Clinicopathologic Features Of Endometrial Cancer With Mismatch Repair Deficiency, 2020 Weill Cornell Medical College
Clinicopathologic Features Of Endometrial Cancer With Mismatch Repair Deficiency, Sushmita Gordhandas, Ryan M. Kahn, Charlotte Gamble, Nizam Talukdar, Brandon Maddy, Becky Baltich Nelson, Gulce Askin, Paul J. Christos, Kevin Holcomb, Thomas A. Caputo, Eloise Chapman-Davis, Melissa K. Frey
Open Access Articles
The inclusion of DNA mismatch repair (MMR) evaluation as a standard of care for endometrial cancer management will result in a growing population of patients with MMR deficiency and negative germline Lynch syndrome testing (MMR-deficient). In this systematic review and study, the clinicopathologic features of endometrial cancer in patients with MMR-intact, MLH1 methylation positive, MMR-deficient or Lynch syndrome are evaluated. A systematic search of online databases between 1990 and 2018 identified studies of endometrial cancer patients with tumour testing (MMR protein immunohistochemistry or microsatellite instability) and germline assessment for Lynch syndrome. Extracted data included tumour testing, germline genetic testing, age ...
Hydrazines As Versatile Chemical Biology Probes And Drug-Discovery Tools For Cofactor-Dependent Enzymes [Preprint], 2020 University of Pennsylvania
Hydrazines As Versatile Chemical Biology Probes And Drug-Discovery Tools For Cofactor-Dependent Enzymes [Preprint], Zongtao Lin, Xie Wang, Katelyn A. Bustin, Lin He, Radu M. Suciu, Nancy Schek, Mina Ahmadi, Kai Hu, Erika J. Olson, William H. Parsons, Eric S. Witze, Paul D. Morton, Ann M. Gregus, Matthew W. Buczynski, Megan L. Matthews
University of Massachusetts Medical School Faculty Publications
Known chemoproteomic probes generally use warheads that tag a single type of amino acid or modified form thereof to identify cases in which its hyper-reactivity underpins function. Much important biochemistry derives from electron-poor enzyme cofactors, transient intermediates and chemically-labile regulatory modifications, but probes for such species are underdeveloped. Here, we have innovated a versatile class of chemoproteomic probes for this less charted hemisphere of the proteome by using hydrazine as the common chemical warhead. Its electron-rich nature allows it to react by both polar and radicaloid mechanisms and to target multiple, pharmacologically important functional classes of enzymes bearing diverse organic ...
In Vivo Biosynthesis Of Inorganic Nanomaterials Using Eukaryotes - A Review, 2020 Lamar University
In Vivo Biosynthesis Of Inorganic Nanomaterials Using Eukaryotes - A Review, Ashiqur Rahman, Julia Lin, Francisco E. Jaramillo, Dennis A. Bazylinski, Clayton Jeffryes, Si Amar Dahoumane
Life Sciences Faculty Publications
Bionanotechnology, the use of biological resources to produce novel, valuable nanomaterials, has witnessed tremendous developments over the past two decades. This eco-friendly and sustainable approach enables the synthesis of numerous, diverse types of useful nanomaterials for many medical, commercial, and scientific applications. Countless reviews describing the biosynthesis of nanomaterials have been published. However, to the best of our knowledge, no review has been exclusively focused on the in vivo biosynthesis of inorganic nanomaterials. Therefore, the present review is dedicated to filling this gap by describing the many different facets of the in vivo biosynthesis of nanoparticles (NPs) using living eukaryotic ...
Gocats: A Tool For Categorizing Gene Ontology Into Subgraphs Of User-Defined Concepts, 2020 University of Kentucky
Gocats: A Tool For Categorizing Gene Ontology Into Subgraphs Of User-Defined Concepts, Eugene Waverly Hinderer Iii, Hunter N. B. Moseley
Molecular and Cellular Biochemistry Faculty Publications
Gene Ontology is used extensively in scientific knowledgebases and repositories to organize a wealth of biological information. However, interpreting annotations derived from differential gene lists is often difficult without manually sorting into higher-order categories. To address these issues, we present GOcats, a novel tool that organizes the Gene Ontology (GO) into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. We tested GOcats performance using subcellular location categories to mine annotations from GO-utilizing knowledgebases and evaluated their accuracy against immunohistochemistry datasets in the Human Protein Atlas (HPA). In comparison to term categorizations ...
