Biochemistry, Biophysics, and Structural Biology Commons^™

Mouse Models Of Spontaneous Atrial Fibrillation, Joshua A Keefe, Mohit M Hulsurkar, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is the most common arrhythmia in adults, with a prevalence increasing with age. Current clinical management of AF is focused on tertiary prevention (i.e., treating the symptoms and sequelae) rather than addressing the underlying molecular pathophysiology. Robust animal models of AF, particularly those that do not require supraphysiologic stimuli to induce AF (i.e., showing spontaneous AF), enable studies that can uncover the underlying mechanisms of AF. Several mouse models of AF have been described to exhibit spontaneous AF, but pathophysiologic drivers of AF differ among models. Here, we describe relevant AF mechanisms and provide an overview of …

Comprehensive Ecg Reference Intervals In C57bl/6n Substrains Provide A Generalizable Guide For Cardiac Electrophysiology Studies In Mice, Manuela A Oestereicher, Janine M Wotton, Shinya Ayabe, Ghina Bou About, Tsz Kwan Cheng, Jae-Hoon Choi, Dave Clary, Emily M Dew, Lahcen Elfertak, Alain Guimond, Hamed Haseli Mashhadi, Jason D Heaney, Lois Kelsey, Piia Keskivali-Bond, Federico Lopez Gomez, Susan Marschall, Michael Mcfarland, Hamid Meziane, Violeta Munoz Fuentes, Ki-Hoan Nam, Zuzana Nichtová, Dale Pimm, Lynette Bower, Jan Prochazka, Jan Rozman, Luis Santos, Michelle Stewart, Nobuhiko Tanaka, Christopher S Ward, Amelia M E Willett, Robert Wilson, Robert E Braun, Mary E Dickinson, Ann M Flenniken, Yann Herault, K C Kent Lloyd, Ann-Marie Mallon, Colin Mckerlie, Stephen A Murray, Lauryl M J Nutter, Radislav Sedlacek, Je Kyung Seong, Tania Sorg, Masaru Tamura, Sara Wells, Elida Schneltzer, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe De Angelis, Jacqueline K White, Nadine Spielmann

Faculty, Staff and Students Publications

Reference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key …

Magnesium Increases Numbers Of Foxp3+ Treg Cells And Reduces Arthritis Severity And Joint Damage In An Il-10-Dependent Manner Mediated By The Intestinal Microbiome, Teresina Laragione, Carolyn Harris, Nasim Azizgolshani, Christine Beeton, Gerold Bongers, Percio S Gulko

Faculty, Staff and Students Publications

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with emerging environmental and microbiome risk factors. The western diet is typically deficient in magnesium (Mg), and there is some evidence suggesting that Mg may have anti-inflammatory properties. But the actual role of Mg supplementation in arthritis or in T cell subsets has not been explored.

METHODS: We investigated the role of a high Mg diet in two different mouse models of RA induced with the KRN serum, and collagen-induced arthritis. We also characterized the phenotypes of splenocytes, gene expression, and an extensive intestinal microbiome analyses including fecal material transplantation (FMT). …

Continuum Modeling Of Active Nematics Via Data-Driven Equation Discovery, Connor Robertson

Dissertations

Data-driven modeling seeks to extract a parsimonious model for a physical system directly from measurement data. One of the most interpretable of these methods is Sparse Identification of Nonlinear Dynamics (SINDy), which selects a relatively sparse linear combination of model terms from a large set of (possibly nonlinear) candidates via optimization. This technique has shown promise for synthetic data generated by numerical simulations but the application of the techniques to real data is less developed. This dissertation applies SINDy to video data from a bio-inspired system of mictrotubule-motor protein assemblies, an example of nonequilibrium dynamics that has posed a significant …

Bola3 And Nfu1 Link Mitoribosome Iron-Sulfur Cluster Assembly To Multiple Mitochondrial Dysfunctions Syndrome, Hui Zhong, Alexandre Janer, Oleh Khalimonchuk, Hana Antonicka, Eric Shoubridge, Antoni Barrientos

