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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Female And Male-Controlled Livestock Holdings Impact Pastoralist Food Security And Women’S Dietary Diversity, Henriette Gitungwa, Christopher Gustafson, E.Y. Jimenez, E. Wesley F. Peterson, M. Mwanzalila, Asha Makweta, E. Komba, R.R. Kazwala, J.A.K. Mazet, Elizabeth Vanwormer Jan 2021

Female And Male-Controlled Livestock Holdings Impact Pastoralist Food Security And Women’S Dietary Diversity, Henriette Gitungwa, Christopher Gustafson, E.Y. Jimenez, E. Wesley F. Peterson, M. Mwanzalila, Asha Makweta, E. Komba, R.R. Kazwala, J.A.K. Mazet, Elizabeth Vanwormer

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Food insecurity is a global problem that requires a One Health approach. As many households in low- and middle-income nations rely on crops and livestock that they produce to meet their household’s needs, food security and nutrition are closely linked to the health of animals and the environment. Resources controlled by women are more often allocated to uses that benefit the entire household, such as food, health, and educating children, than men’s resources. However, studies of gender control of resources among pastoralist societies are scant. We examined the effect of female and male control of livestock resources on food …


College Of Natural Sciences 2021 Year-End Publication, College Of Natural Sciences Jan 2021

College Of Natural Sciences 2021 Year-End Publication, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 2 Welcome, Table of Contents
Page 3 Our Departments: Highlights From 2021
Page 4 Overview of the College
Page 5 Overview of Bold & Blue
Pages 6, 7 Announcing the First Endowed Professorship in the College of Natural Sciences
Page 8 Spooky Science, Astronomy Outreach, SDSU Chemistry Research Features on Journal Cover
Page 9 Students Win Business Plan Competition With Aims to Improve Shelf Life of Produce, Summer Researchers
Page 10 NIH Grant Helps Unravel Rare Inflammatory Genetic Disorders, International Excellence in South Dakota
Page 11 The Next Frontier of Science Education: Virtual Reality, SDSU Researchers Uncover how Cancer …


Impact Of The Histidine‐Containing Phosphocarrier Protein Hpr On Carbon Metabolism And Virulence In Staphylococcus Aureus, Linda Pätzold, Anne-Christine Brausch, Evelyn-Laura Bielefeld, Lisa Zimmer, Greg A. Somerville, Markus Bischoff, Rosmarie Gaupp Jan 2021

Impact Of The Histidine‐Containing Phosphocarrier Protein Hpr On Carbon Metabolism And Virulence In Staphylococcus Aureus, Linda Pätzold, Anne-Christine Brausch, Evelyn-Laura Bielefeld, Lisa Zimmer, Greg A. Somerville, Markus Bischoff, Rosmarie Gaupp

School of Veterinary and Biomedical Sciences: Faculty Publications

Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram‐positive bacteria, catabolite control protein A (CcpA) and the histidine‐containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading …


An Evaluation Of The Anti-Carcinogenic Response Of Major Isothiocyanates In Non-Metastatic And Metastatic Melanoma Cells, Melina Mitsiogianni, Sotiris Kyriakou, Ioannis Anestopoulos, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi Jan 2021

An Evaluation Of The Anti-Carcinogenic Response Of Major Isothiocyanates In Non-Metastatic And Metastatic Melanoma Cells, Melina Mitsiogianni, Sotiris Kyriakou, Ioannis Anestopoulos, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocy- anates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim …


Il-10 As A Th2 Cytokine: Differences Between Mice And Humans, Mahima T. Rasquinha, Meghna Sur, Ninaad Lasrado, Jay Reddy Jan 2021

Il-10 As A Th2 Cytokine: Differences Between Mice And Humans, Mahima T. Rasquinha, Meghna Sur, Ninaad Lasrado, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The discovery of interleukin (IL)-10 more than 30 years ago marked the beginning of our understanding of how cytokines regulate immune responses, based on cross-regulation between T helper (Th)1 and Th2 cytokines. Although multiple cell types were shown to produce IL-10, its identity as a Th2 cytokine remained strong since it was rigidly associated with Th2 clones in mice, whereas both Th1 and Th2 clones could secrete IL-10 in humans. However, as new Th1/Th2 cell functionalities emerged, anti-inflammatory action of IL-10 gained more attention than its inhibitory effect on Th1 cells, which may occur as an indirect consequence of suppression …


Leveraging Chemical And Computational Biology To Probe The Cellulose Synthase Complex, B. Kirtley Amos Jan 2021

