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Articles 61 - 90 of 123

Full-Text Articles in Cell and Developmental Biology

Thermoresponsive, Redox-Polymerized Cellulosic Hydrogels Undergo In Situ Gelation And Restore Intervertebral Disc Biomechanics Post Discectomy, Devika Varma, H. A. Lin, R. G. Long, G. T. Gold, A. C. Hecht, J. C. Iadridis, Steven B. Nicoll Jan 2018

Thermoresponsive, Redox-Polymerized Cellulosic Hydrogels Undergo In Situ Gelation And Restore Intervertebral Disc Biomechanics Post Discectomy, Devika Varma, H. A. Lin, R. G. Long, G. T. Gold, A. C. Hecht, J. C. Iadridis, Steven B. Nicoll

Publications and Research

Back and neck pain are commonly associated with intervertebral disc (IVD) degeneration. Structural augmentation of diseased nucleus pulposus (NP) tissue with biomaterials could restore degeneration-related IVD height loss and degraded biomechanical behaviors; however, effective NP replacement biomaterials are not commercially available. This study developed a novel, crosslinked, dual-polymer network (DPN) hydrogel comprised of methacrylated carboxymethylcellulose (CMC) and methylcellulose (MC), and used in vitro, in situ and in vivo testing to assess its efficacy as an injectable, in situ gelling, biocompatible material that matches native NP properties and restores IVD biomechanical behaviors. Thermogelling MC was required to enable consistent and timely …


Pitx1 Regulates Cement Gland Development In Xenopus Laevis Through Activation Of Transcriptional Targets And Inhibition Of Bmp Signaling, Ye Jin, Daniel C. Weinstein Jan 2018

Pitx1 Regulates Cement Gland Development In Xenopus Laevis Through Activation Of Transcriptional Targets And Inhibition Of Bmp Signaling, Ye Jin, Daniel C. Weinstein

Publications and Research

The cement gland in Xenopus laevis has long been used as a model to study the interplay of cell signaling and transcription factors during embryogenesis. It has been shown that an intermediate level of Bone Morphogenetic Protein (BMP) signaling is essential for cement gland formation. In addition, several transcription factors have been linked to cement gland development. One of these, the homeodomain-containing protein Pitx1, can generate ectopic cement gland formation; however, the mechanisms underlying this process remain obscure. We report here, for the first time, a requirement for Pitx proteins in cement gland formation, in vivo: knockdown of both pitx1 …


Insights Into The Molecular Roles Of Zika Virus In Human Reproductive Complications And Congenital Neuropathologies, Rajendra Ghardbaran, Latchman Somenarain Dec 2017

Insights Into The Molecular Roles Of Zika Virus In Human Reproductive Complications And Congenital Neuropathologies, Rajendra Ghardbaran, Latchman Somenarain

Publications and Research

The recent upsurge in the association of congenital neurological disorders and infection by the Zika virus (ZIKV) has resulted in increased research focus on the biology of this flavivirus. Studies in animal models indicate that ZIKV can breach the placental barrier and selectively infect and deplete neuroprogenitor cells (NPCs) of the developing fetus, resulting in changes of brain structures, reminiscent of human microcephaly. In vitro and ex vivo studies using human cells and tissues showed that human NPCs and placental cells are targeted by ZIKV. Also of concern is the impact of ZIKV on human reproductive structures, with the potential …


Mrna Processing Factor Cstf-50 And Ubiquitin Escort Factor P97 Are Brca1/Bard1 Cofactors Involved In Chromatin Remodeling During The Dna Damage Response, Danae Fonseca, Jorge Baquero, Michael R. Murphy, Gamage Aruggoda, Sophia Varriano, Carmen Saplenza, Oksana Mashadova, Shadaqur Rahman, Frida E. Kleiman Nov 2017

Mrna Processing Factor Cstf-50 And Ubiquitin Escort Factor P97 Are Brca1/Bard1 Cofactors Involved In Chromatin Remodeling During The Dna Damage Response, Danae Fonseca, Jorge Baquero, Michael R. Murphy, Gamage Aruggoda, Sophia Varriano, Carmen Saplenza, Oksana Mashadova, Shadaqur Rahman, Frida E. Kleiman

