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Cell and Developmental Biology

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Articles 1 - 30 of 1976

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

Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani Sep 2019

Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani

Sure-J: Science Undergraduate Research Journal

Background
Breast cancer is a heterogeneous disease that consists of varying genetic, cellular and molecular subtypes with unique characteristics. Due to the multiple subtypes and molecular markers of breast cancer, successful clinical treatment is hampered by the lack of reliable biomarkers. HER2-positive breast cancer is an aggressive subtype associated with poor patient prognosis. Although survival rates have dramatically increased due to the development of Trastuzumab in 1997, many patients develop a resistance to this therapeutic treatment and relapse over time. Rani et al. (2014), have associated the acquirement of resistance to HER2-treatment with Neuromedin U, but the mechanisms by which ...


Endoglin Protein Interactome Profiling Identifies Trim21 And Galectin-3 As New Binding Partners, Eunate Gallardo-Vara, Lidia Ruiz-Llorente, Juan Casado-Vela, María J. Ruiz-Rodríguez, Natalia López-Andrés, Asit K. Pattnaik, Miguel Quintanilla Sep 2019

Endoglin Protein Interactome Profiling Identifies Trim21 And Galectin-3 As New Binding Partners, Eunate Gallardo-Vara, Lidia Ruiz-Llorente, Juan Casado-Vela, María J. Ruiz-Rodríguez, Natalia López-Andrés, Asit K. Pattnaik, Miguel Quintanilla

Papers in Veterinary and Biomedical Science

Endoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause herediatry hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectase, and arteriovenous malformations in internal organs. A circulating form of endoglin (alias soluble endoglin, sEng), proteolytically released from the membrane-bound protein, has been observed in several inflammation-related pathological conditions and appears to contribute to endothelial dysfunction and cancer development through unknown mechanisms. Membrane-bound endoglin is an auxiliary component of the TGF-B receptor complex and ...


9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association Sep 2019

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

MD Anderson Cancer Center Postdoctoral Association Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.


Metnet: Systems Biology Tools For Arabidopsis, Eve Syrkin Wurtele, Ling Li, Dan Berleant, Dianne Cook, Julie A. Dickerson, Jing Ding, Heike Hofmann, Michael Lawrence, Eun-Kyung Lee, Jie Li, Wieslawa Mentzen, Leslie Miller, Basil J. Nikolau, Nick Ransom, Yingjun Wang Sep 2019

Metnet: Systems Biology Tools For Arabidopsis, Eve Syrkin Wurtele, Ling Li, Dan Berleant, Dianne Cook, Julie A. Dickerson, Jing Ding, Heike Hofmann, Michael Lawrence, Eun-Kyung Lee, Jie Li, Wieslawa Mentzen, Leslie Miller, Basil J. Nikolau, Nick Ransom, Yingjun Wang

Eve Wurtele

MetNet (http://metnetdb.org) is an emerging open-source software platform for exploration of disparate experimental data types and regulatory and metabolic networks in the context of Arabidopsis systems biology. The MetNet platform features graph visualization, interactive displays, graph theoretic computations for determining biological distances, a unique multivariate display and statistical analysis tool, graph modeling using the open source statistical analysis language, R, and versatile text mining. The use of these tools is illustrated with data from the bio1 mutant of Arabidopsis.


Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick J. Cullen, James Curtin Sep 2019

Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick J. Cullen, James Curtin

Articles

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma ...


Evaluation Of Epas1 Variants For Association With Bovine Congestive Heart Failure [Version 1; Peer Review: 2 Approved], Michael P. Heaton, Adam S. Bassett, Katherine J. Whitman, Greta M. Krafsur, Sang M. Lee, Jaden M. Carlson, Halden J. Clark, Helen R. Smith, Madeline C. Pelster, Veronica Basnayake, Dale M. Grotelueschen, B. Vander Ley Sep 2019

Evaluation Of Epas1 Variants For Association With Bovine Congestive Heart Failure [Version 1; Peer Review: 2 Approved], Michael P. Heaton, Adam S. Bassett, Katherine J. Whitman, Greta M. Krafsur, Sang M. Lee, Jaden M. Carlson, Halden J. Clark, Helen R. Smith, Madeline C. Pelster, Veronica Basnayake, Dale M. Grotelueschen, B. Vander Ley

Papers in Veterinary and Biomedical Science

Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2α, encoded by the endothelial PAS domain-containing protein 1 gene, EPAS1) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate EPAS1 haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m).