Transgenic Goats Producing An Improved Version Of Cetuximab In Milk [Preprint], 2020 University of Auckland
Transgenic Goats Producing An Improved Version Of Cetuximab In Milk [Preprint], Götz Laible, Sally Cole, Brigid Brophy, Paul Maclean, Li How Chen, Dan P. Pollock, Lisa A. Cavacini, Nathalie Fournier, Christophe De Romeuf, Nicholas C. Masiello, William G. Gavin, David N. Wells, Harry M. Meade
University of Massachusetts Medical School Faculty Publications
Therapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs. Here, we focused on cetuximab, a mAb against epidermal growth factor receptor, that is commercially produced under the brand name Erbitux and approved for anti-cancer treatments. We generated several transgenic goat lines that produce cetuximab in their milk. Two lines were ...
Profiling The Circulating Mrna Transcriptome In Human Liver Disease, 2020 Baruch S. Blumberg Institute
Profiling The Circulating Mrna Transcriptome In Human Liver Disease, Aejaz Sayeed, Brielle E Dalvano, David E Kaplan, Usha Viswanathan, John Kulp, Alhaji H Janneh, Lu-Yu Hwang, Adam Ertel, Cataldo Doria, Timothy Block
Department of Cancer Biology Faculty Papers
The human circulation contains cell-free DNA and non-coding microRNA (miRNA). Less is known about the presence of messenger RNA (mRNA). This report profiles the human circulating mRNA transcriptome in people with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) to determine whether mRNA analytes can be used as biomarkers of liver disease. Using RNAseq and RT-qPCR, we investigate circulating mRNA in plasma from HCC and LC patients and demonstrate detection of transcripts representing more than 19,000 different protein coding genes. Remarkably, the circulating mRNA expression levels were similar from person to person over the 21 individuals whose samples were analyzed ...
Ribosome Engineering Reveals The Importance Of 5s Rrna Autonomy For Ribosome Assembly, 2020 The University of Illinois at Chicago
Ribosome Engineering Reveals The Importance Of 5s Rrna Autonomy For Ribosome Assembly, Shijie Huang, Nikolay A. Aleksashin, Anna B. Loveland, Dorota Klepacki, Kaspar Reier, Amira Kefi, Teresa Szal, Jaanus Remme, Luc Jaeger, Nora Vazquez-Laslop, Andrei A. Korostelev, Alexander S. Mankin
Open Access Articles
5S rRNA is an indispensable component of cytoplasmic ribosomes in all species. The functions of 5S rRNA and the reasons for its evolutionary preservation as an independent molecule remain unclear. Here we used ribosome engineering to investigate whether 5S rRNA autonomy is critical for ribosome function and cell survival. By linking circularly permutated 5S rRNA with 23S rRNA we generated a bacterial strain devoid of free 5S rRNA. Viability of the engineered cells demonstrates that autonomous 5S rRNA is dispensable for cell growth under standard conditions and is unlikely to have essential functions outside the ribosome. The fully assembled ribosomes ...
Deciphering Complex Mechanisms Of Resistance And Loss Of Potency Through Coupled Molecular Dynamics And Machine Learning [Preprint], 2020 University of Massachusetts Medical School
Deciphering Complex Mechanisms Of Resistance And Loss Of Potency Through Coupled Molecular Dynamics And Machine Learning [Preprint], Florian Leidner, Nese Kurt Yilmaz, Celia A. Schiffer
University of Massachusetts Medical School Faculty Publications
Drug resistance threatens many critical therapeutics through mutations in the drug target. The molecular mechanisms by which combinations of mutations, especially involving those distal from the active site, alter drug binding to confer resistance are poorly understood and thus difficult to counteract. A strategy coupling parallel molecular dynamics simulations and machine learning to identify conserved mechanisms underlying resistance was developed. A series of 28 HIV-1 protease variants with up to 24 varied substitutions were used as a rigorous model of this strategy. Many of the mutations were distal from the active site and the potency to darunavir varied from low ...
Hybrid Thermophilic/Mesophilic Enzymes Reveal A Role For Conformational Disorder In Regulation Of Bacterial Enzyme I, Rochelle R. Dotas, Trang T. Nguyen, Charles E. Stewart Jr., Rodolfo Ghirlando, Davit A. Potoyan, Vincenzo Venditti
Conformational disorder is emerging as an important feature of biopolymers, regulating a vast array of cellular functions, including signaling, phase separation, and enzyme catalysis. Here we combine NMR, crystallography, computer simulations, protein engineering, and functional assays to investigate the role played by conformational heterogeneity in determining the activity of the C-terminal domain of bacterial Enzyme I (EIC). In particular, we design chimeric proteins by hybridizing EIC from thermophilic and mesophilic organisms, and we characterize the resulting constructs for structure, dynamics, and biological function. We show that EIC exists as a mixture of active and inactive conformations and that functional regulation ...