Publications and Research

The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. In this study, we provide evidence of the roles of the polyadenylation factor cleavage stimulation factor 50 (CstF-50) and the ubiquitin (Ub) escort factor p97 as cofactors of BRCA1/BARD1 E3 Ub ligase, facilitating chromatin remodeling during the DNA damage response (DDR). CstF-50 and p97 formed complexes with BRCA1/BARD1, Ub, and some BRCA1/BARD1 substrates, such as RNA polymerase (RNAP) II and histones. Furthermore, CstF-50 and p97 had an additive effect on the activation of the ubiquitination of these BRCA1/BARD1 substrates during DDR. Importantly, as …


Comparative Transcriptomics Reveal Developmental Turning Points During Embryogenesis Of A Hemimetabolous Insect, The Damselfly Ischnura Elegans, Sabrina Simon, Sven Sagasser, Edoardo Saccenti, Mercer R. Brugler, M. Eric Schranz, Heike Hadrys, George Amato, Rob Desalle Oct 2017

Comparative Transcriptomics Reveal Developmental Turning Points During Embryogenesis Of A Hemimetabolous Insect, The Damselfly Ischnura Elegans, Sabrina Simon, Sven Sagasser, Edoardo Saccenti, Mercer R. Brugler, M. Eric Schranz, Heike Hadrys, George Amato, Rob Desalle

Publications and Research

Identifying transcriptional changes during embryogenesis is of crucial importance for unravelling evolutionary, molecular and cellular mechanisms that underpin patterning and morphogenesis. However, comparative studies focusing on early/embryonic stages during insect development are limited to a few taxa. Drosophila melanogaster is the paradigm for insect development, whereas comparative transcriptomic studies of embryonic stages of hemimetabolous insects are completely lacking. We reconstructed the first comparative transcriptome covering the daily embryonic developmental progression of the blue-tailed damselfly Ischnura elegans (Odonata), an ancient hemimetabolous representative. We identified a “core” set of 6,794 transcripts – shared by all embryonic stages – which are mainly involved …


Substitutions In Conserved Regions Preceding And Within The Linker Affect Activity And Flexibility Of Trnase Zl, The Long Form Of Trnase Z, Makensie Saoura, Kyla Pinnock, Maria Pujantell-Graell, Louis Levinger Oct 2017

Substitutions In Conserved Regions Preceding And Within The Linker Affect Activity And Flexibility Of Trnase Zl, The Long Form Of Trnase Z, Makensie Saoura, Kyla Pinnock, Maria Pujantell-Graell, Louis Levinger

Publications and Research

The enzyme tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions as a homodimer and is found in all prokaryotes and some eukaryotes. The long form, tRNase ZL, related to tRNase ZS through tandem duplication and found only in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS. tRNase ZL consists of related but diverged amino and carboxy domains connected by a flexible linker (also referred to as a flexible tether) and functions as a monomer. The amino …


The Pulse Vision & Change Rubrics, Version 1.0: A Valid And Equitable Tool To Measure Transformation Of Life Sciences Departments At All Institution Types, Loretta Brancaccio-Taras, Pamela Pape-Lindstrom, Marcy Peteroy-Kelly, Karen Aguirre, Judy Awong-Taylor, Teri Balser, Michael J. Cahill, Regina F. Frey, Thomas Jack, Michael Kelrick, Kate Marley, Kathryn G. Miller, Marcy Osgood, Sandra Romano, J. Akif Uzman, Jiuqing Zhao Oct 2017

The Pulse Vision & Change Rubrics, Version 1.0: A Valid And Equitable Tool To Measure Transformation Of Life Sciences Departments At All Institution Types, Loretta Brancaccio-Taras, Pamela Pape-Lindstrom, Marcy Peteroy-Kelly, Karen Aguirre, Judy Awong-Taylor, Teri Balser, Michael J. Cahill, Regina F. Frey, Thomas Jack, Michael Kelrick, Kate Marley, Kathryn G. Miller, Marcy Osgood, Sandra Romano, J. Akif Uzman, Jiuqing Zhao

