Biochemistry, Biophysics, and Structural Biology Commons^™

Defining A Dynamic Architecture Of Protein Tyrosine Phosphatases, Colin L. Welsh

MUSC Theses and Dissertations

Protein tyrosine phosphatases (PTPs), a critical class of signaling enzymes, are principally responsible for balancing the actions of kinases through the dephosphorylation of tyrosine residues on substrate proteins. As such, this family is involved in myriad pathways and individual members are able to perform both oncogenic and tumor-suppressing roles. However, while clinical success has been achieved in targeting kinases, PTPs have remained therapeutically challenging. Orthosteric inhibition is limited in PTPs due to their highly conserved fold, leading to off-target effects, and their highly charged active site, requiring highly polar molecules with poor bioavailability. These challenges posit the allosteric inhibition of …

Exploring Chilling Stress And Recovery Dynamics In C4 Perennial Grass Of Miscanthus Sinensis, Karolina Sobańska, Monika Mokrzycka, Martyna Przewoźnik, Tomasz Pniewski, Katarzyna Glowacka

Department of Biochemistry: Faculty Publications

The increasing cultivation of perennial C4 grass known as Miscanthus spp. for biomass production holds promise as a sustainable source of renewable energy. Unlike the sterile triploid hybrid of M. × giganteus, which cannot reproduce through seeds, M. sinensis possesses attributes that could potentially address these limitations by effectively establishing itself through seed propagation. This study aimed to investigate how 18 genotypes of M. sinensis respond to chilling stress and subsequent recovery. Various traits were measured, including growth and biomass yield, the rate of leaf elongation, and a variety of chlorophyll fluorescence parameters, as well as chlorophyll …

Mutant Androgen Receptor Induces Neurite Loss And Senescence Independently Of Are Binding In A Neuronal Model Of Sbma, Jordyn Karliner, Y Liu, Diane Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is a slowly progressing neuromuscular disease caused by a polyglutamine (polyQ)-encoding CAG trinucleotide repeat expansion in the androgen receptor (AR) gene, leading to AR aggregation, lower motor neuron death, and muscle atrophy. AR is a ligand-activated transcription factor that regulates neuronal architecture and promotes axon regeneration; however, whether AR transcriptional functions contribute to disease pathogenesis is not fully understood. Using a differentiated PC12 cell model of SBMA, we identified dysfunction of polyQ-expanded AR in its regulation of neurite growth and maintenance. Specifically, we found that in the presence of androgens, polyQ-expanded AR inhibited neurite …

Functional And Structural Analysis Of The Neimann-Pick Disease Type C Pathway To Include Caveolin-1, Anthony Michael Seat

Chemistry and Chemical Biology ETDs

Human disease is often thought of as an all or nothing prospect, either one has the disease or one does not. This does not bear out in clinical or personal experiences, instead demonstrating that disease occurs within a spectrum ranging from presumed unaffected to demonstrably and detrimentally affected.Neimann-Pick disease is one example of this spectrum look into diseased states, with multiple named versions of a phenotypically similar disease. We focus on Neimann-Picktype C (NPC), which is the result of a disruption in the efflux of cholesterol and sphingolipids from the endocytic pathway. NPC demonstrates this concept of a spectrum of …

Role Of Sds-22/Pp1 Phosphatase In Polarizing The Germplasm Of Caenorhabditis Elegans Embryo, Aparna Nurni Ravi

Dartmouth College Ph.D Dissertations

During asymmetric cell division, cell polarity and cell cycle are tightly coupled to ensure robust segregation of cell fate determinants and generation of cellular diversity. In the one-cell C. elegans embryo, multiple cell cycle kinases regulate cell polarization and posterior segregation of germline fate determinants (germplasm). For example, PLK-1 kinase inhibits the retention of its germplasm substrate POS-1 in the anterior, driving POS-1 segregation to the posterior (Han et al., 2018). Additionally, MBK-2 kinase disassembles P granules in the anterior through phosphorylation of the P granule scaffold MEG-3, helping to drive P granule segregation to the posterior (Wang et al., …

