenmaier, Lisa A. Shipley, Meghan J. Camp, Jennifer S. Forbey, Ann E. Hagerman, Abigail E. Brandt, Daniel H. Thornton

Biology Faculty Publications and Presentations

Congeneric species often share ecological niche space resulting in competitive interactions that either limit co-occurrence or lead to niche partitioning. Differences in fundamental nutritional niches mediated through character displacement or isolation during evolution are potential mechanisms that could explain overlapping distribution patterns of congenerics. We directly compared nutritional requirements and tolerances that influence the fundamental niche of mule (Odocoileus hemionus) and white-tailed deer (O. virginianus), which occur in allopatry and sympatry in similar realized ecological niches across their ranges in North America. Digestible energy and protein requirements and tolerances for plant fiber and plant secondary …

Alterations Of Host-Gut Microbiome Interactions In Multiple Sclerosis, Claudia Cantoni, Laura Ghezzi, Emily Evans, Li Deng, Alberto Locca, Robert Mikesell, Kathleen Obert, Amber Salter, Anne H Cross, Phillip I Tarr, Laura Piccio, Yanjiao Zhou, Et Al

Open Access Publications

BACKGROUND: Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder.

METHODS: We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted …

Mitochondrial Pyruvate Carrier Inhibitors Improve Metabolic Parameters In Diet-Induced Obese Mice, Wesley T Hodges, Chaowapong Jarasvaraparn, Daniel Ferguson, Kristine Griffett, Lauren E Gill, Yana Chen, Ma Xenia G Ilagan, Lamees Hegazy, Bahaa Elgendy, Kevin Cho, Gary J Patti, Kyle S Mccommis, Brian N Finck

Open Access Publications

The mitochondrial pyruvate carrier (MPC) is an inner mitochondrial membrane complex that plays a critical role in intermediary metabolism. Inhibition of the MPC, especially in liver, may have efficacy for treating type 2 diabetes mellitus. Herein, we examined the antidiabetic effects of zaprinast and 7ACC2, small molecules which have been reported to act as MPC inhibitors. Both compounds activated a bioluminescence resonance energy transfer-based MPC reporter assay (reporter sensitive to pyruvate) and potently inhibited pyruvate-mediated respiration in isolated mitochondria. Furthermore, zaprinast and 7ACC2 acutely improved glucose tolerance in diet-induced obese mice in vivo. Although some findings were suggestive of improved …

The Foundations And Development Of Lipidomics, Xianlin Han, Richard W Gross

Open Access Publications

For over a century, the importance of lipid metabolism in biology was recognized but difficult to mechanistically understand due to the lack of sensitive and robust technologies for identification and quantification of lipid molecular species. The enabling technological breakthroughs emerged in the 1980s with the development of soft ionization methods (Electrospray Ionization and Matrix Assisted Laser Desorption/Ionization) that could identify and quantify intact individual lipid molecular species. These soft ionization technologies laid the foundations for what was to be later named the field of lipidomics. Further innovative advances in multistage fragmentation, dramatic improvements in resolution and mass accuracy, and multiplexed …

Protocol Versus Practice: Deviations From 2 Guidelines In Low-Risk Twin Deliveries In The United States, Julia M. Morris, Andrea Bertotti

Sociology & Criminology Faculty Research

Background

Medical guidelines recommend vaginal delivery for low-risk twin pregnancies because cesareans increase the probability of maternal morbidity and mortality. Yet, vaginal delivery rates for twins are considerably lower than for comparable singletons. One explanation for this disparity argues that greater risk associated with twins warrants increased surgical intervention. An alternative explanation is that twin deliveries are more likely to deviate from protocols that advise vaginal birth.

Methods

Using the 2017 Natality Detail File (N = 3,197,401), we measured alignment of vaginal birth and trial of labor (TOL) with the American College of Obstetricians and Gynecologists’ guidelines for twin and …

Dna Ligase Iv Mutations Confer Shorter Lifespan And Increased Sensitivity To Nutrient Stress In Drosophila Melanogaster, Rashmi Joshi, Surya Jyoti Banerjee, Jennifer Curtiss, Amanda K. Ashley

Faculty Publications - Biological Sciences

The nonhomologous end-joining pathway is a primary DNA double-strand break repair pathway in eukaryotes. DNA ligase IV (Lig4) catalyzes the final step of DNA end ligation in this pathway. Partial loss of Lig4 in mammals causes Lig4 syndrome, while complete loss is embryonically lethal. DNA ligase 4 (DNAlig4) null Drosophila melanogaster is viable, but sensitive to ionizing radiation during early development. We proposed to explore if DNAlig4 loss induced other long-term sensitivities and defects in D. melanogaster. We demonstrated that DNAlig4 mutant strains had decreased lifespan and lower resistance to nutrient deprivation, indicating Lig4 is required for maintaining health and …