Department of Biochemistry: Faculty Publications

The human mitochondrial ribosome contains three [2Fe-2S] clusters whose assembly pathway, role, and implications for mitochondrial and metabolic diseases are unknown. Here, structure-function correlation studies show that the clusters play a structural role during mitoribosome assembly. To uncover the assembly pathway, we have examined the effect of silencing the expression of Fe-S cluster biosynthetic and delivery factors on mitoribosome stability. We find that the mitoribosome receives its [2Fe-2S] clusters from the GLRX5-BOLA3 node. Additionally, the assembly of the small subunit depends on the mitoribosome biogenesis factor METTL17, recently reported containing a [4Fe-4S] cluster, which we propose is inserted via the …

Silica Concentrations In Dominant Vegetation Species Of Wax Lake Delta, Louisiana, Danielle M. Soileau

LSU Master's Theses

Coastal deltaic wetlands colonize dynamic environments and experience fluctuations of salinity, river connectivity, sediment dredging or deposition, and periods of inundation resulting in unique vegetation and soils. Louisiana’s coastline is experiencing enhanced loss of coastal deltaic wetlands in coastal basins where the Mississippi River no longer is connected to waterways and channels that would normally provide freshwater and sediments representing the abandonment phase of the delta cycle. There is a coastal basin in the central regions of the state, the Atchafalaya Bay, that is still in the active phase of delta cycle resulting in the growth of the Wax Lake, …

Migratory Material: Epigenetics & Weaving At The Us-Mexico Border, Valerie Navarrete

Masters Theses

Discourse often sutures the body shut, disallowing representations of identity to outgrow sociopolitical interests. This issue may originate from borders, but also from the unnamable pathology that generational colonial trauma transmits to the mind, body, and environment. Without a direct form of translatability, this thesis proposes a new materialism that deviates from any object-oriented ontology. Untethered and intra-active, epigenetics and weaving represent objects that transform typical ways of knowing and seeing. Their sensitivity to the environment, in addition to their mobility across generations of time, broaden the spatiotemporal loci of the body and its embodiment. Proposing new materials that expand …

Ethical Issues And Standards Of Responsible Research Conduct And Monitoring In An Adventist Institution Of Higher Learning - The Babcock Experience, Kayode O. Ogunwenmo, Godswill N. Anyasor, Grace O. Tayo

Adventist Human-Subject Researchers Association

Ethical issues and standards of responsible research conduct involving human participants are important considerations in any institution of higher learning and in particular Adventist institutions. Research conduct and ethics are reviewed and approved before they begin by the Babcock University Health Research Ethics Committee (BUHREC)

Artemisinin And Its Derivatives Reactions: Characterization Of The Reaction Products Using Lc/Tof Ms, Kogila Vijayan

Theses and Dissertations

Artemisinin (ART) is a sesquiterpene lactone and a popular malaria drug with potential anticancer properties. In this work, LC/TOF MS was used to investigate the reaction of ART with DNA bases and estradiol. ART-deoxyadenosine and ART-deoxycytidine interactions were studied in the presence of Fe (II) ions. ART-deoxyadenosine and ART-deoxycytidine reaction mixtures gave chromatographic signatures that remained unchanged at room temperature but grew after incubation at 37°C. The change in temperature from room temperature to 37°C was the main driver of adduct formation in these reactions. ART was found to react with Fe (II) ions as observed from several new chromatographic …

Serological Prevalence Of Crimean–Congo Hemorrhagic Fever Virus Infection In Small Ruminants And Cattle In The Gambia, Jerusha Matthews, Arss Secka, David Scott Mcvey, Kimberly A. Dodd, Bonto Faburay