Genetic Diversity Of 1,845 Rhesus Macaques Improves Genetic Variation Interpretation And Identifies Disease Models, Jun Wang, Meng Wang, Ala Moshiri, R Alan Harris, Muthuswamy Raveendran, Tracy Nguyen, Soohyun Kim, Laura Young, Keqing Wang, Roger Wiseman, David H O'Connor, Zach Johnson, Melween Martinez, Michael J Montague, Ken Sayers, Martha Lyke, Eric Vallender, Tim Stout, Yumei Li, Sara M Thomasy, Jeffrey Rogers, Rui Chen

Faculty, Staff and Students Publications

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which …

Conformational Alterations Of The Cell Surface Of Monomeric And Dimeric Β2m-Free Hla-I (Proto-Hla) May Enable Novel Immune Functions In Health And Disease, Mepur Ravindranath, Narendranath Ravindranath, Carly Amato-Menker, Fatiha El Hilali, Edward Filippone

Division of Nephrology Faculty Papers

Human leukocyte antigens (HLAs) are polymorphic glycoproteins expressed on the cell surface of nucleated cells and consist of two classes, HLA class I and HLA class II. In contrast, in mice, these molecules, known as H-2, are expressed on both nucleated cells and erythrocytes. HLA-I molecules (Face-1) are heterodimers consisting of a polypeptide heavy chain (HC) and a light chain, B2-microglobulin (B2m). The heterodimers bind to antigenic peptides and present them to the T-cell receptors of CD8+ cytotoxic T lymphocytes. The HCs can also independently emerge on the cell surface as B2m-free HC monomers without peptides (Face-2). Early investigators suggested …

Use Of Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands And Berberine Chloride As Anti-Cancer Agents Against Triple Negative Breast Cancer, Duaa Rashad Alajroush

Chemistry & Biochemistry Theses & Dissertations

It is a worrying fact that chemotherapeutic options for treating triple negative breast cancer are limited in nature, including the use of inorganic pharmaceuticals such as cisplatin and its analogues. It has been reported that cisplatin has undesirable side effects when used as a chemotherapeutic drug. As such, there is a need to use non-platinum-containing complexes as chemotherapeutic agents. Based on that issue, it has been reported by our research group and others that cobalt- and copper-containing complexes have shown great potential in anti-cancer properties when compared to cisplatin. In this research project, the cytotoxic effects of the following complexes: …

Study Of Atypical Alarmone Synthesis In Clostridioides Difficile, Declan Nathaniel Butler

Chemistry & Biochemistry Theses & Dissertations

Clostridioides difficile is a Gram-positive anaerobic bacterium that causes infections in humans that costs healthcare systems billions per year. C. difficile infection has high rates of recurrence due to multiple antibiotic resistance. When bacteria are in stressful environments, they produce hyperphosphorylated guanosine ribonucleotide signaling molecules called alarmones. The accumulation of alarmones activates the stringent response (SR), in which bacterial cells induce transcription of stress survival genes to delay growth and replication. The C. difficile SR is regulated by enzymatic activity of a bifunctional synthetase/hydrolase, RelA/SpoT homolog (RSH), and a monofunctional small alarmone synthetase (RelQ). Additionally, the SR is potentially regulated …

Exploring The Effects Of An Alfalfa Leaf-Derived Adsorbent On Microbial Community, Ileal Morphology, Barrier Function, And Immunity In Turkey Poults During Chronic Aflatoxin B1 Exposure, Maria De Jesus Nava-Ramirez, Jing Liu, Juan Omar Hernandez-Ramirez, Xochitl Hernandez-Velasco, Juan D. Latorre, Alma Vazquez-Duran, Guolong Zhang, Roberto Señas-Cuesta, Sergio Gomez-Rosales, Andressa Stein, Billy M. Hargis, Guillermo Tellez-Isaias, Abraham Mendez-Albores, Jesus A. Maguey-Gonzalez

Poultry Science Faculty Publications and Presentations

This article follows-up on our recently published work, which evaluated the impact of the addition of an alfalfa leaf-derived adsorbent in the aflatoxin B₁ (AFB₁)-contaminated diet in regard to the production parameters, blood cell count, serum biochemistry, liver enzymes, and liver histology of turkey poults. This paper presents complementary results on microbial community, ileal morphology, barrier function, and immunity. For this purpose, 350 1-day-old female turkey poults were randomly distributed into five groups: (1) Control, AFB₁-free diet; (2) AF, AFB₁-contaminated diet at 250 ng/g; (3) alfalfa, AFB₁-free diet + 0.5% ( …