Role Of The Hyaluronan Receptor, Stabilin-2/Hare, In Health And Disease, 2020 University of Nebraska-Lincoln
Role Of The Hyaluronan Receptor, Stabilin-2/Hare, In Health And Disease, Edward N. Harris, Erika Baker
Biochemistry -- Faculty Publications
Stabilin-2/HARE is the primary clearance receptor for circulating hyaluronan (HA), a polysaccharide found in the extracellular matrix (ECM) of metazoans. HA has many biological functions including joint lubrication, ocular turgor pressure, skin elasticity and hydration, cell motility, and intercellular signaling, among many others. The regulatory system for HA content in the tissues, lymphatics, and circulatory systems is due, in part, to Stabilin-2/HARE. The activity of this receptor was discovered about 40 years ago (early 1980s), cloned in the mid-1990s, and has been characterized since then. Here, we discuss the overall domain organization of this receptor and how it ...
Short Tandem Repeats Diversity In Indian And Pakistani Population Living In United Arab Emirates, 2020 United Arab Emirates University
Short Tandem Repeats Diversity In Indian And Pakistani Population Living In United Arab Emirates, Ruksar Salim Damji
Short Tandem Repeats (STRs), have become increasingly popular markers of choice due to its wide array of advantages in the sector of forensic investigation. It is necessary to expand genetic research into residing populations i.e., Indian and Pakistani, in the same geographic region such as in the United Arab Emirates (UAE). The objectives of this study were to: (1) assess the forensic efficiency parameters and population structure analysis of the autosomal STR loci for the most potent amplification kit (2) estimate the allele frequencies; and (3) determine the significance of increasing the number of STR loci used in forensic ...
Dynamics Of The 4d Genome During In Vivo Lineage Specification And Differentiation, 2020 University of Oxford
Dynamics Of The 4d Genome During In Vivo Lineage Specification And Differentiation, A. Marieke Oudelaar, Daniel Hidalgo, Merav Socolovsky, Douglas R. Higgs, Jim R. Hughes
Open Access Articles
Mammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of regulatory elements, formation of structural chromatin interactions and gene expression during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study chromatin architecture at high spatial and temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis of chromatin accessibility and single-cell expression data shows that regulatory elements gradually become accessible within pre-existing TADs during early differentiation. This is followed by structural re-organization within the TAD and formation of ...
Protonic Capacitor: Elucidating The Biological Significance Of Mitochondrial Cristae Formation, 2020 Old Dominion University
Protonic Capacitor: Elucidating The Biological Significance Of Mitochondrial Cristae Formation, James Weifu Lee
Chemistry & Biochemistry Faculty Publications
For decades, it was not entirely clear why mitochondria develop cristae? The work employing the transmembrane-electrostatic proton localization theory reported here has now provided a clear answer to this fundamental question. Surprisingly, the transmembrane-electrostatically localized proton concentration at a curved mitochondrial crista tip can be significantly higher than that at the relatively flat membrane plane regions where the proton-pumping respiratory supercomplexes are situated. The biological significance for mitochondrial cristae has now, for the first time, been elucidated at a protonic bioenergetics level: 1) The formation of cristae creates more mitochondrial inner membrane surface area and thus more protonic capacitance for ...
Land Application Of Sewage Sludge: Physiological And Biochemical Response Of The Rio Grande Tomato, 2020 Centre national de recherche en biotechnologie, Constantine, Algérie
Land Application Of Sewage Sludge: Physiological And Biochemical Response Of The Rio Grande Tomato, Nabil Charchar, Ali Elafri, Redwane Rais, Halassi Ismahen
Journal of Bioresource Management
Treated wastewater produces sewage sludge as a by-product that may have beneficial implications on agricultural practices. The effects of sludge amendments on growth, morphological and biochemical characteristics of the agro-industrial Tomato cultivar Rio Grande were observed. A pot culture experiment was carried out during 4 months (16 February 2019 to 18 June 2019), at an experimental green house in the locality of Salah Soufi, Guelma, north-eastern Algeria. There were significant differences between soil and sewage sludge samples. Total nitrogen (20.58 mg/kg) was more available in sewage sludge than in soil (N = 2.09 ± 0.3 mg/kg). In ...
Evidence Of Pathogen-Induced Immunogenetic Selection Across The Large Geographic Range Of A Wild Seabird, 2020 Univ Oxford, Dept Zool, Oxford, England
Evidence Of Pathogen-Induced Immunogenetic Selection Across The Large Geographic Range Of A Wild Seabird, Hila Levy, Stephen R. Fiddaman, Julianna A. Vianna, Daly Noll, Gemma Clucas, Jasmine K. H. Sidhu, Michael J. Polito, Charles A. Bost, Richard A. Phillips, Sarah Crofts, Gary D. Miller, Pierre Pistorius, Francesco Bonnadonna, Celine Le Bohec, Andres Barbosa, Phil Trathan, Andrea Raya Rey, Laurent A. F. Frantz, Tom Hart, Adrian L. Smith
Over evolutionary time, pathogen challenge shapes the immunepheno type of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between ''different clades. Inthis study, we examine the ...