School of Veterinary and Biomedical Sciences: Faculty Publications

Crimean–Congo hemorrhagic fever virus (CCHFV) is a widely distributed tickborne zoonotic agent that infects a variety of host species. There is a lack of information on the true geographic distribution of the prevalence and risk of CCHFV in West Africa. A countrywide cross-sectional study involving 1413 extensively managed indigenous small ruminants and cattle at livestock sales markets and in village herds, respectively, was carried out in The Gambia. In sheep, an overall anti-CCHFV antibody prevalence of 18.9% (95% CI: 15.5–22.8%), goats 9.0% (95% CI: 6.7–11.7%), and cattle 59.9% (95% CI: 54.9–64.7%) was detected. Significant variation (p < 0.05) in the prevalence of anti-CCHFV antibodies at sites in the five administrative regions (sheep: 4.8–25.9%; goats: 1.8–17.1%) and three agroecological zones (sheep: 8.9–32.9%; goats: 4.1–18.0%) was also observed. Comparatively, higher anti-CCHFV antibody prevalence was detected in cattle (33.3–84.0%) compared to small ruminants (1.8–8.1%). This study represents the first countrywide investigation of the seroprevalence of CCHFV in The Gambia, and the results suggest potential circulation and endemicity of the virus in the country. These data provide critical information vital to the development of informed policies for the surveillance, diagnosis, and control of CCFHV infection in The Gambia and the region.

Sequential Absorption Of Two Photons Creates A Bistable Form Of Rubyacr Responsible For Its Strong Desensitization, Oleg A Sineshchekov, Elena G Govorunova, Hai Li, Yumei Wang, John L Spudich

Faculty, Staff and Student Publications

Channelrhodopsins with red-shifted absorption, rare in nature, are highly desired for optogenetics because light of longer wavelengths more deeply penetrates biological tissue. RubyACRs (Anion ChannelRhodopsins), a group of four closely related anion-conducting channelrhodopsins from thraustochytrid protists, are the most red-shifted channelrhodopsins known with absorption maxima up to 610 nm. Their photocurrents are large, as is typical of blue- and green-absorbing ACRs, but they rapidly decrease during continuous illumination (desensitization) and extremely slowly recover in the dark. Here, we show that long-lasting desensitization of RubyACRs results from photochemistry not observed in any previously studied channelrhodopsins. Absorption of a second photon by …

Does Caffeine Consumption Affect Work Performance Across Different Job Types?, Bryan Js Goh, Joshua Tan, Cleavon Chong, Sean Ker

Introduction to Research Methods RSCH 202

We propose executing a panel series case study for a large organization in Singapore over a year to examine how caffeine impacts work performance across different job types. Our research question is how does caffeine affect work performance under different conditions due to work type differences. Our dependent variable would be work performance as measured by employees’ Key Performance Indicators (KPIs). We propose to gather data for two of our important independent variables: caffeine use through a recorded pantry system and average sleep hours from a survey. We will analyze the data by using two-factor ANOVA with replication to find …

Identifying The Temporal N-Linked Glycosylation Changes During Liver Disease Progression: From Liver Injury To End-Stage Liver Disease, Shaaron Ochoa-Rios

MUSC Theses and Dissertations

The high mortality rates of liver diseases and primary liver cancers can be attributed to the lack of screening and diagnostic strategies currently available for early detection. Non-alcoholic fatty liver disease (NAFLD) is an early stage of liver disease known to progress to a variety of pre-malignant and malignant conditions, like advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA). Based on the wide variety of diseases that NAFLD can progress to, strategies to understand and detect the progression of NAFLD are of great value. Core fucosylation of N-linked glycans has been demonstrated to be useful for the clinical diagnosis …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

Comprehensive Investigation Of The Role Of Cd38 In Ovarian Nad+ Metabolism And Reproductive Aging, Lauren Haky

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Nicotinamide adenine dinucleotide (NAD+) is a cofactor and coenzyme found in all living cells and is crucial for energy metabolism and tissue homeostasis. It is well documented that several tissues exhibit an age-related NAD+ decline which is strongly associated with aging and age-associated diseases. While the underlying cause of NAD+ decline is unknown, one possibility is that the major NAD+ consuming enzyme, CD38, may drive tissue NAD+ decline during aging. Several studies have previously reported that NAD+ precursor supplementation or CD38 inhibition increased tissue NAD+ levels, overall health, and lifespan in mice.