Structural Analysis Of Dj-1 Glyoxalase Activity By Mix-And-Inject Serial Synchrotron Crystallography, Coleman Dolamore

Department of Biochemistry: Dissertations, Theses, and Student Research

Observing enzyme structures while they are catalyzing a reaction has been a major goal of both enzymology and structural biology for decades. With the advent of time-resolved serial X-ray crystallography using X-ray free electron lasers (XFELs) and synchrotron sources, enzyme reactions can be monitored in real time in crystallo. Here, we use two different approaches to study related enzymes involved in methylglyoxal detoxification. For human DJ-1, we used pink beam mix-and-inject serial crystallography (MISC) at the Advanced Photon Source (BioCARS 14-ID) to probe the controversial mechanism of DJ-1’s action on methylglyoxal by using serial Laue diffraction. The high flux …

Identifying The Relative Abundance Of Cell-Cell Signaling Peptides During Mammalian Hibernation And Anesthetic Administration By Label-Free Peptidomics Analysis, Somayeh Mousavi

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Cell-cell signaling molecules known as neuropeptide and peptide hormones, distributed in both the central nervous system (CNS) and the peripheral nervous system (PNS), regulate a variety of physiological processes including body temperature, feeding, circadian rhythm, reproduction, energy homeostasis, and more. While a number of active neuropeptides structures with physiological functions have been discovered, advances in peptidomic mass spectrometry are enabling researchers to uncover novel, previously unknown, active neuropeptide structures with potential for bioactivities. Using liquid chromatography coupled with tandem mass spectrometry (MS/MS), it is possible to identify a wide range of neuropeptides in single experiments without preselecting specific peptides. Mass …

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …

Wee1 And Cell Size Control In Fission Yeast By The Protein Kinase Cdr2, Rachel Berg-Murante

Dartmouth College Ph.D Dissertations

The mechanisms that govern cell size have long been topics of study in the field of cell biology. In eukaryotic cells this size control is tied to checkpoints, a set threshold of minimum necessary growth linked to cyclin dependent kinase activity regulation. In the fission yeast Schizosaccharomyces pombe, the Cdk1 regulatory network is conserved, and G2/M represents the major size checkpoint. Prior to mitosis, Cdk1 is inhibited by phosphorylation applied by Wee1 during G2 phase. Once S. pombe cells have satisfied the size checkpoint, Cdk1 is activated through dephosphorylation by Cdc25. Wee1 is a dose-dependent regulator of mitotic entry …

Development And Characterization Of Β-Cyclodextrin Inclusion Complexes With Enzalutamide For Easing Administration And Efficacy Of The Drug In Crpc, Meghana Kolli

Theses and Dissertations

Prostate cancer (PC) is prevalent among men in the US, often leading to castration-resistant prostate cancer (CRPC) with therapy. This is marked by androgen receptor (AR) overexpression, resistance, mutations, and splice variants. Enzalutamide (ENZ), a nonsteroidal antiandrogen, surpasses first-gen AR inhibitors like Bicalutamide. It's the go-to drug for CRPC. We explore ENZ for self-assembly complex formation, crucial for CRPC treatment. Using the solvent evaporation method, we developed β-cyclodextrin and ENZ self-assembly complexes (β-CD-ENZ). β-CD acts as both agent and solubilizer, FDA-approved and safe. Efficacy was tested on PC cell lines (C4-2B) and (22Rv1), including 3D cultures for cytotoxicity and a …

Soxb1 Transcription Factors Are Essential For Initiating And Maintaining Neural Plate Border Gene Expression, Elizabeth Schock, Joshua R. York, Austin P. Li, Ashlyn Y. Tu, Carole Labonne