Leveraging Chemical And Computational Biology To Probe The Cellulose Synthase Complex, B. Kirtley Amos

Theses and Dissertations--Plant and Soil Sciences

Cellular expansion in plants is a complex process driven by the constraint of internal cellular turgor pressure by an expansible cell wall. The main structural element of the cell wall is cellulose. Cellulose is vital to plant fitness and the protein complex that creates it is an excellent target for small molecule inhibition to create herbicides. In the following thesis many small molecules (SMs) from a diverse library were screened in search of new cellulose biosynthesis inhibitors (CBI). Loss of cellular expansion was the primary phenotype used to search for putative CBIs. As such, this was approached in a forward …


The Effect Of Cxcl12 Ligand On Internalization And Dimerization Of Cxcr4 Receptors In Live Cells, Loga Iyer Jan 2021

The Effect Of Cxcl12 Ligand On Internalization And Dimerization Of Cxcr4 Receptors In Live Cells, Loga Iyer

Williams Honors College, Honors Research Projects

The primary objective of this project was to determine the effect of CXCL12 ligand binding on the CXCR4 receptor, specifically, how it would impact receptor internalization and dimerization. The CXCL12 ligand derives from the stromal cell-derived alpha family [8]. The CXCR4 receptors, known as C-X-C chemokine receptor type 4 play an essential role in controlling cell proliferation. When misregulated, these receptors can drive tumorigenesis and are thus important targets of cancer therapy. These G protein-coupled receptors stimulate a cascade of signaling pathways in specific tissues [1]. These pathways include the positive transcriptional control of CXCR4 via the Nuclear Respiratory Factor-1 …


Entry And Replication Of Negative-Strand Rna Viruses, Kerri Boggs Jan 2021

Entry And Replication Of Negative-Strand Rna Viruses, Kerri Boggs

Theses and Dissertations--Molecular and Cellular Biochemistry

Hendra virus (HeV) and human metapneumovirus (HMPV) are negative-sense, singled-stranded RNA viruses. The paramyxovirus HeV is classified as a biosafety level 4 pathogen due to its high fatality rate and the lack of a human vaccine or antiviral treatment. HMPV is a widespread pneumovirus that causes respiratory tract infections which are particularly dangerous for young children, immunocompromised individuals, and the elderly. Like HeV, no vaccines or therapies are available to combat HMPV infections. These viruses fuse their lipid envelopes with a cell to initiate infection. Blocking cell entry is a promising approach for antiviral development, and many vaccines are designed …


Reversible Glucan Phosphorylation In The Red Alga, Cyanidioschyzon Merolae, Corey Owen Brizzee Jan 2021

Reversible Glucan Phosphorylation In The Red Alga, Cyanidioschyzon Merolae, Corey Owen Brizzee

Theses and Dissertations--Molecular and Cellular Biochemistry

Starch and glycogen are an essential component for the majority of species and have been developed to maintain homeostasis in response to environmental changes. Water-soluble glycogen is an excellent source of quick, short-term energy in response to energy demands. In contrast, plants and algae have developed the macromolecule starch that is elegantly suitable for their dependence on external circumstances. Semi-crystalline starch is water-insoluble and inaccessible to most amylolytic enzymes, thus plants and algae have developed a coordinated system so that these enzymes can gain access to the denser starch energy cache. Starch-like semi-crystalline polysaccharides are also found in red algae, …


Of Pigs And Men: The Best-Laid Plans For Prevention And Control Of Swine Fevers, Jishu Shi, Lihua Wang, David Scott Mcvey Jan 2021

Of Pigs And Men: The Best-Laid Plans For Prevention And Control Of Swine Fevers, Jishu Shi, Lihua Wang, David Scott Mcvey

School of Veterinary and Biomedical Sciences: Faculty Publications

John Steinbeck drew the title of his novel “Of Mice and Men” from a line in a Robert Burns poem “To a mouse”: “The best-laid plans of mice and men/Go often awry.” Unlike John Steinbeck who used the title to mirror the characters who were struggling during the Great Depression to the mouse whose nest was accidentally destroyed by the poet (Burns 1785), we chose this line to emphasize that the best-laid plan can go wrong in infectious disease control and prevention. Here, we will discuss the contributing factors behind the global successes and failures in the prevention and control …