Methods: Paired samples of clinical cases and ...


The Central Role Of The Tail In Switching Off 10s Myosin Ii Activity, Shixin Yang, Kyounghwan Lee, John L. Woodhead, Osamu Sato, Mitsuo Ikebe, Roger Craig Sep 2019

The Central Role Of The Tail In Switching Off 10s Myosin Ii Activity, Shixin Yang, Kyounghwan Lee, John L. Woodhead, Osamu Sato, Mitsuo Ikebe, Roger Craig

Radiology Publications and Presentations

Myosin II is a motor protein with two heads and an extended tail that plays an essential role in cell motility. Its active form is a polymer (myosin filament) that pulls on actin to generate motion. Its inactive form is a monomer with a compact structure (10S sedimentation coefficient), in which the tail is folded and the two heads interact with each other, inhibiting activity. This conformation is thought to function in cells as an energy-conserving form of the molecule suitable for storage as well as transport to sites of filament assembly. The mechanism of inhibition of the compact molecule ...


Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam Sep 2019

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

All Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of ...


Metnet: Systems Biology Tools For Arabidopsis, Eve Syrkin Wurtele, Ling Li, Dan Berleant, Dianne Cook, Julie A. Dickerson, Jing Ding, Heike Hofmann, Michael Lawrence, Eun-Kyung Lee, Jie Li, Wieslawa Mentzen, Leslie Miller, Basil J. Nikolau, Nick Ransom, Yingjun Wang Aug 2019

Metnet: Systems Biology Tools For Arabidopsis, Eve Syrkin Wurtele, Ling Li, Dan Berleant, Dianne Cook, Julie A. Dickerson, Jing Ding, Heike Hofmann, Michael Lawrence, Eun-Kyung Lee, Jie Li, Wieslawa Mentzen, Leslie Miller, Basil J. Nikolau, Nick Ransom, Yingjun Wang

Ling Li

MetNet (http://metnetdb.org) is an emerging open-source software platform for exploration of disparate experimental data types and regulatory and metabolic networks in the context of Arabidopsis systems biology. The MetNet platform features graph visualization, interactive displays, graph theoretic computations for determining biological distances, a unique multivariate display and statistical analysis tool, graph modeling using the open source statistical analysis language, R, and versatile text mining. The use of these tools is illustrated with data from the bio1 mutant of Arabidopsis.


Hsp90/Axl/Eif4e-Regulated Unfolded Protein Response As An Acquired Vulnerability In Drug-Resistant Kras-Mutant Lung Cancer, Haitang Yang, Shun-Qing Liang, Duo Xu, Zhang Yang, Thomas M. Marti, Yanyun Gao, Gregor J. Kocher, Heng Zhao, Ralph A. Schmid, Ren-Wang Peng Aug 2019

Hsp90/Axl/Eif4e-Regulated Unfolded Protein Response As An Acquired Vulnerability In Drug-Resistant Kras-Mutant Lung Cancer, Haitang Yang, Shun-Qing Liang, Duo Xu, Zhang Yang, Thomas M. Marti, Yanyun Gao, Gregor J. Kocher, Heng Zhao, Ralph A. Schmid, Ren-Wang Peng

Open Access Articles

Drug resistance and tumor heterogeneity are formidable challenges in cancer medicine, which is particularly relevant for KRAS-mutant cancers, the epitome of malignant tumors recalcitrant to targeted therapy efforts and first-line chemotherapy. In this study, we delineate that KRAS-mutant lung cancer cells resistant to pemetrexed (MTA) and anti-MEK drug trametinib acquire an exquisite dependency on endoplasmic reticulum (ER) stress signaling, rendering resistant cancer cells selectively susceptible to blockage of HSP90, the receptor tyrosine kinase AXL, the eukaryotic translation initiation factor 4E (eIF4E), and the unfolded protein response (UPR). Mechanistically, acquisition of drug resistance enables KRAS-mutant lung cancer cells to bypass canonical ...


Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano Aug 2019

Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano

Open Access Articles

JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids ...


An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) And Non-Structural Protein 1 (Ns1) Confers Complete Protection Against Lethal Challenge In A Mouse Model, Arun S. Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Zack P. Guinn, Brianna L. Bullard, Eric A. Weaver, David J. Steffen, Sathish Kumar Natarajan, Thomas M. Petro, Asit K. Pattnaik Aug 2019

An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) And Non-Structural Protein 1 (Ns1) Confers Complete Protection Against Lethal Challenge In A Mouse Model, Arun S. Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Zack P. Guinn, Brianna L. Bullard, Eric A. Weaver, David J. Steffen, Sathish Kumar Natarajan, Thomas M. Petro, Asit K. Pattnaik

Papers in Veterinary and Biomedical Science

Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine ...


Insulin Receptor Substrate-1 (Irs-1) And Irs-2 Expression Levels Are Associated With Prognosis In Non-Small Cell Lung Cancer (Nsclc), Andrew J. Piper, Jennifer L. Clark, Jose R. Mercado-Matos, Asia N. Matthew-Onabanjo, Chung-Cheng Hsieh, Ali Akalin, Leslie M. Shaw Aug 2019

Insulin Receptor Substrate-1 (Irs-1) And Irs-2 Expression Levels Are Associated With Prognosis In Non-Small Cell Lung Cancer (Nsclc), Andrew J. Piper, Jennifer L. Clark, Jose R. Mercado-Matos, Asia N. Matthew-Onabanjo, Chung-Cheng Hsieh, Ali Akalin, Leslie M. Shaw

Open Access Articles

The insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma ...


Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali Aug 2019

Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali

UT GSBS Dissertations and Theses (Open Access)

Recently, a novel class of muscular dystrophy has been discovered in a family due to autosomal recessive missense mutation in POGLUT1. Mutation of this enzyme leads to decreased O-glucosyltransferase activity and impaired Notch signaling, the pathways important for skeletal muscle stem cell (satellite cells) quiescence and activation. We hypothesize that reduced POGLUT1 activity and impaired Notch signaling is causative of this limb girdle muscular dystrophy through dysfunction of muscle stem cells and myogenic progenitors.

To test this, we have used iPSCs for disease modeling and rescue experiments. Using a CRISPR based gene targeting method, we aimed to correct the point ...


Glutathione S-Transferase Class Mu Regulation Of Apoptosis Signal-Regulating Kinase 1 Protein During Vcd-Induced Ovotoxicity In Neonatal Rat Ovaries, Poulomi Bhattacharya, Jill A. Madden, Nivedita Sen, Patricia B. Hoyer, Aileen F. Keating Jul 2019

Glutathione S-Transferase Class Mu Regulation Of Apoptosis Signal-Regulating Kinase 1 Protein During Vcd-Induced Ovotoxicity In Neonatal Rat Ovaries, Poulomi Bhattacharya, Jill A. Madden, Nivedita Sen, Patricia B. Hoyer, Aileen F. Keating

Aileen Keating

4-vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-related kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also ...


Inactivating Mutations And X-Ray Crystal Structure Of The Tumor Suppressor Opcml Reveal Cancer-Associated Functions, James R. Birtley, Zachary Maben, Grant C. Weaver, Mollie M. Jurewicz, Lawrence J. Stern, Chiara Recchi, Hani Gabra Jul 2019

Inactivating Mutations And X-Ray Crystal Structure Of The Tumor Suppressor Opcml Reveal Cancer-Associated Functions, James R. Birtley, Zachary Maben, Grant C. Weaver, Mollie M. Jurewicz, Lawrence J. Stern, Chiara Recchi, Hani Gabra

Open Access Articles

OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 A resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and ...


