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Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie 2023 University of South Dakota

Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie

Dissertations and Theses

Offspring of diabetic and obese mothers (ODOM) have greater risks of heart disease at birth and later in life. However, prevention is hindered because underlying mechanisms are poorly understood. Mounting studies in the Developmental Origins of Health and Disease field suggest that mitochondria play key roles in developmentally programmed heart disease similar to the roles they play in cardiomyopathy in adults with diabetes and obesity. However, whether mitochondria are responsible for the short[1]and long-term cardiac disease seen in ODOM remains unknown. Here, we sought to delineate the roles of mitochondria in the hearts of ODOM, determine whether mitochondria ...


Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson 2022 University of Arkansas, Fayetteville

Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson

Chemistry & Biochemistry Undergraduate Honors Theses

Known to cause gas gangrene, Hathewaya histolytica secretes two sister collagenases, collagenase G (Col G) and collagenase H (Col H), to degrade the triple helical structure of collagen to further infection in a host. Individual domains of Col H have been crystalized in previous studies, but methods in x-ray crystallization of full-length Col H have been unsuccessful. Using Small Angle X-Ray Scattering (SAXS) data, atomistic modeling was used to generate multiple conformations of Col H while accounting for flexibility between domains. Full-length Col H was found to adopt a two-state conformational model exhibiting a majority compact and a minority elongated ...


Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don 2022 University of Massachusetts Amherst

Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don

Doctoral Dissertations

Circadian rhythms are 24–hour activity cycles that exist for all organisms, from yeast and bacteria to mammals. Epidemiological data has shown that disruptions to circadian rhythms are associated with various diseases, including cancers. Circadian rhythms are regulated at the cellular level by a "molecular clock,” whose oscillations in protein transcription and translation control a range of downstream pathways. However, the connections between altered rhythms and diseases at the molecular level is unclear. Therefore, in this project, I tracked circadian rhythms in a high-resolution manner and thoroughly analyzed them to more completely reflect circadian behaviors and clock functioning at the ...


Bio-Vascular 3d, Wisdom Shadrach 2022 Department of Biological and Pharmaceutical Sciences, Munster Technological University, Kerry, Ireland

Bio-Vascular 3d, Wisdom Shadrach

ORBioM (Open Research BioSciences Meeting)

Cardiovascular disease is a leading cause of mortality and morbidity across the world and according to the world health organization account for 32% of mortality rate globally. There still remain a need to develop better in vitro vascular models that would aid further in-depth understanding of cardiovascular pathogenesis and proposed therapeutic intervention.

This study intends to characterize four novel medically relevant synthetic polymer scaffolds, and one hydrogel, for their biocompatibility and potential application in a tissue engineered blood vessel (TEBV). A primary human endothelial cell line derived from the vein of the umbilical cord (HUVEC), and a human primary smooth ...


Short Chain Fatty Acid Combination Treatment Protects Against 6-Ohda Induced Decrease In Neurite Growth In An In Vitro Model Of Parkinson’S Disease., Alex Morris 2022 Department of Biological Sciences, Munster Technological University, Cork, Ireland

Short Chain Fatty Acid Combination Treatment Protects Against 6-Ohda Induced Decrease In Neurite Growth In An In Vitro Model Of Parkinson’S Disease., Alex Morris

ORBioM (Open Research BioSciences Meeting)

Title: Short chain fatty acid combination treatment protects against 6-OHDA induced decrease in neurite growth in an in vitro model of Parkinson’s disease.

Authors: Alex Morris1, Louise M. Collins1,2,3, Gerard W. O’Keeffe2, Caitriona M. Guinane1

1 Department of Biological Sciences, Munster Technological University (MTU), Cork, Ireland.

2 Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.

3 Department of Physiology, University College Cork, Cork, Ireland.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration. This leads to motor dysfunction which is accompanied by gastrointestinal comorbidities such as ...


Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz PhD, Brenda Pratte, Lauren Daugherty 2022 University of Missouri-St. Louis

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial ...


Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip 2022 The Graduate Center, City University of New York

Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip

Dissertations, Theses, and Capstone Projects

Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at ...