Special Issue: Shiga Toxin-Producing Escherichia Coli, Rodney A. Moxley Jan 2021

Special Issue: Shiga Toxin-Producing Escherichia Coli, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Globally, Shiga toxin-producing Escherichia coli (STEC) is an important cause of diarrheal disease, most notably hemorrhagic colitis, and post-diarrheal sequela, such as hemolytic-uremic syndrome (HUS) [1]. Cattle are a major reservoir of STEC, with approx- imately half of the cases in humans attributable to foodborne exposure [2]. Prevention of human illness has mainly been through food safety measures [2]. Despite extensive research, no other generally accepted and effective preventive measures or therapies for STEC infections in human patients are available [3]. Many questions remain about STEC virulence factors, pathogenesis, detection, and other aspects that necessitate a continua- tion of basic …


Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Prativa Majee, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak Jan 2021

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Prativa Majee, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

School of Veterinary and Biomedical Sciences: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canon- ical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for anti- viral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Bio- physical and biochemical analysis of the RNA sequences con- taining these potential GQ sequences …


Molecular And Genetic Studies On A Sipd/Ipad-Related Virulence Spike Protein From Immune-Suppressive Particles Of A Drosophila Parasitoid, Carlo Miguel A. Sevilla Jan 2021

Molecular And Genetic Studies On A Sipd/Ipad-Related Virulence Spike Protein From Immune-Suppressive Particles Of A Drosophila Parasitoid, Carlo Miguel A. Sevilla

Dissertations and Theses

Parasitoid wasps are effective biological control agents that have evolved intricate host immune suppression strategies to overcome host immune defenses. The most important anti-parasite defense mechanism is encapsulation, where the host’s blood cells surround the wasp egg. In the Drosophila/Leptopilina host-parasitoid system, extracellular vesicles (EVs) are oviposited along with the wasp egg. The EVs possess spikes and contain hundreds of proteins, some of which enable wasp eggs to escape encapsulation by changing the morphology and function of hemocytes, or killing them. Previous studies have identified an abundant surface/spike protein (SSp40) from Leptopilina heterotoma EVs. While p40, a predicted …


From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest Jan 2021

From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest

Graduate Theses, Dissertations, and Problem Reports (ETD)

Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …


A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv Jan 2021

A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv

Theses and Dissertations

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of …


Investigation Of Multidrug Efflux Transporter Acrb In Escherichia Coli: Assembly, Degradation And Dynamics, Prasangi Irosha Rajapaksha Jan 2021

Investigation Of Multidrug Efflux Transporter Acrb In Escherichia Coli: Assembly, Degradation And Dynamics, Prasangi Irosha Rajapaksha

Theses and Dissertations--Chemistry

The Resistant Nodulation Division (RND) super family member, tripartite AcrA-AcrB-TolC efflux pump, is a major contributor in conferring multidrug-resistance in Escherichia coli. The structure of the pump complex, and drug translocation by functional rotation mechanism have been widely studied. Despite of all these data, the dynamics of the assembly process of the pump and AcrB during functional rotation in the process of drug efflux remains poorly understood. My thesis focuses on understanding the pump assembly process, dynamics of AcrB in functional rotation mechanism, and also investigate the mechanism of degradation of AcrB facilitated by a C-terminal ssrA tag.

In the …


Developing Synthetic Strategies For Multifaceted Applications Of Stable Gold-Based Complexes, Randall Tyler Mertens Jan 2021

Developing Synthetic Strategies For Multifaceted Applications Of Stable Gold-Based Complexes, Randall Tyler Mertens

Theses and Dissertations--Chemistry

Development of stable gold-based complexes has been a rapidly advancing field due to the popularity of gold complexes, particularly for use in biomedical research and catalytic transformations. Given that auranofin, a gold(I) complex with FDA approval for the treatment of rheumatoid arthritis is used in the clinic, the development of stable gold-based molecules of clinical relevance is urgently needed. Herein are reported, synthetic strategies used for the development of new classes of gold(I) and gold(III) complexes for advancement in mitochondrial modulation for use as chemotherapeutics as well as application to gold catalysis due to the unique geometry of complexes presented …


Monitoring Stem Cell Differentiation Using Raman Microspectroscopy: Chondrogenic Differentiation, Towards Cartilage Formation, Francesca Ravera, Esen Efeoglu, Hugh Byrne Jan 2021

Monitoring Stem Cell Differentiation Using Raman Microspectroscopy: Chondrogenic Differentiation, Towards Cartilage Formation, Francesca Ravera, Esen Efeoglu, Hugh Byrne