Calcineurin Broadly Regulates The Initiation Of Skeletal Muscle-Specific Gene Expression By Binding Target Promoters And Facilitating The Interaction Of The Swi/Snf Chromatin Remodeling Enzyme, Hanna Witwicka, Jumpei Nogami, Sabriya A. Syed, Kazumitsu Maehara, Teresita Padilla-Benavides, Yasuyuki Ohkawa, Anthony N. Imbalzano Jul 2019

Calcineurin Broadly Regulates The Initiation Of Skeletal Muscle-Specific Gene Expression By Binding Target Promoters And Facilitating The Interaction Of The Swi/Snf Chromatin Remodeling Enzyme, Hanna Witwicka, Jumpei Nogami, Sabriya A. Syed, Kazumitsu Maehara, Teresita Padilla-Benavides, Yasuyuki Ohkawa, Anthony N. Imbalzano

Open Access Articles

Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the NFAT transcription factor but also promotes differentiation by counteracting the negative influences of protein kinase C beta (PKCbeta) via dephosphorylation and activation of BRG1, an enzymatic subunit of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzyme. Here we identified four major temporal patterns of Cn-dependent gene expression in differentiating myoblasts and determined that Cn is broadly required for the activation of the myogenic gene expression program. Mechanistically, Cn promotes gene ...


Rapid Irreversible Transcriptional Reprogramming In Human Stem Cells Accompanied By Discordance Between Replication Timing And Chromatin Compartment, Vishnu Dileep, Rachel Patton Mccord, Job Dekker, David M. Gilbert Jul 2019

Rapid Irreversible Transcriptional Reprogramming In Human Stem Cells Accompanied By Discordance Between Replication Timing And Chromatin Compartment, Vishnu Dileep, Rachel Patton Mccord, Job Dekker, David M. Gilbert

Open Access Articles

The temporal order of DNA replication is regulated during development and is highly correlated with gene expression, histone modifications and 3D genome architecture. We tracked changes in replication timing, gene expression, and chromatin conformation capture (Hi-C) A/B compartments over the first two cell cycles during differentiation of human embryonic stem cells to definitive endoderm. Remarkably, transcriptional programs were irreversibly reprogrammed within the first cell cycle and were largely but not universally coordinated with replication timing changes. Moreover, changes in A/B compartment and several histone modifications that normally correlate strongly with replication timing showed weak correlation during the early ...


Endogenous Force Transmission Between Epithelial Cells And A Role For Α-Catenin, Sandeep Dumbali Jul 2019

Endogenous Force Transmission Between Epithelial Cells And A Role For Α-Catenin, Sandeep Dumbali

Mechanical & Aerospace Engineering Theses & Dissertations

In epithelial tissues, epithelial cells adhere to each other as well as to the underlying extra-cellular matrix (ECM). E-cadherin-based intercellular junctions play an important role in tissue integrity. These junctions experience cell-generated mechanical forces via apparent adaptor proteins such as beta (β) catenin, alpha (α) catenin and vinculin. Abnormalities in these junctions may result in skin related diseases and cancers. Here, I devised methods to determine the endogenous intercellular force within cell pairs as well as in large epithelial islands. I further ascertained the factors that affect the level of inter-cellular tension.

Experiments with pairs of epithelial cells exogenously expressing ...


