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Full-Text Articles in Life Sciences

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 …