Articles

Mesenchymal Stem Cells (MSCs) have the ability to differentiate into chondrocytes, the only cellular components of cartilage and are therefore ideal candidates for cartilage and tissue repair technologies. Chondrocytes are surrounded by cartilage-like extracellular matrix (ECM), a complex network rich in glycosaminoglycans, proteoglycans, and collagen, which, together with a multitude of intracellular signalling molecules, trigger the chondrogenesis and allow the chondroprogenitor to acquire the spherical morphology of the chondrocytes. However, although the mechanisms of the differentiation of MSCs have been extensively explored, it has been difficult to provide a holistic picture of the process, in situ. Raman Micro Spectroscopy (RMS) …


A Molecular Toolset For The In Vivo Detection Of A Sulfolobus Islandicus Leucyl Trna Synthetase Paralog, Nicholas Michael Bretz Dec 2020

A Molecular Toolset For The In Vivo Detection Of A Sulfolobus Islandicus Leucyl Trna Synthetase Paralog, Nicholas Michael Bretz

Theses and Dissertations

An ancient and ubiquitous set of enzymes known as the aminoacyl-tRNA synthetases are required for the viability of all organisms. The aminoacyl-tRNA synthetases catalyze the attachment of amino acids onto tRNA molecules. The aminoacylated, or charged, tRNA is then transported and utilized at the ribosome for the synthesis of proteins. The genome of the hyperthermophilic microorganism Sulfolobus islandicus (S. islandicus) harbors a unique leucyl-tRNA synthetase paralog, LeuRS-I, of unknown function. While its duplicate, LeuRS-F, carries out all the classical functions of LeuRS-family enzymes, LeuRS-I fails to charge leucine onto tRNALeu, despite its ability to activate this amino acid and bind …


Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu Dec 2020

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …


Correction: Moxley, R.A., Et Al. Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model. Microorganisms 2020, 8, 263, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David Francis Dec 2020

Correction: Moxley, R.A., Et Al. Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model. Microorganisms 2020, 8, 263, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David Francis

School of Veterinary and Biomedical Sciences: Faculty Publications

The authors wish to make the following corrections to this paper [1]: On page 2, the sentence that reads, “Hence, EHEC is a rare but established cause of HUS in children and adults.” should read, “Hence, EHEC is a rare but established cause of UTI-associated HUS in children and adults.” On page 4, the sentence that reads, “As noted previously, 14 of 126 (13.3%) piglets orally inoculated with EHEC O157:H7 strains developed mild to moderate purulent cystitis within 8 d PI [25] (Table 1).” should read, “As noted previously, 14 of 105 (13.3%) piglets orally inoculated with EHEC O157:H7 strains …


Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff Dec 2020

Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff

Honors Scholar Theses

Mechanotransduction is the process by which a mechanical stimulus is converted to a cellular signal. This process is heavily influential of cell morphology, differentiation, and behavior. However, altered levels of mechanical stimuli are also found in many pathological contexts. For example, cancerous cells have stiffer surrounding tissue than healthy cells, and research suggests that this alters cell behavior and promotes metastasis. Despite these findings, the cellular processes behind these signaling alterations remain widely unknown. Understanding these cascades is critical, as involved proteins can give us a deeper understanding of the role of mechanotransduction, and certain proteins can potentially be targeted …


Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark Dec 2020

Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark

Publications and Research

The fungal cell wall serves as the interface between the cell and the environment. Fungal cell walls are composed largely of polysaccharides, primarily glucans and chitin, though in many fungi stress-resistant cell types elaborate additional cell wall structures. Here, we use solid-state nuclear magnetic resonance spectroscopy to compare the architecture of cell wall fractions isolated from Saccharomyces cerevisiae spores and Cryptococcus neoformans melanized cells. The specialized cell walls of these two divergent fungi are highly similar in composition. Both use chitosan, the deacetylated derivative of chitin, as a scaffold on which a polyaromatic polymer, dityrosine and melanin, respectively, is assembled. …


Supersize It! Developing A "Supercytoplast" Through Platelet Fusion, Taulbee B. Gunter Dec 2020

Supersize It! Developing A "Supercytoplast" Through Platelet Fusion, Taulbee B. Gunter

Animal Science Undergraduate Honors Theses

Stem cell research opens a wide range of possibilities from lab-grown tissues for medical purposes to cloned animals for livestock production. The issue with one of the most popular forms of cell recombination into a stem cell, known as somatic cell nuclear transfer (SCNT), is that it requires an oocyte. The requirement of an oocyte is often the host of public scrutiny for its economic and ethical issues. Platelets may offer a less expensive and more accessible alternative to oocytes as sources of naturally enucleated cells. Thus, the objective of this explorative research project is to isolate and fuse platelets …