The Expression Of Connexin-43 By Cd11c+ Dendritic Cells Is Required To Maintain Cd4+ Foxp3+ Regulatory T Cell Population In Peripheral Lymphoid Organs, Caroline Titus Miller Jul 2019

The Expression Of Connexin-43 By Cd11c+ Dendritic Cells Is Required To Maintain Cd4+ Foxp3+ Regulatory T Cell Population In Peripheral Lymphoid Organs, Caroline Titus Miller

Biological Sciences Theses & Dissertations

Foxp3+ regulatory T cells (TR) are an immunosuppressive subset of CD4+ T cells that maintain homeostasis of the immune system. They are sustained by the interaction between the Major Histocompatibility Complex (MHC) molecules present on antigen presenting dendritic cells and the T Cell Receptor (TCR) expressed on TR cells that is specific for the MHC loaded with an antigenic peptide. Here, we show that in addition to MHC/TCR interaction, Connexin-43 (Cx43) expression by dendritic cells is required to maintain the TR cell population. CD11c+ dendritic cells represent a major subset of antigen presenting cells. Using flow cytometry ...


Knocking Out A Negative Regulator Of Hedgehog Signaling Blocks Differentiation Of Cells Into Neurons, Danielle Margaret Spice, Gregory M. Kelly Ph.D. Jun 2019

Knocking Out A Negative Regulator Of Hedgehog Signaling Blocks Differentiation Of Cells Into Neurons, Danielle Margaret Spice, Gregory M. Kelly Ph.D.

Western Research Forum

Hedgehog (Hh) signaling, one of many different protein signaling pathways found in mammals, is vital in many stage of neural development. A major negative regulator of Hh signaling is a protein known as Suppressor of Fused (SUFU), which acts to sequester the full length Gli transcription factors, proteins that can turn genes on and off, in the cytoplasm or facilitates its conversion to a repressive form. The P19 embryonal carcinoma cell line is a model of hind-brain neuronal differentiation and the involvement of Hh signaling, in particular the role of SUFU in this process has yet to be explored. We ...


Ste5 Membrane Localization Allows Mapk Pathway Signaling In Trans Between Kinases On Separate Scaffold Molecules, Rachel E. Lamson, Matthew J. Winters, Peter M. Pryciak Jun 2019

Ste5 Membrane Localization Allows Mapk Pathway Signaling In Trans Between Kinases On Separate Scaffold Molecules, Rachel E. Lamson, Matthew J. Winters, Peter M. Pryciak

University of Massachusetts Medical School Faculty Publications

The MAP kinase cascade is a ubiquitous eukaryotic signaling module that can be controlled by a diverse group of scaffold proteins. In budding yeast, activation of the mating MAP kinase cascade involves regulated membrane recruitment of the archetypal scaffold protein Ste5. This event promotes activation of the first kinase, but it also enhances subsequent signal propagation through the remainder of the cascade. By studying this latter effect, we find that membrane recruitment promotes signaling in trans between kinases on separate Ste5 molecules. First, trans signaling requires all Ste5 domains that mediate membrane recruitment, including both protein-binding and membrane-binding domains. Second ...


Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito Jun 2019

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Epithelial-mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4 ...


Insulin Signal Transduction Mediates Ethanol-Induced Feeding Dysfunction In A Fly Model Of Fetal Alcohol Spectrum Disorder, Manae Matsubara Jun 2019

Insulin Signal Transduction Mediates Ethanol-Induced Feeding Dysfunction In A Fly Model Of Fetal Alcohol Spectrum Disorder, Manae Matsubara

McNair Research Journal SJSU

Fetal alcohol spectrum disorder (FASD) is the leading cause of congenital intellectual disabilities in the Western World, with a worldwide prevalence of 2-11% of all births. FASD is preventable but recent epidemiological studies suggest that public awareness campaigns have reached the limits of their effectiveness. Therefore, research is shifting from prevention to treatment and mitigation of symptoms. No biological treatments for FASD exist, due in part to the fact the cellular mechanisms of alcohol toxicity are not well-understood. Developmental alcohol exposure (DAE) causes a variety of deleterious effects in both vertebrates and invertebrates, including increased mortality, slow growth, learning and ...


