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Bcr Affinity Influences T-B Interactions And B Cell Development In Secondary Lymphoid Organs, Alec J. Wishnie, Tzippora Chwat-Edelstein, Mary Attaway, Bao Q. Vuong 2021 CUNY Graduate Center

Bcr Affinity Influences T-B Interactions And B Cell Development In Secondary Lymphoid Organs, Alec J. Wishnie, Tzippora Chwat-Edelstein, Mary Attaway, Bao Q. Vuong

Publications and Research

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre- Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B …


Dimeric Allostery Mechanism Of The Plant Circadian Clock Photoreceptor Zeitlupe, Francesco Trozzi, Feng Wang, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao 2021 Southern Methodist University

Dimeric Allostery Mechanism Of The Plant Circadian Clock Photoreceptor Zeitlupe, Francesco Trozzi, Feng Wang, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

In Arabidopsis thaliana, the Light-Oxygen-Voltage (LOV) domain containing protein ZEITLUPE (ZTL) integrates light quality, intensity, and duration into regulation of the circadian clock. Recent structural and biochemical studies of ZTL indicate that the protein diverges from other members of the LOV superfamily in its allosteric mechanism, and that the divergent allosteric mechanism hinges upon conservation of two signaling residues G46 and V48 that alter dynamic motions of a Gln residue implicated in signal transduction in all LOV proteins. Here, we delineate the allosteric mechanism of ZTL via an integrated computational approach that employs atomistic simulations of wild type and …


Exploring The Relationship Between Cellular Senescence, Apolipoprotein E, And Alzheimer’S Disease, Buay Deng 2021 Dominican University of California

Exploring The Relationship Between Cellular Senescence, Apolipoprotein E, And Alzheimer’S Disease, Buay Deng

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Alzheimer’s disease (AD) is the most common form of dementia in the world and currently affects more than 50 million people and has no cure to date. One of its major neuropathological hallmarks is the presence of senile plaques—formed from Amyloid-β (Aβ) oligomers. Aβ has also been associated with the development of cellular senescence in preclinical AD models, suggesting that cellular senescence may be mechanistically involved in disease progression. Cellular senescence is a stress response that occurs when cells are exposed to degenerative factors that puts them into permanent cell cycle arrest, this process increases with age. Apolipoprotein E (ApoE) …


Human Oncoprotein 5mp Suppresses General And Repeat-Associated Non-Aug Translation Via Eif3 By A Common Mechanism, Chingakham Ranjit Singh, M. Rebecca Glineburg, Chelsea Moore, Naoki Tani, Rahul Jaiswal, Ye Zou, Eric Aube, Sarah Gillaspie, Mackenzie Thornton, Ariana Cecil, Madelyn Hilgers, Azuma Takasu, Izumi Asano, Masayo Asano, Carlos R. Escalante, Akira Nakamura, Peter K. Todd, Katsura Asano 2021 Kansas State University

Human Oncoprotein 5mp Suppresses General And Repeat-Associated Non-Aug Translation Via Eif3 By A Common Mechanism, Chingakham Ranjit Singh, M. Rebecca Glineburg, Chelsea Moore, Naoki Tani, Rahul Jaiswal, Ye Zou, Eric Aube, Sarah Gillaspie, Mackenzie Thornton, Ariana Cecil, Madelyn Hilgers, Azuma Takasu, Izumi Asano, Masayo Asano, Carlos R. Escalante, Akira Nakamura, Peter K. Todd, Katsura Asano

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in fragile-X-associated tremor ataxia syndrome (FXTAS), is unknown. Here, we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the preinitiation complex (PIC), thereby increasing the accuracy of initiation. …


Directed Genome Evolution To Identify Genes For Macrophage Survival By Staphylococcus Agnetis, Sonali Lakshika Anne Lenaduwe Lokuge 2021 University of Arkansas, Fayetteville

Directed Genome Evolution To Identify Genes For Macrophage Survival By Staphylococcus Agnetis, Sonali Lakshika Anne Lenaduwe Lokuge