Publications and Research

The PULSE Vision & Change Rubrics, version 1.0, assess life sciences departments’ progress toward implementation of the principles of the Vision and Change report. This paper reports on the development of the rubrics, their validation, and their reliability in measuring departmental change aligned with the Vision and Change recommendations. The rubrics assess 66 different criteria across five areas: Curriculum Alignment, Assessment, Faculty Practice/Faculty Support, Infrastructure, and Climate for Change. The results from this work demonstrate the rubrics can be used to evaluate departmental transformation equitably across institution types and represent baseline data about the adoption of the Vision and Change …


Cellular Mechanisms Of Cortisol-Induced Changes In Mauthner-Cell Excitability In The Startle Circuit Of Goldfish, Daniel R. Bronson, Thomas Preuss Sep 2017

Cellular Mechanisms Of Cortisol-Induced Changes In Mauthner-Cell Excitability In The Startle Circuit Of Goldfish, Daniel R. Bronson, Thomas Preuss

Publications and Research

Predator pressure and olfactory cues (alarm substance) have been shown to modulate Mauthner cell (M-cell) initiated startle escape responses (C-starts) in teleost fish. The regulation of such adaptive responses to potential threats is thought to involve the release of steroid hormones such as cortisol. However, the mechanism by which cortisol may regulate M-cell excitability is not known. Here, we used intrasomatic, in vivo recordings to elucidate the acute effects of cortisol on M-cell membrane properties and sound evoked post-synaptic potentials (PSPs). Cortisol tonically decreased threshold current in the M-cell within 10 min before trending towards baseline excitability over an hour …


Chloride Intracellular Channel Proteins Respond To Heat Stress In Caenorhabditis Elegans, Jun Liang, Yakov Shaulov, Cathy Savage-Dunn, Stéphane Boissinot, Tasmia Hoque Sep 2017

Chloride Intracellular Channel Proteins Respond To Heat Stress In Caenorhabditis Elegans, Jun Liang, Yakov Shaulov, Cathy Savage-Dunn, Stéphane Boissinot, Tasmia Hoque

Publications and Research

Chloride intracellular channel proteins (CLICs) are multi-functional proteins that are expressed in various cell types and differ in their subcellular location. Two CLIC homologs, EXL-1 (excretory canal abnormal like-1) and EXC-4 (excretory canal abnormal± 4), are encoded in the Caenorhabditis elegans genome, providing an excellent model to study the functional diversification of CLIC proteins. EXC-4 functions in excretory canal formation during normal animal development. However, to date, the physiological function of EXL-1 remains largely unknown. In this study, we demonstrate that EXL-1 responds specifically to heat stress and translocates from the cytoplasm to the nucleus in intestinal cells and body …


The Heat Shock Response And Humoral Immune Response Are Mutually Antagonistic In Honey Bees, Mia Mckinstry, Charlie Chung, Henry Truong, Brittany A. Johnston, Jonathan W. Snow Aug 2017

The Heat Shock Response And Humoral Immune Response Are Mutually Antagonistic In Honey Bees, Mia Mckinstry, Charlie Chung, Henry Truong, Brittany A. Johnston, Jonathan W. Snow

Publications and Research

The honey bee is of paramount importance to humans in both agricultural and ecological settings. Honey bee colonies have suffered from increased attrition in recent years, stemming from complex interacting stresses. Defining common cellular stress responses elicited by these stressors represents a key step in understanding potential synergies. The proteostasis network is a highly conserved network of cellular stress responses involved in maintaining the homeostasis of protein production and function. Here, we have characterized the Heat Shock Response (HSR), one branch of this network, and found that its core components are conserved. In addition, exposing bees to elevated temperatures normally …


Mutant Tdp-43 Does Not Impair Mitochondrial Bioenergetics In Vitro And In Viv, Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi May 2017

Mutant Tdp-43 Does Not Impair Mitochondrial Bioenergetics In Vitro And In Viv, Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi

Publications and Research

Background: Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics. Furthermore, it was proposed that TDP-43 mutations cause oxidative phosphorylation impairment associated with respiratory chain defects and that these effects were caused by mitochondrial localization of the mutant …


A Drosophila Model To Examine Collective Migration During Retinogenesis, Caroline Pena, Stephanie Zhang, Mildred Kamara, Tadmiri Venkatesh, Maribel Vazquez Apr 2017

A Drosophila Model To Examine Collective Migration During Retinogenesis, Caroline Pena, Stephanie Zhang, Mildred Kamara, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

Retinal dysfunction is often caused by aberrant neural cell migration during development. In this study, we observed the migration of neural cells of the Drosophila melanogaster after marking cells of the 3rd instar larvae with the GAL4-UAS expression system when exposed to a concentration gradient of FGF-8 through the use of a microfluidic device. The glial and neuronal cell ratio in the developing brain was determined through immunofluorescent staining and observation. In future studies, a microfluidic device that mimics the developing Drosophila brain and retina will be designed in order to better understand the biological factors that affect the migration …


Unique Synergistic Formulation Of Curcumin, Epicatechin Gallate And Resveratrol, Tricurin, Suppresses Hpv E6, Eliminates Hpv+ Cancer Cells, And Inhibits Tumor Progression, Sumit Mukherjee, Priya Ranjan Debata, Rahman Hussaini, Kaushiki Chatterjee, Juliet N. E. Baidoo, Samay Sampat, Anita Szerszen, Joseph P. Navarra, Jimmie Fata, Elena Severinova, Probal Banerjee, Mario R. Castellanos Mar 2017

Unique Synergistic Formulation Of Curcumin, Epicatechin Gallate And Resveratrol, Tricurin, Suppresses Hpv E6, Eliminates Hpv+ Cancer Cells, And Inhibits Tumor Progression, Sumit Mukherjee, Priya Ranjan Debata, Rahman Hussaini, Kaushiki Chatterjee, Juliet N. E. Baidoo, Samay Sampat, Anita Szerszen, Joseph P. Navarra, Jimmie Fata, Elena Severinova, Probal Banerjee, Mario R. Castellanos

Publications and Research

Curcumin (from curry) (C) is highly potent against cervical cancer cells (CCC), but poor bioavailability has limited its clinical use. Similar natural polyphenols resveratrol (from grapes) (R), and epicatechin gallate (from green tea) (E) also display activity against CCC. By treating CCC (HeLa) with C, E, or R, or combinations of these compounds, we computed combination indices and observed a strong synergism among C, E, and R at the unique molar ratio 4:1:12.5. This combination, named as TriCurin, rapidly down regulated HPV18 E6 and NF-kB expression while concomitantly inducing the tumor suppressor protein p53 in HeLa cells. In the mouse …


Expression, Purification, And Monitoring Of Conformational Changes Of Hcb2 Tmh67h8 In Different Membrane-Mimetic Lipid Mixtures Using Circular Dichroism And Nmr Techniques, Elvis K. Tiburu, Jianqin Zhuang, Heidimarie N. A. Fleischer, Patrick K. Arthur, Gordon A. Awandare Feb 2017

Expression, Purification, And Monitoring Of Conformational Changes Of Hcb2 Tmh67h8 In Different Membrane-Mimetic Lipid Mixtures Using Circular Dichroism And Nmr Techniques, Elvis K. Tiburu, Jianqin Zhuang, Heidimarie N. A. Fleischer, Patrick K. Arthur, Gordon A. Awandare

Publications and Research

This work was intended to develop self-assembly lipids for incorporating G-protein coupled receptors (GPCRs) in order to improve the success rate for nuclear magnetic resonance spectroscopy (NMR) structural elucidation. We hereby report the expression and purification of uniformly 15N-labeled human cannabinoid receptor-2 domain in insect cell media. The domain was refolded by screening several membrane mimetic environments. Different q ratios of isotropic bicelles were screened for solubilizing transmembrane helix 6, 7 and 8 (TMH67H8). As the concentration of dimyristoylphosphocholine (DMPC) was increased such that the q ratio was between 0.16 and 0.42, there was less crowding in the cross peaks …


Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy Jan 2017

Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy

Publications and Research

The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a class of small nucleic acid ligands that are composed of single-stranded modified/unmodified RNA/DNA molecules, can be evolved from a complex library using Systematic Evolution of Ligands by EXponential enrichment (SELEX) against almost any molecule. Since its introduction in 1990, in stages, SELEX technology has itself undergone several modifications, improving selection and broadening the repertoire of targets. This …


Identification, Validation, And Targeting Of The Mutant P53- Parp-Mcm Chromatin Axis In Triple Negative Breast Cancer, Wei-Gang Qiu, Alla Polotskaia, Gu Xiao, Lia Di, Yuhan Zhao, Wenwei Hu, John Philip, Ronald C. Hendrickson, Jill Bargonetti Jan 2017

Identification, Validation, And Targeting Of The Mutant P53- Parp-Mcm Chromatin Axis In Triple Negative Breast Cancer, Wei-Gang Qiu, Alla Polotskaia, Gu Xiao, Lia Di, Yuhan Zhao, Wenwei Hu, John Philip, Ronald C. Hendrickson, Jill Bargonetti

Publications and Research

Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous …


The Replication Initiator Of The Cholera Pathogen’S Second Chromosome Shows Structural Similarity To Plasmid Initiators, Natalia Orlova, Matthew Gerding, Olha Ivashkiv, Paul Dominic B. Olinares, Brian T. Chait, Matthew K. Waldor, David Jeruzalmi Dec 2016

The Replication Initiator Of The Cholera Pathogen’S Second Chromosome Shows Structural Similarity To Plasmid Initiators, Natalia Orlova, Matthew Gerding, Olha Ivashkiv, Paul Dominic B. Olinares, Brian T. Chait, Matthew K. Waldor, David Jeruzalmi

Publications and Research

The conserved DnaA-oriC system is used to initiate replication of primary chromosomes throughout the bacterial kingdom; however, bacteria with multipartite genomes evolved distinct systems to initiate replication of secondary chromosomes. In the cholera pathogen, Vibrio cholerae, and in related species, secondary chromosome replication requires the RctB initiator protein. Here, we show that RctB consists of four domains. The structure of its central two domains resembles that of several plasmid replication initiators. RctB contains at least three DNA binding winged-helix-turn-helix motifs, and mutations within any of these severely compromise biological activity. In the structure, RctB adopts a headto- head dimeric configuration …


A Pretargeted Approach For The Multimodal Pet/Nirf Imaging Of Colorectal Cancer, Pierre Adumeau, Kathryn E. Carnazza, Christian Brand, Sean D. Carlin, Thomas Reiner, Brian J. Agnew, Jason S. Lewis, Brian M. Zeglis Sep 2016

A Pretargeted Approach For The Multimodal Pet/Nirf Imaging Of Colorectal Cancer, Pierre Adumeau, Kathryn E. Carnazza, Christian Brand, Sean D. Carlin, Thomas Reiner, Brian J. Agnew, Jason S. Lewis, Brian M. Zeglis

Publications and Research

The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89Zr poses two important clinical complications: high radiation doses …


Myelinating Glia Differentiation Is Regulated By Extracellular Matrix Elasticity, Mateusz M. Urbanski, Lyle Kingsbury, Daniel Moussouros, Imran Kassim, Saraf Mehjabeen, Navid Paknejad, Alicia Meléndez Sep 2016

Myelinating Glia Differentiation Is Regulated By Extracellular Matrix Elasticity, Mateusz M. Urbanski, Lyle Kingsbury, Daniel Moussouros, Imran Kassim, Saraf Mehjabeen, Navid Paknejad, Alicia Meléndez