Markey Cancer Center Faculty Publications

SoxB1 transcription factors (Sox2/3) are well known for their role in early neural fate specification in the embryo, but little is known about functional roles for SoxB1 factors in non-neural ectodermal cell types, such as the neural plate border (NPB). Using Xenopus laevis, we set out to determine whether SoxB1 transcription factors have a regulatory function in NPB formation. Here, we show that SoxB1 factors are necessary for NPB formation, and that prolonged SoxB1 factor activity blocks the transition from a NPB to a neural crest state. Using ChIP-seq, we demonstrate that Sox3 is enriched upstream of NPB genes in …

Response To Replication Stress And Maintenance Of Genome Stability By Wrn, The Werner Syndrome Protein, David K. Orren, Amrita Machwe

Markey Cancer Center Faculty Publications

Werner syndrome (WS) is an autosomal recessive disease caused by loss of function of WRN. WS is a segmental progeroid disease and shows early onset or increased frequency of many characteristics of normal aging. WRN possesses helicase, annealing, strand exchange, and exonuclease activities and acts on a variety of DNA substrates, even complex replication and re- combination intermediates. Here, we review the genetics, biochemistry, and probably physiological functions of the WRN protein. Although its precise role is unclear, evidence suggests WRN plays a role in pathways that respond to replication stress and maintain genome stability particularly in telomeric regions.

An Electronic Health Record Model For Predicting Risk Of Hepatic Fibrosis In Primary Care Patients, Aaron P Thrift, Theresa H Nguyen Wenker, Kyler Godwin, Maya Balakrishnan, Hao T Duong, Rohit Loomba, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease.

AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes.

METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic …

Subspecialty Choices Among Medicine-Pediatrics Graduates: Results From A Four-Year National Program Director Survey, Anoop Agrawal, Daniel Wells, Michael Kisielewski, Savita Misra, Benjamin Doolittle

Faculty, Staff and Students Publications

Background and objectives Dual-trained medicine-pediatrics physicians (med-peds) play an important role in the healthcare ecosystem. Little is known about the subspecialty choices of med-peds residency graduates. This study aims to characterize the subspecialty choices of med-peds residency graduates. Methods The Medicine-Pediatrics Program Directors Association (MPPDA) administers an annual survey to the program directors of all med-peds residency programs accredited by the Accreditation Council for Graduate Medical Education (ACGME). This project represents aggregate survey data from 2020-2023. Results The number of program directors responding to the survey ranged from 80.8% (63/78) to 85.7% (66/77; mean response rate: 82.8%). About 465 of …

Jacc: Advances Expert Panel Perspective: Shared Decision-Making In Multidisciplinary Team-Based Cardiovascular Care, Elizabeth M Perpetua, Roseanne Palmer, Viet T Le, Sana M Al-Khatib, Craig J Beavers, Joshua A Beckman, Biykem Bozkurt, Megan Coylewright, Caroline Lloyd Doherty, Kimberly A Guibone, Marian Hawkey, Patricia A Keegan, James N Kirkpatrick, Jessica Laperle, Sandra B Lauck, Glenn Levine, Brian R Lindman, Michael J Mack, Andrea L Price, Susan Strong, Janet F Wyman, Quentin R Youmans, Martha Gulati

Faculty, Staff and Students Publications

Shared decision-making (SDM) and multidisciplinary team-based care delivery are recommended across several cardiology clinical practice guidelines. However, evidence for benefit and guidance on implementation are limited. Informed consent, the use of patient decision aids, or the documentation of these elements for governmental or societal agencies may be conflated as SDM. SDM is a bidirectional exchange between experts: patients are the experts on their goals, values, and preferences, and clinicians provide their expertise on clinical factors. In this Expert Panel perspective, we review the current state of SDM in team-based cardiovascular care and propose best practice recommendations for multidisciplinary team implementation …

Carbon-Based Nanocomposite Membranes For Membrane Distillation: Progress, Problems And Future Prospects, Chhabilal Regmi, Yuwaraj K. Kshetri, S. Ranil Wickramasinghe

Chemical Engineering Faculty Publications and Presentations

The development of an ideal membrane for membrane distillation (MD) is of the utmost importance. Enhancing the efficiency of MD by adding nanoparticles to or onto a membrane’s surface has drawn considerable attention from the scientific community. It is crucial to thoroughly examine state-of-the-art nanomaterials-enabled MD membranes with desirable properties, as they greatly enhance the efficiency and reliability of the MD process. This, in turn, opens up opportunities for achieving a sustainable water–energy–environment nexus. By introducing carbon-based nanomaterials into the membrane’s structure, the membrane gains excellent separation abilities, resistance to various feed waters, and a longer lifespan. Additionally, the use …