Graduate Theses and Dissertations

Bacterial Chondronecrosis with Osteomyelitis (BCO) is a debilitating infection that negatively impacts animal welfare and costs the broiler industry billions of dollars annually. We have previously isolated Staphylococcus agnetis 908 from BCO samples obtained from broilers at the University of Arkansas research farm. This isolate can induce BCO lameness at greater than 50% in broilers exposed to the pathogen in drinking water. We found that S. agnetis 908 is capable of surviving and escaping macrophages compared to a closely related cattle isolate,1379. Through Directed Genome Evolution (DGE) we identified that this difference is at least partially associated with an alanine …


Host-Parasite Interactions Within Food Webs, Adam Zvanut Hasik 2021 University of Arkansas, Fayetteville

Host-Parasite Interactions Within Food Webs, Adam Zvanut Hasik

Graduate Theses and Dissertations

Parasitism is one of the most common life history strategies employed in nature, yet the effects of parasites are often thought to be minimal, and the vast majority of studies fail to consider parasites and their effects on host organisms. This is likely a problem, as the magnitude of parasite-mediated effects on their hosts can be quite large. Additionally, the effects of parasites are known to extend beyond the host to affect other species interactions. I used a series of approaches to gain a more integral understanding of host-parasite interactions by studying (1) the effects of parasites on biotic interactions …


Divergent Regulatory Roles Of Nurd Chromatin Remodeling Complex Subunits Gatad2 And Chd4 In Caenorhabditis Elegans, Nicole Lynn Golden 2021 Florida Institute of Technology

Divergent Regulatory Roles Of Nurd Chromatin Remodeling Complex Subunits Gatad2 And Chd4 In Caenorhabditis Elegans, Nicole Lynn Golden

Theses and Dissertations

During stress, a protective cellular network known as the heat shock response (HSR) is induced to maintain protein-folding homeostasis, or proteostasis. While the HSR is essential for stress resistance, its misregulation is associated with neurodegenerative disease and cancer. Using the nematode model organism Caenorhabditis elegans, we have identified the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylase) as a novel regulator of the HSR. Here, we begin with a brief introduction of the HSR and chromatin remodeling complexes in C. elegans, prior to presenting our findings in a series of two chapters. In chapter one, we outline a set of …


Distinct Spatiotemporal Regulation Of The Cytoprotective Heat Shock Response In Caenorhabditis Elegans, Rosemary Nadine Plagens 2021 Florida Institute of Technology

Distinct Spatiotemporal Regulation Of The Cytoprotective Heat Shock Response In Caenorhabditis Elegans, Rosemary Nadine Plagens

Theses and Dissertations

Every organism studied to-date utilizes the heat shock response (HSR) to maintain protein-folding homeostasis (proteostasis) during temperature or other protein-folding stress. The HSR has been well characterized using acute heat stress (HS) in single-celled models, but less is known about how distinct cell types and tissues respond to HS. Furthermore, how metazoans respond to prolonged HS at the molecular level remains relatively unexplored. The model organism C. elegans, with its genetic tractability and distinct tissues and behaviors, has been used extensively in the field to characterize the acute HSR, but with considerable variability across labs regarding HS temperature and duration. …


Characterization Of Iron-Sulfur Cluster Biogenesis In Methanogenic Archaea, Thomas Modlin Deere 2021 University of Arkansas, Fayetteville

Characterization Of Iron-Sulfur Cluster Biogenesis In Methanogenic Archaea, Thomas Modlin Deere

Graduate Theses and Dissertations

Iron-sulfur (Fe-S) clusters are among the oldest cofactors on the planet, used by proteins in almost all forms of life on Earth to carry out processes ranging from energy transfer to DNA replication. Among the organisms believed to use these Fe-S proteins more extensively than almost any others are the methanogens, an ancient lineage of archaeal microbes that produce methane as a required product of their metabolism. Methane, the primary component of commercial natural gas, is both a potent greenhouse gas and an important fossil fuel. It can also be renewably produced as a biofuel. Biogenic methane is almost entirely …


