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Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish 2021 West Virginia University

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and ...


Rho Gtpases: Big Players In Breast Cancer Initiation, Metastasis And Therapeutic Responses, Brock Humphries, Zhishan Wang, Chengfeng Yang 2020 University of Michigan

Rho Gtpases: Big Players In Breast Cancer Initiation, Metastasis And Therapeutic Responses, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases ...


The Führer Of All Maladies: Cancer And The Utility Of Metaphors For Its “Independence,” Under The Nazi Regime, Jill K. Jones 2020 Duke University

The Führer Of All Maladies: Cancer And The Utility Of Metaphors For Its “Independence,” Under The Nazi Regime, Jill K. Jones

The Macksey Journal

Work in science studies has demonstrated that metaphors construct a cognitive framework for making sense of both disease and new scientific research. In her 1978 book, Illness as Metaphor, Susan Sontag argued that the dominant metaphor for one disease in particular, cancer, has ultimately become one of war; cancer cells do not just “multiply,” they are invasive—cancer patients do not just “heal,” they “fight a battle.” However, this “war metaphor” for cancer was not always and everywhere so ubiquitous. In the Third Reich, for example, Nazi scientists discussed cancer in terms of independent agency. Cancer cells were viewed not ...


Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu 2020 University of Kentucky

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl ...


Expression And Localization Of The 14-3-3 (Ywha) Protein Family Within Mammals, Neha Kumrah, Santanu De 2020 Nova Southeastern University

Expression And Localization Of The 14-3-3 (Ywha) Protein Family Within Mammals, Neha Kumrah, Santanu De

Mako: NSU Undergraduate Student Journal

The 14-3-3 (YWHA) are a family of homologous, acidic, and highly conserved proteins expressed abundantly and ubiquitously in a wide array of organisms ranging from plants to animals, including humans, which regulate important cellular events. Within mammals, seven isoforms of 14-3-3 exist: β, γ, ε, ζ, η, τ, and σ (stratifin), each of which is encoded by a unique gene. Studies have shown similar expression patterns among mammalian species. The 14-3-3 proteins are commonly expressed and have proven to play critical roles in proper cellular localization, function, and homeostatic regulation. Numerous researchers have investigated the expression and localization patterns of ...


Investigating The Role Of The C-Jun Nh2-Terminal Kinase Pathway In Erbb2-Driven Breast Cancer And Macrophage Polarization, Lola Yu 2020 University of Massachusetts Medical School

Investigating The Role Of The C-Jun Nh2-Terminal Kinase Pathway In Erbb2-Driven Breast Cancer And Macrophage Polarization, Lola Yu

GSBS Dissertations and Theses

Breast cancer is the second most common malignancy in the world, accounting for over 1.7 million new diagnoses and an estimated 500,000 deaths per year (1). Overexpression of the receptor tyrosine kinase ErbB2, also known as Her2 or Neu, occurs in over 30% of breast cancers and correlates with metastasis, poor prognosis, and decreased survival (1, 2). Although therapeutics targeting ErbB2 show clinical efficacy, many patients display no initial response or develop drug resistance over time (2). A deeper understanding of the molecular basis of ErbB2-driven tumorigenesis is thus required for the development of improved therapeutic strategies.

In ...


Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang 2020 Chapman University

Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]4 and c[WR]5 consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in ...


Eating Broccoli: Can It Protect Cancer Patients From Radiation Skin Damage?, Huong Pham 2020 Purdue University

Eating Broccoli: Can It Protect Cancer Patients From Radiation Skin Damage?, Huong Pham

The Journal of Purdue Undergraduate Research

No abstract provided.


Nano-Vesicle (Mis)Communication In Senescence-Related Pathologies, Sherin Saheera, Ajay Godwin Potnuri, Prasanna Krishnamurthy 2020 University of Massachusetts Medical School

Nano-Vesicle (Mis)Communication In Senescence-Related Pathologies, Sherin Saheera, Ajay Godwin Potnuri, Prasanna Krishnamurthy

COVID-19 Publications by UMMS Authors

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role ...


Igf-1r Inhibition Induces Mek Phosphorylation To Promote Survival In Colon Carcinomas, Qing Wang, Yan Zhang, Jiang Zhu, Honggang Zheng, Shuntai Chen, Li Chen, Hsin-Sheng Yang 2020 University of Kentucky

Igf-1r Inhibition Induces Mek Phosphorylation To Promote Survival In Colon Carcinomas, Qing Wang, Yan Zhang, Jiang Zhu, Honggang Zheng, Shuntai Chen, Li Chen, Hsin-Sheng Yang

Toxicology and Cancer Biology Faculty Publications

The insulin-like growth factor 1 receptor (IGF-1R) governs several signaling pathways for cell proliferation, survival, and anti-apoptosis. Thus, targeting IGF-1R appears as a reasonable rationale for tumor treatment. However, clinical studies showed that inhibition of IGF-1R has very limited efficacy due to the development of resistance to IGF-1R blockade in tumor cells. Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. We also found that p70S6K1 activation by IGF-1R inhibition is independent of K-Ras and PIK3CA ...