Publications and Research

The mechanical properties of living tissues have a significant impact on cell differentiation, but remain unexplored in the context of myelin formation and repair. In the PNS, the extracellular matrix (ECM) incorporates a basal lamina significantly denser than the loosely organized CNS matrix. Inhibition of non-muscle myosin II (NMII) enhances central but impairs peripheral myelination and NMII has been implicated in cellular responses to changes in the elasticity of the ECM. To directly evaluate whether mechanotransduction plays a role in glial cell differentiation, we cultured Schwann cells (SC) and oligodendrocytes (OL) on matrices of variable elastic modulus, mimicking either their …


Receptor-Type Guanylyl Cyclase At 76c (Gyc76c) Regulates De Novo Lumen Formation During Drosophila Tracheal Development, Monn Monn Myat, Unisha Patel Sep 2016

Receptor-Type Guanylyl Cyclase At 76c (Gyc76c) Regulates De Novo Lumen Formation During Drosophila Tracheal Development, Monn Monn Myat, Unisha Patel

Publications and Research

Lumen formation and maintenance are important for the development and function of essential organs such as the lung, kidney and vasculature. In the Drosophila embryonic trachea, lumena formde novo to connect the different tracheal branches into an interconnected network of tubes. Here, we identify a novel role for the receptor type guanylyl cyclase at 76C (Gyc76C) in de novo lumen formation in the Drosophila trachea.We show that in embryosmutant for gyc76C or its downsteam effector protein kinase G (PKG) 1, tracheal lumena are disconnected. Dorsal trunk (DT) cells of gyc76C mutant embryos migrate to contact each other and complete the …


Odorant Receptors Can Mediate Axonal Identity And Gene Choice Via Campindependent Mechanisms, Kiavash Movahedi, Xavier Grosmaitre, Paul Feinstein Jul 2016

Odorant Receptors Can Mediate Axonal Identity And Gene Choice Via Campindependent Mechanisms, Kiavash Movahedi, Xavier Grosmaitre, Paul Feinstein

Publications and Research

Odorant receptors (ORs) control several aspects of cell fate in olfactory sensory neurons (OSNs), including singular gene choice and axonal identity. The mechanisms of OR-induced axon guidance have been suggested to principally rely on G-protein signalling. Here, we report that for a subset of OSNs, deleting G proteins or altering their levels of signalling does not affect axonal identity. Signalling-deficient ORs or surrogate receptors that are unable to couple to Gs/Golf still provide axons with distinct identities and the anterior–posterior targeting of axons does not correlate with the levels of cAMP produced by genetic modifications. In addition, we refine the …


Tricurin, A Novel Formulation Of Curcumin, Epicatechin Gallate, And Resveratrol, Inhibits The Tumorigenicity Of Human Papillomaviruspositive Head And Neck Squamous Cell Carcinoma, Longzhu Piao, Sumit Mukherjee, Qing Chang, Xiujie Xie, Hong Li, Mario R. Castellanos, Probal Banerjee, Hassan Iqbal, Ryan Ivancic, Xueqian Wang, Theodoros N. Teknos, Quintin Pan Jul 2016

Tricurin, A Novel Formulation Of Curcumin, Epicatechin Gallate, And Resveratrol, Inhibits The Tumorigenicity Of Human Papillomaviruspositive Head And Neck Squamous Cell Carcinoma, Longzhu Piao, Sumit Mukherjee, Qing Chang, Xiujie Xie, Hong Li, Mario R. Castellanos, Probal Banerjee, Hassan Iqbal, Ryan Ivancic, Xueqian Wang, Theodoros N. Teknos, Quintin Pan

Publications and Research

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and …


Intronic Cleavage And Polyadenylation Regulates Gene Expression During Dna Damage Response Through U1 Snrna, Emral Devany, Ji Yeon Park, Michael R. Murphy, George Zakusilo, Jorge Baquero, Xiaokan Zhang, Mainul Hoque, Bin Tian, Frida E. Kleiman Jun 2016

Intronic Cleavage And Polyadenylation Regulates Gene Expression During Dna Damage Response Through U1 Snrna, Emral Devany, Ji Yeon Park, Michael R. Murphy, George Zakusilo, Jorge Baquero, Xiaokan Zhang, Mainul Hoque, Bin Tian, Frida E. Kleiman