Kinetic Exclusion Assay Of Biomolecules By Aptamer Capture, 2020 Boise State University
Kinetic Exclusion Assay Of Biomolecules By Aptamer Capture, Mark H. Smith, Daniel Fologea
Physics Faculty Publications and Presentations
DNA aptamers are short nucleotide oligomers selected to bind a target ligand with affinity and specificity rivaling that of antibodies. These remarkable features recommend aptamers as candidates for analytical and therapeutic applications that traditionally use antibodies as biorecognition elements. Numerous traditional and emerging analytical techniques have been proposed and successfully implemented to utilize aptamers for sensing purposes. In this work, we exploited the analytical capabilities offered by the kinetic exclusion assay technology to measure the affinity of fluorescent aptamers for their thrombin target and quantify the concentration of analyte in solution. Standard binding curves constructed by using equilibrated mixtures of ...
Proton Pumping Mechanism In Cytochrome C Oxidase, 2020 The Graduate Center, City University of New York
Proton Pumping Mechanism In Cytochrome C Oxidase, Xiuhong Cai
Dissertations, Theses, and Capstone Projects
Cytochrome c Oxidase (CcO), is the terminal electron acceptor in the membrane bound aerobic respiratory chain. It reduces O2 to water. The energy released by this reaction is stored by pumping protons from the high pH, N-side of the membrane to the low pH, P-side. The generated proton gradient provides the motive force for synthesis of ATP by the ATP synthase.
Building a proton gradient across the membrane requires that proton transport must occur along controllable proton pathways to prevent proton leakage to the N-side. It has been suggested that CcO function requires proton transfer channels in both the ...
Dictyostelium Discoideum Protein Kinase C-Orthologue Pkca Regulates The Actin Cytoskeleton Through Interaction With Phospholipase D And P21-Activated Kinase, 2020 The Graduate Center, City University of New York
Dictyostelium Discoideum Protein Kinase C-Orthologue Pkca Regulates The Actin Cytoskeleton Through Interaction With Phospholipase D And P21-Activated Kinase, Sean Singh
Dissertations, Theses, and Capstone Projects
Proper regulation of the actin cytoskeleton is crucial to many cellular processes. Many of these processes are regulated by extracellular signaling cues, which direct changes in the actin cytoskeleton, resulting in changes to cellular morphology, and directed motility. The social amoeba, Dictyostelium discoideum, is used as a simple model system to study the translation of extracellular signals to the actin cytoskeleton. When starved, these unicellular amoebae undergo a multicellular developmental process characterized by a tightly regulated sequence of signaling events. This results in chemotaxis and formation of a multicellular aggregate, and ultimately cell differentiation and the formation of a fruiting ...
Myeloid-Derived Suppressor Cells Infiltration In Non-Small-Cell Lung Cancer Tumor And Mage-A4 And Ny-Eso-1 Expression, 2020 Old Dominion University
Myeloid-Derived Suppressor Cells Infiltration In Non-Small-Cell Lung Cancer Tumor And Mage-A4 And Ny-Eso-1 Expression, Zhenbo Hou, Xiao Liang, Xinmei Wang, Ziqiang Zhou, Guilan Shi
Cancer/testis antigens melanoma‑associated antigen 4 (MAGE‑A4) and New York esophageal squamous cell carcinoma‑1 (NY‑ESO‑1) are of clinical interest as biomarkers and present valuable targets for immunotherapy; however, they are poor prognostic markers in non‑small cell lung cancer (NSCLC). In addition, myeloid derived suppressor cells (MDSCs) are recognized as a key element in tumor escape and progression. The aim of the present study was to investigate the diagnostic and prognostic value of MAGE‑A4 and NY‑ESO‑1, and their association with MDSCs in NSCLC samples. The expression levels of MAGE‑A4 and NY ...
Modeling Single Microtubules As A Colloidal System To Measure The Harmonic Interactions Between Tubulin Dimers In Bovine Brain Derived Versus Cancer Cell Derived Microtubules, 2020 New Jersey Institute of Technology
Modeling Single Microtubules As A Colloidal System To Measure The Harmonic Interactions Between Tubulin Dimers In Bovine Brain Derived Versus Cancer Cell Derived Microtubules, Arooj Aslam
The local properties of tubulin dimers dictate the properties of the larger microtubule assembly. In order to elucidate this connection, tubulin-tubulin interactions are be modeled as harmonic interactions to map the stiffness matrix along the length of the microtubule. The strength of the interactions are measured by imaging and tracking the movement of segments along the microtubule over time, and then performing a fourier transform to extract the natural vibrational frequencies. Using this method the first ever reported experimental phonon spectrum of the microtubule is reported. This method can also be applied to other biological materials, and opens new doors ...