Decisions, Decisions: Dna Damage Induced Modification Of P53 And The Effect Of Modifications On P53 Differential Binding To The Dna, Savannah Gabrielle Keating

Theses and Dissertations

p53 is the most frequently mutated tumor suppressor protein in cancer. It is highly regulated, most often via post-translational modifications (PTMs). Different pathways and target genes are differentially activated by p53 and there is much left to understand how this occurs. The regulation of p53 at the post-translational level is incredibly important to its DNA damage response, and, therefore, it is understood that PTMs are often involved in the differential activation of pathways by p53. This project aimed to identify some of the types and locations of post-translational modifications on p53 in response to different modes of DNA damage with …

Identifying And Training Deep Learning Neural Networks On Biomedical-Related Datasets, Alan E. Woessner, Usman Anjum, Hadi Salman, Jacob Lear, Jeffrey T. Turner, Ross Campbell, Laura Beaudry, Justin Zhan, Lawrence E. Cornett, Susan Gauch, Kyle P. Quinn

Computer Science and Computer Engineering Faculty Publications and Presentations

This manuscript describes the development of a resources module that is part of a learning platform named 'NIGMS Sandbox for Cloud-based Learning' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement. This module delivers learning materials on implementing deep learning algorithms for biomedical image data in an interactive format that uses appropriate cloud resources for data access and analyses. Biomedical-related datasets are widely used in both research and clinical settings, but the ability for professionally trained clinicians and researchers to interpret datasets becomes difficult as the size and …

Achieving Equitable Cardiovascular Care For All: Acc Board Of Trustees Health Equity Task Force Action Plan, Paul L Douglass, Dipti Itchhaporia, Biykem Bozkurt, Robert O Roswell, Akshay Khandelwal, Quinn Capers, Kathryn Berlacher, Modele O Ogunniyi, Alison L Bailey, Phillip D Levy, Aubrey J Grant, Jack Tocco, Angela Natcheva, Akua G Asare, Ami B Bhatt, Jennifer H Mieres, Maghee F Disch, Melvin R Echols

Faculty, Staff and Students Publications

Advancements in cardiovascular (CV) disease management are notable, yet health inequities prevail, associated with increased morbidity and mortality noted among non-Hispanic African Americans in the United States. The 2002 Institute of Medicine Report revealed ongoing racial and ethnic health care disparities, spearheading a deeper understanding of the social determinants of health and systemic racism to develop strategies for CV health equity (HE). This article outlines the strategic HE approach of the American College of Cardiology, comprising 6 strategic equity domains: workforce pathway inclusivity, health care, data, science, and tools; education and training; membership, partnership, and collaboration; advocacy and policy; and …

Optimizing The Expression Of Polyethylene Terephtalate Hydrolase-Encoding Synthetic Gene In Escherichia Coli Arctic Express (De3), Jocelyn Nataniel, Maria Ulfah, Dini Achnafani, Niknik Nurhayati, Gabriela Christy Sabbathini, Sri Rezeki Wulandari, Abinawanto Abinawanto, Is Helianti

Makara Journal of Science

The waste of polyethylene terephthalate (PET) plastic waste in Indonesia is a pressing concern due to its slow degradation and potential environmental damage. One promising solution is to utilize polyethylene terephthalate hydrolase from Ideonella sakaiensis (IsPETase), an enzyme that specifically degrades PET. However, inducing the expression of IsPETase synthetic gene in Escherichia coli BL21 (DE3) has been challenging because much of it remains insoluble. This study aimed to express IsPETase in E. coli Arctic Express (DE3) and optimize the conditions to enhance its production. First, pET22b(+)pelB-IsPETase was inserted into E. coli Arctic Express (DE3). The …

Comparative Performance Of Modern Jumbo Maize Variety And Local Varieties In Fodder Production Under Different Nitrogen Levels, Haseeb Ahmad, Muhammad Arif, Zubair Ahmed Khan, Saifur Rehman, Ikram Ullah, Raja Akram Khan, Uzair Ahmed, Waleed Iqbal