Publications and Research

The DNA damage response involves coordinated control of gene expression and DNA repair. Using deep sequencing, we found widespread changes of alternative cleavage and polyadenylation site usage on ultraviolet-treatment in mammalian cells. Alternative cleavage and polyadenylation regulation in the 3ʹ untranslated region is substantial, leading to both shortening and lengthening of 3ʹ untranslated regions of genes. Interestingly, a strong activation of intronic alternative cleavage and polyadenylation sites is detected, resulting in widespread expression of truncated transcripts. Intronic alternative cleavage and polyadenylation events are biased to the 5ʹ end of genes and affect gene groups with important functions in DNA damage …


A Revisited Phylogeography Of Nautilus Pompilius, Lauren E. Vandepas, Frederick D. Dooley, Gregory J. Barord, Billie J. Swalla, Peter D. Ward May 2016

A Revisited Phylogeography Of Nautilus Pompilius, Lauren E. Vandepas, Frederick D. Dooley, Gregory J. Barord, Billie J. Swalla, Peter D. Ward

Publications and Research

The cephalopod genus Nautilus is considered a “living fossil” with a contested number of extant and extinct species, and a benthic lifestyle that limits movement of animals between isolated seamounts and landmasses in the Indo-Pacific. Nautiluses are fished for their shells, most heavily in the Philippines, and these fisheries have little monitoring or regulation. Here, we evaluate the hypothesis that multiple species of Nautilus (e.g., N. belauensis, N. repertus and N. stenomphalus) are in fact one species with a diverse phenotypic and geologic range. Using mitochondrial markers, we show that nautiluses from the Philippines, eastern Australia (Great Barrier Reef), Vanuatu, …


Innervation Of Gill Lateral Cells In The Bivalve Mollusc Crassostrea Virginica Affects Cellular Membrane Potential And Cilia Activity, Edward J. Catapane, Michael Nelson, Trevon Adams, Margaret A. Carroll May 2016

Innervation Of Gill Lateral Cells In The Bivalve Mollusc Crassostrea Virginica Affects Cellular Membrane Potential And Cilia Activity, Edward J. Catapane, Michael Nelson, Trevon Adams, Margaret A. Carroll

Publications and Research

Gill lateral cells of Crassostrea virginica are innervated by the branchial nerve, which contains serotonergic and dopaminergic fibers that regulate cilia beating rate. Terminal release of serotonin or dopamine results in an increase or decrease, respectively, of cilia beating rate in lateral gill cells. In this study we used the voltage sensitive fluorescent probe DiBAC4(3) to quantify changes in gill lateral cell membrane potential in response to electrical stimulation of the branchial nerve or to applications of serotonin and dopamine, and correlate these changes to cilia beating rates. Application of serotonin to gill lateral cells caused prolonged membrane depolarization, similar …


Spatial Engineering Of Osteochondral Tissue Constructs Through Microfluidically Directed Differentiation Of Mesenchymal Stem Cells, Stephen M. Goldman, Gilda A. Barabino Apr 2016

Spatial Engineering Of Osteochondral Tissue Constructs Through Microfluidically Directed Differentiation Of Mesenchymal Stem Cells, Stephen M. Goldman, Gilda A. Barabino

Publications and Research

The development of tissue engineered osteochondral units has been slowed by a number of technical hurdles associated with recapitulating their heterogeneous nature ex vivo. Subsequently, numerous approaches with respect to cell sourcing, scaffolding composition, and culture media formulation have been pursued, which have led to high variability in outcomes and ultimately the lack of a consensus bioprocessing strategy. As such, the objective of this study was to standardize the design process by focusing on differentially supporting formation of cartilaginous and bony matrix by a single cell source in a spatially controlled manner within a single material system. A cell-polymer solution …


Dengue-Induced Autophagy, Virus Replication And Protection From Cell Death Require Er Stress (Perk) Pathway Activation, E. Datan, S. G. Roy, G. Germain, N. Zali, J. E. Mclean, G. Golshan, S. Harbajan, R. A. Lockshin, Z. Zakeri Mar 2016