Primary Cilia Of The Cardiac Neural Crest & Hedgehog-Mediated Mechanisms Of Congenital Heart Disease, Lindsey A. Fitzsimons 2022 University of Maine

Primary Cilia Of The Cardiac Neural Crest & Hedgehog-Mediated Mechanisms Of Congenital Heart Disease, Lindsey A. Fitzsimons

Electronic Theses and Dissertations

Elimination of primary cilia in cardiac neural crest cell (CNCC) progenitors is hypothesized to cause a variety of congenital heart defects (CHDs), including atrioventricular septal defects, and malformations of the developing cardiac outflow tract. We present an in vivo model of CHD resulting from the conditional elimination of primary cilia from CNCC using multiple, Wnt1:Cre-loxP, neural crest-specific systems, targeting two distinctive, but critical, primary cilia structural genes: Intraflagellar transport protein 88 (Ift88) or kinesin family member 3A (Kif3a). CNCC loss of primary cilia leads to widespread CHD, where homozygous mutant embryos (MUT) display a variety of outflow tract malformations ...


Comparative Studies Between The Murine Immortalized Brain Endothelial Cell Line (Bend.3) And Induced Pluripotent Stem Cell-Derived Human Brain Endothelial Cells For Paracellular Transport, Jiahong Sun, Weijun Ou, Derick Han, Annlia Paganini-Hill, Mark J. Fisher, Rachita K. Sumbria 2022 Chapman University

Comparative Studies Between The Murine Immortalized Brain Endothelial Cell Line (Bend.3) And Induced Pluripotent Stem Cell-Derived Human Brain Endothelial Cells For Paracellular Transport, Jiahong Sun, Weijun Ou, Derick Han, Annlia Paganini-Hill, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Brain microvascular endothelial cells, forming the anatomical site of the blood-brain barrier (BBB), are widely used as in vitro complements to in vivo BBB studies. Among the immortalized cells used as in vitro BBB models, the murine-derived bEnd.3 cells offer culturing consistency and low cost and are well characterized for functional and transport assays, but result in low transendothelial electrical resistance (TEER). Human-induced pluripotent stem cells differentiated into brain microvascular endothelial cells (ihBMECs) have superior barrier properties, but the process of differentiation is time-consuming and can result in mixed endothelial-epithelial gene expression. Here we performed a side-by-side comparison of ...


Genetically Explicit Model May Explain Multigenerational Control Of Emergent Turing Patterns In Hybrid Mimulus, Emily Simmons 2022 William & Mary

Genetically Explicit Model May Explain Multigenerational Control Of Emergent Turing Patterns In Hybrid Mimulus, Emily Simmons

Biology and Medicine Through Mathematics Conference

No abstract provided.


Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed 2022 Chapman University

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 ...


A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang 2022 Chapman University

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa ...


Identifying A Novel Hsp40/J-Domain Protein Inhibitor That Depletes Mutant P53 To Inhibit Cancer Malignancy, Shigeto Nishikawa 2022 Children's Mercy Kansas City

Identifying A Novel Hsp40/J-Domain Protein Inhibitor That Depletes Mutant P53 To Inhibit Cancer Malignancy, Shigeto Nishikawa

Research Days

Background: Accumulation of oncogenic mutant p53 (mutp53) greatly contributes to cancer progression. DNAJA1, which is a member of heat shock protein 40 (HSP40), also known as J-domain proteins (JDPs), plays a crucial role in the stabilization of misfolded forms of mutp53. Knockdown of DNAJA1 results in proteasomal degradation of misfolded mutp53, leading to tumor suppression. Currently, no HSP40/JDPs inhibitors are available in clinics.

Objectives/Goal: The goal of this study is to identify and characterize potential anti-cancer compounds which can induce mutp53 degradation by inhibiting HSP40/JDPs.

Methods/Design: To identify compounds that potentially bind to DNAJA1, we performed ...


Targeting Stress Granule Inhibition As A Novel Vulnerability Of Mutant P53, Elizabeth Thoenen 2022 Children's Mercy Kansas City

Targeting Stress Granule Inhibition As A Novel Vulnerability Of Mutant P53, Elizabeth Thoenen

Research Days

Background: Tumor suppressor p53 (p53) inhibits cancer progression by transactivating genes involved in cell cycle arrest and apoptosis. P53 is mutated in half of all human tumors, which is well correlated with poor patient outcomes. Most of p53 mutations are missense mutations. Missense mutant p53 protein (mutp53) not only loses wild-type p53 (wtp53) transcription factor activity, but also shows oncogenic gain of function that enhances metastasis and drug resistance through protein-protein interactions. However, the exact mechanism by which mutp53 induces drug resistance is poorly described. Moreover, strategies that directly target mutp53 have been challenging.