An Improved Zebrafish Transcriptome Annotation For Sensitive And Comprehensive Detection Of Cell Type-Specific Genes, Nathan D. Lawson, Rui Li, Masahiro Shin, Ann S. Grosse, Onur Yukselen, Oliver A. Stone, Alper Kucukural, Lihua Julie Zhu 2020 University of Massachusetts Medical School

An Improved Zebrafish Transcriptome Annotation For Sensitive And Comprehensive Detection Of Cell Type-Specific Genes, Nathan D. Lawson, Rui Li, Masahiro Shin, Ann S. Grosse, Onur Yukselen, Oliver A. Stone, Alper Kucukural, Lihua Julie Zhu

University of Massachusetts Medical School Faculty Publications

The zebrafish is ideal for studying embryogenesis and is increasingly applied to model human disease. In these contexts, RNA-sequencing (RNA-seq) provides mechanistic insights by identifying transcriptome changes between experimental conditions. Application of RNA-seq relies on accurate transcript annotation for a genome of interest. Here, we find discrepancies in analysis from RNA-seq datasets quantified using Ensembl and RefSeq zebrafish annotations. These issues were due, in part, to variably annotated 3' untranslated regions and thousands of gene models missing from each annotation. Since these discrepancies could compromise downstream analyses and biological reproducibility, we built a more comprehensive zebrafish transcriptome annotation that addresses ...


Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice, Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Czech Academy of Sciences, Harvard Medical School, Boston College 2020 Boston College

Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice, Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Czech Academy Of Sciences, Harvard Medical School, Boston College

University of Massachusetts Medical School Faculty Publications

Members of the insulin/IGF superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single chain (sc), i.e. IGF-1-like, forms of the viral insulin/IGF-1 like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e. more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 ...


Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari 2020 Marshall B. Ketchum University

Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)5C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl3 with [(WR)5C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of ...


Exploiting The Immunomodulatory Potentials Of Inkt Cells In Sepsis And Cancer., Joshua Choi 2020 The University of Western Ontario

Exploiting The Immunomodulatory Potentials Of Inkt Cells In Sepsis And Cancer., Joshua Choi

Electronic Thesis and Dissertation Repository

Invariant natural killer T (iNKT) cells are a unique unconventional T cell subset that recognize glycolipids presented by CD1d expressing cells. The prototypical glycolipid agonist of iNKT cells, α-Galactosylceramide (α-GalCer), can induce the rapid release of an arsenal of cytotoxic effector molecules and enormous amounts of immunomodulatory cytokines as early as two hours after activation. In addition to α-GalCer, various glycolipid agonists are available that allow for specific, in vivo targeting of iNKT cells, and can exert divergent T-helper (TH)1 and/or TH2 immune responses. Therefore, the type of response instigated by iNKT cells can profoundly ...


Uprmt Scales Mitochondrial Network Expansion With Protein Synthesis Via Mitochondrial Import, Tomer Shpilka, Yunguang Du, Qiyuan Yang, Andrew Melber, Nandhitha Uma Naresh, Joshua Lavelle, Pengpeng Liu, Hilla Weidberg, Rui Li, Jun Yu, Lihua Julie Zhu, Lara Strittmatter, Cole M. Haynes 2020 University of Massachusetts Medical School

Uprmt Scales Mitochondrial Network Expansion With Protein Synthesis Via Mitochondrial Import, Tomer Shpilka, Yunguang Du, Qiyuan Yang, Andrew Melber, Nandhitha Uma Naresh, Joshua Lavelle, Pengpeng Liu, Hilla Weidberg, Rui Li, Jun Yu, Lihua Julie Zhu, Lara Strittmatter, Cole M. Haynes

University of Massachusetts Medical School Faculty Publications

As organisms develop, individual cells generate mitochondria to fulfill physiologic requirements. However, it remains unknown how mitochondrial network expansion is scaled to cell growth and impacted by environmental cues. The mitochondrial unfolded protein response (UPRmt) is a signaling pathway mediated by the transcription factor ATFS-1 which harbors a mitochondrial targeting sequence (MTS)1. Here, we demonstrate that ATFS-1 mediates an adaptable mitochondrial expansion program that is active throughout normal development. Developmental mitochondrial network expansion required the relatively inefficient MTS2 in ATFS-1, which allowed the transcription factor to be responsive to parameters that impact protein import capacity of the ...