Dengue-Induced Autophagy, Virus Replication And Protection From Cell Death Require Er Stress (Perk) Pathway Activation, E. Datan, S. G. Roy, G. Germain, N. Zali, J. E. Mclean, G. Golshan, S. Harbajan, R. A. Lockshin, Z. Zakeri

Publications and Research

Avirus that reproduces in a host without killing cells can easily establish a successful infection. Previously, we showed that dengue-2, a virus that threatens 40% of the world, induces autophagy, enabling dengue to reproduce in cells without triggering cell death. Autophagy further protects the virus-laden cells from further insults. In this study, we evaluate how it does so; we show that dengue upregulates host pathways that increase autophagy, namely endoplasmic reticulum (ER) stress and ataxia telangiectasiamutated (ATM) signaling followed by production of reactive oxygen species (ROS). Inhibition of ER stress or ATM signaling abrogates the dengueconferred protection against other cell …


Characterization And Recombinant Expression Of Terebrid Venom Peptide From Terebra Guttata, John Moon, Juliette Gorson, Mary Elizabeth Wright, Laurel Yee, Samer Khawaja, Hye Young Shin, Yasmine Karma, Rajeeva Lochan Musunri, Michelle Yun, Mandë Holford Mar 2016

Characterization And Recombinant Expression Of Terebrid Venom Peptide From Terebra Guttata, John Moon, Juliette Gorson, Mary Elizabeth Wright, Laurel Yee, Samer Khawaja, Hye Young Shin, Yasmine Karma, Rajeeva Lochan Musunri, Michelle Yun, Mandë Holford

Publications and Research

Venom peptides found in terebrid snails expand the toolbox of active compounds that can be applied to investigate cellular physiology and can be further developed as future therapeutics. However, unlike other predatory organisms, such as snakes, terebrids produce very small quantities of venom, making it difficult to obtain sufficient amounts for biochemical characterization. Here, we describe the first recombinant expression and characterization of terebrid peptide, teretoxin Tgu6.1, from Terebra guttata. Tgu6.1 is a novel forty-four amino acid teretoxin peptide with a VI/VII cysteine framework (C–C–CC–C–C) similar to O, M and I conotoxin superfamilies. A ligation-independent cloning strategy with an ompT …


Toward Repurposing Metformin As A Precision Anti-Cancer Therapy Using Structural Systems Pharmacology, Thomas Hart, Shihab Dider, Weiwei Han, Hua Xu, Zhongming Zhao, Lei Xie Feb 2016

Toward Repurposing Metformin As A Precision Anti-Cancer Therapy Using Structural Systems Pharmacology, Thomas Hart, Shihab Dider, Weiwei Han, Hua Xu, Zhongming Zhao, Lei Xie

Publications and Research

Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally …


Characterization Of Induced Pluripotent Stem Cell Microvesicle Genesis, Morphology And Pluripotent Content, Jing Zhou, Shima Ghoroghi, Alberto Benito-Martin, Hao Wu, Uchenna John Unachukwu, Linda Saxe Einbond, Sara Guariglia, Hector Peinado, Stephen Redenti Jan 2016

Characterization Of Induced Pluripotent Stem Cell Microvesicle Genesis, Morphology And Pluripotent Content, Jing Zhou, Shima Ghoroghi, Alberto Benito-Martin, Hao Wu, Uchenna John Unachukwu, Linda Saxe Einbond, Sara Guariglia, Hector Peinado, Stephen Redenti

Publications and Research

Microvesicles (MVs) are lipid bilayer-covered cell fragments that range in diameter from 30 nm–1uM and are released from all cell types. An increasing number of studies reveal that MVs contain microRNA, mRNA and protein that can be detected in the extracellular space. In this study, we characterized induced pluripotent stem cell (iPSC) MV genesis, content and fusion to retinal progenitor cells (RPCs) in vitro. Nanoparticle tracking revealed that iPSCs released approximately 2200 MVs cell/hour in the first 12 hrs with an average diameter of 122 nm. Electron and light microscopic analysis of iPSCs showed MV release via lipid bilayer budding. …