Failure Of Oxysterols Such As Lanosterol To Restore Lens Clarity From Cataracts, Damian M. Daszynski, Puttur Santhoshkumar, Ashutosh S. Phadte, K. Krishna Sharma, Haizhen A. Zhong, Marjorie F. Lou, Peter F. Kador Jun 2019

Failure Of Oxysterols Such As Lanosterol To Restore Lens Clarity From Cataracts, Damian M. Daszynski, Puttur Santhoshkumar, Ashutosh S. Phadte, K. Krishna Sharma, Haizhen A. Zhong, Marjorie F. Lou, Peter F. Kador

Papers in Veterinary and Biomedical Science

The paradigm that cataracts are irreversible and that vision from cataracts can only be restored through surgery has recently been challenged by reports that oxysterols such as lanosterol and 25-hydroxycholesterol can restore vision by binding to αB-crystallin chaperone protein to dissolve or disaggregate lenticular opacities. To confirm this premise, in vitro rat lens studies along with human lens protein solubilization studies were conducted. Cataracts were induced in viable rat lenses cultured for 48 hours in TC-199 bicarbonate media through physical trauma, 10 mM ouabain as Na+/K+ ATPase ion transport inhibitor, or 1 mM of an experimental compound that induces ...


Smooth Muscle Cell-Specific Tmem16a Deletion Does Not Alter Ca2+ Signaling, Uterine Contraction, Gestation Length Or Litter Size In Micedagger, Mingzi Qu, Ping Lu, Karl D. Bellve, Kevin E. Fogarty, Lawrence M. Lifshitz, Fangxiong Shi, Ronghua Zhuge Jun 2019

Smooth Muscle Cell-Specific Tmem16a Deletion Does Not Alter Ca2+ Signaling, Uterine Contraction, Gestation Length Or Litter Size In Micedagger, Mingzi Qu, Ping Lu, Karl D. Bellve, Kevin E. Fogarty, Lawrence M. Lifshitz, Fangxiong Shi, Ronghua Zhuge

Program in Molecular Medicine Publications and Presentations

Ion channels in myometrial cells play critical roles in spontaneous and agonist-induced uterine contraction during the menstrual cycle, pregnancy maintenance and parturition; thus identifying the genes of ion channels in these cells and determining their roles are essential to understanding the biology of reproduction. Previous studies with in vitro functional and pharmacological approaches have produced controversial results regarding the presence and role of TMEM16A Ca2+-activated Cl- channels in myometrial cells. To unambiguously determine the function of this channel in these cells, we employed a genetic approach by using smooth muscle cell-specific TMEM16A deletion (i.e. TMEM16ASMKO) mice. We found ...


Examining Lateral Line Development Through Cxcl14 Modulation Of Cxcl12-Cxcr4 Mediated Gene Expression In Danio Rerio, Ariana Calderon-Zavala May 2019

Examining Lateral Line Development Through Cxcl14 Modulation Of Cxcl12-Cxcr4 Mediated Gene Expression In Danio Rerio, Ariana Calderon-Zavala

Lawrence University Honors Projects

The lateral line is a mechanosensory system used by fish to sense the movement of water. It is evolutionarily related to the inner-ear in humans. For both organisms, the binding of the CXCL12 (SDF-1 ligand) to the CXCR4 receptor induces conformational changes needed to activate signal transduction. This signaling results in numerous cellular responses such as cell fate, chemotaxis, and gene transcription. Interestingly, researchers have found that another signaling molecule, CXCL14, can also bind to the CXCR4 receptor with high affinity (Tanegashima et al., 2013). As a result, we hypothesize that CXCL14 modulates CXCL12-mediated chemotaxis, presumably acting as an allosteric ...


