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Manufacturing of seasonal and pandemic influenza vaccines–A case study
Published in Amine Kamen, Laura Cervera, Bioprocessing of Viral Vaccines, 2023
Cristina A. T. Silva, Shantoshini Dash, Amine Kamen
The influenza viral envelope is composed of a host-derived lipid bilayer that presents three different transmembrane proteins, HA (hemagglutinin), NA (neuraminidase), and M2 (matrix 2). HA, a glycosylated integral membrane protein, is the most abundant on the virus surface (around 80%), being responsible for the initial attachment of the virus to host cell receptors (bearing a terminal sialic acid) and later merging of viral envelope and host cell membrane. NA, which represents approximately 17% of viral surface proteins, cleaves the sialic acid residues in host cell receptors to release new virions, allowing for the spread of the virus [4,7]. Protective immunity against influenza viruses is mediated mainly by neutralizing antibodies against these two surface proteins, which prevents the infection and spread of the virus in host cells [11]. M2, present in minor quantities on the membrane, is an ion channel that has an important role in early phases of the infection. Inside the virus, each RNA segment is wrapped around nucleoprotein (NP) monomers, forming viral ribonucleoprotein (RNP) complexes alongside with the viral polymerases PB1, PB2 and PA. Attached to the inside of the membrane, M1 (matrix) protein interacts with RNP complexes [8].
Nanostructured Cellular Biomolecules and Their Transformation in Context of Bionanotechnology
Published in Anil Kumar Anal, Bionanotechnology, 2018
Ribosomal ribonucleic acid: About two-thirds of ribosomal mass is composed of rRNA, which makes up almost all key sites of ribosomal function. Ribosomes, therefore are ribonucleoprotein, which are often regarded as RNA enzymes or ribozymes. Prokaryotic ribosomes are composed of 30S (small subunit) and 50S (large subunit) The 30S subunit consist of 16S rRNA (RNA molecules with more than 1500 nucleotides) and 21 proteins (referred as S1 through S21), whereas 50S subunit is composed of 23S (RNA molecules with around 2900 nucleotides) and the 5S (RNAs with 120 nucleotides) along with 34 different proteins (referred as L1 through L34). Eukaryotic ribosome, which is slightly larger than prokaryotic ribosome, is composed of 40S small subunit and 60S large subunit. rRNA functions to read the genetic code of mRNA and synthesizes the specific proteins to that particular code. The rRNA of small subunit functions to decode the genetic information and the large subunit functions to add the amino acid onto the growing peptide chain during the protein synthesis (Swayze et al. 2007).
Virus-Based Nanobiotechnology
Published in Yubing Xie, The Nanobiotechnology Handbook, 2012
Magnus Bergkvist, Brian A. Cohen
Perhaps no virus has played a larger role in the development of modern virology than the tobacco mosaic virus (TMV). The intensive study of TMV has resulted in several significant breakthroughs in molecular biology. Investigation into the causes of tobacco mosaic syndrome dating back to 1886 resulted in the identification of an infectious agent that was small enough to pass through candle-filters capable of removing bacteria from solution. This was the first instance of the identification of a “filterable agent” known to cause disease, an agent that would eventually be called a virus. It was the first virus to be purified, crystallized, and shown to be composed of ribonucleoprotein; the first virus to be imaged in an electron microscope; and the first virus shown to have intrinsically infective RNA. Later, TMV mutants were an integral part of the research that proved that the genetic code is nonoverlapping (Creager et al. 1999, Klug 1999, Knipe et al. 2007). Part of the reason that TMV is so well studied is because it is easily produced in large quantities from infected tobacco plants and that it can be assembled in vitro from purified protein and RNA; also as purified virions are remarkably stable, they can remain infective for up to 50 years.
Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis
Published in Journal of Environmental Science and Health, Part C, 2019
Dongying Li, William H. Tolleson, Dianke Yu, Si Chen, Lei Guo, Wenming Xiao, Weida Tong, Baitang Ning
The role of ncRNAs in regulating CYP expression has received increasing attention in the recent decade. It is estimated that 98% of the human genome consists of noncoding genes, producing a large number of ncRNA transcripts of various types.41 NcRNAs comprise a variety of RNA molecules that are not translated into proteins and include transfer RNA (tRNA), ribosomal RNA (rRNA), long noncoding RNA (lncRNA), microRNA (miRNA), small interfering RNA (siRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), piwi-interacting RNA (piRNA), and Y RNA components of the Ro60 ribonucleoprotein essential for DNA replication.42–44 NcRNAs longer than 200 nucleotides are defined as lncRNAs whereas those less than 200 nucleotides long are considered small noncoding RNAs, such as miRNAs, siRNAs, snRNAs, snoRNAs, and piRNAs.42 Of these ncRNA classes, miRNA and lncRNAs have been identified as significant epigenetic modulators of CYP expression.45–49 High-throughput technologies have provided a plethora of genomic and transcriptomic data related to ncRNAs and the analysis of these data using bioinformatics tools has facilitated the characterization of ncRNA functions.50,51
Autoantibodies and cancer among asbestos-exposed cohorts in Western Australia
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Renee N Carey, Jean C Pfau, Marvin J Fritzler, Jenette Creaney, Nicholas de Klerk, Arthur W (Bill) Musk, Peter Franklin, Nita Sodhi-Berry, Fraser Brims, Alison Reid
Immunoassays were performed by the Mitogen Diagnostics Laboratory (Calgary, Alberta, Canada). The levels of antibodies against 13 nuclear antigens were evaluated: dsDNA, Sm, histone (H2A, H2B, H3, H4), Jo-1 (histidyl tRNA synthetase), ribonucleoprotein (RNP), ribosomal P protein, proliferating cell nuclear antigen (PCNA), SSA/Ro60, SSB/La, Ro52/TRIM21, PM-Scl, Scl-70 (topoisomerase 1), centromere B (CENP-B). This multiplexed extractable nuclear antibody (ENA) profile utilized an addressable laser bead immunoassay (ALBIA) provided by TheraDiag (FIDIS: Paris, France). Cutoffs were established using internal calibrators provided by the manufacturers and control sera included with each assay run. Results were expressed as chemiluminescence intensity units (CIU) for ALBIA.
Mitochondrial uncoupling protein 2 is regulated through heterogeneous nuclear ribonucleoprotein K in lead exposure models
Published in Journal of Environmental Science and Health, Part C, 2020
Gaochun Zhu, Qian Zhu, Wei Zhang, Chen Hui, Yuwen Li, Meiyuan Yang, Shimin Pang, Yaobing Li, Guoyong Xue, Hongping Chen
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) belongs to a large family of RNA-binding proteins (RBPs) that fulfill a function on multiple aspects of nucleic acid metabolism. Interestingly, hnRNP K is widely expressed in hippocampal cell nucleus, cytoplasm and mitochondria.21 It has a modular structure with three K homology (KH) domains that interact with RNA and ssDNA,22 and a K interactive region (KI) which recruits various factors such as kinases and regulators.23,24 Besides, hnRNP K has nuclear localization signal (NLS) and nuclear shutting domain (KNS) which mediate hnRNP K translocation between cytoplasm and nucleus. Therefore, hnRNP K is thought a docking platform that integrates signals from multiple kinase cascades or regulators, then exports signals including transcription, mRNA stability, mRNA transport and translation, and eventually triggers diverse cellular responses.23,24 It has been reported that the roles of hnRNP K contribute to regulating transcripts coding synaptic plasticity and forming learning and memory. At excitatory synapses, hnRNP K regulates transcripts coding synaptic proteins including GluN1, GluA1, brain derived neurotrophic factor (BDNF) and calmodulin-dependent protein kinase II (CamKII), then enhances the synaptic NMDAR activities and improves NMDAR-mediated mEPSC and long-term potentiation (LTP) in hippocampal synapses, and finally boosts learning and memory.25 An interesting study has found that adiponectin could facilitate UCP2 mRNA stabilization and its protein synthesis in mitochondria of hepatic endothelial cells in this process involving hnRNP K.15 But, the mechanism that hnRNP K modulates the UCP2 expression in lead exposure has not been reported.