Role Of Β-Glucan Structure In Dectin-1 Homo- And Hetero-Oligomerization In Innate Anti-Fungal Immunity, Eduardo U. Anaya Dec 2020

Role Of Β-Glucan Structure In Dectin-1 Homo- And Hetero-Oligomerization In Innate Anti-Fungal Immunity, Eduardo U. Anaya

Biomedical Sciences ETDs

Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3)-glucan, a structural component of Candida species cell walls. Dectin-1 has eight alternative splice isoforms including, A and B. Innate immunocytes can express one or both isoforms, but neither their relative responsiveness to β-glucan nor the potential for inter-isoform signaling cross-talk is well understood. In this study, we determine how the different structures of soluble β-glucans affect both isoforms and unravel how differences in glucan structure impact the earliest events in Dectin-1 signaling. Using quantitative microscopy techniques, we explored the role of glucan structure on Dectin-1A oligomerization, which is thought to …


Calcium Dyshomeostasis In Neurodegeneration, Nicholas Emanuel Karagas Dec 2020

Calcium Dyshomeostasis In Neurodegeneration, Nicholas Emanuel Karagas

Dissertations and Theses (Open Access)

Neurodegenerative diseases, despite constituting a major and growing cause of mortality globally, have few effective treatments. In order to develop novel therapeutics to combat neurodegeneration, a better understanding of the molecular mechanisms underlying these diseases is needed. Neurons rely on Ca2+ to mediate many of their unique functions, and aberrant Ca2+ signaling has been broadly implicated in neurodegeneration. The goal of this dissertation is to delineate specific examples of Ca2+ dyshomeostasis that I have uncovered in Drosophila models of neurodegeneration.

I first define the role a neurodegeneration-associated mutation plays in perturbing presynaptic [Ca2+], which is …


The Role Of Liver Sinusoidal Endothelial Cells In Liver Malady Homeostasis, Fatima Cabral Dec 2020

The Role Of Liver Sinusoidal Endothelial Cells In Liver Malady Homeostasis, Fatima Cabral

Department of Biochemistry: Dissertations, Theses, and Student Research

Current literature described techniques for the purification of liver cell types through text alone. The techniques described for the isolation of liver sinusoidal endothelial cells as well as hepatocytes described here are modified from a published article in the Journal of Visualized experiments. The video protocol allows for the user to successfully isolate cells as the most difficult parts of the procedure are demonstrated visually. The detection of liver maladies such as the non-alcoholic fatty liver disease, the stage if this disease and differentiation between non-alcoholic and alcoholic fatty liver disease is demonstrated in the development of a unique panel …


P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer Dec 2020

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations and Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …


Sine Oculis Homeobox Homolog 1 (Six1) Plays A Critical Role In The Progression Of Pulmonary Fibrosis., Cory Wilson Dec 2020

Sine Oculis Homeobox Homolog 1 (Six1) Plays A Critical Role In The Progression Of Pulmonary Fibrosis., Cory Wilson

Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia with a median survival time of 2-4 years after diagnosis. The alarming mortality rate is due to the lack of effective treatments. IPF is a chronic disease that is characterized by alveolar destruction due to increasing extracellular matrix deposition that leads to poor lung compliance, impaired gas exchange, and ultimately respiratory failure. Repetitive alveolar epithelial injury is a central process to the underlying pathology with injury to the type II alveolar epithelial cells (AT2) specifically being a key player in the pathogenesis of IPF. Recent studies have shown that …


Ionic Mechanism Of Lysosomal Function And Cell Metabolism, Jian Xiong Dec 2020

Ionic Mechanism Of Lysosomal Function And Cell Metabolism, Jian Xiong

Dissertations and Theses (Open Access)

Two Pore Channels (TPCs) are endolysosomal ion channels that are permeable to sodium and calcium. Defects in TPCs have been implicated to impair vesicle trafficking, autophagy and cell metabolism control; however, the detailed mechanism remains largely unknown. In this study, I show that TPCs are critical for appropriate cargo delivery to the lysosomes and deletion of either TPC1 or TPC2 leads to delayed clearance of autophagosomes, resulting in enlarged lysosomes and accumulated contents inside the lysosomes. Cells with both TPC deleted also exhibit 50% reduction in lysosomal amino acids under normal culture conditions, leading to reduced homeostatic mTORC1 activation.

Glutamine …