Adipocyte Acly Facilitates Dietary Carbohydrate Handling To Maintain Metabolic Homeostasis In Females, Sully Fernandez, John M. Viola, Annmarie Torres, Martina Wallace, Sophie Trefely, Steven Zhao, Hayley C. Affronti, Jivani M. Gengatharan, David A. Guertin, Nathaniel W. Snyder, Christian M. Metallo, Kathryn E. Wellen May 2019

Adipocyte Acly Facilitates Dietary Carbohydrate Handling To Maintain Metabolic Homeostasis In Females, Sully Fernandez, John M. Viola, Annmarie Torres, Martina Wallace, Sophie Trefely, Steven Zhao, Hayley C. Affronti, Jivani M. Gengatharan, David A. Guertin, Nathaniel W. Snyder, Christian M. Metallo, Kathryn E. Wellen

Open Access Articles

Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high-sucrose diet, Acly(FAT-/-) females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas Acly(FAT-/-) males have only mild metabolic phenotypes. We find that ACLY is ...


Serum Deprivation Of Mesenchymal Stem Cells Improves Exosome Activity And Alters Lipid And Protein Composition, Reka A. Haraszti, Rachael Miller, Michelle L. Dubuke, Andrew H. Coles, Marie C. Didiot, Dimas Echeverria, Matteo Stoppato, Yves Y. Sere, John D. Leszyk, Julia F. Alterman, Bruno M. D. C. Godinho, Matthew R. Hassler, Rachel Wollacott, Yan Wang, Scott A. Shaffer, Neil Aronin, Anastasia Khvorova May 2019

Serum Deprivation Of Mesenchymal Stem Cells Improves Exosome Activity And Alters Lipid And Protein Composition, Reka A. Haraszti, Rachael Miller, Michelle L. Dubuke, Andrew H. Coles, Marie C. Didiot, Dimas Echeverria, Matteo Stoppato, Yves Y. Sere, John D. Leszyk, Julia F. Alterman, Bruno M. D. C. Godinho, Matthew R. Hassler, Rachel Wollacott, Yan Wang, Scott A. Shaffer, Neil Aronin, Anastasia Khvorova

Open Access Articles

Exosomes can serve as delivery vehicles for advanced therapeutics. The components necessary and sufficient to support exosomal delivery have not been established. Here we connect biochemical composition and activity of exosomes to optimize exosome-mediated delivery of small interfering RNAs (siRNAs). This information is used to create effective artificial exosomes. We show that serum-deprived mesenchymal stem cells produce exosomes up to 22-fold more effective at delivering siRNAs to neurons than exosomes derived from control cells. Proteinase treatment of exosomes stops siRNA transfer, indicating that surface proteins on exosomes are involved in trafficking. Proteomic and lipidomic analyses show that exosomes derived in ...


Novel Amphiphilic Cyclobutene And Cyclobutane Cis-C18 Fatty Acid Derivatives Inhibit Mycobacterium Avium Subsp. Paratuberculosis Growth, Denise K. Zinniel, Wantanee Sittiwong, Darrell D. Marshall, Govardhan Rathnaiah, Isin Sakallioglu, Robert Powers, Patrick H. Dussault, Raul G. Barletta May 2019

Novel Amphiphilic Cyclobutene And Cyclobutane Cis-C18 Fatty Acid Derivatives Inhibit Mycobacterium Avium Subsp. Paratuberculosis Growth, Denise K. Zinniel, Wantanee Sittiwong, Darrell D. Marshall, Govardhan Rathnaiah, Isin Sakallioglu, Robert Powers, Patrick H. Dussault, Raul G. Barletta

Papers in Veterinary and Biomedical Science

Mycobacterium avium subspecies paratuberculosis (Map) is the etiologic agent of Johne’s disease in ruminants and has been associated with Crohn’s disease in humans. An ective control of Map by either vaccines or chemoprophylaxis is a paramount need for veterinary and possibly human medicine. Given the importance of fatty acids in the biosynthesis of mycolic acids and the mycobacterial cell wall, we tested novel amphiphilic C10 and C18 cyclobutene and cyclobutane fatty acid derivatives for Map inhibition. Microdilution minimal inhibitory concentrations (MIC) with 5 or 7 week endpoints were measured in Middlebrook 7H9 base broth media. We compared the ...