Women experience an irreversible decline in reproductive health …

Effects Of Membrane Components On The Oligomerization Of Amyloid-Β (Aβ) In Alzheimer Disease, Jhinuk Saha

Dissertations

Deposition of extracellular proteinaceous plaques of amyloid-β (Aβ) is one of the major hallmarks of Alzheimer disease (AD). Although, insoluble high molecular fibrils of Aβ are the main constituents of the senile plaques in AD, low molecular weight soluble Aβ oligomers have emerged as the key toxic species involved in memory impairment and neuronal cell death in AD. The process for generation of oligomers can be highly diverse and can involve homotypic interactions of Aβ as well as heterotypic interaction of Aβ with other macromolecules. Previously, the generation of Aβ oligomers with distinct biochemical and biophysical characteristics catalyzed non-esterified fatty …

Investigating The Role Of Tgf-Beta Signaling In Acoel Regeneration & Fission, Franchesca A. Aziz

Undergraduate Honors Theses

Whole-body regeneration and asexual reproduction are widespread in the Metazoa, yet little is known about the genetic systems that drive the regeneration process outside of a few model organisms. While many animals utilize fission followed by regeneration to accomplish asexual reproduction, Convolutriloba longifissura is unusual in performing a double fission, requiring significant anterior-posterior and medial-lateral regeneration that alters the orthogonal body axes in adult tissues. To better understand the process of axial re-specification during postembryonic development, we studied the genetic mechanisms used by C. longifissura to modify and respecify axial polarity during asexual reproduction and subsequent regeneration. Because conserved signaling …

Cardiac Pericytes Mediate The Remodeling Response To Myocardial Infarction, Pearl Quijada, Shuin Park, Peng Zhao, Kamal Ss Kolluri, David Wong, Kevin D Shih, Kai Fang, Arash Pezhouman, Lingjun Wang, Ali Daraei, Matthew D Tran, Elle M Rathbun, Kimberly N Burgos Villar, Maria L Garcia-Hernandez, Thanh Td Pham, Charles J Lowenstein, M Luisa Iruela-Arispe, S Thomas Carmichael, Eric M Small, Reza Ardehali

Faculty, Staff and Students Publications

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac …

Diffusion Of Ionic Liquid-Modified Polymer Nanoparticles Through Nasal Mucus, Mary Vanlandingham

Honors Theses

Mucosal barriers are a natural defense system for preventing the entry of foreign objects into the body; however, they pose as obstacles for effective drug delivery. Coated polymer nanoparticles have been proven to possess improved rates of diffusion across mucus compared to their uncoated, or bare, counterparts. When choline-based ionic liquids (ILs) are introduced to an aqueous system, their dissociation leads to an increase in solution conductivity which ultimately reduces the viscosity of mucus without significantly affecting its structure. Additionally, ILs are highly tunable, so they work well in a range of pHs and conductivities, making ILs an ideal choice …

A Synthetic Approach To The Optimization Of Silicon-Rosindolizine Swir Fluorophores, Timothy Lewis

Honors Theses

Fluorophores emitting within the near-infrared (700 – 1000 nm) or shortwave-infrared (1000 – 1700 nm) regions of the electromagnetic spectrum are of particular interest for their potential to supplement or even outright replace commonly used biological imaging techniques, such as magnetic resonance imaging and computed tomography scanning. Various characteristics make these molecules particularly appealing to researchers, such as their ease of synthetic tunability, generally low toxicity, and high solubility in biological media in comparison to other NIR- and SWIR-emissive fluorophores. Different molecular skeletons have been examined for use as the core of these imaging agents, such as squaraine, cyanine, and …