The Characterization Of Angiopoietin-Like Protein 4 Overexpression In Triple Negative Breast Cancer, Jodi Simeon 2021 University of Arkansas, Fayetteville

The Characterization Of Angiopoietin-Like Protein 4 Overexpression In Triple Negative Breast Cancer, Jodi Simeon

Graduate Theses and Dissertations

Triple Negative Breast Cancer (TNBC) is highly invasive and metastatic with approximately 15% of patients developing liver metastases. The primary treatment of metastatic TNBC is chemotherapy, however, there is an increased chance of resistance to this therapeutic technique. If Breast Cancer Liver Metastasis (BCLM) is left untreated most patients survive only 4 to 8 months with a very rare 5-year survival. Therefore, it is imperative to analyze markers and molecular pathways that TNBC cells use to progress, invade, and metastasize to the liver. The aim of this study was to examine the overexpression of angiopoietin-like 4 (ANGPTL4) in TNBC cells …


Evaluating Bioenergetics And Mitochondrial Dynamics In Patient Fibroblasts With Pathogenic Mitochondrial Dna Mutations Causing Leigh Syndrome, Ajibola Bakare 2021 University of Arkansas, Fayetteville

Evaluating Bioenergetics And Mitochondrial Dynamics In Patient Fibroblasts With Pathogenic Mitochondrial Dna Mutations Causing Leigh Syndrome, Ajibola Bakare

Graduate Theses and Dissertations

Leigh syndrome (LS) is a rare fatal mitochondrial disorder of infants caused by pathogenic mutations in the nuclear (nDNA) or mitochondrial DNA (mtDNA) leading to mitochondrial dysfunction. The extent to which pathogenic mtDNA variants regulate disease severity in LS is not well understood. The heterogeneous nature of this disorder, based in part by complex mitochondrial genetics, and the nuclear and mitochondrial cross-talk has made it particularly challenging to investigate and develop therapies for treating LS . While the prognosis is poor, several studies are underway to understand the pathophysiology of LS. This dissertation provides a comprehensive structural and functional analysis …


A Time-Course Characterization Of Muscle Function And Mitochondrial Markers During Colorectal Cancer-Induced Cachexia In Tumor-Bearing Male Mice, Ana Cabrera Ayuso 2021 University of Arkansas, Fayetteville

A Time-Course Characterization Of Muscle Function And Mitochondrial Markers During Colorectal Cancer-Induced Cachexia In Tumor-Bearing Male Mice, Ana Cabrera Ayuso

Graduate Theses and Dissertations

Cachexia is a multisystemic and multifactorial syndrome prevalent in cancer patients. It is clinically defined by involuntary loss of >5% weight in a six-month window, despite nutritional interventions. A negative energy balance characterizes cancer cachexia (CC), it is associated with weakness and fatigue in skeletal muscle. Impaired muscle function is associated with lower quality of life in cancer patients. Defects in mitochondrial function are strongly associated with muscle wasting. This study explored muscular contractile function and mitochondrial quality control (MQC) markers in soleus, gastrocnemius, and tibialis anterior (TA) muscles of C26-induced male tumor-bearing mice during a 25-day time course. It …


Efficacy Of Conditional And Constitutive Crispr/Cas9 In Rice Genome, Zahra Alizada 2021 University of Arkansas, Fayetteville

Efficacy Of Conditional And Constitutive Crispr/Cas9 In Rice Genome, Zahra Alizada

Graduate Theses and Dissertations

Constitutive expression of Cas9 leads to a higher editing efficiency; however, it also increases the chances of off-target mutations. Thus, transient expression of Cas9 is a desirable approach to achieve higher targeting efficiency and to curb the off-target effects. It was previously shown that heat-inducible expression of Cas9 had an editing efficiency of 45% as compared to the strong constitutive expression, and the heat-shock induced mutations were inherited by the next generation. In this study, cold-inducible promoter, AtRD29a, was used for driving Cas9 expression, and evaluated for its editing efficiency upon cold-treatment on the GUS transgene loci. The expression analysis …