Journal of Bioresource Management

A trial was carried out at Cereal Crop Research Institute Pirsabak, Pakistan by employing a Randomized Complete Block design that was repeated thrice to investigate the performance of different varieties of maize (Jalal, Kaptan and Jumbo) under four nitrogen levels (N1= 0, N2= 100, N3= 150, and N4= 200 kg ha⁻¹). Variation was observed among maize varieties that affected silking and milking days with variety Jumbo recording the longest duration (62 and 80, respectively). Variety Jumbo also had higher leaf number (11.5), SPAD value (47), leaf area index (LAI) (3.4), Plant height (221 cm) and stem diameter (3.22 …

A Structural Role For Tryptophan In Proteins, And The Ubiquitous Trp CΔ1—H&Centerdot;&Centerdot;&Centerdot;O=C (Backbone) Hydrogen Bond, Michal Szczygiel, Urszula Derewenda, Steve Scheiner, Wladek Minor, Zygmunt S. Derewenda

Chemistry and Biochemistry Faculty Publications

Tryptophan is the most prominent amino acid found in proteins, with multiple functional roles. Its side chain is made up of the hydrophobic indole moiety, with two groups that act as donors in hydrogen bonds: the N^ε—H group, which is a potent donor in canonical hydrogen bonds, and a polarized C^δ1—H group, which is capable of forming weaker, noncanonical bonds. Due to adjacent electron-withdrawing moieties, C—H···O hydrogen bonds are ubiquitous in macromolecules, albeit contingent on the polarization of the donor C—H group. Consequently, C^α groups (adjacent to the carbonyl and amino groups of flanking peptide …

Roles Of Mitochondrial Chchd2 And Gpcr-Associated Β-Arrestin2 In The Pathogenesis Of Lewy Body Disorders, Teresa R. Kee

USF Tampa Graduate Theses and Dissertations

Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a mitochondrial protein that plays important roles in cristae structure, oxidative phosphorylation, and apoptosis. Multiple mutations in CHCHD2 have been associated with Lewy body disorders (LBDs), such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), with the CHCHD2T61I mutation being the most widely studied. We generated the first transgenic mouse models expressing human CHCHD2WT and the PD-linked CHCHD2T61I mutation driven by the mPrP promoter. CHCHD2T61I Tg, but not CHCHD2WT Tg mice exhibit perinuclear mitochondrial aggregates, neuroinflammation, and have impaired long-term synaptic plasticity associated with synaptic dysfunction. Dopaminergic neurodegeneration, a hallmark of PD, …

Functional Studies Of Dcaf14 In Replication Fork Stability And Genome Integrity, Neysha Tirado-Class

USF Tampa Graduate Theses and Dissertations

The response to replication stress is critical for ensuring the stability of replication forks and preserving genome integrity. To aid this response, several factors are recruited to stalled replication forks to prevent irreversible collapse of the replication machinery. Replication fork proteomic analyses of stalled forks reveal enrichment of DCAF14, a component of the Cullin4-RING (CRL4) E3 ubiquitin ligase complex, that mediates replication fork protection by blocking nuclease-mediated digestion of nascent DNA. However, little is known about the molecular mechanism by which DCAF14 functions in the context of replication stress. Notably, loss of function mutations in DCAF14 are associated with a …

Group B Streptococcus Intestinal Barrier Disruption And The Protective Role Of Butyrate, Kristen Dominguez

USF Tampa Graduate Theses and Dissertations

Group B Streptococcus (Streptococcus agalactiae; GBS) is a leading cause of neonatal sepsis worldwide. Intrapartum antibiotics in GBS-colonized mothers significantly reduced the incidence of early-onset sepsis occurring in the first week of life; however, there are currently no prophylactic interventions for late-onset sepsis, occurring within the first 3 months of life. GBS is a pathobiont that primarily colonizes the gastrointestinal tract and can cross the intestinal barrier via both the paracellular and transcellular routes, causing invasive disease. Neonatal susceptibility to GBS intestinal translocation is mediated by inadequate epithelial barrier function and microbiome immaturity; however, the mechanisms by which GBS exploits …