Objectives/Goal: Our goal is to ...


Mdm2 Enhances Taxane Sensitivity By Inducing Stmn1 Degradation, Hongyi Ren 2022 Children's Mercy Kansas City

Mdm2 Enhances Taxane Sensitivity By Inducing Stmn1 Degradation, Hongyi Ren

Research Days

Background: MDM2, a major E3 ubiquitin ligase of p53, is overexpressed in ~30% of human cancers. Evidence showed that overexpressed MDM2 has p53-independent oncogenic functions and is correlated with poor prognosis. Given that MDM2 overexpression is cancer-specific, therapies targeting vulnerabilities imposed by MDM2 overexpression may cause cell death specifically in cancer cells with minimum side effects.

Objectives/Goal: Our goal is to identify drugs that specifically kill MDM2-overexpressing cancer cells in a p53- independent manner.

Methods/Design: We generated p53-knockout (p53KO) and p53/MDM2-double knockout (DKO) SJSA-1 osteosarcoma cells in which MDM2 gene is amplified by using the CRISPR-Cas9 system ...


Segmentation Of Dna Lesions In Irradiated Mouse Brain Sections, Nicholas Cirone 2022 Northern Illinois University

Segmentation Of Dna Lesions In Irradiated Mouse Brain Sections, Nicholas Cirone

Honors Capstones

The impacts of microscopy image analysis have resulted in better visualization of foci (spots) in cell nuclei. However, manual analysis of microscopy images is challenging regarding subjectivity in structure counting and identification. Recent computer algorithms have enabled cellular analysis through automatic segmentation that uses computational edges in digital images. In this project, the automatic segmentation workflow in the Zeiss Zen Blue 3.3 software was adapted to more closely reflect visualized foci in a cell. The foci represent DNA double strand breaks. The Zeiss LSM 900 microscope was used to collect maximal intensity projection images of γH2AX foci and super-resolution ...


Integration Of Biomedical Imaging And Translational Approaches For Management Of Head And Neck Cancer, Abdallah Mohamed, Abdallah Mohamed 2022 The University of Texas MD Anderson Cancer Center

Integration Of Biomedical Imaging And Translational Approaches For Management Of Head And Neck Cancer, Abdallah Mohamed, Abdallah Mohamed

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We ...


Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen 2022 University of Arkansas, Fayetteville

Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen

Biological Sciences Undergraduate Honors Theses

My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure ...


Exploring The Effects Of Varied Land Use On Elemental Concentrations Within Streams, Logan Jennings 2022 University of Arkansas, Fayetteville

Exploring The Effects Of Varied Land Use On Elemental Concentrations Within Streams, Logan Jennings

Biological and Agricultural Engineering Undergraduate Honors Theses

It is well documented that human activity influences the chemistry of surrounding waters. As such, it is possible that there is a link between land use within a watershed and the chemical composition of the stream. The objectives of this study are to determine if varied land use does affect the concentrations of macronutrients and trace elements present in the streams of Northwest Arkansas, and if so, to determine what extent urban and agricultural development are responsible for these changes. Water samples were collected across 19 streams in the Northwest Arkansas region between January and March of 2022. Water samples ...


Evaluation Of Selected Nuproxa Feed Additives For Protection Against Lameness And Improving The Wellbeing Of Broilers In A Lameness Challenge Model, Jaren Hernandez 2022 University of Arkansas, Fayetteville

Evaluation Of Selected Nuproxa Feed Additives For Protection Against Lameness And Improving The Wellbeing Of Broilers In A Lameness Challenge Model, Jaren Hernandez

Biological Sciences Undergraduate Honors Theses

A common concern in commercial industries profiting from broiler chickens is their inability to yield a completely healthy flock. Bacterial Chondronecrosis with Osteomyelitis poses a threat to these companies by impairing the birds' proximal and distal tibial and femoral heads. In 2000, roughly 17.3% of broiler chickens were affected by Bacterial Chondronecrosis with Osteomyelitis which caused a substantial economic loss in the industry (McNammee et al., 2000). BCO cannot be tied to a particular bacterial species; this experiment focuses on evaluating the efficacy of certain commercial feed additives while determining the bacterial species causing BCO in this set of ...


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