Recoding Of Stop Codons Expands The Metabolic Potential Of Two Novel Asgardarchaeota Lineages, Jiarui Sun, Paul N. Evans, Emma J. Gagen, Ben J. Woodcroft, Brain P. Hedlund, Tanja Woyke, Philip Hugenholtz, Christian Rinke 2021 The University of Queensland, Australia

Recoding Of Stop Codons Expands The Metabolic Potential Of Two Novel Asgardarchaeota Lineages, Jiarui Sun, Paul N. Evans, Emma J. Gagen, Ben J. Woodcroft, Brain P. Hedlund, Tanja Woyke, Philip Hugenholtz, Christian Rinke

Life Sciences Faculty Research

Asgardarchaeota have been proposed as the closest living relatives to eukaryotes, and a total of 72 metagenome-assembled genomes (MAGs) representing six primary lineages in this archaeal phylum have thus far been described. These organisms are predicted to be fermentative heterotrophs contributing to carbon cycling in sediment ecosystems. Here, we double the genomic catalogue of Asgardarchaeota by obtaining 71 MAGs from a range of habitats around the globe, including the deep subsurface, brackish shallow lakes, and geothermal spring sediments. Phylogenomic inferences followed by taxonomic rank normalisation confirmed previously established Asgardarchaeota classes and revealed four additional lineages, two of which were consistently …


A Global Metagenomic Map Of Urban Microbiomes And Antimicrobial Resistance, David Danko, Daniela Bezdan, Evan E. Afshin, Sofia Ahsanuddin, Chandrima Bhattacharya, Daniel J. Butler, Kern Rei Chng, Daisy Donnellan, Jochen Hecht, Katelyn Jackson, Katerina Kuchin, Mikhail Karasikov, Abigail Lyons, Lauren Mak, Dmitry Meleshko, Harun Mustafa, Beth Mutai, Russell Y. Neches, Amanda Ng, Olga Nikolayeva, Tatyana Nikolayeva, Eileen Png, Krista A. Ryon, Jorge L. Sanchez, Heba Shaaban, Maria A. Sierra, Dominique Thomas, Ben Young, Omar O. Abudayyeh, Josue Alicea, Malay Bhattacharyya, Ran Blekhman, Eduardo Castro-Nallar 2021 Weill Cornell Medicine

A Global Metagenomic Map Of Urban Microbiomes And Antimicrobial Resistance, David Danko, Daniela Bezdan, Evan E. Afshin, Sofia Ahsanuddin, Chandrima Bhattacharya, Daniel J. Butler, Kern Rei Chng, Daisy Donnellan, Jochen Hecht, Katelyn Jackson, Katerina Kuchin, Mikhail Karasikov, Abigail Lyons, Lauren Mak, Dmitry Meleshko, Harun Mustafa, Beth Mutai, Russell Y. Neches, Amanda Ng, Olga Nikolayeva, Tatyana Nikolayeva, Eileen Png, Krista A. Ryon, Jorge L. Sanchez, Heba Shaaban, Maria A. Sierra, Dominique Thomas, Ben Young, Omar O. Abudayyeh, Josue Alicea, Malay Bhattacharyya, Ran Blekhman, Eduardo Castro-Nallar

ISI Best Publications

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and …


Cytoplasmic Polyadenylation Element Binding Protein 2 Alternative Splicing Regulates Hif1Α During Chronic Hypoxia, Emily M. Mayo 2021 University of South Florida

Cytoplasmic Polyadenylation Element Binding Protein 2 Alternative Splicing Regulates Hif1Α During Chronic Hypoxia, Emily M. Mayo