Effect Of Cannabidiol And ∆9-Tetrahydrocannabinol Concentration On Breast Cancer Cell Viability, Dorothy Achiaa Agyemang 2020 University of Northern Colorado

Effect Of Cannabidiol And ∆9-Tetrahydrocannabinol Concentration On Breast Cancer Cell Viability, Dorothy Achiaa Agyemang

Ursidae: The Undergraduate Research Journal at the University of Northern Colorado

-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids that have a potential impact in cancer treatments. Studies have shown that certain cannabinoids cause cancer cells to die, but only with selective concentrations, which have not been well documented. The first study of this thesis was to determine the exact concentration of CBD and THC needed to kill human MCF-7 breast cancer cells rather than create mass multiplication leading to more growth of the cancer. To conduct this experiment, cell culture was performed with a MCF-7 breast cancer cell line. The treatment groups were treated with CBD or THC at varying concentrations ...


The Rna Phosphatase Pir-1 Regulates Endogenous Small Rna Pathways In C. Elegans, Daniel A. Chaves, Hui Dai, Lichao Li, James J. Moresco, Myung Eun Oh, Darryl Conte Jr., John R. Yates III, Craig C. Mello, Weifeng Gu 2020 University of Massachusetts Medical School

The Rna Phosphatase Pir-1 Regulates Endogenous Small Rna Pathways In C. Elegans, Daniel A. Chaves, Hui Dai, Lichao Li, James J. Moresco, Myung Eun Oh, Darryl Conte Jr., John R. Yates Iii, Craig C. Mello, Weifeng Gu

University of Massachusetts Medical School Faculty Publications

Eukaryotic cells regulate 5' triphosphorylated (ppp-) RNAs to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the γ phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR1 family of RNA polyphosphatases remove both the β and γ phosphates from ppp-RNAs. Here we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RdRPs and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in ...


Single-Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie A. Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech 2020 University of Massachusetts Medical School

Single-Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie A. Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech

Open Access Articles

Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate SNFs, and require adipocyte cyclic AMP/protein kinase A (cAMP/PKA) signaling for beige adipocyte appearance, as it is blocked by adipocyte Gsalpha deficiency. Surprisingly, however, in contrast to cold-exposed mice, neither iWAT denervation nor Nrg4 loss attenuated adipocyte browning in iAdFASNKO mice. Single-cell transcriptomic analysis of iWAT stromal cells revealed increased macrophages displaying gene expression ...


The Investigation Of Group 1 Late Embryogenesis Abundant Protein 6 And Its Role In Arabidopsis Thaliana Desiccation Tolerance, Joann Eise Thomson 2020 Grand Valley State University

The Investigation Of Group 1 Late Embryogenesis Abundant Protein 6 And Its Role In Arabidopsis Thaliana Desiccation Tolerance, Joann Eise Thomson

Masters Theses

Like most seeds, Arabidopsis thaliana seed development is divided into three major phases: morphogenesis, storage deposition, and maturation drying. During maturation drying the seed becomes desiccation tolerant (DT) at some point and the seed rapidly loses water until its moisture level is approximately 10% on a fresh weight basis. The ability of the seeds to withstand this extreme water loss is hypothesized to be due, in part, to the accumulation of late embryogenesis abundant (LEA) proteins. In A. thaliana, there are 51 LEA proteins which are divided into seven groups based on amino acid sequence similarities. Group 1 LEA proteins ...


Exploration Of The Relationship Between The Fractal Dimension Of Microcalcification Clusters And The Hurst Exponent Of Background Tissue Disruption In Mammograms, Betelhem Abay 2020 University of Maine

Exploration Of The Relationship Between The Fractal Dimension Of Microcalcification Clusters And The Hurst Exponent Of Background Tissue Disruption In Mammograms, Betelhem Abay

Honors College

Breast cancer is one of the most frequent cancers among women worldwide and holds the second place in cancer-related death. Mammography is the most commonly used screening technique, however, the dense nature of some breasts makes the analysis of mammograms challenging for radiologists. The 2D Wavelet Transform Modulus Maxima (WTMM) is one mathematical approach that is used to for the analysis of mammograms. In 2014, a team from the CompuMAINE Lab characterized differences between benign microcalcification clusters (MC) from malignant MC by calculating their fractal dimension, D, with the aid of the 2D WTMM method. In a different implementation of ...


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