USF Tampa Graduate Theses and Dissertations

Chronic pulmonary hypoxia commonly results in the sustained expression of HIF1 (hypoxia inducible factor 1), a heterodimeric transcription factor, that, if unrestrained, can result in dramatic vasculature remodeling, pulmonary arterial hypertension, and right-sided heart failure. Together, these pulmonary disorders cost approximately $100 billion annually to treat due to the limited therapeutic targets designed to inhibit HIF1 expression. In this study, we introduce a translational regulator of HIF1 expression, known as Cytosolic polyadenylation element binding proteins 2 (CPEB2). Our lab has previously demonstrated in cancer cells that alternatively spliced isoforms of CPEB2 regulate the translation of the HIF1 oxygen-dependent subunit, HIF1α, …


Circrev1 Expression In Triple-Negative Breast Cancer, Meagan P. Horton 2021 University of South Florida

Circrev1 Expression In Triple-Negative Breast Cancer, Meagan P. Horton

USF Tampa Graduate Theses and Dissertations

Triple-negative breast cancer (TNBC) comprises only 24% of breast cancer cases, yet is the second leading cause of cancer mortality in women due to its aggressive nature (1). This increase in mortality is due to the lack of receptors for three targetable growth factors (HER2, progesterone, and estrogen receptors). Our previous studies have indicated that these cancers are highly dysregulated in respect to alternative splicing. Hence, we undertook a study aimed at identifying circular RNAs (circRNAs) generated from back-splicing events which were dysregulated in TNBC. We have identified a novel circRNA transcript, circular REV1 (circREV1), which is upregulated in our …


Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina 2021 Wilfrid Laurier University

Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina

Biology Faculty Publications

Global climate change has broad-ranging impacts on the natural environment and human civilization. Increasing average temperatures along with more frequent heat waves collectively have negative effects on cultivated crops in agricultural sectors and wild species in natural ecosystems. These aberrantly hot temperatures, together with cold stress, represent major abiotic stresses to plants. Molecular and physiological responses to high and low temperatures are intricately linked to the regulation of important plant hormones. In this review, we shall highlight our current understanding of how changing temperatures regulate plant hormone pathways during immunity, stress responses and development. This article will present an overview …


Effect Of Her2 Expression On Nupl2 Protein In Cervical Cancer Cells, Mary E. Eichholz, Margaret J. Ballou, Tristan J. Haight, Jennifer L. Minton, Ryan N. Oates, Jacob J. Adler 2021 Brescia University

Effect Of Her2 Expression On Nupl2 Protein In Cervical Cancer Cells, Mary E. Eichholz, Margaret J. Ballou, Tristan J. Haight, Jennifer L. Minton, Ryan N. Oates, Jacob J. Adler

Kentucky Journal of Undergraduate Scholarship

Recurring cervical cancer patients frequently present overexpressed Human Epidermal Growth Factor Receptor 2 (HER2) protein, which promotes the growth of the cancer. Some HER2-expressing cells and cervical cancer patients have enhanced gene expression of Nucleoporin-like 2 (NUPL2). As part of the nuclear pore complex, the NUPL2 protein serves to selectively export substances from the nucleus to the cytoplasm. In this experiment, HER2 was expressed in cervical cancer cells to examine its effect on NUPL2 protein expression and localization. Interestingly, there was no difference in NUPL2 protein levels between HER2-expressing and non-expressing cells. Importantly, consistent instances of NUPL2 protein …


Molecular Mechanisms Underlying Cell Fate Choice Within Specific Retinal Lineages, Estie Schick 2021 CUNY Graduate Center

Molecular Mechanisms Underlying Cell Fate Choice Within Specific Retinal Lineages, Estie Schick

Dissertations, Theses, and Capstone Projects

During development, retinal progenitor cells (RPCs) divide to form all of the cell types that make up the retina. Multipotent RPCs are competent to generate all retinal cell types, while restricted RPCs form specific lineages of cells. In particular, one genetically-defined RPC type preferentially gives rise to cone photoreceptors and horizontal cells. Many of the mechanisms that are responsible for directing cell fate choice within this lineage are unknown. This thesis largely focuses on examining the development of specific cell types and subtypes from restricted RPCs and on investigating the gene regulatory events that underlie cone photoreceptor and horizontal cell …


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